Pharmacokinetics

Drug Name Mechanism of Action Effects

And
St. Phenobarbital Increase its own metabolism
Johns Phenytoin Increase metabolism of coadministered drug
Wort Rifampin Cytochrome P450 induction Produce toxic levels of reactive drug
Carbamazepine metabolites
And Grapefruit Cimetidine
Juice Toxic concentrations of drug
Ketoconazole
Cytochrome P450 inhibition [also grapefruit juice] Prolong the presence of active drug in the
Amidarone Erythromycin
body
Chloramphenicol
Can become displaced from binding to plasma proteins when administered with a Bleeding
Warfarin
sulfonamide → toxic concentration [may also interact with bile acid sequestrants reducing absorption]
Acetaminophen Overdose increases metabolism by CYP2E1 [rather than conjugation and excretion] to Liver failure
N-acetylcysteine yield toxic levels of NAPQI and reduction of glutathione stores TXT with N-acetylcysteine

Intro To ANS
Muscarinic Receptors: Exhibit PNS effects; found on autonomic effector tissues, NOT ganglia
Adrenergic Receptors: Responsible for “fight or flight”; Found on autonomic ganglia, skeletal NMJ and the adrenal gland

M2 3
M1 Found on heart & M3 1 2
1 2 Equal
Found in CNS presynaptic nerve Found on glands, bladder, and Equal affinity for Epi
Higher affinity for Epi affinity for
and ENS terminals inhibit smooth muscle of the eye & NE
Epi & NE
NE and Ach release
Gq IP3/DAG, Gi cAMP,
Gi cAMP Gq IP3/DAG, Ca2+, PKC Gq IP3/DAG, Ca2+. PKC Gs cAMP, Ca2+ Gs cAMP, PKA Gs cAMP
Ca2+ , PKC IP3/DAG
M3 on endothelial cells Ca2
eNOS NO
Ganglia release cGMP Vasodilation K + channels NE
Vascular and genitourinary Relaxation of smooth mm.
(depolarization and ACh release @
) smooth mm. contraction
If endothelial cells are damaged presynaptic sites Cardiac Output
Bronchodilation
(as in atherosclerosis), M3 HR at the SA node
gluconeogenesis
receptor will be on arterial smooth Ca2+ channels
K + channels opening venous capacitance and glycogenolysis
muscle vasoconstriction contractility of the
venous return= K + uptake in skeletal mm.
insulin atria
HR at the SA node venoconstriction lipolysis
GI gland secretion lipolysis
FA release
Bronchial secretion FA release conduction velocity lipolysis in
conduction gluconeogenesis
Bronchoconstriction aqueous humor at the AV node adipocytes
velocity at the AV glycogenolysis insulin by pancreatic
salivation/sweat production
node TPR=vasoconstriction cells hypokalemia
micturition renin
pupillary dilation (mydriasis)
pupillary constriction (miosis) GI wall relaxation vasoconstriction
contractility of the urethral sphincter contraction glucagon secretion by
erection Platelet aggregation blood volume
atria ejaculation pancreatic cells
ciliary mm contraction adapt for Vascular smooth mm. lipolysis
prostatic smooth mm. aqueous humor
near vision (visual contraction d/t Ca2+
contraction production
accommodation)

opens trabecular meshwork

intraocular pressure for glaucoma
D1 & D5: Gs cAMP in smooth mm. of renal vascular bed relaxation
 Rate limiting step
Na+ dependent
carrier

From
mitochondria
Choline acetyl
transferase

Vesicular
ACh
Transport

Release depends on
extracellular Ca2+

AChE breaks down

ACh choline + acetate

Via Tyrosine
decarboxylase

Dopa decarboxylase

Dopamine B-
hydroxylase
 Direct Acting Cholinergic Agonists
Drug Name Chemical Receptor Effects Uses PK Adverse Effects
Muscarinic Effects:
N and M CVS:
-M3 vasodilation , HR (M2),
Binding to M conduction at the SA/AV nodes
receptor (M2), contractility (M2)
Parasympathetic -@ small doses BP reflex
& sympathetic Acetate- Rapid Muscarinic Syndrome:
tachycardia
activity; sweat hydrolysis by AChE and generalized cholinergic
-@ high doses hypotension (M3)
Used to obtain rapid miosis after cataract stimulation sweating,
Acetylcholine glands and bradycardia (M2) pseudo-cholinesterase
surgery miosis, flushing, salivation,
Nicotinic effects Short t½ bradycardia, hypotension,
Nicotinic Effects: stimulate all
once M bronchospasm
Esters of autonomic ganglia, secretion of Epi
Choline receptors are from adrenal medulla, skeletal mm.,
blocked by high DUMBBELLSS
BP, vasoconstriction etc.
doses of Diarrhea
Quaternary
Atropine Urination
Ammonium LOOK AT Previous chart for all the
Miosis
Compound effects of M and N receptors
Bradycardia
(QAC) poorly Post-op and post-partum urinary retention
Bronchoconstriction
absorbed into
Carbamate- not Emesis
CNS Hypotonic, myogenic, neurogenic atony of the
Bethanechol M Beth activates bowel and bladder hydrolyzed by Lacrimation
bladder
AChE longer t½ Lethargy
Salivation
Ileus, gastroparesis, congenital megacolon
Sweating
Miosis during surgery
Carbamate- not
Miosis and contraction of ciliary hydrolyzed by
Carbachol M and N intraocular pressure after cataract surgery
mm. AChE longer t½
External use only
Glaucoma (use Pilocarpine first)
Slow hydrolysis by AChE-
Diagnosis of bronchial airway hyperreactivity
Methacholine M (little N) resistant to other
in pts w/o clinically apparent asthma
cholinesterases
Muscarine M
No clinical use
Arecoline M and N
2 agent for open angle glaucoma after Timolol
Natural Partial M Contraction of ciliary mm.
Alkaloids Mgmt. of acute close angle glaucoma (along CNS disturbances
Pilocarpine with Timolol, apraclonidine, acetazolamide) Sweating
Tertiary amine Secretions from sweat, salivary,
Salivation
(Can cross BBB) lacrimal, and bronchial glands
TXT of sxs of dry mouth d/t radiotherapy or
Sjogren’s Syndrome
Low dose: sympathetic and
parasympathetic ganglion Acute Nicotinic Poisoning:
depolarization Highly liposoluble nausea, salivation,
CVS: Sympathomimetic d/t abdominal pain, vomit,
Nn>Nm catecholamine release ( HR, BP) Fast absorption via oral diarrhea, cold sweats,
Ganglion GI and UG: Parasympathomimetic mucosa, lungs, GI mental confusion, weakness
Nicotine Smoking cessation therapy
Stimulant Tertiary amine nausea, diarrhea, vomit, voiding & mucosa, and skin Hypotension with weak,
(Can cross BBB) salivary/bronchial secretions rapid, irregular pulse
High doses: ganglion blockade d/t Crosses placenta and is Can lead to respiratory
prolonged depolarization secreted in breast milk arrest (central or
(desensitization) or neuromuscular peripheral) death
blockade
 Indirect Acting Cholinergic Agonists: AChE Inhibitors endogenous ACh
These drugs have less of an effect on BP and vascular smooth mm than direct acting cholinergic agonists b/c most of the vasculature is not directly innervated
Large toxic doses of these drugs cause more marked bradycardia (sometimes tachycardia) and hypotension
Drug Name Chemical MOA Effects Uses PK Adverse Effects
Diagnosis of Myasthenia Gravis (rapid mm. strength after Enzyme-
Reversible binding to CNS: convulsions, coma, dose) inhibitor
Simple Alcohol
active site of AChE respiratory arrest complex has
Edrophonium (QAC) poorly
and Reverses the neuromuscular blockade caused by non- no covalent
absorbed into CNS
butyrylcholinesterase PNS action in the eye, depolarizing muscular blockers (Can be used for recovery bond
respiratory tract, GI tract, after surgery) Lasts 2-20 min
and urinary tracts High dose CNS effects
(convulsions),
CVS: PNS and SNS bradycardia, skeletal
activation, but PNS action mm. paralysis
Carbamates- TXT for anticholinergic overdose
predominate (-)ve
Physostigmine Tertiary Amine
chronotropic, Contraindicated in
crosses BBB
dromotropic, and atropine over dose suspected TCA
inotropic effects CO & Spontaneous overdose aggravates
Form covalent bond
hypotension hydrolysis w/i depression of cardiac
with AChE
30min-6hrs conduction
NMJ: low doses Reverses the neuromuscular blockade caused by non- Salivation
contraction in mm. depolarizing muscular blockers (tubocurarine) Flushing
Carbamates- weakened by curare-like BP (hypotension)
Neostigmine
QAC does not NM blocking agents/MG; 2nd line TXT for myasthenia gravis nausea
enter CNS High doses mm. abdominal pain
fibrillation Prevention/TXT of post-op distention and urinary retention diarrhea
Pyridostigmine TXT of myasthenia gravis (most common) bronchospasm
Chronic open-angle glaucoma NOT
Phosphorylate the liposoluble
Echothiophate
active Subacute/chronic closed-angle glaucoma after iridectomy does not enter
site extremely or when surgery is refused/contraindicated CNS
Organophosphates stable covalent bond Thiosulfate insecticides (farmer spraying his field…) Organophosphate
Malathion Synthetic Activated in the body by overdose txted w/
Parathion compounds Ageing: conversion to O2 analogs Parathion more dangerous as it is not detoxified Pralidoxime or Atropine
Can cross the
strengthening of the effectively in humans BEFORE ageing has
BBB
Tabun bond making it more Nerve agents most occurred
Sarin difficult to split potent synthetic toxic Terrorism
Soman agents known CNS toxicity
Tacrine
Donepezil Centrally acting AChE
Alzheimer’s Disease Orally active
Rivastigmine inhibitor
Galantamine
Indirect Acting Cholinergic Agonists: Reactivator of AChE
Drug Name Chemical Effects Uses Other
Synthetic Reactivate inhibited AChE after organophosphate Not used for carbamate intoxication Positively charged does not enter the CNS not effective in
Pralidoxime
Compound poisoning (before ageing) short lived and spontaneously reversible reversing central effects
 Cholinergic Antagonists: Muscarinic Antagonists
Little or no action at NMJ or autonomic ganglia
These drugs bind competitively to muscarinic receptors both centrally and peripherally
Drug Name Chemical Effects Uses PK Adverse Effects
Eye: mydriasis, unresponsive to light, cycloplegia Antisialogogue before surgery to
(paralysis of ciliary mm. loss of accommodation and secretions of resp. tract
adaptation)
HR or AV block in pts with Readily absorbed Atropine flush: cutaneous vasodilation,
GI: antispasmodic effect motility with NORMAL HCl bradycardia or AV block d/t esp. in upper body
production does not promote healing of ulcer excessive vagal tone Partial metabolism
Atropine by liver Anti-PS: dry mouth, blurry
Belladonna UG: hypermobility of bladder OD of cholinergic drugs vision(cycloplegia/mydriasis), sandy eyes,
Alkaloids Excreted in urine tachycardia, constipation, urinary
CSV: low dose initial bradycardia (presynaptic M2); Death cap mushroom poisoning retention, flushing, fever, agitation, ileus
Tertiary mod-high dose tachycardia (atrial M2) T½= 4hrs
Amine can Alleviate muscarinic side effects CNS: restless, confusion, hallucinations,
cross BBB Secretions: salivary, sweating, lacrimation (inhibition of AChE inhibitors delirium, depression shock and death
of sweat may cause high body temp)
Greater action on CNS than Atropine Contraindicated in the elderly with angle-
Longer duration of closure glaucoma IOP may
DOC for motion sickness action in CNS than exacerbate glaucoma
Blocks short term memory
Scopolamine Atropine
Mydriasis and cycloplegia Caution in pts w/ BPH detrusor
Sedation, but at high doses excitement
Transdermal contraction and urinary retention
Ipratropium TXT of COPD and adjuvant therapy
Bronchodilation (M3) Inhalational drugs Low doses Bradycardia and sedation
Tiotropium for asthma
QAC Orally to Inhibit GI motility High doses tachycardia and CNS
Glycopyrrolate Oral or parenteral hyperexcitation (delirium, seizures,
Parenterally to prevent hallucinations)
bradycardia during surgery
Homatropine Shorter duration of Elderly= sensitive to cholinergic blockade
Cyclopentolate Mydriasis and cycloplegia action (preferred (d/y cholinergic hypofxn/dysfxn in ageing
Tropicamide over atropine) and dementia) acute encephalopathy,
Tertiary Parkinsonism falls, exacerbation and decomposition of
amine can underlying cognitive, fxnal, and behavioral
Benztropine Restores balance of input after loss of dopaminergic
cross BBB Extrapyramidal effects of deficits
Trihexyphenidyl neurons in the nigrostriatal pathway
antipsychotics (Drug induced
movement disorders of D2 drugs)
Tolterodine Relaxes smooth mm. TXT of overactive bladder
 Cholinergic Antagonists: Nicotinic Receptor Antagonists
Ganglion Blockers
Block ACh at the nicotinic receptors of both PNS and SNS autonomic ganglia; may also block the ion channel that’s gated by the nicotinic cholinoreceptor
Mechanism is one of two ways: (1) prolonged depolarization as done by nicotine which can block ganglia after initial stimulation (2) antagonism of nicotinic receptors
Effects can be predicted by knowledge of which division of the autonomic nervous system is dominant in each organ
Drug Name Receptor/MOA Effects Adverse Effects Other
Arterioles and veins are under predominant sympathetic control
(Adrenergic) dilation, blood flow, hypotension, peripheral pooling of Vasodilation
blood, venous return, CO Venodilation
Historically used to TXT HTN, but
Hypotension
Hexamethonium Antagonize nicotinic receptors have been replaced d/t many
Block parasympathetic (muscarinic) control in heart (tachycardia), Tachycardia
Mecamylamine in both PNS and SNS autonomic undesirable effects
iris(mydriasis), ciliary mm(cycloplegia), GI tract ( tone & motility, Mydriasis
Trimethaphan ganglia
constipation, gastric/pancreatic secretions), UG tract (urinary retention), GI/urinary motility
Dirty drugs
salivary glands (xerostomia) xerostomia
anhydrosis
Sweat glands lose sympathetic control anhydrosis
Neuromuscular Blockers
Block cholinergic transmission b/w motor nerve endings and the nicotinic receptors on the neuromuscular end-plate of skeletal mm.
Used during surgery to produce complete muscle relaxation
All are structural analogs of ACh
Drug Name Receptor/MOA Uses/Effects PK Adverse Effects
Adjunct in Anesthesia muscle weakness and flaccid paralysis
“Non-depolarizing” IV oral absorption in minimal Block M receptors
Tubocurarine Competitive antagonist binds Poor membrane penetration
Action can be overcome by ACh in the synaptic cleft (i.e.
to Nm prevents depolarization DOES NOT cross the BBB Histamine release
AChE-I like neostigmine/Edrophonium)
Malignant hyperthermia AD disorder
Continuous IV infusion
d/t XS release of Ca2+ from SR (usually
“Depolarizing”
when combined with a halogenated
Binds to Nm depolarization When rapid endotracheal intubation is needed Rapid hydrolysis by plasma
anesthetic)
Succinylcholine transient disorganized cholinesterase
contraction desensitization Electroconvulsive Therapy (ECT)
*TXT w/ Dantrolene block Ca2+ release
flaccid paralysis Brief duration 5-10 min
from SR heat production and tone
Rapid onset 1-1.5 min
of mm.

Hemicholinium
-
Cholinergic Antagonists: Drugs Acting Presynaptically
Drug Name Receptor/MOA Uses/Effects
Blocks choline transporter (CHT1) prevent
Hemicholinium-3 Research
uptake and synthesis of ACh
Blocks vesicular ACh-H+ antiporter (VAChT) Vesamicol
Vesamicol
prevent storage of ACh
Research -
Local injection
Neurotoxin produced by C. botulinum that
TXTs conditions w/ XS mm.
prevents synaptic fusion of the vesicle with the
Botulinum Toxin tone torticollis, achalasia, strabismus,
axon terminal (via synaptobrevin) inhibit ACh
blepharospasm, and more
release
Wrinkles, headache and pain
 Direct Acting Adrenergic Agonists: Endogenous Catecholamines and D1 Agonists
Drug Name Receptor Uses/effect PK Adverse effects Other
High doses=potent vasopressor: ↑ BP [systolic>diastolic] → +ve
chronotropic and inotropic effects [β1] and vasoconstriction [α1] Synthesized from tyrosine in the
→ ↑CO [& ↑ O2 demand from heart] adrenal medulla
CNS disturbances:
Low doses → ↓ PVR [β2], rise in systolic and drop in diastolic BP
Restlessness, fear,
with the MAP staying the same [no reflex, β1]; tachycardia [β1] Rapid onset Polar molecule: does not enter
apprehension, headache
α & β2 Brief Duration CNS in therapeutic doses
and tremor [may be
Bronchodilation [β2]
secondary to effects
Low dose: β Relaxed GI smooth muscle with contracted sphincters Administered through IV in Metabolized by COMT and MAO
outside of CNS]
effects Relaxed detrusor [β2] and contracted sphincter [α1] can lead emergencies → VMA and metanephrine
[vasodilation] to urinary retention
Epinephrine Intracranial hemorrhage
Prostatic smooth mm. contraction Other routes include SC, ET Hyperthyroidism may enhance
due to increased BP
High dose: α tube, inhalation, and CV actions due to upregulation of
effects Metabolic: hyperglycemia due to ↑ glycogenolysis and glucagon topically in the eye receptors
Cardiac arrhythmias –
[vasoconstriction] release [β2]; net inhibition of insulin secretion [α2 inhibits while
especially in patients on
β2 enhances secretion] Do not give orally due to Cocaine prevents re-uptake
digitalis
↑ Lipolysis through β3 activation [↑ cAMP and HSL] inactivation by intestinal
enzymes Β-blockers cause predominate α
Pulmonary edema
DOC for patients in anaphylactic shock; cardiac arrest; asthma effects such as ↑ TPR and BP
attacks combined with local anesthetics to increase duration;
glaucoma [decreased production of aqueous humor]
Vasoconstriction [α1] → increased PVR → ↑ SBP/DBP & MAP

Bradycardia due to decreased sympathetic outflow following

the baroreceptor response [indirect effect through M2] Baroreceptor reflex counteracts
local action which can be blocked
NE may cause kidney
Norepinephrine α & β1 > β2 Induces hyperglycemia [less potent than epi] by pretreatment with atropine…
shutdown
reveals direct effect of
Limited therapeutic value: can treat shock, but dopamine is tachycardia
better due to preservation of renal blood flow

Used to control BP and TXT of septic/cardiogenic shock

Central regulator of movement

CVS: low doses vasodilate through D1 receptors [cAMP]

especially at renal, mesenteric and coronary
Overdose causes
sympathomimetic
DOC for cardiogenic and hypovolemic shock: ↑GFR, renal blood
symptoms
flow and Na+ excretion → preservation of renal function
Ineffective when given
Dopamine D&α&β orally due to metabolism Can cause nausea, HTN, & Dopamine does not cross BBB
Inotropic effect at intermediate concentration [β1] and
by MAO and COMT arrhythmia but it is short
increasing release of NE
lived due to rapid
metabolism to HVA
Increase in systolic BP &MAP

High concentration → α1 mediated vasoconstriction ↑BP

TXT for severe CHF

Peripheral vasodilation→ used in short term management of Give continuously via IV,
Fenoldopam D1
inpatient HTN not a bolus
 Direct Acting Adrenergic Agonists: -agonists
Major role in treatment of bronchoconstriction
Drug Name Receptor Uses/effect PK Other
CVS: ↑CO through rate and force of contraction [AV block or Cardiac arrest] via β1
↑lipolysis
↓TPR through vasodilation [β2] because there is no α1 opposing it
Slight ↑SBP; ↓MAP and ↓DBP, tachycardia
Most reliable when given
Isoproterenol β1 & 2 Hyperglycemia ↑glycogenolysis Similar adverse effects compared to Epi
parenterally or inhaled
Bronchodilation and GI smooth muscle relaxation mediated by β2

Stimulate heart in emergency in pts. w/ bradycardia or heart lock + cardiogenic

shock
Racemic mixture:
Acute management of congestive heart failure: increases contractility
Can build up tolerance -ve: α1 & weak β1 agonist;
Dobutamine β1 ↑ CO with little change in heart rate → O2 demands of the myocardium are not
with long term use +ve: α1 antagonist and potent β1 agonist
significantly affected gives it an advantage over other sympathomimetics
Net: selective β1
Resorcinol ring→ not
Bronchodilator metabolized by COMT Selectivity is lost at high concentrations
Terbutaline Emergency treatment of status asthmaticus giving it a longer duration
Reduces uterine contractions in premature labor Used in treatment of asthma without having effects on
β2 Oral, Inhalation or SC the heart
Albuterol Inhalant bronchodilator; relief of symptoms in asthma
Slow onset, but Adverse effects: tremor, restlessness, apprehension and
Salmeterol Bronchodilator
prolonged action [12 anxiety
Formoterol Long acting → not used for prompt relief of bronchospasm
hours] after inhalation

Direct Acting Adrenergic Agonists: -agonists

Drug Name Receptor MOA Uses/Effect/Actions PK Adverse Effects
Vasoconstrictor: ↑SBP and ↑DBP
Nasal decongestant
Mydriasis
Phenylephrine 1 Peripheral vasoconstriction TXT of supraventricular tachycardia Oral or topical

NO direct effect on heart, but does cause reflex

bradycardia after parenteral administration
Partial agonist: activation of central α2 Acute rise in BP due to transient Centrally acting antiadrenergic
Clonidine receptors suppresses sympathetic Antihypertensive vasoconstriction when given IV, drugs:
outflow but not when given orally Sedation
Mental lassitude
Metabolized to α-methylnorepinephrine which causes effects similar to clonidine: ↓TPR
α2 Impaired concentration
Methyldopa Central acting anti-HTN and BP… prodrug
Xerostomia
DOC in pregnant patients with HTN [safety]
Lethargy
↓ aqueous humor production along with
Brimonidine ↓ intraocular pressure in glaucoma Ocular administration
increased outflow
 Indirect Acting Adrenergic Agonists
Releasing Agents potentiate actions of endogenous NE by causing its release from presynaptic vesicles
Drug Name Receptor MOA Uses/Effect/Actions PK Adverse Effects
↑ BP through α1 and β effects

Little effect on Displaces catechol from storage vesicle Central stimulatory action:
Fatigue and depression following
Amphetamine post synaptic Weak inhibitor of MAO Alertness insomnia
stimulation
α and β Blocks catecholamine reuptake ↓fatigue & appetite

TXT of depression, narcolepsy and appetite suppression [in the past]

ADHD in children
Methylphenidate Structural analog of amphetamine
Narcolepsy
Byproduct of tyrosine Serious vasopressor episodes in
Not clinically useful, but is found in
Tyramine metabolism, normally oxidized patients on MAO-I’s after release of
fermented foods [cheese and wine]
by MAO NE

Indirect Acting Adrenergic Agonists: Drugs That Act Presynaptically

All are Monoamine reuptake inhibitors
Drug Name Receptor MOA Uses Adverse Effects
DAT Sympathomimetic Therapeutic use: blockage of
Blocks dopamine [major effect], serotonin and NE Intense euphoria from blockage of dopamine reuptake in
Cocaine SERT voltage gated Na+ channels → local anesthetic
transporters→ potentiation and prolonged effects the limbic system
NET of the respiratory tract

Atomoxetine NET Selective NET inhibitor ADHD

NET Inhibit NE and Dopamine transporters NE,

Modafinil Narcolepsy
DAT Dopamine, serotonin, glutamate & ↓GABA

Adrenergic Agonists: Mixed Acting

Drug Name Receptor MOA Uses/Effects/Actions PK Adverse Effects Other
Vasoconstriction and cardiac stimulation → ↑ BP
NOT a catecholamine → poor
Bronchodilation [prophylactic TXT of asthma substrate for COMT and MAO→
because it is slower onset and less potent than epi or longer duration of action Herbal supplements Induces release of NE and
isoproterenol] banned in 2004 due to activates adrenergic receptors
Ephedrine Excellent oral absorption life-threatening
Synergistic effect with Anti-AChE in treatment of cardiovascular Use declining due to better drugs
α and β
myasthenia gravis Enters CNS reactions with fewer side effects

Mild CNS stimulation [alertness] and increased Eliminated unchanged in urine

athletic performance
Ephedrine
Pseudoephedrine Nasal decongestant with an H1 histamine antagonist
enantiomer
 Adrenergic Antagonists: α-antagonists
Primary effect on blood pressure: vasculature is under tonic sympathetic control so blockade of these receptors reduces tone and decreases TPR
Epinephrine Reversal: all α-blockers inhibit Epi induced vasoconstriction, but not the β effect of vasodilation → ↓BP in response to Epi in the presence of phenoxybenzamine [NE is only
diminished]
Selective α1 blockers can cause dizziness, lack of energy, nasal decongestant, HA, drowsiness, orthostatic hypotension; tendency to retain Na+ and fluid→ give with a diuretic
Drug Name Receptor MOA Effects Uses Adverse Effects
Alkylation irreversibly CVS: prevents
DOC for pheochromocytoma: blocks effects of Postural hypotension
blocks receptor vasoconstriction of
excess catecholamines [may require a β blocker Nasal stuffiness
peripheral blood
to control tachycardia after α blockade is Nausea and vomiting
Slightly α1 selective vessels→ reflex
Phenoxybenzamine established] Inhibit ejaculation
Also blocks H1, M and 5-HT tachycardia
receptors
Historically used to lower BP, but was Contraindicated in pts with ↓ coronary
Presynaptic α2
unsuccessful [block presynaptic α2] perfusion due to reflex tachycardia
inhibits NET block→ ↑CO
Dx & control hypertensive episodes of
Nonselective
pheochromocytoma
α
Postural hypotension –baroreceptor reflex and
Prevents dermal necrosis when NE is released α2 blockade on cardiac nerves
Reversible α blocker
Phentolamine Antihypertensive in stimulant overdose Arrhythmia & angina
Serotonin blocker
Muscarinic, H1 and H2 agonist
Sudden withdrawal of sympatholytics Contraindicated in pts with ↓ coronary
[clonidine] perfusion

Interactions between MAO-Is and tyramine

↓TPR through relaxation of ↓ BP without reflex
Prazosin arterial and venous smooth tachycardia […α2]
muscle Suppress sympathetic outflow from CNS
Selective α1 Not the DOC for primary HTN
↓ LDL/TAG, ↑HDL
Structural analog of prazosin →
Terazosin TXT of HTN, BPH
Useful in longer t1/2 → Less frequent First dose effect may cause exaggerated
Doxazosin Improves urinary
treatment of dosing hypotensive response and syncope [adjust 1st
blood flow
HTN dose ¼ of normal]
Relaxes
Selective for α1A receptor found Used in TXT of BPH with little effect on BP
Tamsulosin genitourinary
in genitourinary smooth muscle [reduced orthostatic HTN]
smooth muscle
α2 blocker→ indirect adrenergic TXT of erectile dysfunction, but has been Can reverse effects of α2 agonists like Clonidine
Yohimbine α2 ↑NE release→ ↑BP
agonist replaced by PDE-5 inhibitors [bad]

Adrenergic Antagonists: Partial Agonists

Drug Name Receptor MOA Uses/Effects

Causes a smaller reduction in resting HR and BP

Pindolol β β blocker with intrinsic sympathomimetic activity helps manage HTN
Preferred in pts with diminished cardiac reserve or propensity to bradycardia
 Adrenergic Antagonists: β-antagonists
Drug Name Receptor MOA Effects/Uses Adverse Effects Other
Does not induce postural
Bronchoconstriction→ Contraindicated in patients with
CVS: ↓ HR, hypotension because α1 receptors
COPD or asthma
↓contractility & remain active
Used in treatment of:
↑TPR [β2]
HTN [through ↓CO, not the DOC] Migraine [blocks Contraindicated in pts w/ variant angina
↓HDL and LDL/TAGs [block
vasodilation] Hyperthyroidism
Propranolol Metabolic: ↓ activation of HSL] β1 selective
Chronic angina [↓O2 requirement] A-fib, MI Impair recovery from hypoglycemia in insulin dependent
[prototype] glycogenolysis and actually improve the lipid profile
[protective] patients→ syncope
glucagon
DOC for performance anxiety/stage fright *tachycardia seen in such episodes will mask the signs of
secretion→ severe Abrupt withdrawal→ HTN,
β1 & β2 Essential tremor hypoglycemia
hypoglycemia in pts tachycardia, ischemia d/t up
on insulin regulation of β receptors after long
CNS: sedation, dizziness, lethargy, fatigue, depression
term use
Longer duration of
Nadolol Long term treatment of angina and HTN
action

HTN
Timolol
prophylaxis for migraines Glaucoma [open angle]
Management of HTN in pts with impaired pulmonary
Atenolol function or IDDM Less likely to induce bronchospasm contraindicated in
Metoprolol asthmatics
Long term mgmt. of pts w/ angina pectoris/acute MI
β1
Useful in controlling arrhythmia [supraventricular or
Cardioselective PK: Ultra short acting: t1/2 is about 10
thyrotoxicosis]
minutes
Esmolol Associated with hepatic injury
Administered IV
Perioperative HTN
Safer in critically ill patients
MI in acutely ill pts

Adrenergic Antagonists: Combined 1 and β-antagonists

Drug Name Receptor MOA Uses/Effects PK Adverse Effects
Decrease in BP:
More potent β antagonist
α1→ relaxation of arterial smooth muscle Orthostatic hypotension and
Labetalol Oral: chronic HTN
β1→ blocks sympathetic reflex dizziness [α1]
IV: emergencies
α1 & β β2→ sympathomimetic action contributes to vasodilation
Used on pts with CHF and HTN
Carvedilol More potent β antagonist
Antioxidant properties

Adrenergic Antagonists: Drugs Acting Presynaptically

Drug Name MOA Uses/Effects PK Other

α-methyltyrosine Blocks NE [& Epi] synthesis through competitive Used in adjuvant therapy with phenoxybenzamine in treatment of malignant
(metyrosine) inhibition of tyrosine hydroxylase pheochromocytoma [when surgery is not possible]
Unable to concentrate and store NE and dopamine in the vesicle→ continuous breakdown Slow onset and Historical TXT of
Reserpine Irreversible damage to VMAT→ ↓NE and dopamine
by MAO long duration HTN
[Obsolete] availability→ sympatholytic response
↓BP and ↓HR
Reversible inhibitor of VMAT ↓catecholamines
Tetrabenzine Chorea associated with Huntington’s Disease
presynaptically
 Autacoids: Histamine Agonists
Autacoids have diverse physiological and pharmacological activities; have brief lifetime and act near their site of synthesis
Formed by decarboxylation of L-histidine
Exists in bound form in granules of mast cells or basophils and in enterochromaffin-like cells in the fundus of the stomach release histamine to activate parietal cells
Drug Name Receptor Mechanism Indication/Effects Storage and Release
CVS: Immunologic release: Type I HSN
-Vasodilation with H1 and H2 receptors -Ag binds to IgE on mast cells/ basophils Ca2+ mediated
H1 receptors: higher affinity but rapid and short lived; degranulation release histamine, ATP and other mediators
-linked to G-proteins stimulation leads to release of NO
-constitutive activity active even in the absence of histamine (anti-histamines H2 receptors: develops slowly and is more sustained Chemical/Mechanical release:
are thus inverse agonists) -Amines (morphine and tubocurarine) displace bound histamine from
Heart: heparin complex; no energy required
- H2mediated contractility and conduction velocity -mast cell injury causes degranulation and histamine release
- H1 mediated contractility and capillary permeability edema Adverse Effects
-Located on postsynaptic membranes in brain -Triple response: intradermal injection causes a localized red
-present in endothelium, smooth mm., nerve endings spot(vasodilation), brighter red flush/flare (stimulation of axon Histamine Toxicity: dose related
Histamine H1 -Gq: PLC IP3/DAG Ca2+ reflexes) and a wheal (reflects capacity to cause edema) -Flushing
-Hypotension
GI Tract: H1 mediated contraction -Reflex tachycardia d/t vasodilation
-Located on postsynaptic membranes in brain
-Headache
H2 -present in gastric mucosa, cardiac muscle cells & immune cells
Bronchioles: H1 mediated bronchoconstriction -GI upset
-Gs Adenylyl cyclase cAMP
-bronchoconstriction
Reduces transmitter release from histaminergic and other neurons
H3 CNS: H1 mediated sensory never stimulation (esp. pain/itching) -wheals
-Found on leukocytes in the BM and blood
Secretory Tissue: H2 mediated activation of gastric parietal cells -Urticaria (hives) d/t capillary permeability
-Chemotactic on eosinophils and mast cells
HCl secretion, pepsin/IF production -Anaphylaxis: txt with Epinephrine
H4 -Role in inflammation and allergies
Clinical Uses: Pulmonary Function Testing provokes bronchial DO NOT give to asthmatics or patients with PUD/GI bleed
hyperactivity
Autacoids: Histamine Antagonists
Drug Name Class/Description Mechanism/Effects Uses Adverse Effects
Physiological Antagonist DOC for Anaphylaxis and other
Epinephrine Acts at a separate receptor conditions that involve massive
Actions on smooth mm. cells opposite to histamine histamine release
Cromolyn Mast cell stabilizer Reduce mast cell degranulation via unknown
Asthma
Nedocromil (release inhibitor) mechanism ( -2 agonists may have same effect)
-Sedation (caution with other drugs that cause sedation
Chlorpheniramine
Inverse Agonist constitutive activity contraindicated while operating machinery)
Cyclizine 1st generation alone: motion
First Generation H1 Antagonists -Dry mouth d/t anticholinergic effects
Dimenhydrinate sickness and nausea;
Also block cholinergic, -adrenergic, serotonin -Autonomic blocking actions are additive with those of muscarinic
Diphenhydramine somnifacient insomnia
Cross the BBB Sedative effects and local anesthetic receptor sites (unrelated to antagonists and -antagonists
Hydroxyzine
More likely to block autonomic receptors their blocking of H1 receptors) -Acute poisoning: common in young children; hallucinations,
Meclizine Allergic conditions:
excitement, ataxia, convulsions; untxted coma and collapse of
Promethazine -allergies caused by antigens acting
cardiorespiratory system
of IgE-antibody sensitized mast
Cardiac toxicity: involves blockade of HERG K+ channels in heart
cells
prolongation of the action potential by blocking cardiac K+ channels
Second generation H1 Antagonist
Fexofenadine -Astemizole and Terfenadine withdrawn from US torsades de
DOC in controlling sxs of allergic
Loratadine pointes (potentially fatal)
Less sedating b/c they are less able to cross the BBB less Inverse Agonist constitutive activity rhinitis and urticaria
Cetirizine -Combo with ketoconazole, itraconazole, macrolide antibiotics
liposoluble
Astemizole (erythromycin) or grapefruit juice toxicity by inhibiting CYP3A4
actively pumped out of brain by P-glycoprotein Ineffective in txt of bronchial
Terfenadine antihistamine concentration in blood
transporter asthma
**Fexofenadine lacks cardiac toxicity effects
Peptic ulcers (promotes healing) -Extremely safe and usually don’t occur: HA, dizzy, diarrhea,
constipation, muscular pain
Competitively and reversible H2 inhibitors Acute stress ulcers associated with - IV confusion, hallucination, agitation (more common w/
cAMP gastric acid secretion induced by major trauma in ICU pts. cimetidine)
Cimetidine
histamine or gastrin NOT secretion induced by - Rapid IV infusion bradycardia and hypotension (give over 30min)
Ranitidine
H2 Antagonist muscarinic agonists GERD prevention and txt (may not -blood dyscrasias and reversible liver abnormalities (Rare)
Famotidine
work for at least 45min)
Nizatidine
Can cross placenta but have not shown harmful Cimetidine:
effects give only when necessary - inhibits CYP450 slow metabolism of other drugs
-binds to androgen receptors gynecomastia, sperm count,
galactorrhea
 Autacoids: Serotonin Agonists and Antagonists
Formed from L-tryptophan via hydroxylation followed by decarboxylation
Stored or rapidly inactivated by MAO mediated oxidation
Found in enterochromaffin cells in the GI tract, platelets, and raphe nuclei of the brain stem (where the cell bodies of serotonergic neurons are found)
Precursor of melatonin in the pineal gland
Brain serotonergic neurons involved in mood, sleep, appetite, temperature regulation, perception of pain, blood pressure regulation and vomiting
Drug Name Class/Description Mechanism/Effect Uses Adverse Effects
Seven families of
GI tract:
5-HT receptor
-5-HT2 mediated GI motility
subtypes
-5-HT4 mediated ACh release mediates
prokinetic effects of serotonin agonists
Serotonin (5-HT) -5-HT3 is the only No clinical applications as a drug overproduction of 5-HT severe diarrhea
CVS: 5-HT2 mediated constriction of veins/arteries
ligand-gated ion
Platelets: 5-HT2A mediated platelet aggregation
channel, all
CNS: 5-HT3 mediated vomiting reflex and pain/itch
others are G-
perception
protein coupled
DOC for acute severe migraines (not
-Reduce both sensory activation in the periphery prophylaxis)
5-HT 1D/1B
Sumatriptan and nociceptive transmission in the brainstem
Agonist
(prototype) trigeminal nucleus diminish central sensitization Migraines are d/t calcitonin gene-related
(Triptans)
-cause vasoconstriction peptide, substance P and neurokinin A
vasodilation
Prokinetic Agent promote and organize gut
motility Somnolence, Nervousness, & Dystonic rxns
-facilitates ACh release from enteric neurons Extrapyramidal effects & tardive dyskinesia (Rare)
Galactorrhea (infrequent)
Gastroparesis
Metoclopramide Central anti-dopaminergic actions antinauseant,
5-HT4 Agonist Emesis
Cisapride antiemetic Cisapride no longer available in US d/t cardiac effects
GERD
action potential QT prolongation v-tach, v-fib,
Peripheral anti-dopaminergic actions enhance torsades de pointes (esp. with other drugs that inhibit
prokinetic activity by counteracting the inhibitory CYP3A4)
effect of D2 receptors
Allergic/ Vasomotor rhinitis
Allergic conjunctivitis
Potent H1 blocking actions
Cold urticaria
Dermatographism
Cyproheptadine 5-HT2 Antagonist Blocks smooth mm. effects of serotonin and
Carcinoid Tumor effects on smooth mm.
histamine, but has no effect on gastric acid
Serotonin Syndrome ( 5-HT1A and 5-HT2
secretion
stimulation hyperthermia, mm. rigidity,
myoclonus can be fatal)

controls severe nausea and vomiting in

Ondansetron 5-HT3 Antagonist Powerful anti-emetic
patients undergoing chemotherapy

Ergotamine Nausea and vomiting (most common)

Migraine
Dihydroergotamine
Bromocriptine Ergotamine and Ergonovine- vasospasm
Agonist, partial agonist, and antagonist actions at Hyperprolactinemia d/t pituitary tumor
Cabergoline
-adrenoceptors and 5-HT receptors
Contraindicated in pregnant women, pts with
Ergot Alkaloids Postpartum Hemorrhage when oxytocin is
peripheral vascular disease. CAD, HTN, and impaired
Agonist or partial agonist action at CNS dopamine ineffective
Ergonovine hepatic/renal fxn
receptors
Methylergonovine
Ergonovine: provoke coronary artery
Should not be used concurrently with drugs that cause
spasm diagnose variant angina
vasoconstriction
 Autacoids: Eicosanoids and Eicosanoid Antagonists
Subgroups includes prostaglandins, prostacyclins, thromboxanes, and leukotrienes
Generated de-novo from arachidonic acid found esterified in phospholipids; not found preformed
Direct activation of phospholipase A2 or Ca2+ can activate eicosanoid synthesis
Cyclo-oxygenase pathway: initiates biosynthesis of PGs, Prostacyclins and thromboxanes
o COX1 found in most cells as a constitutive enzyme and the PGs it produces are involved in normal homeostasis
o COX2 found in inflammatory cells and is expressed by growth factors, tumor promoters, and cytokines (LPS endotoxin associated)
Lipoxygenase Pathway: initiate the synthesis of leukotrienes and lipoxins via 5-lipoxygenase
o Present in inflammatory cells
o Associated with asthma, anaphylactic shock, and cardiovascular disease
o LTC4 and LTD4 potent bronchoconstriction and are primary components of slow-reacting substance of anaphylaxis (SRS-A) secreted in asthma and anaphylaxis
o LTB4 is a potent neutrophil chemoattractant

Drug Name Class Description MOA Uses

Ripen cervix at or near term
Dinoprostone PGE2
Abortion

Ripen cervix at or near term

Postpartum hemorrhage
Misoprostol PGE1 synthetic derivative Abortion when used in combination with a progesterone
antagonist (mifepristone/methotrexate)
Act in autocrine and paracrine fashion
Prevention of peptic ulcers in patients taking doses of NSAIDS
Bind to G-protein coupled receptors (Gs, Gi or Gq)
Carboprost Postpartum hemorrhage
15-methyl-PGF2
Tromethamine Eicosanoids Abortion
Contractile effects on smooth mm. are mediated by release of
Ca2+ IV maintain patency of the ductus arteriosus in infants with
transposition of the great vessels
Alprostadil PGE1 Relaxing effects are mediated by elevation in cAMP
Impotence
Severe pulmonary HTN ( peripheral, pulm, and coronary
PGI2
Epoprostenol resistance)
Prostacyclin
Prevents platelet aggregation in dialysis machines

Latanoprost PGF2 Glaucoma ( outflow of aqueous humor)

Zileuton Inhibits 5-lypoxygenase Moderate-severe asthma in pts. who are poorly controlled by
Eicosanoid
Zafirlukast Leukotriene inhibitors conventional therapy or experience adverse effects with
Antagonists Inhibits binding of LTD4 to its receptor on target tissues
Montelukast corticoids

Stimulate lipocortin Inhibit cytosolic phospholipase A2

block arachidonic acid
Glucocorticoids Anti-inflammatory actions
Inhibit COX-2 synthesis

NSAIDs Inhibit COX 1 and COX 2 Antipyretic, analgesic and anti-inflammatory activity
 Diuretics
Block specific transport fxns of the renal tubules rate of urine flow & excretion of Na+ and Cl- (H2O will follow)
blood volume venous pressure preload CO arterial pressure
venous pressure capillary hydrostatic pressure capillary fluid filtration & capillary fluid reabsorption edema if present
Long term use systemic vascular resistance
Major clinical uses: management of edema or TXT of HTN
Urine
Drug Name Class/Receptor Effects MOA Uses PK Adverse Effects
Composition
Ototoxicity (hearing issues, vertigo,
Most Effective → tinnitus, sense of fullness in ears)
DOC for mgmt. of edema
produces a lot of Hyperuricemia gout
associated with heart ↑ Ca2+,
urine Hypomagnesemia
Loop failure or renal/hepatic ↑Na+, ↑K+,
InhibitsNa+/K+/2Cl- Hypocalcemia
“High Ceiling” disease ↑Mg2+ Oral &
Furosemide ↑ renal blood flow cotransporter in the HSN for sulfa-based drugs
parenteral
Torsemide via decreased ascending loop of Henle Acute hypovolemia d/t depleted
Acute pulm edema Increased t1/2 = 2L4h
NKCC2 resistance
HTN (moderate-severe) Volume
Na+ hyponatremia or hypotension
Hypokalemia hypochloremic alkalosis
Hypercalcemia
↑ PG synthesis & cardiac arrhythmias
Hyperkalemia
[COX2] Contraindicated in post-menopausal
osteopenic women d/t Mg and Ca
HTN Oral only t1/2 =
Mild heart failure 40h
Hydrochlorothiazide
Premenstrual edema
Hypokalemia
↑Na+, ↑K+, 1-3 weeks for
Thiazides ↓ PVR and BP Hyponatremia
Hypercalciuria (useful for ↑Cl-, ↑Mg2+ stable effects
[Sulfa even after volume Hyperuricemia
derivatives] kidney stones) ↓ Ca2+ Most potent
recovery Block Na/Cl cotransporter Volume Depletion
Na excretion in
Metolazone in DCT Hyperglycemia
Diabetes Insipidus Increased advanced kidney
NCCT All have equal
hyperosmolar urine volume failure
Hyperlipidemia
maximum effects HSN
Long duration of
Chlorthalidone HTN (given once daily) action
t1/2 = 40-60hrs
Competitively inhibit 1° hyperaldosteronism
GI upset & peptic ulcers
aldosterone at cytoplasmic Edema
K+ sparing Oral & strongly Endocrine → irregular menstrual cycles
Spironolactone receptors [preventing HTN
protein bound gynecomastia, impotence
Spironolactone active metabolite translocation] Liver cirrhosis
T1/2= 2-3 days Hyperkalemia (monitor levels closely)
Eplerenone Aldosterone canrenone Acts at collecting duct Nephrotic syndrome ↑ Na+
Nausea
antagonist Adjunct to prevent cardiac ↓ K+
Induces CYP450 Lethargy
Used in combination with remodeling in HF and in
Mental confusion
other diuretics acne/hirsutism increase urine
glucose tolerance volume
1° hyperaldosteronism Hyperkalemia
K+ sparing induce Blocks Na+ transport
Heart failure Hyponatremia
Amiloride photosensitization, channels
Hypokalemia (prevent K+ Leg cramps
Triamterene interstitial → ↓Na/K exchange Acts at
ENaC nephritis and renal collecting duct
loss associated with GI upset
thiazides and loop) Dizziness, pruritus, HA, visual changes
stones
 Diuretics Continued
Urine
Drug Name Class/Receptor Effects MOA Uses PK Adverse Effects
Composition
Glaucoma [↓ production Metabolic acidosis
of aqueous humor] Oral Hyponatremia
Acts mainly in IV for glaucoma Hypokalemia
↑Na+, ↑K+,
Carbonic the PT Prevents formation of H+ Mountain sickness T1/2= 3-6hrs Crystalluria Renal stones
↑HCO3-
Acetazolamide Anhydrase needed for Na+ prophylaxis Malaise, fatigue, depression, HA, GI
↑urine
(CA) inhibitor Less efficacious reabsorption in the PT ↑ urine pH → upset, drowsiness and paresthesia
volume
than others Epilepsy alters solubility
of other drugs Contraindicated in hepatic cirrhosis due
Metabolic Alkalosis to ↓ NH4+ excretion
↑urine flow in pts w/ Nearly all Extracellular H2O expansion→
Does not affect
Filtered into glomerulus and acute renal failure electrolytes: hyponatremia
Na+ excretion
act everywhere ↑Na+, ↑K+, Tissue dehydration
directly
Mannitol Osmotic ↓ICP & cerebral edema ↑HCO3-, IV only Oral → osmotic diarrhea
↑Osmotic pressure draws ↑Ca2+,
Only drug to truly
H2O into tubular fluid promote excretion of toxic ↑Mg2+, Contraindicated in CHF, pulm edema &
↑urine volume
substances ↑phosphate pts w/ active chronic bleeding
Nephrogenic diabetes insipidus
IV only Infusion site rxns
ADH SIADH ↑ Plasma
Inhibits ADH Thirst
antagonist Euvolemic hyponatremia Na+
Renders CT ↓aquaporins in the Metabolized by Atrial fibrillation
Conivaptan Hypervolemic ↓ H2O
impermeable to collecting duct and potent GI and electrolyte disturbances
hyponatremia reabsorption
V1 & V2 H2O
HF (only if benefits>risk) → dilute urine
inhibitor of
CYP3A4 Contraindicated in Renal failure &
hypovolemic hyponatremia
 Antihypertensive Drugs
Results from peripheral vascular smooth mm. tone arteriolar resistance & venous Anti-HTN goal CO and PVR. This can be done through action at the resistance arterioles,
capacitance (most cases the cause is unknown) capacitance venules, output of the heart or volume retention by the kidneys
Normal: <120/<80; PreHTN: 120-139/80-89; Stage 1 HTN: 140-159/90-99; Stage 2 HTN: >160/>100 Stage 1 HTN controlled w/ single drug: ACE-I, ARBs, Ca2+ channel blocker or a thiazide [all first
Arterial BP CO and PVR which are controlled by baroreflexes mediated by SNS and renin- line agents]
angiotensin-aldosterone system Stage 2 HTN controlled w/ multiple drugs→ add a drug to minimize adverse effects; if still not
under control, add a vasodilator
Drug Name Class/Receptor Description MOA Uses PK Adverse Effects
HTN– most effective in young
No reflex tachycardia, etc. white pts [black and elderly Hyperkalemia, dry hacking cough, rash, fever, altered taste,
↓ PVR → ↓ BP [indirect, 2° mechanisms] usually have low renin add a and hypotension
diuretic]
First line agents Inhibit ACE ↓Na+ and H2O Angioedema [supervise 1st dose]
Captopril ACE Inhibitors
particularly for diabetics retention Chronic HF Acute renal failure in pts w/ bilateral renal aa. stenosis
Enalapril
and patients with CKD: ↓vasoconstriction on efferent → ↓GFR → elevated creatinine
Lisinopril 1st line agents
↓ diabetic nephropathy ↑renin & ↑Angiotensin I DOC for Post-MI HTN
↓ albuminuria Contraindicated in pts w/ bilateral renal aa. stenosis and
↑bradykinin [potent vasodilator] Preserve renal fxn in pts w/ Pregnancy →congenital malformation; fetal hypotension,
diabetic or non-diabetic renal failure, anuria
nephropathy
Angiotensin Very similar to ACE-I’s Same as ACE-I’s
receptor Alternative to ACE-I ↓ PVR → ↓ BP Similar to ACE-Is excepts that angioedema risk is much lower
Losartan blockers ↓aldosterone ↓Na+ and H2O Losartan will ↓uric acid by [related to bradykinin] and NO dry cough
Valsartan [ARB’s] Blocks the ATII type 1 retention inhibiting URAT1
receptor ↓ diabetic nephrotoxicity transporter helps pts w/
1st line agents No effect on bradykinin gout
Inhibits renin prevent
Renin New alternative agent in conversion of angiotensinogen to Similar to ACE-Is excepts that angioedema risk is much lower
Aliskiren
Inhibitor treatment of HTN ATI production of both ATII & [related to bradykinin] and NO dry cough
aldosterone
Non Dihydropyridine Bind to L-type Ca2+ channels in the Constipation
Angina
Least selective heart and muscle of the Contraindicated in pts on -blockers,
Verapamil SVT tachyarrhythmia Oral
Cardiac and vascular peripheral vasculature→ 2n/3rd AV block or severe LV systolic
HTN (black and/or elderly pts)
smooth muscle effects ↓calcium entry → relaxation of dysfxn
Migraine
muscle → -ve inotropism and/or
Non Dihydropyridine Cerebral vasospasm
vasodilation Oral
A little more selective for Contraindicated in pts on -blockers,
Diltiazem Calcium the vasculature than Useful in pts with asthma, 2n/3rd AV block or severe LV systolic
Intrinsic natriuretic effect no Good side effect
Channel verapamil but still affects diabetes, and peripheral dysfxn
need for diuretic profile
Blockers heart vascular resistance
Dihydropyridine
1st line agents HTN (black and/or elderly pts)
2nd gen has little
Greater affinity for vasculature Ca Angina Oral High Hypotension
interaction with digoxin
Nifedipine [1st gen] channels No ↓CO dose risk of MI so Peripheral edema
and warfarin
Useful in pts with asthma, sustained release Dizzy, HA, fatigue, flushing
Amlodipine [2nd gen] Intrinsic natriuretic effect no diabetes, and peripheral preparations are Gingival hyperplasia
DOESN’T treat cardiac
need for diuretic vascular resistance preferred Reflex tachycardia
arrhythmia
 Antihypertensive Drugs Continued
Drug Name Class/Receptor Description MOA Uses PK Adverse Effects
Counteract Na+ & H2O
Hypokalemia
retention caused by other
↑Na+ & H2O excretion → Hyperuricemia
anti HTN drugs [useful in
Chlorthalidone Thiazide Diuretic ↓ECF → ↓CO & renal blood Hyperglycemia
First line agents combination therapy]
Hydrochlorothiazide flow [in the long term, there Oral Hypomagnesemia
Lower BP 10-15 mmHg
Metolazone 1st line agents is normal plasma volume, but Hyperlipidemia
DOC for Blacks and elderly
↓ PVR]
[with normal renal and
Contraindicated in diabetics
cardiac fxn]
DOC for pts with poor
Furosemide Prompt action in pts with poor ↓ renal vascular resistance renal function or More potent and can cause more side
Loop Diuretics
Torsemide renal function or heart failure ↑ renal blood flow unresponsive to other effects
diuretics i.e. thiazides
Amiloride Used in combo with other
K+ sparing Decrease the K+ lost in urine caused by thiazide or loop diuretics
Triamterene diuretics
diuretics
1st line in patients with
Spironolactone Aldosterone antagonists → inhibition of Na+ and H2O retention Reduced K+ excretion → risk of
HTN and severe LV
Eplerenone 2nd line agents → inhibition of vasoconstriction hyperkalemia
dysfunction
Atenolol β1 Selective
Bradycardia, CNS effects, hypotension,
Metoprolol Most widely used
↓CO, contractility & ↓libido, impotence, lipid disturbance
Propranolol Nonselective β1 & 2
HR ↓BP [↓HDL, ↑TAG]
Nonselective β1 & 2 partial More effective in
May take Abrupt withdrawal→ angina and MI in pts
Β-Blockers agonist young/white pts
↓CNS sympathetic output weeks to with heart disease
[especially with exercise] develop full
2nd line agents [Intrinsic sympathomimetic DOC only for patients with
Pindolol effects Propranolol is contraindicated in asthma &
activity] CAD, HF or post-MI
↓NE & renin (β1)→ ↓ ATII & COPD
Aldosterone secretion
Preferred β-Blocker in
Mask symptoms of hypoglycemia
pregnancy
↓PVR and MAP by relaxation Mild to moderate HTN in Reflex tachycardia and orthostatic hypotension may be
Competitive inhibition of α1 of arterial and venous smooth combination with seen with first dose, but not long term (α2 blocks
receptors muscle propranolol or a diuretic response by inhibiting NE) → add β-blocker
Doxazosin
α-blockers [less common now due to
Prazosin
Na+ & H2O retention→ usually Minimal change in CO, renal adverse effects] Dizziness, drowsiness, HA, fatigue, nausea, palpitations
give with a diuretic blood flow & GFR → no long
term tachycardia BPH Doxazosin has been shown to ↑rate of CHF
Long term treatment of
NO reflex tachycardia or ↑CO HTN Orthostatic hypotension
Mixed α/β Oral
Labetalol [β1 effect is greater]
blocker Parenteral
Safe in pregnancy HTN emergencies: IV Contraindicated in pheochromocytoma
admin→ rapid drop in BP
 Antihypertensive Drugs Continued
Drug Name Class/Receptor Description MOA Uses PK Adverse Effects
Sedation, dry mouth, dizziness, HA,
↓sympathetic outflow[NE] by
2nd line when HTN does sexual dysfunction common
acting on presynaptic auto-
Clonidine not respond to TXT with 2+ Oral; Well
receptors→ ↓PVR and CO→
drugs absorbed. Abrupt withdrawal Rebound HTN
↓BP
Admin. w/ (avoid use w/ -blocker)
Central acting α2- Does NOT ↓ renal blood flow
diuretic [Na
agonist or GFR Same as Clonidine + nightmares, mental
DOC for pregnancy & H2O
Methyldopa → ↓ sympathetic outflow → ↓ depression, vertigo
induced HTN retention]
Methyldopamine PVR and BP
Methyl-NE [CO not affected] +ve coombs test can develop hemolytic
Renal Insufficiency
anemia, hepatitis & drug fever
DOC: pregnancy induced
Oral or IV
Hydralazine Never 1st line hypertensive emergencies
HA, tachycardia, nausea, sweating,
related to eclampsia
flushing
Direct acting smooth muscle
relaxants Opening of K+ channels in
Lupus like syndrome [NAT]
Direct Vasodilators smooth muscle → Arteriolar
[3rd line] Reflex tachycardia, dilation Severe malignant HTN
Minoxidil Reflex tachycardia and fluid retention
↑plasma renin → Na+ & H2O [NOT venous] Oral
[Rogaine] [coadminister with a diuretic & β-blocker]
retention Male pattern baldness
Volume overload → edema and CHF
Causes hypertrichosis

Lowers peripheral, pulmonary Continuous Flushing, HA, jaw pain, diarrhea,

Epoprostenol Prostaglandin Synthetic PGI2
and coronary resistance IV infusion arthralgia
Non selective
Blocks endothelin mediated vasoconstriction by blocking initial
Bosentan endothelin Pregnancy category X
transient depressor (ETA) and the prolonged pressor (ETB)
receptor blocker Pulmonary HTN
HA, flushing, dyspepsia, cyanopsia
Phosphodiesterase (seeing everything blue)
Sildenafil PDE5 inhibitor ↑cGMP vasodilation
Inhibitor
Contraindicated: Nitrates
 Drugs Used In Hypertensive Emergencies
A hypertensive crisis is characterized by severe, acute elevations in BP that can lead to vascular injury and organ damage
DBP>150mmHg (w/ SBP>120mmHg) in a healthy person; DBP>120 in pts w/ pre-existing complications
Hypertensive Emergency: Severe HTN with signs of damage to target organs [brain, CVS, kidneys]; immediate BP reduction is required with short acting titratable IV drugs
Hypertensive Urgency: Very high BP without target organ damage; immediate reduction is not required [start on 2 drug oral combination and follow up on outpatient basis]
Causes: essential HTN, renal parenchymal disease, renovascular disease, pregnancy (eclampsia), endocrine (pheochromocytoma, Cushing’s, renin producing tumors), drugs (cocaine, crack,
sympathomimetics, amphetamines, MAO-Is, tyramine), drug withdrawal (clonidine, Nifedipine), CNS disorders (stroke etc.), autonomic hyperreactivity
Abrupt decreases in BP can lead to MI, stroke, or visual changes
Drug Name Description Effects PK Adverse Effects
IV only→ can be Hypotension [overdose]
poisonous Abdominal cramping, nausea, vomiting, goose bumps
Sodium Prompt vasodilation and venodilation
DOC for hypertensive emergencies
Nitroprusside Reflex tachycardia [also given β-blocker]
t½= 1-2 min→ Cyanide toxicity: can be treated with sodium thiosulfate
continuous infusion infusion→ thiocyanate→ elimination
IV bolus or infusion Contraindicated in pts with asthma, COPD
Labetalol Combined α/β blocker NO reflex tachycardia
t½=3-6h 2nd or 3rd degree AV block Bradycardia
Arteriolar dilation
Peripheral D1 agonist
Maintains renal perfusion as it lowers BP [protects IV for HTN
Fenoldopam Contraindicated in patients with glaucoma
the kidney] t½= 30 min
Safe in pts with renal insufficiency
Promotes natiuresis
IV
Nicardipine Ca2+ Channel blocker (Dihydropyridine) Vascular smooth muscle relaxation Reflex tachycardia
t½= 30 min
DOC for HTN emergencies in pts with
Nitroglycerin cardiac ischemia, angina, or past cardiac Vasodilation (veins>arteries) t½= 2-5min
bypass
Arteriolar dilation→ prevents vascular smooth
muscle contraction by opening K+ channels and Hypotension
stabilizing the membrane potential Reflex tachycardia
Diazoxide t½= 24hrs
Na+ and H2O retention
Can also be used to treat hypoglycemia secondary
to an Insulinoma by inhibiting insulin release
Phentolamine DOC for pts with catecholamine release emergencies [pheochromocytoma]
Esmolol Used for aortic dissection or post-op HTN
Hydralazine DOC for pregnancy induced hypertensive emergencies related to eclampsia
 Heart Failure
Drugs Used in HF:
Diuretics (reduce blood volume):
o Thiazide diuretics: preferred over loop diuretics in pts with mild fluid retention and inc BP
o Loop diuretics: necessary to restore and maintain euvolemia in HF; maintain effectiveness even with impaired renal function
o Aldosterone antagonists: attenuate cardiac fibrosis and remolding; combined with ACE-I; decrease pro-inflammatory state and oxidative stress caused by aldosterone
Vasodilators: reduce peripheral resistance
o ACE-I: dec afterload, dec peripheral resistance; dec Na+ and H2O retention dec preload
Positive inotropy increase in CO
o ARBs
Positive chronotropy increase in HR
o Renin inhibitors Positive Dromotropy increase in conduction velocity
Cardioinhibitory drugs (reduce HR and contractility) B-blockers, Ca2+ channel blockers Positive lusitropy increase in rate of relaxation
Inotropic agents (Stimulate contractility) digoxin
Inotropic agents used in ACUTE HF Inamrinone, Milrinone, dopamine, dobutamine, glucagon
Classification of HF according to NYHA
Classification of HF according to AHA Class I: no symptom limitation with ordinary physical activity
Stage A: High risk of developing heart failure [selected pts receive ACE-I’s/ARB’s] Class II: ordinary physical activity somewhat limited by dyspnea (long walks, climbing 2
Stage B: Asymptomatic heart failure [selected pts receive ACE-I’s/ARB’s or β-blocker] stairs)
Stage C: Symptomatic heart failure [routine drugs include diuretics, ACE-I & β-blocker] Class III: exercise limited by dyspnea w/ moderate workload (short walks, climbing 1
Stage D: Refractory end stage heart failure [end of life care or extraordinary measures] stairs)
Class IV: dyspnea at rest w/ very little exertion
Heart failure occurs when the CO is inadequate to provide the O2 needed by the body
SXS: tachycardia, ↓ exercise tolerance, dyspnea, peripheral and pulmonary edema, cardiomegaly
Most common cause in the US is CAD and HTN
Systolic failure (HFrEF): dec contractility (associated with a dilated ventricle) dec SV inc EDV dec EF inc in preload d/t compensatory action of inc blood volume
Diastolic failure (HFpEF): stiffening and loss of adequate relaxation → abnormal ventricular filling and reduced CO even though the EF may be normal [does not respond to +ve inotropes]
CHF: abnormal increase in blood volume and interstitial fluid leading to dyspnea and peripheral edema
Physiologic compensation → chronic activation of the SNS and RAAS associated with tissue remodeling → additional neurohormonal activation → viscous cycle → death
There are four factors that affect cardiac performance:
1. Preload (force stretching ventricles): Frank Starling mechanism→ stretching of the myocardial cells
increases contractility, but only up to a certain point after which contractility suffers and CHF begins;
could result in pulm. edema if too high d/t volume overload
2. Afterload: Force against which the ventricles must act; basically dependent on vascular resistance and
aortic blood pressure
3. Contractility: Directly related to intracellular Ca2+ concentration
4. Heart Rate: If HR becomes too fast, there is not enough time to adequately fill the ventricles and CO
decreases; HR increases d/t SNS activation of 1- receptors
Goal of treatment is to minimize the compensatory mechanisms→ reduce symptoms, slow progression and
manage acute episodes
Drugs used to treat systolic failure include: diuretics, spironolactone, ACE-I’s, ARB’s, direct vasodilators, β-blockers and inotropic agents
Drugs used to treat diastolic failure include: diuretics (txt pulm edema), Ca2+ channel blockers (not used in systolic dysfxn b/c the dec inotropy and SV; improve ventricular relaxation and dec
HR) and β-blockers (improve ventricular relaxation and dec HR); do NOT use +ve inotropes which can lead to increased outflow obstruction
 Drugs Used in Heart Failure
Drug Name Class Description MOA Uses PK Adverse Effects
Chlorthalidone Relieve pulmonary congestion & peripheral edema Loop: more effective than thiazides
Thiazide
Hydrochlorothiazide ↓ symptoms of volume overload [orthopnea]
Diuretics
Metolazone Thiazides: pts with hypertensive heart disease [with
↓ plasma volume → ↓ venous return i.e. preload → congestive symptoms] ineffective by itself due to its
Furosemide Loop Diuretics decreased workload and O2 demand weak diuretic effect
↓ Afterload
Hyperkalemia
GI: gastritis, PUD
Advanced heart disease or pts with LV dysfunction CNS: lethargy, confusion
Prevents Na+ retention, myocardial hypertrophy & K+
Eplerenone Aldosterone after an MI (these pts have elevated aldosterone due Endocrine: gynecomastia, ↓libido,
loss
Spironolactone Antagonist to angiotensin stimulation and reduced hepatic menstrual irregularities
[When combined with ACE-I’s→ ↓M&M of severe HF]
clearance)
Contraindicated in pts on K+
supplements
↓PVR → ↓BP/afterload → Pts with symptomatic HF
DOC in heart failure Oral Persistent dry cough Hypotension
↑CO
Dilates arterioles and Renal insufficiency
Captopril ACE-I Asymptomatic pts with
veins Food Hyperkalemia
Enalapril ↓Na+ and H2O retention → ↓LVEF or history of MI
↓absorption Angioedema
Lisinopril Vasodilator ↓preload
All pro-drugs except Teratogenic contraindicated in
High risk pts: diabetes, HTN,
captopril t½ = 2-12 hrs pregnancy
↓long term remodeling atherosclerosis, obesity
Valsartan is used for HTN Hypotension
ARB Candesartan is used for CHF Renal insufficiency
Candesartan No effect on
Block AT-I receptor Oral & 1/day dosing Hyperkalemia
Valsartan bradykinin
Vasodilator Used in pts intolerant to ACE- Teratogenic contraindicated in
I’s [no cough/angioedema] pregnancy
Combination: Hypotension,
Pt’s that are intolerant to ACEI’s/ARBs or β-blockers or
↑venodilation → ↓preload dizziness, reflex tachycardia,
black patients with advanced HF [adjuvant TXT]
Hydralazine Direct ↑arterial dilation → ↓PVR/↑SV & afterload Na+/H20 retention, GI issues
Isosorbide Dinitrate Vasodilator Hydralazine dilates the arterioles Hydralazine: tachycardia,
Sustained improvement of LVEF when both oral
Nitrates dilates the veins and venules peripheral neuritis and a lupus like
vasodilators are combined
syndrome
Initial treatment can cause fluid
retention
Start at low dose→ Abrupt withdrawal unstable
-blocker
Can reverse cardiac ↓HR and RAAS [-ve inotrope] gradually titrate to angina, MI, death
Carvedilol Heart disease [stage B and C]
remodeling and Prevents deleterious effects of effective dose Hypoglycemia
Metoprolol Cardioinhibitory in addition to an ACE-I
reduce mortality NE on cardiac muscle fibers [avoid sudden CNS effects
drugs
exacerbation of SXS
Use cautiously in pts with asthma
or severe bradycardia/ AV block
 Drugs Used in Heart Failure Continued
Drug Name Class Description MOA PK Adverse Effects
Extensive inhibition of ATPase can lead to dysrhythmias
+ve inotropic Complicated, t½= 36-40h in pts w/
Toxicity [very common]:
-ve chronotropic + normal renal fxn
Inhibits Na/K ATPase → ↓Na Cardiac: Atrial arrhythmia, AV block
gradient→ indirect inhibition of Anorexia, nausea, vomiting, Headache, fatigue, confusion,
From foxglove plant Widely distributed including the
Na+/Ca2+ exchange→ blurred/yellow vision, altered color perception, halos on
CSF
↑cytoplasmic Ca2+→ dark objects d/t narrow therapeutic window
Widely used in the treatment
↑contractility
of HF Accumulates in muscle→ high Vd;
Treatment of toxicity: Withdraw or reduce dose; Monitor
requires a loading dose
Inotropic ↓SNS, RAAS & PVR → ↓HR ECG, plasma concentration and K+ levels
Very small difference
Agent: V-tach: treat with lidocaine and Mg2+ or ↑[K+]
Digoxin between therapeutic and Sensitivity varies between
Enhanced vagal tone → ↓O2 Severe toxicity: treat with digitalis antibodies
[digitalis] toxic dose [narrow patients and may change during
Cardiac demand
therapeutic window] therapy
glycoside Hypothyroidism ↑conc. of digoxin
↓conduction through AV node; Hyperthyroidism ↓conc. of digoxin
↓SXS of HF & hospitalization Hypokalemia→ digoxin toxicity
↑effective refractory period Diuretics indirectly act with digoxin to ↓K+ levels
↑Exercise tolerance [competes with K+ for binding
Quinidine, Verapamil, Amiodarone & NSAIDS displace
Does NOT ↑survival sites on ATPase]
baroreceptor desensitization digoxin from tissue protein binding sites and compete for
sustained elevation of plasma renal excretion ↑conc. of digoxin
Indicated in pts with heart Hypercalcemia ,↓Mg2+ or
NE
failure with A-fib along with hypokalemia facilitate digoxin
Contraindicated in: Diastolic or right side HF (leads to
ACE-I and β-blocker action
outflow obstruction), uncontrolled HTN, bradyarrhythmias,
non-responders/ intolerant pts, and hypokalemic pts
PDE-III inhibitor
↑cAMP→ +ve inotropic effects and ↑CO [similar to β1] Arrhythmia
Milrinone
Systemic and pulmonary vasodilation→ ↓preload and afterload Hypotension
Inamrinone IV for acute/short term ↑CO
Slight ↑AV conduction Thrombocytopenia (more common with inamrinone)
in pts w/ intractable HF
Low dose: D1 → dilate renal and mesenteric blood vessels may
Used in the treatment of
induce natiuresis and ↑urine output Arrhythmia
shock that persists after
volume replacement
Dopamine Intermediate dose: dopaminergic and β1 receptors→ ↑ force and High doses ↑myocardial O2 demand worsen ischemia in
Inotropic rate of contraction and renal vasodilation some pts with CAD
Stimulates both 1, 1/ 2 and
Agents
dopaminergic (D1) receptors
High dose: α1 receptors→ vasoconstriction [not helpful]
Β-agonist +ve inotropic effects and vasodilation
Racemic mixture ↑cAMP [Gs]→ … phosphorylation of Ca2+ channels with ↑Ca2+ entry
Dobutamine into myocardium→ ↑contraction less arrhythmogenic than dopamine
Used to ↑CO in acute mgmt. Little or no effect on HR
of HF(cardiogenic shock, MI) ↑CO w/o inc O2 demands major advantage
Mgmt. of severe β-blocker Gs→ ↑cAMP→ ↑contractility [without using β-receptors]
Glucagon
overdose +ve inotropic & chronotropic effects
HF Treatment Conclusions
All pts w/ HF and systolic dysfxn should take an ACE-I, a -blocker, AND a diuretic (if volume overloaded)
ARBs pts who can’t tolerate an ACE-I
Aldosterone antagonist addition to triple therapy can be beneficial for pts with moderate-severe HF or pts w/ LV dysfxn after an MI
Hydralazine/isosorbide dinitrate addition to triple therapy can be beneficial
Digoxin addition to triple therapy can decrease symptoms but NOT increase survival
 Anti-Anginal Drugs
Angina is characterized by transient episodes of pressure like discomfort resulting from myocardial ischemia that do not cause cell death [MI] and last for 15 seconds to 15 minutes
Results from an imbalance b/w the O2 demand of the heart and the O2 supplied to it via the coronary vessels
Different types include:
o Stable: d/t narrowing of coronary arteries; pain usually associated w/ a predictable threshold of physical activity
o Unstable: d/t clots that form in response to plaque rupture (coronary thrombosis) OR diseased endothelium can’t produce NO & prostacyclin which inhibit aggregation & clots
o Variant [Prinzmetal]: d/t coronary vasospasm; enhanced sympathetic activity such as emotional stress coupled w/ dysfxnal endothelium and precipitate variant angina
Treatment rationales include increasing O2 delivery through coronary vasodilators or antithrombotic agents, or decreasing O2 demand via vasodilators and cardiac depressants
Decreasing the O2 demand is the only therapy that can be used in Prinzmetal angina, but stable and unstable can use either method
Drug Name Class Description MOA Uses PK Adverse Effects
Longer onset and duration than HA→ cerebral vasodilation
nitroglycerin Postural hypotension
Isosorbide
Indicated for ALL anginas Oral prophylaxis of angina t1/2 = 2-8 min Flushing
Mononitrate
Metabolites are active Onset > 1 Reflex tachycardia
Mimic the action of endogenous Nitrates activate guanylyl cyclase converts hour
NO GTP into cGMP ↑cGMP aids in the de- Similar to nitroglycerin but Desensitization/overcome
Isosorbide phosphorylation of myosin light chains→ tolerance → “nitrate free
Ongoing attack longer action- 100%
Dinitrate interval” of 10-12 hours needed
Rapid reduction in myocardial O2 smooth muscle relaxation bioavailability
Organic demand [via systemic
IV→ unstable angina and High 1st pass metab.→
Nitrates vasodilation] and relief of ↓coronary vasoconstriction→ ↑myocardial Contraindicated in pts taking
acute HF parenteral admin
symptoms perfusion Sildenafil Inhibits PDE5
Nitroglycerin
which breaks down
Sublingual→ 1st line Onset in 2-5min
Functions of NO: Large venous dilation→ ↓preload and work cGMP leading to an even greater
treatment of acute SXS and lasts for 30min increase in cGMP
Vasodilation of the heart
Anti-thrombotic t½ = < 3min
Direct NO donor→ HTN
Sodium Anti-inflammatory Continuous IV infusion Severe nausea, vomit, HA
emergencies & severe HF in
Nitroprusside Protect from light due to cyanide poisoning
emergency settings
conversion to Cyanide
Rebound HTN or angina if drug is
Propranolol is NOT cardioselective discontinued abruptly [upregulate
↓ heart rate and contractility
Acebutolol Metoprolol and atenolol are β1 receptors]
↓ O2 demand Recommended in ‘all’ pts
Atenolol cardioselective
-blockers ↓ frequency and severity of stable/unstable with stable angina who have
Metoprolol Contraindicated in asthma, COPD,
angina attacks [RAAS not as important here LV dysfunction
Propranolol No reflex tachycardia d/t inotropic Diabetes, PVD
as in HTN]
& chronotropic actions Sinus bradycardia/partial AV block
& Prinzmetal angina
-Minimal effect on conduction or heart rate more selective for vascular
Flushing, Reflex tachycardia, HA,
smooth muscle
Hypotension, Peripheral edema,
Amlodipine Ca2+ is increased in ischemia -Entry of Ca2+ via L-type channel blocked→ ↓smooth muscle tone & PVR→
Oral (sustained release not the Constipation, Bradycardia, AV
Felodipine due to hypoxia induced arteriolar vasodilation→ ↓BP
short acting) block, anorexia, constipation,
Nifedipine membrane depolarization -used in combo with B-blockers when B-blockers are not successful or is
Calcium edema
contraindicated
Channel
Angina is improved by -Nifedipine should always be used with B-blocker to avoid reflex tachycardia
Blockers Verapamil/Diltiazem:
coronary and peripheral -Slows AV conduction directly→ ↓HR, contractility, BP, O2 demand
Verapamil Contraindicated in pts w/
vasodilation and reducing -cardioselective greatest depressant effect on heart
Cardioselective preexisting depressed cardiac
contractility
function or AV conduction
abnormalities
Diltiazem DOC for Variant Angina Slows AV conduction similar to Verapamil, but decreases HR to a lesser extent
Use with caution in pts taking
digoxin
QT prolongation
Na+/Ca2+ exchanger reverses Nausea, constipation
direction in ischemia
Dizziness
(Indirectly ↓Ca2+ levels by
↓ contractility Prophylaxis for pts in which
Na+ Channel blocking this exchanger)
Ranolazine ↓ O2 demand all other antianginal Metabolized by CYP3A4 Contraindicated in pts with
Blocker
May modify fatty acid oxidation therapies have failed prolonged QT torsade’s de
May also produce myocardial
relaxation pointes and ventricular
tachyarrhythmia
Treatment strategies:
Stable/Unstable:
Acute attacks are promptly relieved by rest or nitroglycerin
Maintenance therapy is best with long acting nitrates and β
blockers
Ca2+ channel blockers are used when β-blockers are not
successful or contraindicated
Ranolazine is a last ditch effort when all else fails
Patients should also take aspirin and modify their lifestyle

Prinzmetal[Variant]:
symptoms respond to nitroglycerin and Ca2+ channel
blockers [all types]; choice of drug based on the patient
 Phase 0: Fast Upstroke Phase 3: Repolarization
Na+ channels open fast inward current L-type Ca2+ channels close
Upstroke ends as Na+ channels are inactivated K+ channels open outward(polarizing) current
Net result: gain of Na+ and loss of K+ (imbalance is
corrected by Na+/K+ ATPase
Phase 1: Partial Repolarization
Na+ channels inactivate
K+ channels rapidly open & close transient outward Phase 4: Forward current
current Increasing depolarization d/t gradual increase in
Na+ permeability cell is brought to threshold of
Phase 2: Plateau next action potential
L-type Ca2+ channels open slow inward
(depolarizing) current balances slow outward
(polarizing) movement of K+

All arrhythmias result from disturbances in impulse formation or disturbances in impulse conduction and can
be supraventricular (at or above the AV node) or ventricular

Effects:
Bradycardia
Tachycardia
Sinus tachycardia/bradycardia (originates from the SA node)
Atrial fibrillation (most common cause)

Factors that precipitate arrhythmias: Ischemia, Hypoxia, Acidosis/alkalosis, Electrolyte abnormalities, Excessive
catecholamine exposure, Autonomic influences, Drug toxicity (Especially antiarrhythmics)

Use/Sate dependence: drugs bind more rapidly to open or inactivated Na+ channels, not channels that are at rest;
cells discharging at abnormally high frequency are preferentially blocked

Non-drug therapies:
Electrical Cardioversion: admin short acting anesthesia electric shock to synchronize heart
Pacemaker: sends small electrical impulses to heart to maintain HR prevents bradycardia
Implantable cardioverter-defibrillator (ICD): TXTs V-tach & V-fib; monitors rhythm constantly & will
deliver energy to make heart rhythm normal when needed
Catheter Ablation: high-frequency electrical energy delivered via catheter to the tissue that’s causing
the abnormal rhythm. TXTs PSVTs, atrial flutter, atrial-fib & some atrial/ventricular tachycardia
Abnormal Automaticity Re-entrant circuits Afterdepolarization Accessory Tract Pathways
Areas other than the SA node generate Most common cause; unidirectional block Normal AP triggers extra depolarizations Arise in the bypass tract and
competing stimuli → abnormal conduction pathway Early → when they occur during phase 2 or 3 and re triggered by are faster than SA and AV
(Disturbance in impulse formation) (Disturbance in impulse conduction) drugs prolonging the AP [i.e. QT prolongation] node AP’s
Late → after complete repolarization during phase 4 i.e. Bundle of Kent

Goal of most antiarrhythmics is to block Na+ Prevention of re-entry by slowing conduction Prevented by slowing conduction and/or increasing the refractory
or Ca2+ channels → ↓ slope of phase 4 and/or and/or increasing the refractory period period (Disturbance in impulse
increase the threshold → ↓ frequency of The unidirectional block is converted into a formation)
discharge bidirectional block (Disturbance in impulse formation)
 Antiarrhythmic Drugs
Types of Arrhythmias:
Premature Atrial Contractions: extra early beats that originate in the atria harmless and do not require treatment
Premature Ventricular Contractions (PVCs): common; occur in pts with or w/o heart disease; skipped beats caused by stress, nicotine, exercise etc. usually harmless and do not require treatment
Atrial Fibrilation: very common irregular heat rhythm results in the atria contracting abnormally
Atrial Flutter: caused by one or more rapid circuits in the atrium; ocurrs in pts with heart disease and in the 1st week following heart surgery; converts to atrial fibrillation
Paroxysmal Supraventricular Tachycardia (PSVT): rapid HR w/ regular rhythm; begins and ends suddenly; two types accessory path tachycardias or AV nodal reentrant tachycardias
Ventricular Tachycardia (V-Tach): rapid heart rhythym orginiating from the ventricles; requires immediate treatment
Ventricular fibrillation: erratic, disorganized firing of impulses from the ventricles; ventricles are unable to contract/pump bloof; medical emergency
Sinus Node Dysfunction: slow HR d/t abnormal SA node; requires txt with a pacemaker
Classification Mechanism Effect
Inhibit phase 0 depolarizationby blocking Na+ channels
excitability and conduction velocity

Na+ Channel Blocker Block K+ channels refractory period in atria & ventricles
(phase 3) QT interval prolongation
(Fast channel blockers)
Class IA threshold for excitation & inhibition of ectopic pacemaker
Suppress Ventricular and activity myocardial excitability
Supraventricular arrhythmias
Intermediate speed of binding & dissociation

Posess Use/state dependance

Drug Description Uses PK Adverse Effects
+ Torsades de pointes
Concomitant class III activity (block K channels)
Rapid oral absorption SA & AV block/asystole
Pro-arrhythmic QT interval
Nausea, vomiting, diarrhea
Replaced by Ca2+ antagonists’ d/t toxicity A-fib
Forms active metabolites via Thrombocytopenic purpura
Quinidine CYP3A4 Hemolytic anemia
Contraindicated in pts w/ complete heart block; Suppress ventricular and
Toxic dose V-tach (worsened by hyperkalemia)
caution in pts w/ QT interval, Torsades de pointes, supraventricular arrhythmias
Inhibits CYP2D6, CYP3A4, and Chinchonism blurry vision, tinnitus, HA, psychosis
incomplete heart block, uncompensated HF,
P-glycoprotein Mixed -block and antimuscarinic properties
myocarditis, and myocardial damage
digoxin by renal clearance
Derivative of local anesthetic procaine DOC for mgmt. of stable pre-
Pro-arrhythmic QT interval excited A-fib IV
Block Na+ channels in activated state Metabolized by cyp2D6 Reversible lupus like syndrome
Block K+channels Suppress ventricular and Toxic dose asystole, v-tach
Procainamide Antimuscarinic properties supraventricular arrhythmias Partly acetylated to N- CNS depression, hallucination, psychosis
acetylprocainamide (NAPA) Weak anticholinergic effect
Contraindicated in HSN, complete heart block, 2nd Reserved for life-threatening prolong duration of AP Hypotension
degree AV block, SLE, torsades de pointes, QT arrhythmias d/t pro arrhythmic (class III)
prolongation, CHF; caution in pts w/ HF and HTN effect
Strong (-) ve inotropic effect
Strong antimuscarinic properties Pronounce (-)ve inotropic effect
Suppress ventricular and
Causes peripheral vasoconstriction ( resistance) Severe antimuscarinic effects (dry mouth, urinary retention,
supraventricular arrhythmias
Disopyramide Blocks K+channels blurry vision, constipation etc.)
Pro-arrhythmic QT interval Can induce hypotension and cardiac failure w/o pre-existing
A-fib
myocardial dysfunction
Contraindicated in pts with uncompensated HF
 Antiarrhythmic Drugs Continued
Classification Mechanism Effect

Slow Phase 0 & decrease slope of phase 4

Na+ ChannelBlocker Shorten phase 3 repolarization Decrease duration of AP

(Fast channel blockers)
Class IB Little effect on depolarization phase of AP in normal cells
Suppress Ventricular arrhythmias
Rapidly associated and dissociate with Na+ channels
only
Posess Use/state dependance

Drug Description Uses PK Adverse Effects

Wide toxic therapeutic ratio
Local anesthetic
DOC for termination of V-tach and prevention of V- IV only CNS drowsiness, slurred speech, agitation etc.
More effect on ischemic/diseased tissue
fib after cardioversion (extensive Little effect on LV fxn
Lidocaine
first pass NO (-) ve inotropic effect
LITTLE EFFECT on K+channels, atrial arrhytmias or
Txt of digitalis-induced arrhythmia metabolism) Cardiac arrhythmias
AV junction arrhythmias
Toxic dose convulsions, coma
Mexiletine Orally active derivative of Lidocaine Mgmt. of severe ventricular arrhythmias Oral and IV Mainly CNS and GI
Classification Mechanism Effect

Markedly depress Phase 0 of AP marked slowing of conduction

Na+ Channel Blocker of AP, but little effect on duration or ventricular effective
refractory period
(Fast channel blockers)
Class IC Associate and re-associate slowly with Na+ channels
Suppress Ventricular and
Supraventricular arrhythmias Show prominent effects even at normal HR
(most potent of all Class I)

Drug Description Uses PK Adverse Effects

(-)ve inotropic effects worsens CHF
Decreases slope of phase 0 w/o affecting the Symptomatic ventricular arrhythmias, PVC, or V-tach
CNS: dizziness, blurry vision, HA
duration of the AP
Gi: nausea, vomiting, diarrhea
Life threatening ventricular arrhythmia & prevent
Flecainide Slight prolongation of refractory period paroxysmal A-fib Oral
Associated with potential for fatal ventricular arrhythmias&
V-tach in persons with structural heart disease
Automaticity is reduced by increase in threshold Suppression of atrial arrhythmias in a structurally
potential (slope of phase 4 not affected) normal heart
Contraindicated in pts w/ post-MI PVC
-blocking activity
(-)ve inotropic effects worsens CHF
Decreases slope of phase 0 w/o affecting the Life threatening ventricular arrhythmia & maintain CNS: dizziness, blurry vision, HA
duration of the AP sinus rhythm in pts w/ symptomatic A-fib Gi: nausea, vomiting, diarrhea
Propafenone -blocker activity bronchospasm worsens CHF etc.
Prolongs conduction and refractoriness in all areas Suppression of atrial arrhythmias in a structurally
of the myocardium normal heart Associated with potential for fatal ventricular arrhythmias&
V-tach in persons with structural heart disease
Reduces spontaneous automaticity
 Antiarrhythmic Drugs Continued
Classification Mechanism Effect

Reduce HR and contractility ( 1)

-Blockers
Slow conduction of impulses
Class II Suppress Ventricular and Reduce rate of spontaneous depolarization in cells with
Supraventricular arrhythmias pacemaker activity (block adrenergic release)

Little effect on AP

Drug Description Uses PK Adverse Effects

Reduce incidence of sudden arrhythmic death after MI Bradycardia
Propranolol
Control supraventricular tachycardia (a-fib, a-flutter, AV nodal re-entrant tachycardia) Hypotension
Metoprolol
V-tach (Catecholamine induced arrhythmias, digoxin toxicity) CNS effects
Acute arrhythmias occurring during surgery or IV
Esmolol Short acting 1 Selective antagonist Contraindicated in acute CHF, severe bradycardia or heart block
emergencies t½= 9min
and severe hyperactive airway disease
Classification Mechanism Effect

Block repolarizing K+ channels

K+ Channel Blocker Prolong AP (QT interval) w/o altering Phase 0 or resting

membrane potential
Class III
Suppress Ventricular and
Prolong effective refractory period
Supraventricular arrhythmias
All have potential to induce arrhythmias

Drug Description Uses PK Adverse Effects

Oral and IV (well >50% show AE w/ long term use dose related and reversible on
Structurally related to thyroxine (contains I-) Most common antiarrhythmic absorbed) decreasing dose:
Shows Class I, II, and III (some IV) effects interstitial pulmonary fibrosis, GI intolerance, tremor, ataxia,
Dominant effect= K+ channel blockers Mgmt. of ventricular & supraventricular arrhythmias t½=several weeks dizzy, hyper/hypothyroidism, liver toxicity, photosensitivity,
AV conduction & sinus node fxn (high Vd in neuropathy, mm. weakness
Amiodarone
Blocks mostly inactivated Na+ channels DOC for acute VT refractory to cardioversion shock adipose) need Blue skin discoloration d/t iodine
Weak Ca2+channel blocker loading dose
Inhibits adrenergic stimulation ( & blocker) Low dose maintain normal sinus rhythm in pts w/ Contraindicated in pts taking Digoxin, Theophylline, Warfarin
Antianginal and antiarrhythmic activity A-fib may to up to 6 wks to and Quinidine and in pts w/ bradycardia, SA/AV block, severe
see full clinical effects hypotension, respiratory failure
Potent non-selective blocker Life threatening ventricular arrhythmias
Lowest rate of acute/long term AE
Inhibits outward K+ current Maintain sinus rhythm in pts w. A-fib, A-flutter
Sotalol Torsades de pointe (prolonged QT interval)
Prolongs repolarization and duration of AP DO NOT use for asymptomatic arrhythmias d/t pro-
Cation in pts. with renal impairment
Lengthens refractory period arrhythmic effects
Conversion of a-fib/a-flutter to normal sinus rhythm
Excreted in urine 80% HA, chest pain, dizziness, V-tach
Dofetilide Potent and pure K+ channel blocker Maintain sinus rhythm in pts w. chronic A-fib, A-
unchanged Oral Torsades de pointes (prolongs QT interval)
flutter of longer than 1 week
 Antiarrhythmic Drugs Continued
Classification Mechanism Effect
Block L-type Ca2+ channels

inward Ca2+ current rate of phase 0 depolarization

Ca2+ Channel Blockers
Slows conduction in tissues dependent on Ca2+ current (AV node
and SA node)
Class Iv Suppress Supraventricular
arrhythmias Major effects on both bascular and cardiac smooth muscle

contractility (-ve inotropy)

HR (-ve chronotropy)
conduction velocity (-ve Dromotropy)
Drug Description Uses PK Adverse Effects
Verapamil Selective for myocardium and is less (-) ve inotropes
effective as a systemic vasodilator drug Transient BP
More effective against atrial than VT arrhythmias Oral
Diltiazem Intermediate selectivity for CNS effects HA, fatigue, dizziness
Verapamil SV-tach
myocardium GI constipation, nausea
Diltiazem ventricular rate in A-fib and A-flutter Verapamil extensively
Use/state dependent bind only to open,
HTN & angina metabolized by liver
depolarized channels preventing repolarization Verapamil concentration of digoxin, Dofetilide, simvastatin
slow conduction and effective refractory period & lovastatin
Miscellaneous Antiarrhythmics
Drug Description MOA Uses Adverse Effects
HF: +ve inotrope Intracellular Ca2+

refractory period in atrial & Arrhythmias:

ventricular myocardial cells Direct AV blocking effects (inhibits Ca2+ currents) &
Control of ventricular response rate in A- Toxic dose ectopic ventricular beats V-tach
Digoxin vagomimetic effects (activate ACh-mediated K+ current)
fib and A-flutter w/ impaired LV fxn or HF and V-fib
effective refractory period &
conduction velocity in AV node Indirect actions:
Hyperpolarization, atrial AP, AV refractoriness( fraction
of impulses conducted through the AV node & PR interval)
P1 receptor agonist Short t½= 15s ; given IV
Low toxicity flushing, burning, chest pain,
Adenosine High dose conduction velocity, K+ conductance + cAMP-mediated Ca2+ influx DOC for abolishing acute SV-tach hypotension, bronchoconstriction in
refractory period, automaticity in hyperpolarization esp. in AV node asthmatics
AV node
Torsades de Pointes (prolonged QT)
Magnesium Functional Ca2+ agonist Digitalis-induced arrhythmias
Prophylaxis of arrhythmia in acute MI
Atropine Will decrease vagal tone HR Bradyarrhythmias
Atrial Fibrillation:
Most common arrhythmias
Can be paroxysmal (intermittent) or persistent (Chronic) but not life-threatening
Mgmt. focused on symptom control and prevention of long-term mortality/morbidity
Two TXT approaches based on pt. characteristics and preference
o Rhythm control: induction/maintenance of sinus rhythm Class IC and Class III
o Rate control: -ve dromotropic agents Ca2+ blockers, -blockers, Digoxin (1st line txt in
pts. with EF or CHF) or Amiodarone (when other agents can’t be used)
Prevent Thromboembolism:
o Heparin (IV) used in unstable pts. who need immediate cardioversion
o Warfarin (oral) used in stable pts where cardioversion should be delayed 3-4 wks until
pt. develops adequate anticoagulation and continued for 4wks after cardioversion
o
 Antihyperlipidemic Drugs
Hyperlipidemia: cholesterol and/or TAGs, or HDL
risk of cardiovascular mortality linked to LDL and HDL; TAG independent risk factor & can cause acute pancreatitis
Other risk factors for cardiovascular diseases smoking, HTN, obesity, and diabetes
Disorders are detected by measuring serum lipids after a 10 hr. fast TAGs, cholesterol(TC) and HDL measured directly; LDL= TC- (HDL+TG/5) when TAGs are <400mg/dL and pts are fasting
Statins=Lipid-lowering agents of first choice; adjunct to diet, exercise, smoking cessation; can reduce the risk of first cardiovascular events and death in pts with risk factors
Primary (Familial) Hyperlipidemia Secondary Hyperlipidemia
Causes: monogenetic disease, genetic polymorphisms, gene-environment interactions MCC: sedentary lifestyle with XS dietary intake of saturated fat, cholesterol, and trans FAs
Most common cause of dyslipidemia in children Most common cause of dyslipidemia in adults
Fredrickson Classification of Lipid Disorder: Excess alcohol VLDL production
Disease Lipid Profile Etiology Hypertriglyceridemia in Type II DM d/t VLDL synthesis and chylomicron/VLDL catabolism
Type I o Insulin resistance increased VLDL production since insulin normally inhibits VLDLs
Chylomicrons Deficiency in LPL or apoCII (Rare)
Familial Hyperchylomicronemia
Type IIA
o Insulin resistance increased apoCII chylomicron/VLDL
LDL /non-fxnal LDL receptor
Familial Hypercholesterolemia
Type IIB
LDL, VLDL
Overproduction of VLDL by liver Hypertriglyceridemia Hypercholesterolemia
Familial Combined hyperlipidemia (relatively common) Diabetes Mellitus Hypothyroidism
Type III
IDL Abnormal ApoE Chronic renal failure Nephrotic syndrome
Familial dysbetalipoproteinemia
Overproduction/impaired
Hypothyroidism Obstructive liver disease
Type IV Alcohol excess glucocorticoids
VLDL catabolism of VLDL (relatively
Familial Hypertriglyceridemia
common) Contraceptives
Type V production/ clearance of VLDL -blockers
Chylomicrons, VLDL
Familial mixed hypertriglyceridemia &chylomicrons
Glucocorticoids
Drug Class Description MOA Uses Adverse Effects
Analogs of 3-OH-3-methylglutarate
(HMG) aminotransferases (must be monitored)
Rosuvastatin
Atorvastatin Lovastatin and simvastatin are Myopathy and rhabdomyolysis (measure CK)
Competitively inhibit HMG-CoA reductase (RLE
Simvastatin prodrugs inactivate lactones myoglobinuria renal injury
HMG-CoA for de novo cholesterol synthesis)
Lovastatin DOC for LDL
reductase hydrolyzed in GI active - intracellular cholesterol HMG-CoA reductase
Pravastatin Patients who are homozygous for familial
inhibitors hydroxyl derivatives & LDL receptors LDL clearance
Fluvastatin cardiovascular hypercholesterolemia benefit less from this TXT
mortality d/t lack of fxnal LDL-r
“Statins” LDL, TAG, small HDL Best when used in combo with resins, niacin or
*in order of most
endothelial fxn ezetimibe
potent to least Contraindicated in women who are
platelet aggregation
potent pregnant/lactating/want to be pregnant
inflammation
Category X
plasma CRP
Intense cutaneous flush after each dose (PG-
mediated so it can be blocked by aspirin)
Activate Gi adenylyl cyclase cAMP & DOC for HDL
PKA inhibit HSL FA transport TAG
Pruritus, rashes, dry skin, and acanthosis nigricans
synthesis VLDL production/release Useful in patients
HDL significantly with combined
Niacin Nausea and abdominal discomfort
Niacin VLDL, LDL, and Lp(a) LPL activity chylomicron & VLDL clearance hyperlipidemia and
(Nicotinic Acid)
Only one to Lp(a) HDL levels
Hepatotoxicity transaminases
HDL catabolism HDL
Insulin resistance hyperglycemia
Adjunct therapy with
(Caution in pts with diabetes)
fibrinogen, t-PA reverse endothelial dysfxn statins
uric acid gout
TAG (best one) Activate PPAR- (peroxisome proliferator
Mild GI disturbances
HDL activated receptor ) expressed in liver and DOC for severe
Myositis
Gemfibrozil brown adipose tissue hypertriglyceridemia
Fibrates Rhabdomyolysis
Fenofibrate Gemfibrozil inhibits uptake of
Cholelithiasis d/t cholesterol excretion
statins concentration of both TAG d/t LPL, apoC-III & hepatic oxidation
Avoid in pts with hepatic/renal dysfxn
drugs rhabdomyolysis of FA
 Antihyperlipidemic Drugs Continued
Drug Class Description MOA Uses Adverse Effects
Little effect on pts with dysfxn LDL-r
H20 insoluble, MW, polymeric
Binds to anionic bile acids in
anion exchange resins NOT Used with statins/niacin Bloating, cramping & constipation
intestine prevents
Cholestyramine Bile Acid- absorbed or metabolized 100% to LDL reduction (Colesevelam is better tolerated than others)
reabsorption production in liver
Colestipol Binding excretion in feces
intracellular cholesterol upreg LDL-r LDL
Colesevelam Resins DOC for children and Contraindicated in pts. w/ very high LDL
(partially offset by cholesterol synthesis)
Useful only in pregnant
Modest HDL
hypolipoproteinemia’s with LDL Cholestyramine & Colestipol interfere with
absorption of other drugs and Vit. ADEK
Selectively inhibit NPC1L1 in jejunal
enterocytes cholesterol cholesterol Reversible impaired hepatic fxn
Inhibits absorption of cholesterol Combo with statin in pts.
Cholesterol synthesis & upreg of LDL-r LDL
and phytosterols LDL who can’t reach their LDL
Ezetimibe absorption Myositis
goal
inhibitors Effective even in absence of cholesterol b/c it
Complimentary actions to statins
inhibits reabsorption of cholesterol excreted in Absorption inhibited by bile acid sequestrants
bile
EPA Fish oils that TAG in a dose
DHA dependent way LDL-C Adjunct to
TAG synthesis and FA oxidation in the liver
Lovaza -3 Fatty Contains both EPA and DHA diet in adults
May total LDL as they TAG
Acids TAG with very
impact on HDL varies
Vascepa Ethyl ester of EPA without high TAG
LDL
 Anti-Coagulants
Hemostasis: cessation of blood loss after injury; 4 stages: vascular spasm, platelet plug formation (1 ), blood coagulation (2 ), and dissolution of fibrin clot (3 )
1 hemostasis: injury exposes collagen, vWF and other components which bind to GPVI and GPIb on platelet platelet activation and adherence to subendothelium granules containing ADP, Ca2+, ATP, serotonin, vWF, and platelet factor 4 are
secreted
o ADP platelet aggregation via P2Y1 receptor (Gq Ca2+) and P2Y12 receptor (Gi AC)
o Active platelets is enhanced by thrombin (Gq)
o Aggregation via fibrinogen binds to GPIIb/IIIa receptor (shift to high affinity receptor once activation occurs) on 2 separate platelets cross-linking formation of plug
2 hemostasis: coagulation by transformation of fibrinogen into fibrin via thrombin and coagulation cascade
o Coagulation factors= proenzymes of serine proteases cleaved to activate intrinsic/extrinsic pathways
o Intrinsic activated via factor XII (Hageman factor) and extrinsic via tissue factor/thromboplastin activating factor VII
o Both pathways come together to create factor X cleaves prothrombin to thrombin converts fibrinogen into fibrin
Factors II. VII. IX, X, protein C and S vitamin K-dependent post translational modification -carboxylation of glutamic acid residues -carboxyglutamyl residues bind Ca2+ (needed for interaction with platelet plasma membranes) binds to
phospholipids on surface of platelets via -glutamyl carboxylase and requires O2, CO2 and the reduced vitamin K cofactor vitamin K cofactor becomes vitamin K epoxide
o Vit K a regenerated from the epoxide via Vitamin K epoxide reductase
PGI2- cAMP inhibit platelet aggregation and cause vasodilation
Antithrombin III inactivates thrombin and Factors IXa, Xa, XIa, and XIIa
Protein C is activated by thrombin and need Protein S as a cofactor to degrade Factors Va and VIIIa
Tissue factor pathway inhibitor (TFPI) prevents excessive activation of tissue factor mediated activation of factors IX and X
Plasminogen from the liver is cleaved to form plasmin via tissue plasminogen activator (t-PA) degradation of fibrin (fibrinolysis)
Predisposition to thrombosis via Virchow’s triad (endothelial injury, abnormal blood flow, and hypercoagubility)
Venous thrombus: d/t blood stasis or inappropriate activation of clotting cascade; clots are rich in fibrin, with fewer platelets than in arterial clots
Arterial Thrombus: usually d/t atherosclerosis of medium-sized vessels; clots are platelet rich
Drugs Used to Reduce Clotting
Drug Name Class Description MOA Uses PK Adverse effects /Contraindications
Prophylaxis for transient cerebral
Irreversible acetylation of ischemia
Anuclear platelet= no new
COX blocks TXA2 synthesis
Aspirin COX inhibitor COX synthesized during 10 risk of bleeding 5-7 days after drug cessation
interferes with platelet incidence of recurrent MI
day lifetime
aggregation and bleeding time
mortality in post-MI pts.
risk of bleeding 5-7 days after drug cessation (no antidote)
Clopidogrel is a prodrug
activated by CYP2C19 (DO Thrombocytopenic purpura
Prevent cerebrovascular, cardiovascular
Clopidogrel Irreversible inhibition of P2Y12 NOT use with
and peripheral vascular disease
platelet aggregation and omeprazole/CYP2C19 Contraindicated in CYP2C19 poor metabolizers with acute coronary
Platelet ADP Receptor bleeding time inhibitors) syndrome/ pts. undergoing percutaneous coronary
rate of MI, stroke, and death in pts.
Aggregation blockers intervention(PCI) cardiovascular event rates
with recent MI or stroke d/t peripheral
Inhibitors inhibit CYP450 Interfere w/ risk of bleeding 5-7 days after drug cessation (no antidote)
artery disease or acute coronary
metabolism of other drugs
syndrome
Ticlopidine 1 hemostasis Thrombocytopenic purpura

formation/action Neutropenia
of chemical Prophylactic txt of angina pectoris
cAMP inhibit
signals that
phosphodiesterase or blocks
promote Adjunct to warfarin in prevention of
uptake of adenosine (acts at A2 Little or no beneficial
Dipyridamole aggregation post-op thromboembolism
Phosphodiesterase receptors to activate platelet AC) effect by itself
inhibitor
Adjunct to aspirin 2 prophylaxis of
Coronary vasodilator
cerebrovascular disease
Promotes vasodilation and
Cilostazole Intermittent claudication
inhibition of platelet aggregation
chimeric mouse-human
Abciximab monoclonal Ab Prevent thrombotic events in pts with
Irreversible antagonist NSTE-ACS Parenteral IIb/IIIa receptor for fibrinogen and vitronectin mainly, but also for
GPIIb/IIIa receptor
Cyclic peptide fibronectin and vWF- patients lacking this receptor have a bleeding
Eptifibatide blockers
Reversible antagonist Adjunct to PCI for prevention of cardiac Abciximab t½=18-24hrs disorder called Glanzmann’s Thrombasthenia
Non-peptide tyrosine analogue ischemic complications
Tirofiban
Reversible antagonist
 Anti-Coagulants Continued
Drugs Used to Reduce Clotting
Drug Name Class Description MOA Uses PK Adverse effects /Contraindications
Heterogeneous 5 carbohydrate residue sequence on heparin is critical Injectable, rapidly acting
mixture of straight for binding to Antithrombin III conformational
chain, sulfated change more rapid interaction with proteases Monitor heparin to maintain
Bleeding (reverse with Protamine), liver
Heparin mucopolysaccharides (thrombin, factor IXa and Xa) Adjunct to warfarin for txt of venous effect within therapeutic range
transaminases, osteoporosis, HSN rxns
Unfractionated thrombosis and pulm embolism until and prevent bleeding use aPTT
(standard) heparin Fxns as a cofactor for Antithrombin-protease rxn warfarin achieves full effects assay tests the intrinsic and -
Heparin-induced thrombocytopenia (HIT):
(UFH) without being consumed common pathways
Type I=more common and less severe;
Anticoagulants Initial mgmt. of unstable angina or -Equal efficacy to UFH but higher
Type II=systemic hypercoagulable state in pts
2° Hemostasis inactivation of thrombin: heparin must bind acute MI bioavailability, longer half-life,
txt with UFH for a min of 7 days thrombosis
simultaneously to thrombin and Antithrombin and less frequent dosing
Low molecular weight and thrombocytopenia d/t platelet
Indirect ternary complex Prevent thrombosis during coronary requirements
heparins (LMWH) consumption DVT, pulm embolism, MI or
Enoxaparin thrombin and balloon angioplasty -Weight based dosing of
produced by chemical stroke
Dalteparin factor Xa inactivation of factor Xa: heparin must only bind to LMWH= no need to monitor
or enzymatic
Tinzaparin inhibitors Antithrombin DOC for anticoagulation during heparin levels except in pts with
depolymerization of TXT of HIT: stop drug use and give direct
pregnancy renal insufficiency, obesity, or
UFH thrombin inhibitor or Fondaparinux
LMWH have less of effect on thrombin b/c the cant pregnancy (potency can be
form the ternary complex, while UFH efficiently monitored with anti-factor Xa
inactivates both assays)
-Selective, indirect inhibitor of factor Xa, with
Synthetic Potency monitored with anti-Xa
Fondaparinux negligible Antithrombin activity Prophylaxis and TXT of DVT
pentasaccharide assay
-Contains the 5 carbohydrate sequence
Powerful and specific Excreted by
Actions are independent from Antithrombin III can
thrombin inhibitor Prevents further thromboembolic kidney Caution in patients with renal
Lepirudin each and inactivate both free and fibrin bound
(recombinant of complication in pts with HIT Monitored by the insufficiency no antidote exists
thrombin in clots
Hirudin found in leech) aPTT
Synthetic congener of Bivalent inhibitor of thrombin Pts undergoing percutaneous
Bivalirudin Parenteral
Anticoagulants Hirudin Inhibits platelet activation coronary intervention (PCI)
2° Hemostasis -Prophylaxis/TXT of thrombosis in pts Given IV
with HIT Monitored by the
Argatroban Direct Small molecule Thrombin inhibitor -Pts with/at risk for HIT undergoing aPTT
thrombin percutaneous coronary intervention
inhibitors (PCI)
-Oral
Prodrug rapidly -Produces predictable response
Dabigatran -Prevention of thromboembolic
converted to Reversibly blocks the active site of thrombin so monitoring is not necessary No antidote but is dialyzable
Etexilate stroke in pts with non-valvular a-fib
dabigatran -Excreted in urine (not
metabolized by liver)
-Prophylaxis/TXT of DVT and pulm
-Oral
Apixaban Anticoagulants Direct Factor Xa embolism
Direct Factor Xa inhibitors -Produces predictable response No antidote to reverse anticoagulant effect
Rivaroxaban 2° Hemostasis inhibitors
so monitoring is not necessary
Inhibits vitamin K epoxide reductase cant γ-
carboxylase Factors II, VII, IX, and X (Factor VII is the Prevents progression/recurrence of a Oral
first to go) previously formed clot (acute DVT or Peak effect seen at 72-96hours
-Hemorrhage
pulm embolism) and secondary Duration of single dose= 2-5days
Anticoagulants -Cutaneous necrosis d/t protein C (Associated
Coumarin Inhibit metab: Cimetidine, chloramphenicol, thromboembolic complications Narrow therapeutic index w/
Warfarin 2° Hemostasis with venous thrombosis)
anticoagulant disulfiram, fluconazole, metronidazole, following initial course of heparin many drug interactions
-Contraindicated in pregnancy (Category
phenylbutazone, sulfinpyrazone, and TMP-SMX monitor every 2-4 weeks using
X) birth defects/abnormal bone formation
Effect overcome by vitamin K admin. PT(INR) tests extrinsic an
Stimulate metab: barbiturates, carbamazepine, (takes about 24hr) common pathways
phenytoin, rifampin
Acute MI Catalyzes the degradation of
Protein produced by - Convert zymogen plasminogen to active protease Acute pulm embolism fibrinogen and factors V and VII
Streptokinase Contraindicated in pts with healing wounds,
hemolytic strep plasmin digests fibrin Arterial thrombosis by forming complex with
pregnancy, hx of cerebrovascular accidents or
Occluded access shunts plasminogen
metastatic cancer
Human enzyme from
Urokinase neonatal kidney cells directly converts plasminogen plasmin Lysis of pulm emboli Found in urine
Thrombolytics
grown in culture
Activate
Mgmt. of acute MI and acute
Alteplase plasmin
Recombinant t-PA ischemic stroke (given w/i 4.5 hrs of t1/2= 3-6min
3° Hemostasis -Hemorrhage
stroke)
Tissue plasminogen activators (t-PA)
Modified recombinant t1/2= 14-18min
Reteplase “fibrin selective” rapidly activates plasminogen -Contraindicated in pts with healing wounds,
human t-PA (less fibrin- Mgmt. of acute MI double bolus- 2 boluses 30 min
bound to fibrin in a thrombus or plug pregnancy, hx of cerebrovascular accidents or
specific) apart
metastatic cancer
mutant t-PA (more t1/2= 20-24min
Tenecteplase Mgmt. of acute MI
fibrin-specific) single IV bolus
 Anti-Coagulants Continued
Drugs Used to Treat Bleeding
Adverse effects
Drug Name Class Description MOA Uses PK
/Contraindications
Adjunct therapy in hemophilia Oral or IV
Aminocaproic Acid Synthetic inhibitors of Competitively inhibit plasminogen activation
t-PA inhibitors Intravascular thrombosis
Tranexamic Acid fibrinolysis
Therapy for bleeding from fibrinolytic therapy Excreted in urine
Chemical antagonist of heparin: positively charged Interfere in coagulation when
Low molecular weight Reverses the effects of heparin (most active against UFH,
protein interacts with negatively charged given in the absence of
Protamine Sulfate protein partially active against LMWHs and inactive against IV
heparin stable complex with no anticoagulation heparin HSN, dyspnea, flushing,
High in arginine Fondaparinux)
activity bradycardia and hypotension
Carboxylates clotting factors
Antidotes Stops bleeding induced by oral anticoagulants (Warfarin) Oral
Vitamin K Response is complete in 24 hours, onset in 6
Hypoprothrombinemia in babies parenteral
Fresh frozen plasma used for immediate hemostasis
Classic hemophilia or hemophilia A Factor VIII
Plasma Fractions Replace coagulation factors that are deficient in certain genetic disorders
Christmas disease or hemophilia B Factor IX

Aminocaproic Acid/
- Tranexamic Acid
 Anemias
Anemia: number of RBCs or Hb concentration
Macrocytic RBCs vitamin B12 or folate deficiency
Microcytic RBCs iron deficiency anemia: results from acute/chronic blood loss, insufficient intake or in heavily menstruating/pregnant women
Normocytic RBCs acute blood loss
Iron is stored as ferritin in intestinal mucosal cells
Phlebotomy → for chronic iron overload without anemia
Vitamin B12 cofactor for many rxns; deficiency microcytic megaloblastic anemia and neurologic abnormalities
o Ultimate source: microbial synthesis not synthesized by plants or animals (found in meat, eggs and dairy)
o stored in the liver; would take about 5 years to develop the anemia from depleting stores
o absorbed only after its formed a complex w/ intrinsic factor in the distal ileum via receptor-mediated transport system
o deficiency results from malabsorption d/t lack of IF (pernicious anemia) or defective transporter or d/t nutritional deficiency as seen in strict vegetarians, partial or total gastrectomy and any condition that affects the distal ileum
o deficiency prevents synthesis of purines required for DNA synthesis
o deficiency causes accumulation of homocysteine and methylmalonyl-CoA
o SXS include neurologic syndrome paresthesia in peripheral nerves, weakness and progresses to spasticity, ataxia and other CNS dysfxn
o admin of folic acid will NOT prevent neurologic SXS even though it will correct the anemia
Folic acid cofactor for many rxns; deficiency microcytic megaloblastic anemia
o Deficiency can develop within 1-6mon after intake has stopped
o deficiency prevents synthesis of purines required for DNA synthesis
o deficiency causes accumulation of homocysteine
o deficiency is often caused by inadequate dietary intake (alcoholics and liver disease), increased demand (pregnant women, pts with hemolytic anemia), malabsorption syndromes affecting the jejunum, or certain drugs (methotrexate,
trimethoprim and pyrimethamine or long term therapy with phenytoin) ** phenytoin does not cause megaloblastic changes
Drug Name Class Description Uses Pharmacodynamics Adverse effects
/Contraindications
Nausea
Ferrous Sulfate Iron deficiency anemia hypochromic microcytic anemia Epigastric discomfort
Ferrous gluconate Oral iron therapy Abdominal cramps
Ferrous iron is most
Ferrous fumarate TXT should continue 3-6mon after correction of the cause of the iron loss Constipation
Iron efficiently absorbed only
Diarrhea
preparations ferrous salts should be
Iron deficiency anemia hypochromic microcytic anemia used
Iron dextran
Sodium ferric gluconate complex Parenteral iron therapy
Reserved for pts who can’t tolerate oral iron or in pts w/ chronic anemia who
Iron sucrose
can’t be maintained on oral iron alone
Acute Iron Toxicity: seen in young children who ingest iron pills necrotizing
Deferoxamine gastroenteritis with vomiting, abdominal pain, and bloody diarrhea followed
by shock, metabolic acidosis coma and death
Binds to iron which has
Chronic Iron Toxicity/Hemochromatosis: XS iron is deposited in the heart,
already been absorbed
Iron chelator Given parentally liver, pancreas, etc. organ failure and death; seen in pts with inherited
promotes excretion in
hemochromatosis or pts receiving many red cell transfusions (thalassemia
Deferasirox urine and feces
major pts)

Acute Iron Toxicity

Therapy must be continued for life in
Vitamin B12 deficiency megaloblastic, macrocytic anemia Two reactions: pts with pernicious anemia
Cyanocobalamin homocysteine →
Parenteral Vitamin B12
Hydroxocobalamin Hydroxocobalamin preferred b/c it is more highly protein-bound and this methionine Deficiency of cobalamin can cause
Vitamins remains longer in circulation methylmalonyl → succinyl neurologic abnormalities due to
(macrocytic)
increased homocysteine
Folic acid deficiency and B12 deficiency Required for purine
Deficiency is a lot more common than Masking of neurologic deficits in B12
Folic Acid Prevents neural tube defects (spina bifida) in the fetus when given to a synthesis Need B12 to form
B12, but can be easily corrected deficiency
pregnant woman THF → folate trap
Stimulates erythroid proliferation and
differentiation via JAK/STAT Produced in the kidney in
Erythropoietin
Anemia with renal disease [can’t produce endogenous EPO → best response to hypoxia
Hyperviscosity → HTN & thrombosis
Induces release of reticulocytes from BM responders]
3x Longer acting than EPO clearance in comparison
Darbepoetin
Hematopoietic Two CHO chains to erythropoietin
Growth Filgrastim (G-CSF) production/fxn of neutrophils
Myeloid growth factors with JAK/STAT C-CSF bone pain
Factors Sargramostin (GM-CSF) production/fxn of neutrophils +production of other
Filgrastim receptors GM-CSF fever, arthralgia, and
myeloid megakaryocyte progenitors
Sargramostin capillary damage with edema
(cytokine receptor) Allergic rxns=rare
Primary and secondary neutropenia; after cancer chemotherapy
Txt of pts with prior episode of thrombocytopenia after chemo
IL-11 Megakaryocyte growth factor
Reduced need for platelet transfusions
Sickle cell Anemia
Sickle cell Increases fetal Hb dilute HbS relieve Bone marrow suppression
Hydroxyurea Chronic myelogenous leukemia
Agents painful crisis Cutaneous vasculitis
Polycythemia Vera
 Pharmacogenomics: study of the role of inheritance in variation in drug response
® Factors that influence the drug response phenotype: age, gender, underlying disease and genetic variation
® Important b/c adverse drug rxns are a major cause of mortality and morbidity
® SNPs: when one nucleotide is exchanged for anotherà results in differences that constitute each person’s genetic individualityàaffects each person’s response to drug txt
® Genotype determination is now increasingly dependent on DNA-based testing
Drug Enzyme Polymorphism Genetic Variation Effect Adverse Effects Other
¯metabolism at the synapseà prolonged
Succinylcholine Butyrylcholinesterase
depolarizationàprolonged flaccid paralysis
(depolarizing (BChE) Defect in BChE gene
neuromuscular aka Autosomal Recessive
TXT: continued mechanical ventilation until mm. returns
blocker) pseudocholinesterase
to normal
Isoniazid Neuropathy & hepatotoxicity
Hydralazine Slow acetylators: ¯metabolism & ­blood drug levels
N-Acetyltransferase 2 SLE (drug induced lupus) Slow acetylatorsà homozygous
Procainamide
(NAT2) for AR allele
Fast acetylators: ­metabolism & ¯blood drug levels HSN rxn, hemolytic anemia &
Sulfonamides
SLE
Pharmacokinetic Poor metabolizerà
Variation in Codeineàineffective in poor homozygous for recessive
enzymes that metabolizers (requires alleles
catalyze drug Poor metabolizer à ¯Codeine activation CYP2D6 catalyzed conversion
metabolism to morphine) Extensive metabolizersà
Codeine (prodrug)
CYP2D6 Ultrarapid metabolizers à­morphine heterozygous/homozygous for
+ many other drugs
Ultrarapid metabolizers: OD “wild type” allele
Most other drugs metabolized by CYP2D6 on standard
doseàrespiratory Ultrarapid metabolizersàsome
depression/arrest have multiple copies of the
CYP2D6 gene
TPMT catalyzes S-methylation of
Thiopurine S-methyl-
6-mercaptopurine ¯TPMT activityà pts. must be treated with 1/10 of the Myelosuppression with the anticancer Thiopurines
transferase
Azathioprine standard dose standard dose
(found in 1/300)
Methylation=inactivation
Pharmacodynamic
Gain of function mutation
Epidermal Growth Variation in drug
ATP binding site mutation of the tyrosine kinase domain
Gefitinib Factor Receptor (EGFR) targets or
enhances drug effects EGFR overexpressed in
mutation associated
NSCLCàtargeted therapy
pathways
CYP2C9 Combined Pts w/ variant alleles௠metabolism of S-warfarin ­risk of hemorrhage
Pharmacokinetic S-Warfarin (metabolized by
and CYP2C9) is 3-5x more potent
Warfarin Vit K epoxide reductase Dose may vary two-fold depending on the polymorphism
Pharmacodynamic Hemorrhage and thrombosis than R-warfarin (metabolized by
complex 1 (VKORC1) (there are many polymorphism in this gene)
Multiple genes CYP3A4 + other isoforms)
involved
Most common polymorphism
involves a cSNP that causes an
Primaquine Drugs (fava beans) ­ a.a substitution
Idiosyncratic Drug 90-95% ¯ in G6PD fxnà ¯NADPHà ¯glutathioneà
(Sulfonamides + G6PD deficiency (A-) oxidative stressàhemolytic
Metabolism ¯detoxification of free radicals and peroxides
chloramphenicol) anemia A- allele present in Africansà
thought to protect against
malaria
 Asthma and Respiratory Drugs
Asthma: reversible airway obstruction d/t hyper-reactivity, airway inflammation, mucous plugs, and smooth mm. hypertrophy
Observe for exacerbation of asthma, COPD, and peptic ulcer after giving cholinomimetic agents
Asthma medications for exacerbation ASTHMA: Albuterol, Steroids, Theophylline, Humidifier O2, Mg2+, Anticholinergics
COPD treatment COPD: Corticosteroids, oxygen, prevention control, dilators
Drugs that may cause pulm fibrosis amiodarone, busulfan, bleomycin, carmustine, methotrexate, nitrofurantoin
Drug Name Class Description MOA Uses Adverse Effects Other

Short Acting 2 -DOC for acute relief of bronchospasm

Albuterol
agonist -Prevent exercise-induced bronchoconstriction Tremors
Pirbuterol
cAMP relaxation of bronchial for 2-4hrs Tachycardia
Terbutaline
Rapid onset smooth muscle bronchodilation -Acute COPD/asthma attacks Arrhythmia
Adrenergic Hyperglycemia Genetic
-Long term control and prevention of sxs in
Bronchodilators

Agonists Long Acting 2 Inhalation minimizes systemic polymorphism in 2

moderate-severe asthma/COPD when used in
Salmeterol agonist side effects (poorly absorbed via Tolerance w/ excessive use receptors risk of
combo w/ inhalational corticosteroids
Formoterol the lungs) worsening asthma,
-Prevent exercise-induced bronchoconstriction
Slow onset Paradoxical bronchospasm exacerbations,
for 12-24hrs
death
-Asthma -Dry mouth Poor systemic
Short acting Competitively Blocks PSN
Ipratropium Muscarinic -Prevents vagal mediated bronchoconstriction -Caution in pts with glaucoma, absorption
inhalant bronchoconstriction &
Antagonists and drug induced bronchospasm BPH and bladder neck
mucous secretion
Tiotropium Long acting COPD obstruction Duration: several hrs
Inhibits PDE Inhibit phosphodiesterase Tremor, Insomnia, GI distress CYP inducers
Asthma; limited role d/t small therapeutic
Theophylline Methylxanthine cAMP bronchodilation Hypokalemia effect
window
Aminophylline derivatives Blocks adenosine Hyperglycemia CYP inhibitors
Prophylactic against nocturnal attacks!
receptor Oral slow release lasts 12hrs Seizures & arrhythmias effect
Beclomethasone Inhibit PLA2 arachidonic DOC for prophylaxis of asthma Cough
Inhaled steroid Prevent remodeling
Fluticasone acid synthesis of -Acute exacerbation: oral glucocorticoids Oral thrush
use in the txt of of respiratory tract
Budesonide leukotrienes, cytokines, and -dexamethasone and prednisolone in status Dysphonia
chronic asthma
Flunisolide prostaglandins asthmaticus (Severe refractory asthma) Pharyngeal candidiasis
Corticosteroids need for 2
Anti-Inflammatory Agents

-TXT chronic rhinitis (beclomethasone and

Abnormal glucose metabolism agonist
Dexamethasone IV steroids Bind to glucocorticoid response flunisolide) effects not seen for 2 wks
appetite, weight gain, HTN,
Prednisolone (systemic) elements (GREs) in the -Dexamethasone before birth for prophylaxis of
adrenal suppression 2 responsiveness
nucleus inflammation RDS
Inhibits 5-
Zileuton Oral administration block Elevated liver enzymes
lipoxygenase -Prevent exercise-induced asthma up to 24hrs in Not beneficial in
Leukotriene synthesis of LTs or block LT
50% of patients Vasculitis and systemic acute
Zafirlukast Inhibitors LTD4 receptor receptors inflammation and
-Prevent antigen and aspirin induced asthma eosinophilia resembling bronchospasm
Montelukast antagonist bronchoconstriction
Churg-Strauss (rare)
Binds to IgE on sensitized mast -Prophylactic mgmt. of severe refractory asthma
Expensive;
Omalizumab Antibody cells prevent activation and when inhaled corticosteroids are inadequate (pts Anaphylaxis
parenteral
release of LTs + other mediators older than12)
Infrequent laryngeal edema
Unknown release of Ophthalmic, nasopharyngeal and Cough Inhaled aerosol
Cromolyn Release Possibly mast cell
mediators from mast cells gastrointestinal allergy Wheezing lasting 3-6hours
Nedocromil inhibitors stabilizers
Not for acute attacks Rarely used for prophylaxis of asthma Nedocromil unpleasant
taste
Codeine Act via G-proteins depress CNS Acute debilitating cough (Wakes up from sleep)
Opioids Cough Lasts 30min-1hr
Dextromethorphan cough center cough reflex
medications
Cough and Rhinitis

N-acetylcysteine Mgmt. of acetaminophen OD

Mucolytic agent antitussives Breaks disulfide bonds in mucus
(NAC) CF
Hay fever, angioedema, motion sickness, oral
Diphenhydramine Sedation and anticholinergic
1st generation OTC sleep aide, parenteral for dystonias Lasts 6-8hrs
Chlorpheniramine Competitive H1 effects
Allergic rhinitis
H1 antagonist inhibitors blocks histamine
Loratadine
release Hay fever, angioedema Oral admin.
Fexofenadine 2nd generation
Allergic rhinitis Lasts 12-24hrs
Cetirizine
Decongestant HTN Oral, inhalant, or
Phenylephrine -agonist Nonspecific Binds to 1 and 2 receptors Mydriasis Stroke parenteral
Neurogenic hypotension MI Lasts 15min-1hr