Cardiovascular

Pharmacology

Dr Muhamad Ali Sheikh Abdul Kader

MD (USM) MRCP (UK)
Cardiologist, Penang Hospital
 Cardiovascular drugs
A. Inotropes/ Vasopressors
– Adrenaline, Noradrenaline, Dobutamine,
Dopamine, Milrinone, Amrinone, Digitalis,
Atropine
B. Anti-Arrhythmics
– Adenosin, Amiodarone, Bretylium, Digoxin,
Flecanide, Lignocaine, Mexilitine, Phenytoin,
Procanamide, Propafenone, Quinidine, Sotalol,
Verapamil 
C. Anti-coagulants
Warfarin,Unfractionated Heparin, Low
Molecular Weight Heparin--- Enoxoparin,
Fraxiparin
D. Heparin Antagonist
Protamine
E. Thrombolytic
Streptokinase, Alteplase, Urokinase
F. Glycoprotein IIa/IIIb inhibitors
Abciximab, Tirofiban
 G. Anti-platelet
Aspirin, Dipyridamole, Ticlopidine, Clopidrogel
H. Anti-ischemic Drug
Nitrates,Beta Blocker,Calcium Channel Blocker,
Cytoprotective Agent—Trimetazidine
I. Anti-heart failure
Diuretics, ACE Inhibitors, Angiotensin II Receptor
Blockers, Digitalis Glycosides, Beta Blockers
(Metoprolol, Bisoprolol, Carvedilol), Low Dose
spironolactone
 

 
 J. Antihypertensives
a. Alpha Blockers--Prazosin, Terazosin
b. Beta Blockers--Atenolol, Bisoprolol,
Labetolol, Metoprolol, Propanolol
c. Diuretics--Chlorothiazide, hydrochlorothiazide,
Indapamide, Bumetanide, Ethacrynic acid
d. Diuretics (K sparing)--Amioloride,
Spironolactone, Triamterene
e. Calcium Channel Blockers
(I) Dihydropyridines– Nifedepine, Amlodepine,
Felodepine
(II) Non-dihydropyridines--Verapamil, Diltiazem
f. Angiotensin Converting Enzyme (ACE)
inhibitors--Captopril, Enalapril, Perindopril,
Ramipril
g. Angiotensin II Receptor Blockers
Lorsartan, Valsartan, Irbesartan, Telmesartan, Candesartan 
h. Central Acting Drugs--Methyldopa 
i . Direct Vasodilators--Diazoxide, Hydralazine,
Nitroprusside, Minoxidil 
j. Fixed low dose combination
Moduretic--- Amioloride + Thiazide
CoDiovan--- Valsartan + Hydrochlorothiazide
Hyzar--- Losartan + Hydrochlorothiazide
  K. Lipid Lowering Drugs 
1 Fibrate--- Gemfibrozil, Fenofibrate
2 Statin--- Simvastatin, Pravastatin,
Atrovastatin, Lovastatin, Fluvastatin
3. Others--- Niacin, Cholestyramine,
Colestipol, Probucol
 
 Physiology of Autonomic
Nervous System
 1 receptor
– Postsynaptic region
– Positive inotropic
– Negative chronotropic
– vasoconstriction
 2 receptor
– Presypnaptic region
– Counter regulatory mechanism
– Inhibit release of Noradrenaline
1 receptor
•Positive inotropic and chronotropic effect

2 receptor
•Vaso-dilation
•Relaxation of bronchial, uterine and GIT smooth
muscle
•Modulate fat and sugar metabolism
•Drive K+ intracellularly
•Renin release

•Dopaminergic receptor
•Renal and mesenteric vasodilation
“ Whoever Will Not Endure
The Affliction Of Being
Taught, Will Stay Forever In
The Debasement Of
Ignorance”
Saidina Ali r.a.
 Adrenaline/ Epinephrine
• Actions
– Both  and  adrenergic agonist
  systemic vascular resistance (peripheral
vasoconstriction)
  SBP and DBP
  coronary and cerebral flow
  strength of myocardial contraction
  automaticity and electrical activity of the heart
  myocardial O2 consumption
•Indications
•VF
•Pulseless VT
•Asystole
•Electrical Mechanical Dissociation (EMD)/
Pulseless Electrical Activity (PEA)
•Profound bradycardia
•Profound hypotension
•Severe asthma/ anaphylaxis
•Dosage
•I/V
•1mg every 3-5 min
•Higher dose may be used (5 mg) after the
initial few doses of 1mg (associated with
neurological deficit)
•Endotracheal
• 2-3 mg diluted in 5ml N/S
•Intracardiac
•During open heart massage or when other routes of
administration are not available
•Complications: laceration of coronary artery,
cardiac tamponade, pneumothorax.
•Continuous IV infusion
•1mcg/min
•Subcutaneous
•0.1-0.5 mg
•Precautions
•Alkaline pH may cause auto-oxidation, therefore
should not be added to infusion bag that contain
alkaline solution
•Digitalis and Tricyclic Antidepressant may potentiate
arrhythmogenic effect
•Other sympathomimetics enhance cardiac effect and
cardiotoxicity
•Continuous infusion should be administered via
central line
•DM pts may need higher dose of insulin or OHA
(Adrenaline  blood sugar)
•Adverse effects
•Arrhythmias,  BP, cerebral haemorrhage,
angina,
•Tremor, apprehensiveness, sweating,
nausea,vomiting
•Metabolic acidosis, tissue necrosis
•Relative contraindication
•Close angle glaucoma
 Noradrenaline/ Norepinephrine
• Actions
– Potent  agonist
• Vasoconstriction--- Cardiac output may diminish
due to increase peripheral resistance
 1 receptor agonist
• Positive inotropic--- increase myocardial O2
consumption (may cause ischemia)
– Minimal effect on 2 receptor
•Indication
•Hypotension (especially due to septic or
neurogenic shock)
•Dosage
•Initial infusion of 0.5 to1.0 mcg/min
•Maintenance: 2-12 mcg/min
•Precautions
•Infusion via CVP line (extravasation may
cause necrosis)
•Infusion should be discontinued as soon as
possible (slowly)
•May cause angina or arrhythmia

•Contraindication
•Hypovolemic shock
 Dopamine
• Action
– Stimulate release of NA
– Low dose (<2.5mcg/kg/min)---
• Stimulate dopaminergic receptor
• Vasodilation of cerebral, renal and mesenteric arteries
– High dose (2-10mcg/kg/min)---
• Stimulate both  and 1 receptors
• Vasoconstriction and positive inotropic
– Dose of > 10mcg/kg/min
  adrenergic effect predominates
– Dose of > 20mcg/kg/min
• Heamodynamic effect = NA
 Indication
• Hypotension (in the absence of
hypovolemia)
Precautions
•May exacerbate angina and arrhymias
•Extravasation may cause necrosis
•Nausea and vomiting
•Slowly inactivated in alkaline pH
 Dobutamine
• Action
– Synthetic agent
– Stimulating myocardial  and 1 receptor
– Stimulating peripheral 2 receptor > than 
receptor
  Cardiac output and  peripheral resistance
(mild vasodilatory effect)
– Does not  release of endogenous NA
Indication
•Pulmonary congestion and low CO
•Hypotension

Dosage
•2-20 mcg/kg/min

Side effects
•Headache, nausea, tremor, hypoK+mia
 Digoxin
• Action
– Inhibit membrane bound Na-K-ATPase (
Ca concentration in the sacroplasmic
reticulum---  contractility)
– Depress AV node conduction
Indication
•CCF
•Ventricular control in AF

Dosage
•Loading dose: 10-15mcg/kg, IV route or oral
•Maintenance: 0.0625-0.25 mg
Toxicity
•7-20%
•Arrhythmias
•All type of arrhythmias may occur
•Commonest arrhythmias: atrial or ventricular ectopics,
ventricular bigeminy
•Characteristic arrhythmias: SVT with2:1 block or higher level
of AV block

•Nausea, vomiting, diarrhoea, xanthopsia, changes in

mental status
•Precipitating factors: K, Mg, Ca
Management of toxicity
•With-hold digoxin
•Measure serum concentration (may not be accurate)
•Correct hypoKmia
•Antiarrhythmias (phenytoin, lignocaine) or temporary
pacer may be needed to control arrhythmias
•Electrical cardioversion may be dangerous (may induce
VT/VF), use low energy if indicated
•Anti-dioxin Ab is used to treat massive toxicity
 Atropine
• Action
– Parasympatholytic drug
– Direct vagolytic effect
– Enhances both SA automaticity and AV
conduction
• Indications
– Symptomatic bradycardia
– First degree and Mobitz I heart block
– Asystole
 Dosage
• Without cardiac arrest
– IV 0.5-1.0 mg, may be repeated every 5 min
• Bradyasystolic cardiac arrest
– IV 1mg every 3-5 min
• Dosage of < 0.5mg may produce parodoxical
bradycardia due to central or peripheral
parasympathomimetic effects of low dose
atropine. This may precipitate VF
• Endotracheal administration
– Onset same as IV
– 1-2 mg diluted with 10 ml NS
 Precaution
• May induce tachycardia and causing angina
• May induce VF and VF
  dose may cause anticholinergic
syndrome: tachycardia, delirium, flush and
hot skin, ataxia and blurred vision
 Vaughan Williams Classification
• Group1---fast Na Channel blocker
– 1A--- prolonged action potential
Procainamide, Quinindine, Disopyramide
– 1B--- shorten action potential
Lignocaine, Mexilitine, Phenytoin
– 1C--- Flecanide, Propafenone
• Group2---B-blocker
• Group3---K channel blocker, prolong repolarization
– Bretylium, Amiodarone, Sotalol
• Group4---Ca channel blocker
– Verapamil
 Lignocaine/ Lidocaine
• Action
– Suppress ventricular arrhythmia by 
automaticity
– Local anesthetic property help to suppress
ventricular ectopic after MI
• Indication
– VT/ VF
– Suppression of ventricular ectopic
– Drug of choice for wide complex tachycardias
of unknown origin
 Dosage
• VF/ Pulseless VT
– 1-1.5mg /kg bolus
– Maintenance: 2-4mg/min
• ET tube administration
– 2-2.5 times of IV dose
  50% maintenance dose in
– Liver impairment
– Elderly
– CCF
 Precautions
  dose may cause neurological changes,
myocardial and circulatory depression
• Neurological toxicity
– Drowsiness,  hearing ability, paraesthesia,
muscle twitching, agitation
  dose may induce heart block
 Amiodarone
• Class III antiarrhythmic agent
• Actions:
– blocks potassium channels
– some ß- and alpha-blocking activity
– blocks sodium and calcium channels
 EFFECTS ON THE ECG
• Slowing of the sinus rate
• Prolongation of the PR interval and the
atrioventricular (AV) nodal refractory
period
• Widening of the QRS complex
• Prolongation of the QT interval
 CLINICAL INDICATIONS
• Atrial arrhythmias
– atrial flutter or fibrillation---it slows the ventricular
response
– converts the arrhythmia to sinus rhythm
– can maintain sinus rhythm in patients with paroxysmal
and persistent arrhythmias
• Postoperative atrial fibrillation
• Ventricular arrhythmias
– recurrent ventricular tachycardia (VT) and fibrillation
(VF)
 CLINICAL INDICATIONS
• Pediatric use – Amiodarone and flecainide
are effective in the treatment of many
tachyarrhythmias in children
• Newer uses of amiodarone –
– lessen mortality in congestive or hypertrophic
cardiomyopathy and after a recent myocardial
infarction.
 Major side effects
• The use of lower doses (200 to 300 mg/day)
may allow amiodarone to be given safely and
effectively in atrial arrhythmias such as atrial
fibrillation or flutter
• However, even low doses of therapy are
associated with significant adverse effects,
particularly thyroid, neurologic, skin, ocular,
and bradycardic events
 THYROID DYSFUNCTION
• Due to impaired deiodination of T4 to T3
• Hypothyroidism
– Subclinical hypothyroidism with small increases in
serum TSH concentrations and low-normal serum
T4 concentrations occurs in about 20 percent of
patients
• Hyperthyroidism
– About 3%patients become hyperthyroid, between
four months and three years after the initiation of
amiodarone
 PULMONARY DISEASE
• Interstitial infiltrates and fibrosis
• Symptoms can occur as early as one month
or as late as five years after amiodarone is
begun.
• The incidence is generally lower with lower
maintenance doses
• a clinical picture of pneumonitis or acute
respiratory distress syndrome
• Early diagnosis is essential because of the
potential for severe disease.
• Serial monitoring of lung function and the
chest radiograph (which may show nodular
consolidation due to the iodine deposits) 
 ELECTROPHYSIOLOGIC
TOXICITY AND
PROARRHYTHMIAS
• sinus bradycardia and AV nodal block
• prolongation of repolarization and the
QT interval
• the incidence of proarrhythmia is very
low with amiodarone, with an incidence
of torsade de pointes below one percent
 OTHER
• Elevation of serum hepatic enzyme
concentrations
• Corneal microdeposits
– microdeposits occur in most patients
receiving long-term amiodarone therapy
– dose-dependent and is reversible  
– do not cause visual disturbances, but may
cause corneal cysts and abscesses
•Skin reactions--- characterized by photosensitivity or blue-
gray discoloration of skin
•Genitourinary effects – Sterile epididymitis with pain or
swelling in the scrotum
•Serum lipid abnormalities--- Amiodarone-induced
hypercholesterolemia is associated with decreased low-
density lipoprotein (LDL) receptor mRNA levels.
•Gastrointestinal side effects – Gastrointestinal side effects
include nausea, vomiting, anorexia, abdominal discomfort and
constipation
•Neurologic dysfunction – Neurologic toxicity may take
many forms including tremor, ataxia, peripheral neuropathy,
fatigue, and weakness
•DRUG INTERACTIONS –amiodarone can interfere with the
hepatic metabolism of several antiarrhythmic drugs (such as
quinidine, procainamide, and digoxin)
 Dose and route of
administration
• ORAL DOSING
– loading dose of 800 to 1600 mg/day for one to
three weeks during hospitalization
– 800 mg/day in divided doses for approximately
one month followed by a further reduction to
the maintenance dose
– The daily maintenance dose for long-term
outpatient management ranges from 200 to 600
mg (5 to 10 mg/kg).
– The lowest effective dose to control the
arrhythmia should be used
 INTRAVENOUS DOSING
• Acute treatment and prevention of
ventricular fibrillation and hemodynamic
destabilizing ventricular tachycardia
(VT) refractory to other treatment
• Loading: 300mg infusion over 30 min
• Maintenance: 600-900mg infusion over
24hour
 Precautions
• Negative inotropic activity that is
accentuated in critically ill patients.
• Hypotension will occur if the drug is
given either at too high a dose or too
quickly.
• Phlebitis--- can be avoided by
administration through a central venous
line
 ‘Why do the most
simple things in life
turn out to be the
most difficult to do?’
HRH Prince
Charles
 Adenosine
• Action
– Endogenous purine nucleoside
– Slows AV conduction
– Interrupts AV reentry pathway--- terminate PSVT
– Short half life (<10 seconds)
• Indication
– Diagnostic: transient AV and VA block may reveal
diagnosis of underlying SVT
– Therapeutic: terminates reentry PSVT
 Dosage
• IV 6 mg rapid bolus over 1-3 seconds and
immediately flushed with 20ml saline
• In no response, 12mg repeat dose may be
given in the similar way
• Pts on Theophylline--- dosage
• Cardiac transplant recipients---  dose
 Precautions
• Transient, common side effects:
– Flushing, SOB, chest pain
• Transient sinus bradycardia and ventricular
ectopy are common after termination of
PSVT
• Contraindications:
– 2nd or 3rd degree heart block, sick sinus
syndrome (unless pacemaker is inserted)
 Practical approach to rhythm
disorders
• Bradycardia
– Atropine or pace
• Tachycardia--- narrow complex
– Adenosine, Verapamil, B-blocker
– Cardioversion
• Tachycardia--- broad complex
– Amiodarone, lignocaine
– Defibrillation
Terima Kasih ☺