ANTIHYPERTENSIVE DRUGS:

Blood pressure means the force exerted by the blood against any unit area of the vessel wall.
Hypertension is the sustained elevation of systemic arterial blood pressure ≥ 140/90.
Physiological control of blood pressure and sites of drug action:

ANTIHYPERTENSIVE DRUGS:
A- Diuretics:
Mechanism of antihypertensive action:
Diuretics decrease blood volume by increasing renal excretion of Na and H2O→ ↓ venous return
(filling pressure) →↓ stroke volume→ ↓ BP. They may also reduce vascular resistance→ ↓ BP.
a- Loop diuretics:
Drugs include: Furosemide, bumetanide, torsemide
Mechanism of action: Block Na+/K+/2Cl− transporter in thick ascending limb. They cause
powerful diuresis and increased Ca2+ excretion.
Uses: Heart failure, pulmonary edema, severe hypertension; other forms of edema;
hypercalcemia.
Side effects: Hypokalemia, metabolic alkalosis, hypovolaemia, Ototoxicity, allergy.

Dr. HAMAD ALSHABI

b- Thiazide diuretics:
Drugs include: Hydrochlorothiazide, chlorthalidone.
Mechanism of action: Inhibit Na+/Cl– transporter in distal convoluted tubule. Cause moderate
diuresis and reduced excretion of calcium.
Uses: Hypertension, mild heart failure, hypercalciuria with stones.
Side effects: Hypokalemia, Metabolic Alkalosis, allergy, Hypercalcemia.
c- Potassium-Sparing Diuretics:
Drugs include: spironolactone
Mechanism of action: antagonist of aldosterone receptor in cortical collecting ducts→ Increase
Na excretion and decrease K and H+ excretion.
Uses: used in heart failure, Hypertension, used with thiazides, loop diuretics to decrease K+ loss.
Side effects: Hyperkalemia, Metabolic Acidosis, Gynecomastia.
B- Drugs that Alter Sympathetic Nervous System Function:
a- Centrally Acting Sympathoplegic Drugs:
Drugs include: Clonidine, Methyldopa.
Mechanism of action: They activate α2 in CNS which results in: ↓ sympathetic discharge →↓
PVR, ↓HR (↓CO) and ↓ BP.
Uses: Hypertension (Methyldopa is a preferred drug for treatment of hypertension during
pregnancy).
Side effects: sedation, severe rebound hypertension if drug is suddenly stopped (Clonidine).
b- β-Adrenergic antagonists:
Drugs include: propranolol, metoprolol, Esmolol.
Mechanism of action: block beta receptor → ↓ cardiac output and ↓ renin release.
Esmolol has a short half-life (9–10 minutes) and is administered by intravenous infusion. It is
used for management of intraoperative and postoperative hypertension, and sometimes for
hypertensive emergencies.
c- Selective α1- Adrenergic antagonists:
Drugs include: prazosin, terazosin, doxazosin
Mechanism of action: selectively block α1- receptor→ ↓ vascular resistance and ↓venous return
(↓CO) → ↓BP.

Dr. HAMAD ALSHABI

C- Ca2+ channel blockers:
Drugs include:
Dihydropyridines: amlodipine, felodipine, nicardipine, Clevidipine (IV only).
Non-dihydropyridines: verapamil, diltiazem.
Mechanism of action: They block L- type calcium channel in heart and blood vessels, ↓
intracellular Ca2+ so they are effective vasodilators (↓PVR) and also (↓CO).
Dihydropyridines have greater vasodilator than cardio-depressant effects.
Non-dihydropyridines have moderate vasodilator with strong cardio-depressant effects.
Uses: They are used in hypertension, angina and arrhythmias (only verapamil, diltiazem) and
Raynaud's phenomenon.
IV Clevidipine is used in acute hypertension occurring during surgery.
Side effects: excessive cardiac depression (especially verapamil, diltiazem), constipation,
flushing and dizziness, reflex tachycardia (only dihydropyridines) and edema.

Dr. HAMAD ALSHABI

D- Drugs that affect the renin- angiotensin system:

a- Angiotensin-converting enzyme inhibitors:

Drugs include: captopril, enalapril, lisinopril
Mechanism of action: they inhibit angiotensin converting enzyme→ ↓ reduce angiotensin II
synthesis→ reduce vasoconstriction (↓ PVR) and aldosterone secretion (↓ Na and H2O
retention)→↓ Bp.
They also increase bradykinin. They reduce cardiac remodeling.
Uses: Hypertension (good for hypertension with diabetes), Diabetic nephropathy, heart failure.
Side effects: acute renal failure in renal artery stenosis, hyperkalemia, {dry cough and
angioedema (due to ↑ bradykinin)}.
b- Angiotensin II receptor blockers (ARBs):
Drugs include: losartan, candesartan, valsartan.
Mechanism of action: they block the angiotensin II type 1 (AT1) receptor.
They have same effects of ACE inhibitors but no increase in bradykinin.

Dr. HAMAD ALSHABI

Uses: Hypertension, heart failure, Diabetic nephropathy.
Side effects: Same as ACE inhibitors but less cough.
E- Direct Vasodilators:
- Hydralazine:
Mechanism of action: It releases nitric oxide→ arteriolar dilation→↓PVR
Uses: moderate to severe hypertension, also used in heart failure in combination with isosorbide
dinitrate.
Side effects: Tachycardia, salt and water retention, lupus-like syndrome.
- Nitroprusside:
Mechanism of action: Releases nitric oxide→ both arteriolar and venules dilation →↓PVR and
venous return.
Uses: hypertensive emergency.
Side effects: Excessive hypotension; tachycardia, salt and water retention • prolonged infusion
may cause thiocyanate and cyanide toxicity.
- Fenoldopam:
MOA: Activates dopamine D1 receptors resulting in dilation of peripheral arteries & natriuresis.
Uses: hypertensive emergencies and postoperative hypertension.
Side effects: reflex tachycardia, headache, and flushing.

Dr. HAMAD ALSHABI

Drugs Used in the Treatment of Angina Pectoris

Angina pectoris is the principal syndrome of ischemic heart disease, anginal pain occurring when
oxygen delivery to the heart is inadequate for myocardial requirement.

Types of angina pectoris:

1- Stable/classic angina (angina of effort or exercise) is due to coronary atherosclerotic
occlusion that can impair coronary blood flow and lead to symptoms of angina when myocardial
O2 demand increases, as with exertion.
2- Vasospastic or variant angina (Prinzmetal) is due to a reversible decrease in coronary blood
flow (coronary vasospasm). It occurs at any time even at rest.

ANTIANGINAL DRUGS:

1- NITRATES

Drugs include:

- Nitroglycerin: sublingual, transdermal, and IV formulations

- Isosorbide dinitrate, isosorbide mononitrate: oral, extended release for chronic use.
Note: Due to their Significant first-pass metabolism in the liver their oral bioavailability is low.
Mechanism of action:
Releases nitric oxide (NO), increases cGMP (cyclic guanosine monophosphate), and relaxes
vascular smooth muscle→ Venodilation →↓ preload →↓ cardiac work →↓ oxygen requirement.
Uses:
- Sublingual form for Acute angina pectoris (first choice)
- oral and transdermal forms for prophylaxis of angina
- IV form for acute coronary syndrome
Side effects:

Dr. HAMAD ALSHABI

Flushing, headache, orthostatic hypotension, Reflex tachycardia and fluid retention.
B- CALCIUM CHANNEL BLOCKERS (CCBs):
Mechanism of action: They block L- type calcium channel.
Preferential arterial vasodilation ⇒ afterload reduction and reduction of heart rate,
contractility→↓ cardiac O2 demand (beneficial effect in angina of effort).
Reduction of coronary artery spasm→↑ blood supply (beneficial effect in variant angina).
Uses: Prophylaxis of angina (for both atherosclerotic (Second choice) and vasospastic (First
choice)), hypertension, arrhythmias (Diltiazem and verapamil).
Side effects: excessive cardiac depression (especially verapamil, diltiazem), constipation,
flushing and dizziness, reflex tachycardia (only dihydropyridines) and edema.
C- Β-ADRENERGIC ANTAGONISTS:
Mechanism of action: They block β-receptor in the heart→↓ heart rate, ↓blood pressure, and ↓
contractility→ ↓ myocardial oxygen requirements at rest and during exercise. They have
negative inotropic and negative chronotropic effects.
Uses: First choice for Prophylaxis of angina of effort but contraindicated in vasospastic angina.
Also used for Hypertension, post myocardial infarction, arrhythmias, migraine prophylaxis.

Dr. HAMAD ALSHABI

DRUGS USED IN HEART FAILURE
Heart Failure is a condition in which cardiac output is insufficient for the needs of the body.
Compensatory responses that occur during congestive heart failure:

DRUGS USED FOR THE TREATMENT OF CHF:

A- POSITIVE INOTROPIC DRUGS:
1- Cardiac glycosides: Digoxin
Mechanism of Action:
Inhibits Na+/K+ ATPase sodium pump and increases intracellular Na+, decreasing Ca2+
expulsion and increasing cardiac contractility.
Cardiac parasympathomimetic effect (slowed sinus heart rate, slowed atrioventricular
conduction).
Uses: Chronic symptomatic heart failure and rapid ventricular rate in atrial fibrillation.
Side effects: Nausea, vomiting, diarrhea and cardiac arrhythmias. Low therapeutic index.
2- Sympathomimetics:
Dobutamine, Dopamine, Epinephrine, Norepinephrine

Dr. HAMAD ALSHABI

Mechanism of Action:
Stimulate beta 1→ ↑ cardiac contractility.
Uses: used only for Acute decompensated heart failure.
Side effects: arrhythmias.

3- Phosphodiesterase Inhibitors (inodilator):

Bipyridines: milrinone
Mechanism of action: They inhibit phosphodiesterase isozyme 3 (PDE-3)→↑ cAMP→↑
activated protein kinase→:
1- Phosphorylation of Ca2+ channels→↑ Ca2+ influx→↑ contractility.
2- Vasodilation (reduction of both afterload and preload).
Uses: Acute decompensated heart failure
Side effects: arrhythmias.

Dr. HAMAD ALSHABI

Drugs Without Positive Inotropic Effects Used in Heart Failure:
1- Diuretics: Furosemide, Hydrochlorothiazide, Spironolactone
Effects: increased excretion of salt and water, reduces cardiac preload and afterload, reduces
pulmonary and peripheral edema. Spironolactone also reduces remodeling.
Uses: Acute and chronic heart failure.
2- Angiotensin-Converting Enzyme Inhibitors
Effects: Arteriolar and venous dilation • reduces aldosterone secretion • reduces cardiac
remodeling.
Uses: First choice in treating heart failure.
3- Angiotensin Receptor Blockers: Like ACE inhibitors, used in patients intolerant to ACE
inhibitors.
4- BETA BLOCKERS: Bisoprolol, Carvedilol, Metoprolol, Nebivolol
Effects: reduces cardiac remodeling.
Uses: Chronic stable failure.
5- Vasodilators:
Isosorbide dinitrate (Venodilators) with Hydralazine (Arteriolar dilators) used for Heart failure
in African Americans.
Nitroprusside: Combined arteriolar and venodilator, used for acute decompensated heart failure.

Dr. HAMAD ALSHABI