1. ANTI-HYERTENSIVE DRUGS: Therapeutic overview
DR BUSARI. A.A
(MB.BS, M.Sc., MMCP, FWACP)
Consultant Nephrologist & Lecturer
Dept. Of Pharmacology, Therapeutics and Toxicology

2. Outline What is hypertension? Epidemiology, Types and Classification
Physiology of Blood pressure
Classes of anti-hypertensive
Pharmacology of individual drugs.
Non- pharmacological treatment of hypertension
Conclusion

3. What is hypertension?
Hypertension; Systemic arterial hypertension (HTN)
Defined as sustained elevated Blood Pressure(BP) ≥ 140/90mmHg.
Most common cardiovascular dx.
Asymptomatic in most cases.
Untreated, usually lead to complications such as stroke, heart failure, kidney failure, ischaemic heart dx and death.

4. Epidemiology Prevalence is increasing world wide.
25% of adult population in the U.S. More prevalent in Nigeria %.
Affect all races and gender.
Mainly 2 types
Primary (Essential) HTN – 90%, idiopathic, but associated risk factors
Secondary HTN – “RENVA”.

5. Classification

6. Physiology of Blood pressure
BP = Cardiac Output X Peripheral Vascular Resistance.
Arterial pressure affected by:
– the autonomic nervous system (fast)
– the renin-angiotensin system (hours or days)
– the kidneys (days or weeks)

7. Physiology of Blood pressure

8. Classification of anti-hypertensive by site or mechanism of action
A. Sympatholylic drug
ß Adrenergic receptor antagonist (Beta blockers):
atenolol
metoprolol
nadolol
nebivolol
oxprenolol
pindolol
propranolol
timolol

9. Classification of anti-hypertensive by site or mechanism of action
2. α Adrenergic receptor antagonist (alpha blockers):
Doxazosin
phentolamine
indoramin
phenoxybenzamine
prazosin
terazosin
tolazoline

10. Classification of anti-hypertensive by site or mechanism of action
3. Mixed adrenergic antagonist:
carvedilol
labetalol
Bucindolol
4. Centrally acting agent/ α2 receptor agonist:
α -methyldopa
clonidine
guanabenz
guanfacine
Moxonidine
5. Adrenergic neuron blockers:
Reserpine
Guanadrel

11. Classification of anti-hypertensive by site or mechanism of action
B. Calcium channel blockers
1.dihydropyridines:
amlodipine
cilnidipine
felodipine
isradipine
lercanidipine
levamlodipine
nicardipine
nifedipine
nimodipine
nitrendipine
2. Non-dihydropyridines:
diltiazem
verapamil

12. Classification of anti-hypertensive by site or mechanism of action
C. Angiotensin-converting enzyme Inhibitors(ACEI):
captopril
enalapril
fosinopril
lisinopril
perindopril
quinapril
ramipril
trandolapril
benazepril

13. Classification of anti-hypertensive by site or mechanism of action
D. Angiotensin II receptor antagonists
candesartan
eprosartan
irbesartan
losartan
olmesartan
telmisartan
valsartan

14. Classification of anti-hypertensive by site or mechanism of action
E. Vasodilators
Aterial vasodialators
Hydralazine
Minoxidil
diazoxide
2. venous vasodialators
Sodium nitroprusside

15. Classification of anti-hypertensive by site or mechanism of action
F. Diuretics
1.Loop diuretics:
furosemide
bumetanide
ethacrynic acid
Torsemide
2. Thiazide diuretics:
epitizide
hydrochlorothiazide
bendroflumethiazide

16. Classification of anti-hypertensive by site or mechanism of action
4. Thiazide-like diuretics:
indapamide
chlorthalidone
metolazone
5. Potassium-sparing diuretics:
amiloride
triamterene
spironolactone

17. Potential drug targets:
• CNS, ANS: decrease sympathetic tone
• Heart: decrease cardiac output
• Veins: dilate => decrease preload
• Arterioles: dilate => decrease afterload
• Kidneys: increase diuresis; inhibit RAA system

18. Potential drug targets:

19. Potential drug targets:

20. Rational pharmacotherapy of hypertension.
1.Reduce LV systolic performance (reduce the ESPVR): negative inotropes (betablockers (metoprolol, atenolol, propranolol) and calcium channel blockers (verapamil, diltiazem)).
2. Reduce blood volume and thus drop LVEDV: diuretics (thiazide – hydrochlorothiazide, loop diuretics – furosemide, bumetanide and potassium sparing diuretics – spironolactone, amiloride, triamterene).

21. Rational pharmacotherapy of hypertension.
3.Reduce venous tone and thus venous return: Central sympatholytics such as clonidine act to reduce overall sympathetic tone.
4. Reduce arterial tone (i.e. resistance) and thus reduce Ea: Effective arterial dilators include angiotensin converting enzyme inhibitors (ACE inhibitors – lisinopril, captopril), angiotensin receptor blockers (ARB’s – valsartan, losartan), calcium channel blockers (nifedipine, amlodipine), potassium channel openers (minoxidil), nitric oxide donors (nitroprusside), alpha1 blockers (prazosin, terazosin, doxazosin), and mixed alpha and beta-blockers (labetalol)

22. THANK YOU