1. Drugs acting on
Cardiovascular system

2. The drugs acting on cardiovascular
system are divided into four groups:




Cardiotonic drugs
Anti-hypertensive drugs
Anti-arrhythmic drugs
Anti-anginal drugs

3. Cardiotonic drugs
 Drugs which increase the force of contraction of
the heart, are called cardiotonic drugs.
 Classification:
1. Cardiac glycosides
3. Anticholinergic drugs
– Digoxin
– Digitoxin
2. Sympathetic drug
-Adrenaline
-Dopamine
-Isoprenaline
-Atropine
-Scopolamine
4. Xanthines
-Theophylline
-Theobromine

4. Cardiac glycosides
• Cardiac glycosides are those glycosides
which have specific action to the failing heart.
• Increase the force of contraction of failing
heart and lower the heart rate and thereby
maintain an effective circulation.
• Classification of cardiac glycosides:
Natural
A). Plant source
– From leaves of foxgloves:
• Digitalis purpurea: Digoxin, Digitoxin
• Digitalis lanata: Digoxin, Lanatoside-C

5. – From the seeds of foxgloves:
• Strophanthus kombe: Cymarin, Cymarol
• Strophanthus gratus: Ouabain squill
B) Animal source: Toad venom: Bufotoxin
Synthetic:
-Digitoxigenin
-Digoxigenin
-Gitoxigenin

6. Digitalis
• Digitalis is a powerful inhibitor of Na+/K+
ATPase. As a result they increase the
efficiency of failing heart increasing Na+
concentration within cell membrane;which
enhances Ca++ availability to the
contractile apparatus and increase the
contractility.

7. Mechanism of action:
• It alters ion transport system by inhibiting
membrane bound enzyme Na+/K+ ATPase,
which is associated with Na+ pump. So
– It decreases active transport of Na+ out of the cell
increasing intracellular Na+ concentration; this in
turn decreases Ca++ transport out of cell.
– Release of stored Ca++ from the sarcoplasmic
reticulum increases.
– Permeability of Ca++ increases. The net effect is
increased intracellular Ca++ ions which increases
the force of contraction of the cardiac muscles.

8. • Pharmacological actions:
 Cardiac effects:
On normal heart
– Direct positive inotropic action
– Decrease heart rate so decrease cardiac output
– Increase systolic and mean systemic arterial pressure
due to direct arteriolar contraction
– Decrease central venous pressure
On failing heart
– Direct action: Positive inotropic action
– Indirect action: decrease sinus rate, so decrease
heart rate

9. • Extra-cardiac effects:
1. Kidneys:
– Diuresis(due to increase renal perfusion)
– oedema(due to aldosterone antagonism)
2. Eye: Xanthopsia (appearance of yellow-green
tings cause visual disturbance
3. CNS: paraesthesia, toxic psychosis
4. Blood vessels: vasoconstriction, venodilation
5. GIT: anorexia, nausea, vomiting
6. Gynaecomastia (due to prolonged use)

10. Indications of Digitalis:
1. Congestive heart failure due to ischemia,
hypertensive or valvular heart disease.
2. Atrial fibrillation
3. Atrial flutter
4. Paroxysmal supraventricular tachycardia
5. Left ventricular failure

11. Contraindications
– Digitalis toxicity
– CVS
• Recent myocardial infarction
• Heart block
• Arrhythmia
– renal impairment
– Hepatic failure
– Electrolyte imbalance specially hypokalaemia
and hypocalcaemia

12. • Digitalisation: Subjection of a patient to the
action of digitalis is called digitalisation.
• Cautions:
– Therapeutic index of digitalis is low ( therapeutic
dose is very near to toxic dose)
– The dose of digitalis should be individualized.
– Danger signs of digitalis toxicity after initial dose
are: nausea, vomiting, sinus bradycardia
(HR<60beats per min)

13. • Digitalisation is done by three ways:
1. Emergency digitalisation
2. Rapid digitalisation
3. Slow digitalisation
 Total digitalisation dose (TDD):
It is the initial loading dose of digoxin.
-Oral route: 0.75-1.25mg
-i/v route: 0.5-1mg

14. • Maintenance dose:
Oral route: 0.125-0.5mg
i/v route: 0.25mg

15. Anti-hypertensive drugs
• Hypertension: Persistent rise of blood
pressure above the upper limit of normal level
according to the age and sex of the individual
is called HYPERTENSION (HTN)
• Normal limits of blood pressure:
– Systolic: 100-140 mm Hg(120±20)
– Diastolic: 60-90 mm Hg (75±15)

18.  Causes of hypertension:
• Primary hypertension (90-95%):
– also called as essential hypertension
– Unknown etiology or idiopathic
• Secondary hypertension(5-10%):
– Renal disease
– Endocrine diseases (Conn’s disease, acromegaly,
Phaeochromocytoma)
– Cushing's disease
– Vascular causes (renal artery stenosis, coarctation of aorta)
– Drugs (sympathomimetics, NSAIDs, contraceptive pills,
steroids

19. • Risk factors:
–
–
–
–
Age
Hereditary
Anxiety
Obesity and lack of
exercise
– Alcohol consumption
– Salt intake
• Special patient groups
–
–
–
–
–
–
–
Race
Elderly
Diabetes
Renal disease
Stroke
Pregnancy
Hormone replacement
therapy
– Oral contraceptives

20. Management of hypertension
Non-pharmacologic approaches:
 Weight reduction in obese patients: reduces
about 2.5/1.5 mm Hg per kg wt. lost
 Restriction to salt intake: not more than 6 g NaCl
 Dietary considerations: legumes, fresh fruits and
vegetables, whole grains
 Regular exercise
 Restricted alcohol intake
 Smoking cessation to reduce cardiovascular risk

21.  Pharmacologic approach:
 Classification:
A. Diuretics:
–
–
–
–
–
B.
Carbonic anhydrase inhibitors : acetazolamide
Loop diuretics: Furosemide, ethacrynic acid , mercurials
Thiazide diuretics: Hydrochlorthiazide
Potassium sparing: amiloride , triamterene, spironolactone
Osmotic diuretics : mannitol
Sympatholytics:
–
–
–
–
Centrally acting: Methyl-dopa, Clonidine
Beta-blockers: Atenolol, Propranolol, Metoprolol
Alpha-blockers: Prazosin, Phentolamine
Adrenergic neuron blockers: Guanethidine, Reserpine

22. C. Direct vasodilators:
•
Arteriolar dilators
•
•
•
•
•
Diazoxide
Hydralazine
Minoxidil
Prazosin
Vasodilators (non-selective)
•
•
Nitroprusside
Prazosin

23. D. Calcium Channel blockers:
– Nifedipine
– Verapamil
– Diltiazem
E. Angitensin converting enzyme (ACE) inhibitors:
–
–
–
–
Captopril
Enalapril
Lisinopril
Ramipril

25. α-Methyl dopa
• It is useful in treatment of mild to moderately severe
hypertension.
• It reduces the BP chiefly by reducing peripheral vascular
resistance.
• It inhibits noradrenaline synthesis:
DOPA
Dopamine
DOPA decarboxylase
α-methyl dopa
methyldopamine
α methylnoradrenaline
• Remains inside the vesicles and released in the same way as
noradrenaline.

26. Mechanism of Action
• α-Methyl dopa forms false neurotransmitter α-Methyl
noradrenaline which combines with α-adrenoceptors
present in the surface of the lower brain stem, inhibiting
the neurons of nucleus of tractus solitarius of vagus
which in turn decrease central and peripheral
sympathetic activities resulting in decreased BP.
• It also inhibits the decarboxylation of DOPA and 5-HT,
thus decreased sympathetic tone.
• It also directly reduces renin activity which is responsible
for conversion of angiotensin-I to angiotensin-II thereby
reducing BP.

27. • Pharmacokinetics:
–
–
–
–
–
Well absorbed from the GIT
Half-life: 1.5 hrs
Antihypertensive effects; 4-6 hrs
Effective twice daily
Dose: 1-2 g in divided doses
• Indications:
–
–
–
–
Moderate to severe hypertension
Hypertensive crisis
Pheochromocytoma
Malignant carcinoid

28. • Adverse effects:
–
–
–
–
–
–
–
–
–
–
Mental symptoms (sedation, lassitude, vertigo)
Electrolyte imbalance
Thrombocytopenia
Headache
Psychic depression
Lactation
Dryness of mouth
Oedema
Postural hypotension
Allergic reaction

29. Unique side effects:
• Flushing of skin
• Failure of ejaculation
• Depression
• Hemolytic anemia
• Granulocytopenia
• Hepatic disturbance

30. Clonidine
• It is centrally acting sympatholytic agent (α2
adrenoceptor agonist) and acts by decreasing
central sympathetic activity.
• Mechanism of action: It combines with α2 –
receptors of lower brainstem which in turn
inhibits release of noradrenaline from the
neurons. It decreases sympathetic activity which
results in decreased cardiac output due to
decrease heart rate and relaxation of capacitance
vessels. Thus BP is decreased.

31. Pharmacological actions of Clonidine:
1. CNS: suppress sympathetic outflow
2. CVS: decrease heart rate; decrease CO
3. Blood vessels: reduction in resistance and
relaxation of capacitance vessels
Indications:
1. Hypertension
2. Prophylaxis of migraine
3. Diagnosis of pheochromocytoma

32. • Adverse effects:
– Sedation
– Dry mouth
– Drowsiness
– Rebound hypertension

33. • Pharmacokinetics of Clonidine:
–
–
–
–
Bioavailability: 75%
Half-life : 8-12 hours
Excretion: half of the drug excreted unchanged
Dose: 0.2 and 1.2 mg/day
• Sudden withdrawal effects:
It can result in life threatening crisis. Patient
exhibit nervousness, tachycardia, headache and
sweating if one or two dose is omitted.
Note: sudden withdrawal of the drug must be
avoided. If required should be done gradually.

34. Calcium channel blockers
• Calcium is the chief ion required for
– Cardiac contraction
– Smooth muscle contraction
– Propagation of cardiac impulse
• Classification of Ca++ channel blockers
1. Dihydropyridine family:
–
–
–
–
–
Nifedipine
Nicardipine
Nisoldipine
Amlodipine
isradipine

35. 2. Miscellaneous:
– Verapamil
– Deltiazem
– Bepridil
• General pharmacokinetics for Ca++ channel
blockers
–
–
–
–
Orally administered
Highly protein bound
Hepatic first pass metabolism
Renal excretion

36. • Mechanism of action:
Calcium channel blockers bind with voltage
dependent Ca++ channel (L-type) in
depolarised membrane. The resultant effect is
relaxation of the smooth muscles and negative
ionotropic and chronotropic action in the
heart.

38. • Pharmacological action of Calcium channel blockers
1. CVS:
1.
2.
3.
4.
•
Dilates main coronary vessels: improves myocardial perfusion
Negative chronotropic effect: cardiac slowing and AV block
Negative ionotropic effect: decrease force of contraction
Vasodilation: decrease total peripheral resistance Smooth
muscles
Smooth muscles:
1.
2.
3.
Vascular smooth muscle: generalized relaxation
Coronary vasodilation: antianginal action
Visceral smooth muscle: relaxation of biliary tract; uterus and
bladder.

39. • Indications:
1.
2.
3.
4.
Angina pectoris (variant)
Hypertension
Cardiac arrhythmias
Prevention of ischemic neurological damage due
to subarachnoid damage
5. Raynaud’s disease
6. Migraine
7. Premature labour

40. • Contraindication:
– Heart failure
– Bradycardia
– Second or third degree AV block
– Sick sinus syndrome
– Wolf Parkinson-White syndrome

41. • Adverse effects:
• Due to vasodilation:
– Postural hypotension, reflex tachycardia
– Bradycardia, palpitation
– Headache, flushing, dizziness, ankle edema
• Gastrointestinal
– Constipation
– Nausea, vomiting
– Gum hypertrophy

42. ACE-Inhibitors
• Angiotensin converting enzyme (ACE) inhibitors
are :
–
–
–
–
Captopril
Enalapril
Lisinopril
Ramipril
• ACE inhibitors act by inhibiting the conversion of
angiotensin I to angiotensin II; which is a
powerful vasoconstrictor. It acts preferably on
angiotensin sensitive vascular bed of kidney,
brain and brain.

43. Mechanism of Action
• It inhibits the conversion of angiotensin I to
angiotensin II, thus vasoconstrcitive action of
angiotensin II is inhibited.
• Also ACE causes inactivation of bradykinin
(vasodilator peptides) but in presence of ACE
inhibitors bradykinin is active and causes
vasodilation which in turn decrease TPR and
finally BP.

44. Pharmacological actions
1. Vasodilation (reduction of TPR)
2. Reduce preload and afterload
3. Reduction in the secretion of aldosterone so
decreased salt and water retention.
4. Increase in renal blood flow.

45. Indications
• Hypertension
•
•
•
•
Renovascular hypertension due to excess renin
Malignant hypertension
Hypertensive crisis of scleroderma
End stage renal disease
• Refractory heart failure
• Ischemic heart disease

46. Adverse effects
•
•
•
•
•
•
•
•
•
•
First dose hypotension
Dry cough
Angioneurotic oedema
Hyperkalaemia
Loss of appetite
Stomatitis
Abdominal pain
Neutropenia
Proteinuria
Blood disorders

47. Contraindications
•
•
•
•
Systolic blood pressure < mm Hg
Bilateral renal artery stenosis
Second and third trimester of pregnancy
Renal failure

48. Angiotension receptor blockers
• These are the agents that act on the
angiotensin type I (AT1) receptor.
• Drugs:
– Losartan
– Valsartan
– Candesartan
– Eprosartan
– Irbesartan
– Telmisartan

49. • Unique features of ARBs from ACE-inhibitors:
– These agents are unique from ACE –inhibitors in
that they don’t have effect on bradykinin.
– They cause more complete inhibition of
angiotensin action because besides ACE other
enzymes are present which can angiotensin II.

50. Losartan:
Mechanism of action: It causes antagonism in
the angiotensin receptor thus causing a
complete blockade of angiotensin II activity.
Pharmacokinetics:
– Orally administered
– Extensively metabolized; metabolites retain
activity
– Plasma half-life: 2 hrs
– Dose: 50 mg/d; can range from 25-100 mg/d

51. • Indications:
– Hypertension
• Adverse effects: similar to ACE-inhibitors
except that no angioedema and cough is
present; both of which are mediated via
bradykinin.
• Contraindications:
– pregnancy

52. • Saralasin is an analog and competitive
inhibitor of angiotensin II at its receptors.
• It also blocks the pressor and aldosterone
releasing effect of infused angiotensin II and
reduce blood pressure in high renin activity
state such as renal artery stenosis.
• It has been withdrawn from market due to its
unpredictable pharmacological outcomes.

53. Vasodilators
• Drugs:
1. Oral vasodilators:
•
•
Hydralazine
Minoxidil
2. Parenteral vasodilators:
•
•
•
Nitroprusside
Diazoxide
Fenoldopam
• Mechanism of action : This class of compounds
cause the dilation of arteries or both arteries and
veins; thus reducing overall peripheral resistance
and in turn decreases the blood pressure.

54. • Hydralazine:
– It is a hydrazine derivative and is known to dilate arterioles only
but not veins.
– It causes tachyphylaxis to hypertensive effects developed
rapidly.
– It can be used in combination.
• Pharmacokinetics:
–
–
–
–
–
Orally administered
Extensive 1st pass metabolism
Low bioavailability
Half-life 2-4hrs
Dose: 40-200mg/day.

55. • Adverse effects:
– Headache
– Nausea
– Anorexia
– Palpitations
– Seating
– Flushing
– Systemic lupus erythrematosus (SLE)

56. • Minoxidil
– Orally active; half life-4hrs; 5-10mg/d in two doses
– Vasodilation results due to opening of K+ ions
which brings the membrane to hyperpolarized
state, producing relaxation.
– It also dilates arterioles but not veins.
– Headache, sweating and hypertrichosis,
tachycardia and angina and edema are side effects

57. • Fenoldopam:
• It is indicated for severe hypertension and
postoperative hypertension.
• Acts as Dopamine (D1 receptors) agonist
resulting dilation of peripheral ateries.
• Given parenterally (i.v. infusion); extensively
metabolized and very short half-life of 5 mins.
• Very small dose of 0.025-0.05µg/kg/min.

58. Individualised care approach
Calcium channel blockers :
Suited for :
1) Elderly
2) Isolated systolic
hypertension
3) Asthma/COPD patients
4) Raynauds disease/
migraine
5) Pregnant hypertensive
Avoid in :
1) CHF
2) Conduction defects
3) Patients receiving beta
blockers
4) IHD/ post MI
5) Left ventricular
hypertrophy
6) Males with enlarged
prostate
7) GERD

59. ACE Inhibitors
• Suited for :
1) High renin cases or those on
low salt
2) Physically active
3) Diabetics/ with nephropathy
4) Co existing angina / post MI
cases
5) Coexisting Left ventricular
failure / left ventricular
hypertrophy
6) Gout/PVD?Dyslipidemic
patients
• Avoided in :
1) Bilateral renal artery
stenosis
2) Pregnancy
3) Hyperkalemia
4) Pre existing dry cough

60. Beta adrenergic blockers
• Suited for :
1) Angina or post MI cases
2) Coexisting anxiety or
techycardia
3) Non obese high renin
hypertensive
4) Pregnancy
• Avoided in :
1) CHF
2) Bradycardia , conduction
defects
3) Asthma / PVD
4) Diabetic or borderline
glucose tolerance
5) Abnormal lipid profile
6) Patient to remain physically
active

61. Diuretics :
• Suited for :
1) Elderly patients
2) Low renin hypertensive
3) Isolated systolic
hyeprtension
4) Obese with volume
overload
5) Renal disease with salt
retention
6) Low cost therapy
•
1)
2)
3)
4)
5)
Avoided in :
Young active hypertensive
Diabetes
Gout
Abnormal lipid profile
Pregnancy induce
hypertension

62. Combination therapy
1) Drugs increasing renin activity ( diuretics . Vasodilators
, CCBs, ACE inhibtors ) with drugs having low renin
activity ( beta blockers , clonidine , methyl dopa )
2) Drugs causing fluid retention( adrenergic blockers
except beta blockers ) with diuretics
3) Drugs causing tachycardia ( hydralazine , DHPs)
with non selective beta blockers
4) ACE inhibitors / AT1 blockers with diuretics
5) CCB with diuretics
6) Beta blocker + prazosin

63. • Combinations to be avoided :
1) Adrenergic blocker with clonidine
2) Hydralazine with prazosin
3) Verapamil/diltiazem with beta blocker
4) Methyl dopa + clonidine

64. Hypertension in pregnancy
Suitable drugs
1) Methyl dopa
2) Hydralazine
3) Dihydropyridine CCBs
4) Cardioselective adrenergic
blockers ( atenolol,
pindolol, acebutolol)
5) Prazosin
6) Clonidine
Drugs to be avoided
1) Diuretics
2) ACE inhibitors
3) Reserpine
4) Non selective beta blockers
5) Sod nitroprusside

65. ABCD method of drug sequencing
Younger and non black
• Step 1 : A
Older and black
• Step 1: C or D
• Step 2: A+ c or D
• Step 3 : A+C+ D
• Step 4 : Add alpha blocker or spironolactone
or Beta blocker

66. Diabetes
• First line therapy :
Type 1 :
monotherapy :ACE inhibitors / AT1 blockers
Combination : + beta blockers / CCBs / thiazides/
alpha blockers
Type 2 :
ACE inhibitors / AT1 blockers / CCBs

67. Renal disease
• ACE inhibitors
• Thiazide diuretics not used in severe renal
impairment, instead loop diuretics are used

68. Anti-anginal drugs
• Angina pectoris
– It is a clinical syndrome characterized by pre-cardiac
pain or discomfort due to myocardial ischemia, which
is precipitated by exercise and relief by rest or
sublingual nitro-glycerine.
– It occurs when coronary blood flow is insufficient to
meet the metabolic requirement of the heart muscle.
– Myocardial oxygen demand mainly depends on
• Preload,
• After load and
• Heart rate

69. • atherosclerotic angina, classic angina(angina
of effort)
• vasospastic or variant angina(Prinzmetal's
angina)
• Unstable angina

70. Determinants of Myocardial Oxygen
Consumption.
•
•
•
•
•
•
Wall stress
Intraventricular pressure
Ventricular radius (volume)
Wall thickness
Heart rate
Contractility

71. Regulation of smooth muscle
contraction and relaxation
1) Increasing cGMP: dephosphorylation of
myosin light chains, nitric oxide
2) Decreasing intracellular Ca2+:
3) Stabilizing or preventing depolarization of
the vascular smooth muscle cell membrane:
increase the permeability of K+ channels,
4) Increasing cAMP in vascular smooth muscle
cells: cAMP increases the rate of inactivation
of myosin light chain kinase

72. • Drugs:
Organic nitrites and nitrates:
– Nitrites: sodium nitrite, amy-nitrite, octyl-nitrite
– Nitrates: glyceryl trinitrate, isosorbide dinitrate
and isosorbide mononitrate
Calcium channel blockers:
– Nifedipine
– Verapamil
– deltiazem

73. Beta-adrenoceptor blockers
– Atenolol
– Propranolol
– Oxaprenolol
Xanthines:
– Theophylline
– Aminophylline
Miscellaneous
– Dipyradimol

74. Drugs or Drug Groups under
Investigation for Use in Angina.
•
•
•
•
•
•
•
•
•
Metabolic modulators:eg, ranolazine
Direct bradycardic agents, eg, ivabradine
Potassium channel activators, eg, nicorandil
Rho-kinase inhibitors, eg, fasudil
Sulfonylureas:eg, glibenclamide
Thiazolidinediones/glitazones
Nitric oxide donors: eg, L-arginine
Capsaicin
Amiloride

75. Organic nitrates
•
•
•
•
•
•
•
Pharmacokinetics of organic nitrates:
Glyceryl trinitrate is a short-acting
Undergoes 1st pass metabolism if given orally
Given sublingually usually 500mg tab/day
Onset of action within 15-30 mins
Duration:20-30mins
Used mainly in acute attack.

76. • Isosorbide di-and mono-nitrates are long
acting
• Orally given
• Systemic availability more than GTN
• Used in prophylaxis.

77. Mechanism of action:
Organic nitrates act by relaxing smooth muscles of
blood vessels. It occurs in following steps:
1. Denitration of org. nitrates ( org nitrates into
inorganic)
2. Inorganic nitrates converted to NO (like EDRF)
3. Activation of guanylyl cyclase i.e. raised cGMP
4. Reduces intracellular Calcium concentration
5. Relaxation of vascular smooth muscles

79. • Pharmaclogical actions:
• CVS:
– Reduces preload (due to venodilation)
– Reduces afterload (due to generalized vasodilation)
– Dilates coronary arteries and increase blood flow to
ischemic areas
• Others:
– Relaxation of bronchial smooth muscle
– Relaxation of GIT smooth muscle i.e. decreased motility
– Relaxation of smooth muscle of biliary tract, urethra and
uterus.

80. • Indications:
– Angina pectoris
– Congestive heart failure
– Myocardial infarction
• Adverse effects:
–
–
–
–
–
Flushing of face
Throbbing headache
Postural hypotension
Syncope
Nitrate tolerance

81. • Contraindication:
– Organic nitrate intolerence
– Angina due to severe anemia
– High intra-cranial pressure
– Glaucoma
– Migraine

82. • Nitrate tolerance:
• During long term use , the nitrate effects is
gradually lowered and finally resulting in
partial or complete loss of its benefit.
• Mechanism is reduced production of cGMP in
vascular smooth muscles.
• Nitrate free period of 1-2 hours every 24 hrs
helps prevent development of tachyphylaxis.

83. Anti-arrhythmic drugs
• Cardiac arrhythmias:
The disorder in rate and rhythm of cardiac
contraction due to myocardial damage is known
as cardiac arrhythmias.
• Cardiac arrhythmias consist of cardiac
depolarizations that deviate form the normal in
one or more aspects;
– Abnormality at site of origin of impulse
– Its rate and regularity
– Its conduction

85. • Vaughan Williams classification
Class-I: Na+ channel blocker
Group A:
 Quinidine
 Procainamide
 Disopyramide
Pharmacological actions:
– Membrane stabilizing action
– Prolongs refractory period
– Prolongs action potential

86. Group B:
 Lidocaine
 Mexiletine
 Tocainide
 Phenytoin
Membrane stabilizing action
Shortens refractory period
Shortens action potential

87. Group C:
 Flecainide
 Encanide
Membrane stabilizing action
No effect on action potential

88. Class-II drugs: β-blockers (counteracts
catecholamines)
 Propranolol
 Atenolol
 Metoprolol
 Sotalol
Abolish SA firing
Decrease contractility
Increase AV refractoriness

89. Class-III drugs: Repolarization prolonging
 Amidarone
 Bretylium
Prolongs refractory period
Prolongs action potential
Prevents re-entry rhythm

90. Class-IV drugs: Calcium channel blockers
 Verapamil
 Deltiazem
Inhibits slow Calcium channels
Depress contractility of AV node.

91. Quinidine
• It is a class-I anti-arrhythmic drug. It is an
optical isomer of quinine (anti-malarial drug).
Pharmacokinetics:
– Orally active; i.v. in emergency; i.m. painful
– 80% bound to plasma proteins
– Half-life: 4-6 hrs
– Metabolized by liver (75%)
– Excretion: unchanged fraction by kidney

92. Pharmacological actions of quinidine:
– Cardiac tissue:
•
•
•
•
•
Reduce automaticity
Reduce excitability
Reduce conductivity
Prolong refractory period
Reflex tachycardia
– Other action:
• Anti-malarial
• Anti-pyretic
• Decrease B.P (vasodilation)

93. • Adverse effects:
–
–
–
–
–
–
–
–
–
–
Heart block
Sinus arrest
Myocardial depression
Q-T prolongation
Ventricular fibrillation
Nausea
Vomiting
Diarrhoea
Rash
Oedema

94. • Indications:
• As anti-arrhythmic used in,
–
–
–
–
–
Atrial fibrillation and flutter
Ventricular fibrillation and flutter
Paroxysmal supra-ventricular tachycardia
Premature supra-ventricular tachycardia
Atrial, nodal and ventricular premature beats
• Also as anti-malarial
• Anti-pyretic
• During digitalis therapy

95. • Cinchonism:
– Headache, vertigo
– Blurred vision
– Tinnitus
• Contraindications:
–
–
–
–
–
Quinidine intolerance
Digitalis intoxication
Heart failure
Hypotension
hypokalemia

96. • Propranolol as anti-arrhythmic drug:
– It blocks β-receptors in heart, thereby exerts
•
•
•
•
Negative inotropic effect
Negative chronotropic effect
Depress atrioventricular conduction
Depresses automaticity
– It has:
• Anti-arrhythmic effect
• Anti-hypertensive effect
• Anti-anginal-effect in CVS.

97. Lidgnocaine
• It is a local-anesthetic agent.
• Can terminate arrhythmia if quinidine fails
• Parenteral administration: i.v./i.m
Indications:
– As local anesthetic
– As anti-arrhythmic

98. • Mechanism of anti-arrhythmic effect of
lignocaine:
– It has membrane stabilizing effect by blocking
both activated and inactivated sodium channels;
which in turn supresses SA node and also ectopic
beats.
– Shortens refractory period and action potential;
make uniform rhythm

99. • Adverse effects:
– Bradycardia
– Hypotension
– Dizziness
– Blurred vision
– Sleepiness
– Confusion
– Convulsion