‫بسم هللا الرحمن الرحيم‬

Ibn Sina University

Faculty of Medicine
Fourth year
Pharmacology
Lecture 23
Antihypertensive drugs
Khalid Suleiman Taha
2025
 Lecture goals
⬢ By the end of the lecture, the student will be able
to:
o Classify anti-hypertensive drugs.
o Identify and describe the pharmacological properties
of anti-hypertensive drugs.
o Use anti-hypertensive drugs effectively in
management of hypertensive patients.
⬢ Control of BP:
⬢ A. Baroreceptors and the sympathetic nervous system.
⬢ B. Renin-angiotensin-aldosterone system.
 HYPERTENSION
⬢ Is increase of either systolic BP or diastolic BP or both.
⬢ HTN is silent killer causes end organ damage
1. Heart :causes Coronary artery disease (angina – MI) -
Left ventricular hypertrophy-CHF
2. Kidney : Renal failure.
3. Brain: Transient or multiple ischemic attack, Stroke or
hemorrhage
4. Eye causes retinopathy lead to blindness.
Classification:
⬢ Hypertension emergency:
⬢ Hypertensive crisis (DBP ≥ 120mmHg with end organ
damage).
⬢ Hypertensive urgency (DBP ≥ 120mmHg without end
organ damage).
⬢ Malignant hypertension (DBP ≥ 130mmHg with end
organ damage)
 ⬢ Etiology :
1. Primary HTN (essential)
⬡ No obvious causes.

⬡ Affect 90-95%.

⬡ Multifactorial origin (genetic and environmental

factors like obesity, alcohol use and salt
consumption)
2. Secondary HTN
⬡ Defined causes
 ⬢ Pathogenesis :
1. Cardiac functions increase lead to Pump based or high
output hypertension
⬡ Persistent increase in COP with normal SVR:
⬡ Occur due to increase in sympatho-adrenal activity
and/or increase heart sensitivity to basal neuro-
hormonal activity.
⬡ Common in younger Pt with essential hypertension.
⬡ Respond effectively to beta-blockers.
2. Vascular function defect result in vascular resistant based
hypertension:
⬡ Increase in SVR with normal COP.
⬡ Defect in vascular response due to endothelium damage
or abnormal equilibrium between vasodilators and
vasoconstrictors factors and also ion channel defect.
⬡ Most increase in SBP.
⬡ Common mechanism in elderly.
⬡ Respond well to thiazide diuretics.
3. Renal function defect result in volume based
hypertension:
⬡ Abnormal increase in intravascular volume due to renal
disease which decrease nephron mass or increase renin
release and renovascular disease (renal artery stenosis
which decrease renal perfusion and increase renin
release) renin lead to production of angiotensin which
causes vasoconstriction and sodium -water retention.
⬡ Both COP and SVR increased.
⬡ Common in black Pts.
4. Dysfunction in neuro-hormonal mechanisms like stress
which increase sympathetic tone, pheochrmocytoma,
hyperaldosteronism and excessive production of
thyroid hormone.
ANTI HYPERTENSIVE MEDICATIONS
 A-DIURETICs

1. Loop diuretics
2. Thiazide diuretics
3. Potassium sparing diuretics
⬢ Site of action : kidney
⬢ Mode of action : increase sodium and water
excretion by different biological mechanisms.
⬢ Loop diuretics e.g. Furosemide
(have powerful diuretic effects
called high ceiling diuretics)
⬢ Site :loop of Henle lead to:
1. Block sodium and water
reabsorption.
2. Block potassium reabsorption.
⬡ Causes hypokalemia.
3. Block calcium reabsorption.
⬢ Thiazide diuretics:
⬡ Hydrochlorothiazide -Indapamide.
⬢ Site :distal convoluted tubule
result in:
1. Block Na+ - Cl- reabsorption.
2. Block potassium reabsorption.
o Causes hypokalemia.
3. Increase calcium reabsorption.
4. Decrease urate excretion.
⬡ Cause hyperuricemia and
precipitate gout.
⬢ K+- Sparing Diuretics:
⬢ Site :collecting tubule
⬢ They are two major categories:
⬢ 1- Na+-channel Antagonists:
(Amiloride & Triametrine)
⬢ 2- Aldosterone-receptors Antagonist:
(Spironolactone)
⬢ Aldosterone acts to promote Na+
uptake in exchange for K+ secretion.
⬡ Cause mild Na/water excretion.
⬡ Not affect K-excretion.
 ⬢ Hemodynamic effect:
1. Initially :reduce blood volume →
reduce COP → increase PVR by
compensatory rennin pathway .this
effect due to water excretion.
2. Thiazide diuretics only has direct
vasodilation effect after 4-8 weeks
decrease PVR this effect is due to
unclear mechanisms.
⬡ Full effect seen after 4-8 weeks
⬢ Clinical uses :
• Thiazide diuretics used in mild to moderate
hypertension (not effective in severe)
● Have a longer duration so given as once daily
dose improve pt compliance.
● Reduce BP in doses not cause full diuresis so
use in small possible dose to decrease SEs .
• Loop diuretics used only in hypertension
emergencies in patient with renal failure
(powerful diuretics ) but not suitable for long
term due to lack of vasodilation effect.
⬢ K-sparing diuretics have modest effect in hypertension
and used when thiazide or loop developed
hypokalemia.

Aldosterone antagonism have

special indication in secondary
HTN caused by
hyperaldosteronism.
⬢ Diuretics can be used as first-line drug therapy for
hypertension unless there are compelling reasons to
choose another agent.
Good candidate include mild to moderate hypertension in
blacks (whose hypertension is volume dependent), elderly
and renal impairment.
Bad candidate include severe uncontrolled hypertensive
pt. and non compliance pt. (discussed as micturition rate
in first weeks)
⬢ ADRs (Thiazide)
1. Hypokalemia
2. Hyperuricemia.
3. Hyperglycemia
4. Hyperlipidemia.
5. Impotence.
6. Lethargy.
⬢ Drug interactions
1. NSAIDs (decrease effect)
2. Digoxin (increase digoxin toxicity with hypokalemia)
3. Some antiarrhythmic (amiodarone and lignocaine )
both of them affected by hypokalemia.
4. Use of ACEIs and K-supplement with K-sparing
diuretics concomitantly result in life threatening
hyperkalemia.
 ⬢ B-Sympatholytic:
1. β-blockers (Classes??)
⬢ Site : heart and kidney.
⬢ Mode of action (refer to autonomic pharmacology)
⬢ Hemodynamic effect:
⬢ Clinical uses:
1. The effect is racial dependent as 70-80% of black not
respond to beta-blockers unless in combination with
diuretics.
⬡ Used mainly in white young pt. (the lower response rate
seen in elderly.)
2. Proved to reduced complication (IHD-CHF-arrhythmia)
⬡ First line agent when the hypertension accompany with
other CVS diseases.
3. Labetalol (mixed alpha-beta blockers) used in emergency
situations.
⬢ ADRs and → contraindication (refer to ANS
pharmacology)
2. Alpha-1 blockers
⬢ Site of action : blood vessels.
⬢ Mode of action : refer to autonomic pharmacology.
⬢ Hemodynamic effects:
1. Prevent effect of NA at vascular bed
→vasodilatation→↓PVR.
2. Causing sodium and water retention with less reflex
tachycardia than non selective one (compensatory
mechanism)
⬢ Include prazocin doxazocin……..
⬢ Clinical uses:
1. No longer effective as mono-therapy it combined with
either beta blockers or diuretics.
⬡ Due to compensatory response
⬡ Non selective alpha blockers like phenoxybenzamine
associated with more compensatory response and
not used unless in phoecrmocytoma.
2. Not affect lipid profile.
3. Proven to be effective in pt with BPH.
⬢ Other sympatholytic
⬢ Their use decline due to ADR and appearance of more

effective and safe drugs.

Centrally acting: α2-selective agonist (methyldopa)
⬡ MD reduces vascular resistance without causing
much change in cardiac output or heart rate.
⬡ Methyldopa used only in pregnancy induced
hypertension (have no effect in fetus)
 C-Modulators of renin-angiotensin system

1. Angiotensin converting enzyme inhibitors.(ACEIs)

2. Angiotensin receptor blockers.(ARBs)
3. Renin inhibitors.
1. ACEIs (april)
⬢ Captopril (older short acting), Lisinopril ,Enalapril
(prodrug) are long acting
⬢ Mode of action & hemodynamic effect:
⬢ Therapeutic effects & clinical uses:
1. Decrease BP in hyper –reninemic hypertensive Pt and also
effective in Pt with low or normal renin level ( may be due to
bradykinin effect)
2. It decrease loss of kidney function in diabetic Pt and Pt with
CKD.(beneficial effects on renal function may result from
decreasing intraglomerular pressures, due to efferent arteriolar
vasodilation).
3. Useful in white and black young pt. (Effectiveness increase in
combination with diuretics for black patients.)
4. Useful in pt with CHF or after MI (Angiotensin linked to
pathogenesis of these conditions and associated with
ventricular enlargement due to its trophic effects)
 ⬢ ADRs
1. Hyperkalemia when used with other drugs
that can cause K+ retention, including the
K+-sparing diuretics, NSAIDs, K+
supplements, and beta receptor blockers.
2. Dry cough due to bradykinin effect on
lung.
3. It cause rare angioedema and first dose
hypotension (bradykinin vasodilatory
effect)
4. Rash and fever (mainly seen with older
shorter agents like captopril).
 ⬢ Cautions and CI:
1. Precipitate reversible renal failure in patients with
intravascular volume depletion or bilateral renal
artery stenosis( or unilateral in patients with single
kidney)
⬡ Interfere with essential required RAAS function in
these pts.
2. Absolutely contraindicated in pregnancy due to
teratogenic effect.
2. AT1-angiotensin II receptor blockers :Losartan,
candesartan, valsartan (sartan drugs)
⬢ The AT1 angiotensin II-receptor subtype is located
predominantly in
1. Vascular and myocardial tissue (trophic effects and
vasoconstriction)
2. Kidney and adrenal glomerulosa cells, which
secrete aldosterone (salt retention)
3. Brain (not known)
⬢ Hemodynamic effect : similar to ACEIs without affecting
the bradykinin system .
⬢ Clinical uses and therapeutic effects:
⬢ They decrease hypertrophic effects caused by angiotensin
(note that there are other angiotensin come from other
pathways newly discovered?)
⬢ Alternative to ACEIs in non adherent Pt( i.e. with cough)
⬢ Side effects and CIs:
⬢ Cause hypotension, hyperkalemia, and reduced renal
function and they are fetotoxic (like ACEIs)
⬢ Cough, an adverse effect of ACE inhibitors, is less frequent
and Angioedema occurs very rarely.
3. RENIN INHIBITOR: aliskiren
⬢ MOA: directly inhibits renin and, thus, acts earlier in
the renin-angiotensin-aldosterone system than do
ACE inhibitors or ARBs.
⬢ Therapeutic effects: equal to ACEIs and ARBs.
⬢ SEs and CIs: like ACEIs.
⬢ D-Vasodilators:
⬢ The major mechanisms of action of the arterial
vasodilators include
1. Blockade of Ca+2 channels (calcium channel
blockers)
2. Opening of metabotropic K +channels (minoxidil)
3. Release NO from endothilium (sodium nitroprusside)
1. CCBs
⬢ Classified to :
A. Non-dihydropyridine cardio selective CCBs (verpamil
and diltiazim)
B. Dihydropyridine arterioselective CCBs
(nifidipine,amlodipine,filodipine……etc.)
Mode of action: block calcium channels decrease
intracellular calcium decrease heart contractility (NON-
DHP) and decreases arteriolar (but not venules
)constriction(DHP)
⬢ Hemodynamic effect:

⬢ NON-DHP: ↓force of contraction ↓COP.

⬢ DHP:↓arteriolar constriction ↓PVR (Reflex tachycardia)

⬢ Therapeutic effects and clinical uses:
⬢ Have intrinsic natriuretic activity (not required
diuretic combination)
⬢ Useful in the treatment of hypertensive patients who
also have asthma, diabetes, angina (except short
acting), and good response seen in black patients.
⬢ Dihydropyridine calcium antagonists may be useful in
elderly patients with isolated systolic hypertension.
⬢ ADRs
⬢ Verpamil commonly causes
constipation.
⬢ Headache and dizziness seen
mainly with agents cause
excess vasodilatation
(nifidipine)
2. Other vasodilators:
⬢ Dilate vessels by direct action on smooth muscle cells.
⬢ Hemodynamic effect :↓PVR and reflex increase in HR
and Na retention
⬢ Mode of action:
1. K+-channel openers: (Minoxidil )
⬡ Opening K+ channels in smooth muscle and thereby

permitting K+ efflux, it causes hyperpolarization and

relaxation of smooth muscle.
⬡ Causes dilation of arterioles but not of venules.
2. Hydralizine (oral or parenteral)
⬡ Causes arteriolar dilatation by unknown
mechanism.
3. Na nitoprusside: is a nitro vasodilator that acts by
releasing nitric oxide thus dilates both arterioles
and venules.(is a nonselective vasodilator).
⬢ Therapeutic effects and clinical uses:
⬢ Hydralizine:
⬢ Combined with sympatholytic agents and diuretics with greater
therapeutic success.
⬡ Not used alone (Tachycardia &tolerance)
⬡ Proven as efficacious in patients with the most severe and
drug-resistant forms of hypertension (in combination)
⬡ Used primarily to treat hypertensive emergencies in
pregnant women (alone)
⬢ Minoxidil & Na nitoprusside: administer by IV restricted to
hypertensive emergency resistant to other drugs)
⬢ Adverse effects
⬢ General ADR due to excessive vasodilatation include
headache, tachycardia, nausea, sweating, arrhythmia,
and precipitation of angina.
⬢ Individual toxicity:
⬢ Hydralazine.
⬡ A lupus-like syndrome can occur with high dosage, but it is
reversible on discontinuation of the drug.
⬢ Minoxidil :Hypertrichosis.
⬢ Na nitoprusside (metabolized to thiocyanate)
⬡ Prolonged use causes thiocyanate accumulation and
toxicity (weakness, nausea and inhibition of thyroid
function).
A lupus-like
syndrome
caused by
hydralazine
Treatment of HTN with concomitant diseases
⬢ Race and age
⬢ There are some predictable differences in the
response to antihypertensive drugs among patient
groups, which can be summarized by the
⬢ AB/CD guidelines:
⬢ For young (and also white) patients, consider starting
with an ACE inhibitor(A) or β-blocker (B).
⬢ For older (and also black) patients, consider stating on
a calcium-channel blockers (C) or diuretic (D).