Lecture 8 - Antihypertensive Agents
Lecture 8 - Antihypertensive Agents
Lecture 8 - Antihypertensive Agents
Agents
1
Hypertension is defined as either a sustained systolic blood
pressure (SBP) of greater than 140 mm Hg or a sustained
diastolic blood pressure (DBP) of greater than 90 mm Hg.
2
Classification of Blood Pressure
3
Etiology of Hypertension
Primary Hypertension
Specific cause unknown
90% of the cases
Also known as essential or idiopathic
hypertension
Secondary Hypertension
Cause is known (such as eclampsia of pregnancy,
renal artery disease, pheochromocytoma)
10% of the cases
4
Major factors influencing blood pressure
5
Antihypertensive Agents:
Categories
1. Adrenergic antagonists
2. Angiotensin-converting enzyme inhibitors
3. Angiotensin II receptor blockers
4. Calcium channel blockers
5. Diuretics
6. Vasodilators
6
7
1. Adrenergic antagonists:
A. Beta-blockers
Reduce blood pressure primarily by decreasing cardiac
output. They may also decrease sympathetic outflow from
CNS and inhibit the release of renin from the kidneys,
thus decreasing the formation of angiotensin II and the
secretion of aldosterone.
The prototype is propranolol, which acts at both β1 and
β2 receptors. Selective blockers of β1 receptors, such as
metoprolol and atenolol are among the most commonly
prescribed β2-blockers. The selective β2-blockers may be
administered cautiously to hypertensive patients who also
have asthma, for which propranolol is contraindicated due
to its blockade of β2-mediated bronchodilation.
8
9
Adverse effects
1. Common effects: They may cause bradycardia and CNS side
effects such as fatigue, lethargy, insomnia, and hallucinations; these
drugs can also cause hypotension
2. Alterations in serum lipid patterns: They may disturb lipid
metabolism, decreasing high-density lipoprotein cholesterol and
increasing plasma triacylglycerol.
3. Drug withdrawal: Abrupt withdrawal may induce angina,
myocardial infarction, or even sudden death in patients with
ischemic heart disease. Therefore, the dose of these drugs must be
tapered over 2 to 3 weeks in patients with hypertension and
ischemic heart disease. 10
α1-Adrenoceptor Blocking Agents
ᴥ Prazosin, doxazosin and terazosin produce a competitive block of
α1-adrenoceptors.
12
2. Angiotensin-Converting Enzyme Inhibitors
(ACE Inhibitors)
16
17
ACE Inhibitors: therapeutic uses
Drugs of choice in HTN patients with CHF
Side Effects:
Fatigue Dizziness
Headache Hyperkalemia
Impaired tasteRash
Dry cough due to increased levels of bradykinin in
the pulmonary tree.
18
3. Angiotensin II Receptor Blockers (ARBs)
20
4. Calcium Channel Blockers
Cause smooth muscle relaxation by blocking the
binding of calcium to its receptors, preventing
muscle contraction
This causes decreased peripheral smooth muscle
tone, decreased systemic vascular resistance.
Result: decreased blood pressure
Therapeutic uses:
Angina
Hypertension
Dysrhythmias
peripheral vascular disease
21
Classes of Calcium Channel Blockers
Benzothiazepines:
Diltiazem (Cardizem)
Diphenylalkamines:
Verapamil (Isoptin)
Dihydropyridines:
Amlodipine , Bepridil,
Nicardipine
Nifedipine, Nimodipine
Side Effects
Hypotension, palpitations, tachycardia, constipation,
nausea, rash, peripheral edema, dermatitis
22
5. Diuretics
Drugs that accelerate the rate of urine
formation through removal of sodium and
water.
Decrease the plasma and extracellular fluid
volumes
Results: decreased preload
decreased cardiac output decreased
workload of the heart decreased blood
pressure
23
Loop Diuretics
Furosemide (Lasix)
Act directly on the ascending loop of Henle to inhibit sodium
and chloride resorption.
Potassium-Sparing Diuretics
Spironolactone (Aldactone)
Work in collecting ducts and distal convoluted tubules.
Interfere with sodium-potassium exchange
Thiazide
Chlorothiazide
Act primarily in the ascending loop of Henle and early distal
tubule. Inhibit tubular sodium and chloride resorption.
24
25
6. Vasodilators
Directly relaxes arteriolar smooth muscle
Result: Peripheral vasodilation
Decreased systemic vascular resistance
Decreased afterload
● It is almost always administered in combination with a
β-blocker, such as propranolol (to balance the reflex
tachycardia), and a diuretic (to decrease sodium
retention).
Examples:
Diazoxide
Hydralazine
Minoxidil
Sodium Nitroprusside
26
IV sodium nitroprusside and diazoxide are used for the
management of hypertensive emergencies
Side effects:
Hydralazine:
Dizziness, headache, tachycardia, nausea, sweating,
arrhythmia, and precipitation of angina.
Sodium nitroprusside:
Bradycardia, hypotension, possible cyanide toxicity