ANTIHYPERTENSIVE DRUGS

1. Antihypertensive Drug
Presented by
Monika Devi
M.Sc.(N)

2. Antihypertensive Drugs
• Antihypertensives are a class of drugs that are used to
treat hypertension (high blood pressure).
• Antihypertensive therapy seeks to prevent the complications of high
blood pressure, such as stroke and myocardial infarction.

3. Antihypertensive Drugs Classification
1. Diuretics.
2. Beta adrenergic blockers.
3. Calcium channel blockers.
4. Angiotensin converting enzyme inhibitors.
5. Angiotensin receptor blockers.
6. Sympatholytic and adrenergic blockers.
7. Direct arterial vasodilators.

4. Diuretics
• Diuretics, also called water pills, are medications designed to
increase the amount of water and salt expelled from the body as
urine. They’re often prescribed to help treat high blood pressure,
but they're used for other conditions as well.

5. Types
The three types of diuretic medications. All of them make the body excrete
more fluids as urine.
1. Thiazide diuretics:- Are the most commonly prescribed diuretics. They’re
most often used to treat high blood pressure. These drugs not only decrease
fluids in the body, they also relax the blood vessels. Thiazides are sometimes
taken with other medications used to lower blood pressure. Examples of
thiazides include:
• Chlorothiazide
• Chlorthalidone
• Hydrochlorothiazide
• Metolazone
• Indapamide

6. Cont…
2. Loop diuretics :- Loop diuretics are often used to treat heart failure.
Examples of these drugs include:
• Torsemide
• Furosemide
• Bumetanide
• Ethacrynic acid

7. Cont…
3. Potassium-sparing diuretics :- Potassium-sparing diuretics reduce fluid
levels in the body without loosing potassium. The other types of diuretics
cause to lose potassium, which can lead to health problems such
as arrhythmia. Potassium-sparing diuretics may be prescribed for people
at risk of low potassium levels, such as those who take other drugs that
deplete potassium. Examples of potassium-sparing diuretics include:
• Amiloride
• Spironolactone
• Triamterene
• Eplerenone

8. Mechanism of Action
• Initial effects:- through reduction of plasma volume and cardiac
output.
• Long term effect:- through decrease in total peripheral vascular
resistance.

9. Advantages
• Documented reduction in cardiovascular morbidity and
mortality.
• Least expensive antihypertensive drugs.
• Best drug for treatment of systolic hypertension and for
hypertension in the elderly.
• Can be combined with all other antihypertensive drugs.

10. Side effects
• More common side effects the more common side effects of
diuretics include:
• Too little potassium in the blood
• Too much potassium in the blood (for potassium-sparing diuretics
only)
• Low sodium levels
• Headache
• Dizziness
• Thirst
• Increased blood sugar
• Muscle cramps
• Increased cholesterol
• Skin rash
• Diarrhea

11. Cont…
Serious side effects
In rare cases, diuretics may cause serious side effects. These can
include:
 Allergic reaction
 Kidney failure
 Irregular heartbeat

12. Drug interactions
These include:
• Cyclosporine
• Antidepressants such as fluoxetine and venlafaxine
• Lithium
• Digoxin
• Other drugs for high blood pressure

13. 2. Beta - Adrenergic Blocking Agents
Beta-adrenergic blocking agents, are a class of drugs that works by
blocking the neurotransmitters norepinephrine and epinephrine from
binding to receptors. There are three known types of beta receptors,
known as beta1 (β1), beta2 (β2) and beta3 (β3).
• β1-adrenergic receptors are located commonly in the heart and
kidneys.
• β2-adrenergic receptors are located mainly in the lungs, gastrointestinal
tract, liver, uterus,vascular smooth muscle, and skeletal muscle.
• β3- adrenergic receptors are located in fat cells.

14. Mechanisms of Action
• Initial decrease in cardiac output, followed by reduction in
peripheral vascular resistance.
• Other actions include decrease plasma renin activity, resetting of
baroreceptors, release of vasodilator prostaglandins, and
blockade of pre-junctional beta-receptors.

15. Advantages
• Documented reduction in cardiovascular morbidity and mortality.
• Cardio protection: primary and secondary prevention against
coronary artery events (i.e. ischemia, infarction, arrhythmias,
death).
• Relatively not expensive.

16. Practical Considerations
• Beta blockers are used with caution in patients with
bronchospasm.
• Contraindicated in heart block.
• Do not discontinue abruptly.

17. Side Effects
• Bronchospasm and obstructive airway disease.
• Bradycardia
• Coldness of extremities.
• Fatigue.
• Mask symptoms of hypoglycemia.
• Metabolic effects (raise triglycerides levels and decrease HDL
cholesterol; may worsen insulin sensitivity and cause glucose
intolerance). Increased incidence of diabetes mellitus.

18. Special Indications
• First line treatment for hypertension as an alternative to diuretics.
• Hypertension associated with coronary artery disease.
• Hypertension associated with supraventricular tachycardia,
• Migraine, essential tremors
• hypertrophic cardiomyopathy.

19. • Calcium channel blockers (CCB),or calcium antagonists are
medications that disrupt the movement of calcium (ca2+)
through calcium channels. calcium channel blockers are used
as antihypertensive drugs.
3. Calcium channel blockers

20. Types
• Dihydropyridine: used to reduce systemic vascular resistance and
arterial pressure. This CCB class is easily identified by the suffix "-
dipine".
• Nifedipine
• Nimodipine (nimotop) this substance can pass the blood-brain
barrier and is used to prevent cerebral vasospasm.
• Amlodipine
• Felodipine
• Lacidipine.

21. Cont…
2. Non dihydropyridine : The Non-dihydropyridine Calcium Chanal
Blockers such as verapamil (Isoptin) and diltiazem (Cardizem) cause
less vasodilation and more cardiac depression than dihydropyridine
Calcium Chanal Blockers.
They have negative effects at the SA and AV nodes, and cause
reductions in heart rate and contractility. E.g
• Phenylalkylamine:- Verapamil.
• Benzothiazepine:- Diltiazem

22. Mechanisms of action
• Decrease in the concentration of free intracellular calcium ions
results in decreased contraction and vasodilation.
• Diuretic effect through increase in renal blood flow and
glomerular filtration rate.
• Inhibition of aldosterone secretion.

23. Advantages
• No metabolic disturbances: no change in blood glucose,
potassium, uric acid and lipids.
• May improve renal function.
• Maintain optimal physical, mental, and sexual activities.

24. Special Indications
• Ischemic heart disease: when beta blockers are ineffective or
contraindicated and in vasospastic angina.
• Elderly hypertensives: second agent of choice after diuretics.
• Peripheral vascular disease.

25. Side Effects
• Dihydropyridine: flushing, headache, and lower limb
edema.
• Non dihydropyridine: aggravation of heart failure and
heart block.

26. Practical considerations
Short acting dihydropyridine should be combined with beta
blockers in coronary artery disease, and should be avoided in
stroke, and hypertensive crisis.

27. 4. Angiotensin Converting Enzyme Inhibitors
• Angiotensin-converting enzyme (ACE) inhibitors help relax blood
vessels. ACE inhibitors prevent an enzyme in the body from producing
angiotensin II, which narrows blood vessels and releases hormones
that can raise blood pressure. This narrowing can cause high blood
pressure and force the heart to work harder.
Types:-
• Class I: Captopril
• Class II (prodrug) : e.g., ramipril, enalapril, perindopril
• Class III ( water soluble) : lisinopril.

28. Advantages
• Reduction of cardiovascular morbidity and mortality in
patients with atherosclerotic vascular disease, diabetes, and
heart failure.
• Improvement in glucose tolerance and insulin resistance.
• Renal glomerular protection effect especially in diabetes
mellitus.
• Do not adversely affect quality of life.

29. Special Indications
• Diabetes mellitus, particularly with nephropathy.
• Congestive heart failure.
• Following myocardial infraction.

30. Side Effects
• Cough (10 - 30%): a dry irritant cough with tickling sensation in
the throat.
• Skin rash (6%).
• Postural hypotension in salt depleted or blood volume depleted
patients.
• Renal failure: rare, high risk with bilateral renal artery stenosis.
• Hyperkaliemia

31. 5. Angiotensin receptor blockers
The class of drugs called angiotensin receptor blockers (ARBs), as the
class name suggests, are drugs that block the action of angiotensin.
Mechanism of action:-
• They act by blocking type I angiotensin II receptors generally,
producing more blockade of the renin - angiotensin - aldosterone axis.

32. Advantages
• Similar metabolic profile to that of ACE-I.
• Renal protection.
• They do not produce cough.

33. Practical Indications:-
• Patients with a compelling indication for ACE-I
• who can not tolerate them because of cough or allergic
reactions.

34. 6. Sympatholytic And Alpha Adrenergic Blockers
Sympatholytic drugs :
Drugs that inhibit nerve impulses in the sympathetic nervous system. Th
ey may block the effect of alpha-adrenergic receptors which is used to
reverse pupillary blockage or the effect of beta- adrenergic receptors
called beta-blockers ( which block beta 1 receptors; timolol maleate,
levobunolol, metipranolol and carteolol which block beta 1 and beta
2 receptors) Beta-blockers are used in the treatment of glaucoma.
• Alpha 1-receptor blockers: prazocin, doxazocin.
• Centrally acting alpha 2- agonists: methyldopa, clonidine.
• Peripherally acting adrenergic antagonists: reserpine.
• Imidazoline receptor agonists: rilmenidine, moxonidine.

35. Advantages
• Alpha1- receptor blockers and imidazoline receptor agonists improve
lipid profile and insulin sensitivity.
• Methyldopa: increases renal blood flow. Drug of choice during
pregnancy.
• Reserpine: neutral metabolic effects and cheap.

36. Special indications
• Diabetes mellitus: alpha1- receptor blockers, imidazoline receptor
agonists.
• Dyslipidemia: alpha 1- receptor blockers, imidazoline receptor
agonists.
• Prostatic hypertrophy: alpha 1- receptor blockers.
• When there is a need for rapid reduction in blood pressure: clonidine.

37. Side Effects
• Prazocin: postural hypotension, diarrhea, occasional tachycardia,
and tolerance (due to fluid retention).
• Methyldopa: sedation, hepatotoxicity, hemolytic anemia, and
tolerance.
• Reserpine: depression, lethargy, weight loss, peptic ulcer, diarrhea,
and impotence.
• Clonidine: dry mouth, sedation, bradycardia, impotence, and
rebound hypertension if stopped suddenly.

38. 7. Direct Arterial Vasodilators
These drugs act directly on the blood vessel walls, relaxing muscles to
allow blood to flow more easily. Direct vasodilators are used only in
individuals with hypertension that is extremely difficult to control;
they are also sometimes used to treat a hypertensive crisis
• hydralazine, diazoxide, nitroprusside, and minoxidil.

39. Patients’ compliance to antihypertensive medications:-
 Poor adherence to antihypertensive therapy remains a major
therapeutic challenge contributing to the lack of adequate control
of blood pressure in more than two thirds of patients with
hypertension.
 One half of all patients discontinue antihypertensive medications
within one year.

40. Causes of Poor Compliance
• Hypertension has no symptoms and treatment has to continue
indefinitely.
• Poor communication with the patient. Very long intervals between
follow-up visits, and frequent change of doctors impair the doctor-
patient relationship.
• Logistic barriers e.g. expense of medications, inability to read
instructions, complicated multi-dose regimens, etc….
• Adverse drug effects.

41. Strategies to Improve Compliance
• Educate patients about the disease and involve their families in the
treatment.
• Stress that treatment is life-long.
• Consider cost while prescribing.
• Consider adverse effects at initial prescription and follow up visits.
• Prescribe simple once-daily regimens.
• Allow extra visits for blood pressure measurement at no extra
charge to the patient.
• Arrange follow-up visits at intervals no more than three months
apart, during the first year.
• Encourage life style modifications.

42. BIBLIOGRAPHY
• (1) Kumar P. Pharmacology For Nurses Second Edition 2008 JAYPEE
BROTHERS MEDICAL PUBLISHERS (P) LTD new Delhi
• (2) Kumar P. medical Pharmacology fifth edition 2017 CBS Publishers
& Distributors PVT. LTD new.
• (3)Shenoy S, Shanbhag T Pharmacology For medical Graduates 3rd
Edition, Elsevier Publication, RELX India Private Limited, Barakhamba
road, LTD. ltd

43. Thank you