In this all drugs included except diuretics

1. Antihypertensiv
e Drugs
Presented by
Abhaya S S
Roll no 59

2. Contents
▪ Introduction
▪ ACE Inhibitors
▪ ARBs
▪ Beta Adrenergic blockers
▪ Alpha Adrenergic blockers
▪ Calcium channel blockers
▪ Vasodilators
▪ Central Sympatholytics
▪ Beta + Alpha Adrenergic blockers
▪ Selection of drug
2

3. Introduction
Hyertension
Systolic Blood
Pressure
(SBP)
>140 mm Hg
Diastolic Blood
Pressure
(DBP)
>90 mm Hg
3

4. Classification of Drugs
Ace Inhibitors Captopril, enalapril, lisinopril, perindopril,
ramipril.
Angiotensin
antagonists
Losartan, irbesartan, candesartan
Calcium channel
blockers
Verapamil, diltiazam, nifedipine, felodipine,
amlodipine, lacidipine
Diuretics Thiazide=hydrochlorothiazide, chlorthalidone.
indapamide
High ceiling = furosemide
K+ sparing = spironolactone.amiloride,
4

5. Classification of Drugs
ß - Adrenergic
blockers
Propranolol, metaprolol, atenolol.
+ß Adrenergic
blockers
Labetalol, carvedilol. sodium
 - Adrenergic
blockers
prazosin., terazosin, phentolamine
Central
Sympatholytic
Clonidine, methyldopa
Vasodilators Hydralazine, minoxidil
Renin inhibitors Aliskiren
5

6. 1. ACE Inhibitors
What is Renin - Angiotensin? Physiology
Angiotensin Converting Enzyme
Renin
Angiotensinogen
AngiotensinI
AngiotensinII
Bindsto ZGand cell
surfacereceptor
AngiotensinIII
AldosteroneProduction (Adrenacortex)
Renal Arterial
Pressure
[Na*] in Renal
Tubular Fluid
Renal Sympathetic
NerveActivity
Na+ & Water
Retention
Vasocontriction
Risein BP
Increased Blood
Volume
Kidney

7. ACE Inhibitors
▪ Captopril
▪ lisinopril
▪ enalapril
▪ ramipril
▪ fosinopril
Angiotensin Converting Enzyme inhibito
7

8. Mechanism of action
This group of drugs inhibit the enzyme kininase
II or ACE. So these drugs decreases the
activity of RAAS and also potentiate the
vasodilatory action of bradykinin.
Angiotensin Converting Enzyme inhibitors
8

9. Adverse effects
▪ Cough – persistent brassy cough in 20% cases – inhibition of bradykinin
and substanceP breakdown in lungs
▪ Hyperkalemia in renal failure patients with K+ sparing diuretics, NSAID
and beta blockers (routine check of K+ level)
▪ Hypotension (in hypovolemic states) – sharp fall may occur
– 1st dose
▪ Acute renal failure- CHF and bilateral renal artery stenosis
▪ Angioedema - swelling of lips, mouth, nose etc.
▪ Rashes, urticaria etc
▪ Dysgeusia - loss or alteration of taste
9

10. Adverse effects
▪ Foetopathic - hypoplasia of organs, growth retardation
etc
▪ Neutropenia
▪ Contraindications - Pregnancy, bilateral renal artery
stenosis, hypersensitivity and hyperkalaemia
10

11. 2.ARBs
▪ Losartan
▪ Candesartan
▪ Irbesartan
▪ Valsartan
▪ Telmisartan
Angiotension receptor blockers
11

12. Mechanism of action
Angiotension receptor blockers
12
Angiotensiogen
Angiotensiogen I
Angiotensiogen II
AT2 receptorAT1 receptor
Renin
ACE
ARBS

13. Mechanism of action
These drugs act by antagonizing the action of
angiotensin II at AT1 receptors. Theses drugs
do not increase bradykinin and thus have less
chances for causing cough and angioedema
Angiotensin receptor blockers
13

14. ADR
▪ Headache , hypotension, weakness, rashes,
nausea, vomiting and teratogenic effects.
▪ They may cause hyperkalemia in patients
with renal failure or in patients on potassium
sparing diuretics.
Angiotension receptor blockers
14

15. 3.Renin inhibitors
▪ Aliskiren , remikiren and enalkiren are the
drugs that inhibit the enzyme renin.
▪ Thus these drugs decrease the activity of
RAAS causing fall in BP.
▪ ADR
▪ Aliskerin can cause diarrhea at higher doses
▪ Aliskerin can also cause cough and
angioedema but probably less often than 15

16. 4.Beta-adrenergic blockers
▪ Selective  blockers (block only 1)
▪ Atenolol , metoprolol, esmolol, betaxolol etc
▪ Nonselective beta blockers (block both 1
and 2)
▪ propranolol and timolol.
16

17. Mechanism of action
Inhibition of beta 1 receptors leading to decreased cardiac
output.
Decrease in renin release due to inhibition of β1 receptors in
JG cells of kidney , along with this inhibit AT-II and
aldosterone production, and lower peripheral resistance
17

18. Contd.
Inhibition of central and
peripheral sympathetic outflow
due to inhibition of presynaptic
stimulatory β receptors on
adrenergic neurons.
18

19. Advantages of cardio-
selective over non-selective:
▪ In asthma
▪ In diabetes mellitus
▪ In peripheral vascular disease
19

20. ADR
▪ Fatigue, lethargy – decreased work capacity
▪ Loss of libido – impotence
▪ Cognitive defects – forgetfulness
▪ Difficult to stop suddenly- withdrawal syndrome.
▪ Can precipitate CHF and bronchospasm in
susceptible individuals.
▪ Therefore cardio-selective drugs are preferred now
20

21. 5.-Adrenergic Blockers
▪ Prazosin
▪ Terazosin
▪ Doxazosin
▪ Phentolamine
▪ Phenoxybenzamine
21

22. Mechanism of action
These drugs produce a competative block of alpha
1 adrenoceptors. They decrease PVR and lowers
arterial BP by causing relaxation of both arterial
and venous smooth muscle.
Therefore long term tachycardia does not occur but
salt and water retention does.
-Adrenergic Blockers
22

23. -Adrenergic Blockers
▪ Non selective alpha blockers are not used in
chronic essential hypertension
(phenoxybenzamine, phentolamine), only used
sometimes as in phaechromocytoma
▪ Specific alpha-1 blockers like prazosin, terazosin
and doxazosine are used
23

24. ADR
▪ Prazosin causes postural hypotension – start 0.5
mg at bed time with increasing dose and upto10
mg daily
▪ Fluid retention in monotherapy
▪ Headache, dry mouth, weakness, dry mouth,
blurred vision, rash, drowsiness and failure of
ejaculation in males.
24

25. 6.α-β Adrenoceptor blocking
agents
▪ Labetalol and carvedilol are two drugs having
antagonistic activity at both adrenergic receptors
(i.e block both α1 and β1 and β2 receptors).
▪ They are mainly used for controlling hypertension
in pheochromocytoma.
▪ Carvedilol due to its antioxidant and antimitogenic
property is also useful in CHF.
25

26. 7 .Calcium Channel Blockers
Classification
26
Calcium Channel
blockers
Diphenylalkylamine
s Verapamil
Benzothiazepines Diltiazem
Dihydropyridines
1st
generation
Nifedipine
2nd
generation
Isradipine
Nicardipine
Felodipine
3rd
generation
Amlodipine

27. Mechanism of action
▪ CCBs block the inward movement of calcium by
binding to L type calcium channels in the heart
and in smooth muscle of the coronary and
peripheral vasculature.
▪ This causes vascular smooth muscle to relax
,dilating mainly arterioles.
Calcium Channel Blockers
27

28. ADR
▪ Constipations occur in 10% of patients treated with
Verapamil.
▪ Dizziness , headache, and feeling of fatigue
caused by decrease in BP are most frequent with
dihydropyridines.
28

29. 7. Vasodilators
▪ Arteriolar = Hydralazine, minoxidil,
diazoxide.
▪ Arteriolar + Venous = Sodium
nitroprusside.
29

30. Mechanism of action
Hydralazine molecules combine with receptors in
the endothelium of arterioles – NO release –
relaxation of vascular smooth muscle – fall in BP
Subsequent fall in BP – stimulation of adrenergic
system leading to
 Cardiac stimulation producing palpitation and
rise in CO even in IHD and patients – anginal
attack
▪ Tachycardia
Arteriolar vasodilators
30

31. Contd.
31
 Increased Renin secretion – Na+ retention
 These effects are countered by administration of
beta blockers and diuretics

32. Mechanism of action
Minoxidil
Powerful vasodilator, mainly 2 major uses –
antihypertensive and alopecia
Prodrug and converted to an active metabolite which
acts by hyperpolarization of smooth muscles and
thereby relaxation of SM – leading to hydralazine like
effects
Arteriolar vasodilators
32

33. ADR
Hydralazine
Headache, tachycardia, nausea, sweating, arrhythmia
and precipitation of angina. A lupus like syndrome can
occur with high dosage but it is reversible on
discontinuation of the drug.
Minoxidil
This drug causes serious sodium and water retention
leading to volume overload ,edema and CHF.
33

34. Sodium Nitroprusside
▪ Rapidly and consistently acting vasodilator
▪ Relaxes both resistance and capacitance vessels
and reduces PVR and CO (decrease in venous
return)
▪ Unlike hydralazine it produces decrease in cardiac
work and no reflex tachycardia.
▪ Improves ventricular function in heart failure by
reducing preload 34

35. Mechanism of action
In the body it functions as a prodrug,
reacting with sulfhydryl groups on
erythrocytes, albumin, and other proteins
to release NO.
NO, or endothelium derived relaxing
factor, stimulates guanyl cyclase to
produce cyclic GMP, sequestering
calcium and inhibiting cellular contraction.
Sodium Nitroprusside
35

36. Contd.
Uses: Hypertensive Emergencies, 50 mg is
added to 500 ml of saline/glucose and infused
slowly with 0.02 mg/min initially and later on
titrated with response (wrap with black paper)
Adverse effects: ADRs are due to release of
cyanides (“thiocyanate” which is a metabolic
outcome of nitroprusside) – palpitation, pain
abdomen, disorientation, psychosis, weakness
and lactic acidosis.
36

37. 8. Centrally acting
sympatholytics
▪Clonidine
▪Alpha methyldopa
37

38. Mechanism of action
Clonidine binds α2-AR with higher affinity than α1-AR.
The α2-agonistic activity contributes to its BP-lowering
effect due to negative feedback at the presynaptic
neurons.
When given i.v., clonidine induces a brief rise of BP,
which is followed by prolonged hypotension.
Clonidine
38

39. Mechanism of action
▪ The metabolite, α-methylnorepinephrine, is stored in
neurosecretory vesicle in place of NE.
▪ When released, α-methyl-NE is a potent α-AR
agonist and in PNS is a vasoconstrictor.
▪ Its CNS effect is mediated by α2-AR, resulting in
reduced adrenergic outflow from the CNS and an
overall reduced total peripheral resistance.
Alpha methyldopa
39

40. 40

41. ADR
Clonidine
Dryness of mouth and eyes, sedation ,depression,
bradycardia, impotence, nausea, dizziness, parotid
gland swelling, and pain. Postural hypotension may
occur in some case.
Sudden stoppage of clonidine after prolonged use
may cause withdrawal syndrome- headache,
nervousness, tachycardia, sweating, tremors,
palpitation and rebound hypertension
41

42. ADR
Alpha methyldopa
Nasal stuffiness, headache, sedation, depression,
dryness of mouth, bradycardia, impotence,
gynaecomastia, hepatitis and rarely haemolytic
anaemia.
42

43. Selection of Antihypertensive Drugs
Selection of anti hypertensive drugs in individual
patients depends on
1. Comorbidity
2. Associated complications
3. Age
4. Sex
5. Cost of the drug
6. Concomitant drugs
43

44. Selection of Antihypertensive Drugs
Preferred drugs for initial treatment of hypertension:
ACE inhibitors, ARBs, CCBs and thiazides.
Therapy usually started with a single agent.
Combination therapy is used in patients who do not
respond to single drug, can be used as initial therapy
in patients with high BP.
44

45. 45

46. 46

47. 47

48. References
▪ Lippincott’s illustrated reviews
▪ K D Tripathi essentials of medical pharmacology
48

49. Thank You