1. The document discusses various classes of cardiovascular drugs including antihypertensives, antianginal drugs, and drugs for congestive heart failure and arrhythmias. 2. It provides details on the mechanisms, indications, and side effects of different classes of antihypertensive drugs including diuretics, beta-blockers, calcium channel blockers, ACE inhibitors, and alpha-blockers. 3. Non-pharmacological measures for hypertension such as exercise, diet modification, and reducing alcohol and sodium intake are also summarized. Guidelines for treatment of hypertension based on age, race, and severity are presented.

1. CARDIOVASCULAR DRUGS
• ANTIHYPERTENSIVES
• ANTIANGINAL DRUGS
• DRUGS USED IN
CONGESTIVE CARDIAC
FAILURE (CCF)
• ANTIARRYTHMICS

2. • Hypertension or High blood pressure is defined
as persistent rise in blood pressure measured
by systolic blood pressure (SBP) 140 mm Hg or
more, or a diastolic blood pressure (DBP) of 90
mm Hg or more.
• Blood pressure = cardiac output × peripheral resistance

3. TYPES:
According to etiology:
1. Essential (Primary) hypertension:
- common (90%)
- unknown cause (empirical)
- therapy is directed to reduce BP
2. Secondary hypertension:
- uncommon
- known cause (e.g. renovascular,
pheochromocytoma, hyperthyroidism, drugs
etc)
- therapy directed to treat the cause

4. Why hypertension should be controlled?
• Because chronic raise in BP damages
blood vessels in kidney, heart & brain &
leads to an increased incidence of renal
failure, coronary disease, heart failure &
stroke.
• Effective pharmacological lowering of BP
prevent damage to blood vessels & leads
to reduced morbidity & mortality rates.

5. NONPHARMACOLOGICAL MEASURES
 Regular exercise & correcting obesity
 Restricting salt intake
 Reducing alcohol intake (≤2 drinks / day)
 Increasing consumption of fruit & vegetables
 Quitting smoking
 Adopting low saturated fat diet
 Drugs that increase BP (Nasal decongestant,
NSAIDs, OCPs, Tricyclic antidepressants & some
herbal preparations) should be avoided

6. Pharmacological measures
 Drug selection depends on:
 Level of BP
 Presence and severity of end organ damage
 Presence of other diseases
 Severe HTN require more rapid treatment
with more efficacious drugs
 Most pt. of essential HTN, therapy is best
initiated in gradual fashion with
individualized drug & dose

7. Younger (<55 yrs)
& non black
Older (≥55 yrs)
or black
Step 1 A (or B) C (or D)
Add either α- blocker or
spironolactone or other diuretic
A (or B) + C + D
A (or B) + C (or D)
Step 4 (Resistant
HTN)
Step 3
Step 2
Key:
A= ACEI/ARB
B = β- blocker
C= CCB
D= Diuretic
(Thiazides)
Guidelines recommended by British Hypertension Society

8. Pharmacotherapy contd……
HYPERTENSION IN PREGNANCY
 Possible situations:
 Hypertensive patient become pregnant
 Pregnancy induced HTN (Preeclampsia)
 Antihypertensives to be avoided during
pregnancy: Diuretics, ACE inhibitors, ARB, Non
selective β blockers, Sod. nitroprusside
 Antihypertensives found safer during
pregnancy: α-methyldopa, CCB (DHP), β1 blocker,
Hydralazine, Prazosin & Clonidine

9. 1. Diuretics
Thiazides: Hydrochlorothiazide, Chlorthalidone, Indapamide
High ceiling: Furosemide, Torsemide, Bumetanide
K+ Sparing: Spironolactone, Amiloride
2. ACE inhibitors: Captopril, Enalapril, Lisinopril, Ramipril
3. Angiotensin (AT1) receptor blockers: Losartan, Telmisartan
4. Direct renin inhibitor: Aliskiren
5. Calcium channel blockers: Verapamil, Nifedipine, Amlodipine
6. Sympatholytics
β Adrenergic blockers: Propranolol, Metoprolol, Atenolol
β + α Adrenergic blockers: Labetalol, Carvedilol
α Adrenergic blockers: Prazosin, Doxazosin, Phentolamine
Central sympatholytics: Clonidine, Methyldopa
7. Vasodilators
Arteriolar: Hydralazine, Minoxidil, Diazoxide
Arteriolar + venous: Sodium nitroprusside
ANTIHYPERTENSIVES

10. Diuretics:Thiazides:
Drug of choice for mild - moderate HTN
Inhibit Na+-Cl- symport in Distal Tubules
Lowers blood pressure by:
a. Initially, ↑Na+ excretion → reduce plasma & e.c.f.
volume → decrease CO
b. On long-term use, there is reduction in PVR
c. PVR reduction is facilitated by salt restriction
Have long half life (given OD)
Unlike other diuretics, they decrease Ca2+ excretion
so suitable for elderly people
Potentiate action of other antihypertensive drugs
Cheaper

11. DIURETICS

12. Side effects (Dose dependent):
 Hypokalemia (hazardous in patient some patient )
 Impair glucose tolerance
 Increase serum lipid concentration
 Increase serum uric acid concentration
low dose (equivalent to 12.5-25 mg/ day of
hydrochlorothiazide) thiazides are
recommended as first line
Low dose thiazides have maximum anti-
hypertensive effect with very less side effects
Other drug is added if this dose is not sufficient

13. High ceiling diuretics (Furosemide):
Strong diuretics
Inhibit Na+, K+ 2Cl- cotransport in thick ascending
loop of henle
Lowers BP by reducing plasma & e.c.f. volume and
decreasing CO
No reduction in PVR
Short (4-6 hr) diuretic action
Side effects are same like thiazides except, it also
causes hypocalcemia
Valuable in:
a) Severe HTN b) HTN with Chronic renal failure
c) HTN with coexisting refractory CHF
d) resistant to combination therapy containing a thiazide
or marked fluid retention

14. Potassium sparing diuretics:
(Spironolactone, Amiloride)
Weak diuretics
Lowers BP slightly
Combined with other diuretics:
augment antihypertensive action and also
prevent hypokalemia

15. β-Blockers
• Good patient acceptability & cardioprotective
• Mild antihypertensive, no significant effect on
normotensive
• Lowers blood pressure by:
Blocking β1 receptor on heart → ↓CO
Decreasing renin release from JG cells
Reduce NA release
• Slow (1-3 weeks) & sustained hypotensive action
• Used in mild-moderate HTN: In severe HTN it
prevent reflex tachycardia caused by vasodilators

16. Drawbacks
• Not suitable for asthmatic patient, diabetic patient &
angina patient
• Altered lipid profile
• Peripheral vascular disease severity
• Tiredness & reduced exercise capacity
• Nightmares, forgetfulness
• Sexual distress in male
Precautions:
• Should not be withdrawn abruptly after chronic use
• Should not be used in diabetic patients receiving
insulin, Why?

17. • Atenolol/Metoprolol preferred over Propanolol
Low incidence of side effects (cardioselective)
CNS effects are less (low lipid solubility)
Less effects on lipid profile
Less effects on exercise capacity
Long duration of action (Atenolol more than Metoprolol)
Do not produce postural hypotension
• β-Blockers are Drugs of choice for:
Young nonobese hypertensive
Hypertensive with IHD
With stable heart failure

18. α-Blockers
• Lowers BP by dilating resistance & capacitance
vessels
• Fast action
• BP falls more in standing posture than supine
Drawbacks:
• First dose effect may persist in elderly
• Fluid retention so risk of CHF, development of
tolerance
• More side effects (Nasal congestion, Headache,
Drowsiness, dry mouth, weakness, blurred vision)
• Ejaculation is impaired in males

19. Prazosin, Terzosin, Doxazosin & Tamsulosin
• These are selective competitive blockers of the α1
receptor.
• Prazosin, Terzosin & Doxazosin are useful in the
treatment of hypertension as they cause dilation of
artery. It can cause first dose effect so started at low
dose at bedtime. They are orally effective with high
plasma protein bound, metabolised in liver &
excreted from bile.
β-Blockers + α-Blockers
• Act faster than β-Blockers with dilating blood
vessels
• Used i.v for rapid BP reduction in cheese reaction,
Clonidine withdrawl (rebound HTN)

20. Central Sympatholytics:
CLONIDINE:
Imidazoline derivative
I.v. infusion (not oral) cause transient rise in BP
followed by prolong hypotensive response
Oral- slow and prolong fall in BP
 Mechanism of fall in BP:
↓ central sympathetic out flow & ↓ release
of NA from peripheral adrenergic nerve by
acting on prejunctional α2 receptor

21.  Optimum hypotensive action: 0.2-2.0 ng/ml (serum)
Maintain renal blood flow, reduced renin release
Good oral absorption (~100%) , effect observed
after 1-3 hrs
 Dose: 100 mcg OD/ BD, Max. 300 mcg TDS orally/ i.m.
 Side effects (common):
a. dry mouth, sedation, sexual dysfunction,
bradycardia, hypotension (dose related & can be
minimised by transdermal administration )
b. Withdrawl reaction: ↑ BP, tachycardia,
restlessness, anxiety, sweating etc even in missing
drug for 2-3 days

22. Methyldopa:
Prodrug
Limited use due to side effect but safe in pregnancy
Mechanism of fall in BP: convert to
α-methylnorepinephrine which ↓ central
sympathetic out flow by stimulating α2 receptor
Moderately efficacious
Effect seen in 4-6 hrs and lasts for 12-24 hrs
Side effects
a. Sedation, depression, dryness of mouth, libido,
parkinsonian sign, gynecomastia (common)
b. Hemolytic anemia
Preferred for HTN during pregnancy
Dose: 250mg BD (starting)

23. Calcium Channel Blockers (CCBs)
• Verapamil, Diltiazem, Amlodipine, Nifedipine
• MOA: CCBs blocks the influx of Ca++ inside the
cells. It particularly blocks L-type voltage
sensitive calcium channels. It causes:
• negative chronotropic effect
(decreases heart rate)
• negative ionotropic effect
(decreases force of contraction)
• negative dromtropic effects
(decreases conduction rate)

24. • Classification:
• Dihydropyridines (DHP): Nifedipine,
Amlodipine, Nimodipine, Felodipine
• Non-Dihydropyridines: Verapamil, Diltiazem
• Useful for patients with diabetes & angina.
• CCBs are orally active, high plasma protein
bound
• Verapamil & diltiazem are used i.v

25. PHARMACOLOGICAL EFFECTS
 Cardiac and smooth muscle effects are
the main actions
 Verapamil preferentially affect HEART,
Dihydropyridines (DHPs)- Smooth muscles
Diltiazem is intermediate
SMOOTH MUSCLES:
 Relax arterioles more than vein
 Also relax bronchial, biliary, intestinal,
vesical, uterine
 DHPs have most prominent action on
Smooth muscles and least by Verapamil

26. CCB contd…….
HEART:
 Impulse generation in SA node and AV
node conduction is reduced or blocked
(-ve chronotropic/ dromotropic)
 Reduce cardiac contractility (-ve
inotropic effect) in dose dependent
manner
 Verapamil have the most depression
effect than Diltiazem
 DHPs have no direct effect on heart

28. INDICATIONS:
 Hypertension
 Cardiac Arrhythmias: Verapamil and
Diltiazem are used e.g. PSVT
 Angina pectoris (short acting DHPs should
be avoided)
 Hypertrophic cardiomyopathy: verapamil
can be used
 Premature labour: Nifedipine can be used
 Verapamil can be used in migraine &
nocturnal leg cramp
 Raynaud’s episodes: DHP can be used

29. Adverse effects
• Arterial dilation: headache, flush, dizziness, ankle swelling.
• Bradycardia and AV block (verapamil).
• Verapamil + beta-blockers: potentiate cardiodepression.
• Constipation (verapamil 8%; nifedipine 3%)
• Verapamil/diltiazem may worsen CHF and cardiac conduction
defects
• By their smooth muscle relaxant action, the DHPs can worsen
gastroesophageal reflux.
• CCBs (especially DHPs) may accentuate bladder voiding
difficulty in elderly males.
• Haemorrhagic gingivitis
Contraindication: Heart failure, Bradycardia
Second or third degree AV block
Sick sinus syndrome
Wolf Parkinson-White syndrome

30. Verapamil
 Dilates artery directly as well as α-blocking action
 Adverse effects:
 nausea, constipation, bradycardia
 Flushing, headache, ankle edema are less
common
 Cardiac arrest may occur when given i.v. or
given in sick sinus
 Interaction: should not be given along with β
blocker, increases digoxin by decreasing its
excretion
Diltiazem
• Clinical dose produce consistent fall in BP with little
change or decrease in HR.
• It dilates coronaries. I.V. injection decreases total
peripheral resistance & elict reflex cardiac effects.

31. Nifedipine
• Rapidly dilates arteries
• Short acting
• Decreases total peripheral resistance & causes
fall in BP
• Negative ionotropic effect
• Dose: 5-20mg BD
Adverse effects
• Palpitation, flushing, ankle edema, hypotension,
headache, drowsiness & nausea
• Hampers diabetes & urine voiding difficulty

32. Amlodipine
• Slow acting & long duration of action
• High oral bioavailability & large volume of
distribution
• Less side effects so SAFE!
• Dose: 5-10mg OD
• AMLOD, MYLOD

33. Angiotensinogen
(Plasma)
AT1 receptors
Angiotensin II (A
II)
Angiotensin I (A
I)
Vascular/ Cardiac
growth: (Prolong effect)
1. Hyperplasia
2. Hypertrophy
3. Matrix production
Vasoconstriction:
1. Direct
2. Release of NA
Salt retention:
1. Aldosterone
secretion
2. Tubular Na+
reabsorption
ACE
Renin
RAAS

34. RAS & ACEI contd…….
Renin
 release is rate limiting step for A-II
formation
 t1/2 15 min
 A-II inhibit
of renin release
Renin release
β1 agonist
Low Macula
densa Na+
Low glomerular
afferent pressure
↑Sympathetic activity
due to ↓BP

35. RAS & ACEI contd…….
Renin is synthesized, stored & secreted by the
granular juxtaglomerular (JG) cell of afferent
arterioles

36. RAS & ACEI contd…….
Angiotensin Converting Enzyme (ACE)
 Enzyme present mainly on luminal surface
of vascular endothelial cells (esp. in lungs)
 Rapidly convert A-I (decapeptide) to A-II
(octapeptide)
 Identical to kininase II which
inactivate bradykinin and other
potent vasodilator peptides

37. RAS & ACEI contd…….
Renin release
β1 agonist
Low Macula
densa Na+
Low glomerular
afferent pressure
↑Sympathetic activity
due to ↓BP
1

38. RAS & ACEI contd…….
Angiotensinogen
(Plasma)
AT1 receptors
Angiotensin II (A
II)
Angiotensin I (A
I)
ACE
Renin
Action
2
3
4

39. ACE-Inhibitors
• Angiotensin converting enzyme (ACE) inhibitors are :
– Captopril
– Enalapril
– Lisinopril
– Ramipril
• MOA: ACE inhibitors act by inhibiting the conversion
of angiotensin I to angiotensin II, which is a powerful
vasoconstrictor.
• 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.

40. RAS & ACEI contd…….
Bradykinin
Angiotensin II
Angiotensin I
Effects
Inactive
Metabolites
ACE
(Kininase)
↑ PG
synthesis
Vasodilation
ACE
Inhibitor

41. 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.
Indications
• Hypertension
• Renovascular hypertension due to excess renin
• Malignant hypertension
• Hypertensive crisis of scleroderma
• End stage renal disease
• Refractory heart failure
• Ischemic heart disease
• Dose: 5-20 mg OD or BD

42. Adverse effects
• First dose hypotension
• Dry cough
• Angioneurotic oedema
• Hyperkalaemia
• Loss of appetite
• Stomatitis
• Abdominal pain
• Neutropenia
• Proteinuria
• Blood disorders
Contraindication
 Systolic blood pressure < mm
Hg
 Bilateral renal artery stenosis
 Second and third trimester of
pregnancy
 Renal failure

43. Angiotension Receptor Blockers
• These are the agents that act on the angiotensin type
I (AT1) receptor.
• Competitive blocker of AT1 receptor.
• Drugs:
– Losartan
– Valsartan
– Candesartan
– Eprosartan
– Irbesartan
– Telmisartan
• Unique features of ARBs from ACE-inhibitors:
– These agents are unique from ACE –inhibitors in that they
don’t have effect on bradykinin. Do not interfere
bradykinin degradation so cough is rare.

44. Bradykinin
Angiotensin II
Angiotensin I
Effects
Inactive
Metabolites
ACE
(Kininase)
↑ PG
synthesis
Vasodilation

45. Losartan:
Mechanism of action: It causes antagonism in the
angiotensin receptor thus causing a complete
blockade of angiotensin II activity.
• Indications:
– Hypertension
Dose 25-100mg OD
• Adverse effects: similar to ACE-inhibitors except that
no angioedema and cough is present; both of which
are mediated via bradykinin.
• Contraindications:
– pregnancy

46. Hydralazine
• Directly acting vasodilator
• MOA: hydralazine molecules combine with
receptors in the endothelium of arterioles – NO
release – relaxation of vascular smooth muscle
– fall in BP
• Uses:
• 1) Moderate hypertension when 1st line fails –
with beta-blockers and diuretics
• 2) Hypertension in Pregnancy,
• Dose 25-50 mg OD

47. Sodium nitroprusside:
Rapidly (within second) & short (2-5min) acting
Dilates arterioles & venules
Effect titrated with rate of i.v. infusion
MOA: Endothelial cells, RBCs split it to form NO
which dilate blood vessels
Side effects:
1. Due to excessive vasodilation (common)
2. Less commonly, from conversion of nitroprusside to cynide
and thiocyanate (lactic acidosis,anorexia, dysorientation,
psychosis)
 Uses: Hypertensive emergency, to produce controlled
hypotension in CHF
Precautions: Should be prepared fresh and should not be
exposed to light / alkali, Avoid prolong use

48. Minoxidil
• Powerful vasodilator, mainly 2 major uses –
antihypertensive and alopecia
• MOA: K+ channel opener, prodrug, powerful aterial
dilator
• Rarely indicated in hypertension especially in life
threatening ones
• More often used in alopecia to promote hair growth
• MOA of hair growth:
• Enhanced microcirculation around hair follicles and
also by direct stimulation of follicles
• Alteration of androgen effect of hair follicles
• Orally not used any more
• Topically as 2-5% lotion/gel and takes months to get
effects

49. DIAZOXIDE (K+ Channel opener)
Given (rapid i.v.) in severe hypertension in place
of Sod. Nitroprusside (where close monitoring is
not possible)
RESERPINE : NOT used

50. Combination therapy
1) Drugs increasing renin activity ( diuretics, Vasodilators, CCBs, ACE
inhibtors) with drugs having low renin activity ( beta-blockers,
clonidine, methyldopa )
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
Combinations to be avoided :
1) Adrenergic blocker with clonidine
2) Hydralazine with prazosin
3) Verapamil/diltiazem with beta blocker
4) Methyldopa + clonidine