Sympathomimetics and Sympatholytics o Glycogenolysis

SNS- running and the pupilary dilation due increase vision o Cardiac stimulation
periphery Dopaminergic Receptors
Mimics the responsesof the sympathetic nervous system - Additional adrenergic receptor
Must Know Terms - Stimulated by dopamine
Anorexiant - Primary response: dilation (increased blood flow)
Drug that decreases appetite o Renal
Catecholamine o Mesenteric
Dihydroxyphenlethylamine derivative readily o Coronary
metabolized by catechol-o-methyltransferase o Cerebral
Decongestant
Alpha agonist drug that reduces conjunctival, nasal, Sympathomimetics
or oropharyngeal mucosal vasodilation by Catecholamines
constricting blood vessels in the submucosal tissue - Produce a sympathomimetic response
Mydriatic ( pupil dilate) o Endogenous (epinephrine, norepinephrine,
Drug that causes dilation of the pupil; opposite of dopamine)
miotic (pupil constriction) o Synthetic (isoproterenol, dobutamine,
Selective alpha or beta adrenoceptor agonist phenylephrine)
Drugs that have greater effects on alpha or beta Classification
adrenoceptors; none are absolutely specific Spectrum of Action
Sympathomimetic - Alpha, beta, or dopamine receptors (further into
Drug that mimics stimulation of the sympathetic subgroups)
autonomic nervous system - Prototypes:
Reuptake Inhibitor o epinephrine (alpha & beta agonist)
Drug that increases activity of transmitters in the phenylephrine (alpha agonist)
synapse by inhibiting their reuptake into the isoproterenol (beta agonist)
presynaptic nerve ending o little effect on dopamine receptors
- Dopamine (given as a drug itself) also activates:
Receptors o beta receptors (moderate doses)
Sympathomimetics
o alpha receptors (higher doses)
- Mimic the effects of norepinephrine (NE) and
Mode of Action
epinephrine (EPI)
- Direct activation (binds directly to the receptor and
- Located throughout the body
causes a physiologic response)
- Receptors for sympathetic neurotransmitters
- Indirect activation (increase concentration of the
o Alpha adrenergic receptors 
endogenous catecholamine transmitter in the
norepinephrine
synapse)
o Beta adrenergic receptors  epinephrine
o Cause release of stored catecholamines
(amphetamines and tyramine)
Alpha Adrenergic Receptors
o Inhibit reuptake of catecholamines (cocaine
- Divided into alpha1 and alpha2 receptors (based on
and TCA)
their locations on nerves)
o Increase stores of catecholamine;
o Alpha1  postsynaptic effector cells (cell,
potentiates indirect acting agents (MAO
muscle, organ that nerves stimulate)
inhibitors)
o Alpha2  presynaptic nerve terminals (control
Pharmacokinetics
release of neurotransmitters) - Relatively inactive by oral route; must be given
- Predominant response: parentally
o Vasoconstriction o Epinephrine
o CNS stimulation o Norepinephrine
o Dopamine
Beta Adrenergic Receptors
Mechanism of Action
- Divided based on their locations:
- Alpha receptor effects
o Beta1 adrenergic receptors  heart (primarily) o Mediated by the trimeric coupling protein
o Beta2 adrenergic receprots  smooth muscles of G4.
bronchioles, arterioles, and visceral organs o G4 activation  phospholipase C activation
- Primary response:
 release of inositol 1,4,5-triphosphate
o Smooth muscle relaxation (bronchial,
(IP3) and diacylglycerol (DAG) from
gastrointestinal, and uterine smooth muscle
membrane lipids  calcium released by
relaxation)
IP3; enzymes activated by DAG
 - Beta adrenergic agents (B1)  cardiac stimulation
(myocardium, AV and SA nodes) Toxicity
- Little toxicity to the CNS because of their limited
o Increased: ability to penetrate into the brain
 Force of contraction (positive - Effects are more evident in the periphery
inotropic effect)
 Heart rate (positive chronotropic ADRENOCEPTOR BLOCKERS
effect) Adrenergic Blockers
 Conduction through AV node - Bind to adrenergic receptors but inhibit or block
(positive dromotropic effect) stimulation of the sympathetic nervous system
- Dopaminergic agents - Have opposite effect of adrenergic agents
o Depend on the dose (mixed activation of - Adrenergic antagonists or sympatholytics
receptors) - Sympatholytics
Clinical Uses o Inhibit or lyse sympathetic
 Anorexiant neurotransmitters (norepinephrine and
o Adjuncts to diet in the short-term epinephrine)
management of obesity Sympatholytics
o Drugs: benzphetamine - Classified as either:
phentermine o α1 and α2 receptor blockers
dextroamphetamine o β1 and β2 receptor blockers
Dexedrine - Other classifications depend on reversibility and
 Anaphylaxis duration of action
o Epinephrine (drug of choice for immediate
treatment of anaphylactic shock Alpha Blockers
[hypotension, bronchospasm, and Classifications
angioedema]) a. Phenoxybenzamine
o Antihistamines and corticosteroids are also o Irreversible, long-acting
used but not as effective as epinephrine o Prototype alpha blocker
 CNS o Slightly alpha1 selective
o Amphetamine (narcolepsy, and weight b. Phentolamine
reduction) o Reversible, short-acting
o Methylphenidate (ADHD) o Competitive antagonist
o Often abused for purposes of deferring o Does not distinguish between alpha1 and
sleep and mood-elevating, euphoria- alpha2 receptors
producing effect (cocaine) c. Prazosin
 Eye o Reversible
o Phenylephrine and tetrahydrozoline o Highly selective alpha1 blocker
(reduce conjunctival itching and congestion o Similar drugs: Doxazosin
 from allergy and irritation) Terazosin
o Phenylephrine (mydriatic) Tamsulosin
o Apraclonidine and brimonidine (glaucoma) d. Yohimbine
 Bronchi o Alpha2 selective blocker
o Drugs of choice for acute asthmatic o Used primarily in research applications
bronchoconstriction o Similar drug: Rauwolscine
o Drugs: albuterol
metaproterenol Pharmacokinetics (alpha blockers)
terbutaline - Active through oral and parenteral route
 Cardiovascular o Phentolamine (rarely given orally)
o Heart failure Mechanism of Action
o Septic and cardiogenic shock - Phenoxybenzamine covalently binds to the alpha
(norepinephrine) receptor
 Genitourinary o Irreversible blockade
o Ritodrine and terbutaline (beta2 agonists) - All the rest are competitive antagonists
are used to suppress labor o Effects can be counteracted by increased
 Cardiac stimulant effect may be concentrations of agonists
hazardous to the mother and child Note: important in the treatment of
o Ephedrine may be used for children pheochromocytoma (massive
(enuresis) and elderly (urinary incontinence) release of catecholamines may
 overcome reversible
blockade)
Effects Receptor Selectivity
Non-selective blockers: A. Beta1 selective
- Most important are on the cardiovascular system o Advantageous in treating asthma patients
(reduction in vascular tone  decrease in arterial (functioning B2 receptors are necessary to
and venous pressures) prevent bronchospasm)
- No significant direct cardiac effects o Drugs: Acebutolol
- Cause baroreceptor-mediated tachycardia (due to Atenolol
drop in mean arterial pressure) Esmolol
o May be exaggerated Metoprolol
o Alpha2 receptors in the heart (which B. Non-selective
reduce the net release of norepinephrine) o Nadolol
are also blocked o Propanolol
Selective alpha blockers o Timolol
- Because they block alpha1 receptors more effectively
than alpha2 receptors, induce less reflex tachycardia o Note: except for those starting with
(than non-selectives) “c” and “l”, all blockers
- Useful in relaxing smooth muscles in the prostate starting with letters from “a” to
“m” are beta1 selective
Clinical Uses
Non-selective alpha blockers o Carvedilol and Labetalol have combined
- Limited clinical applications alpha and beta-blocking activity
- Pre-surgical management of pheochromocytoma
(may have severe hypertension and reduced blood Partial Agonist Activity
volume  must be corrected prior to surgery) A. Intrinsic sympathomimetic activity
o Phenoxybenzamine (preparatory phase) o Advantageous in treating patients with
o Phentolamine (occasionally used during asthma
surgery) o In theory, less likely to cause bronchospasm
- For reversal of accidental local infiltration of alpha o Drugs: Pindolol
agonists (epinephrine) may cause severe tissue Acebutolol
ischemia and necrosis (uses phentolamine)
- Substance abuse/overdose (amphetamines, cocaine, Local Anesthetic Activity
or phenylpropanolamine) may be reversed A. Membrane-stabilizing activity
- Raynaud’s phenomenon (sometimes responds) but o Disadvantage when beta blockers are used
efficacy is not well-documented on the eye (decreases protective reflexes 
- Erectile dysfunction increases risk of ulceration)
o Phentolamine  Timolol (only one with absent local
o Yohimbine anesthetic effects, and used in
glaucoma)
Selective alpha blockers
- Hypertension (prazosin, doxazosin, and terazosin) Effects and Clinical Uses
- Prevent urinary distention in benign prostatic - Remarkably broad:
hyperplasia (+ tamsulosin, and silodosin) o Eye (open angle glaucoma)
o Heart(hypertension, angina, arrhythmia)
Toxicity  maybe heart failure  labetalol,
- Orthostatic hypotension carvedilol, and metoprolol
- Reflex tachycardia (non-selective alpha blockers) o Pheochromocytoma  combined alpha
and beta blocker agents (when producing
BETA BLOCKERS norepinephrine and epinephrine)
Classification o Infantile hemangioma  propanolol
- All are competitive antagonists
Toxicity
- Prototype drug is propanolol
- Bradycardia
- Subgroups:
- AV blockade
o Receptor selectivity
- Heart failure
o Partial agonist activity
o Local anesthetic action
o Lipid-solubility