Antihypertensive

Question 1

I- Diuretics

Answer 1

Diuretics act on the kidney with the primary purpose of reducing blood
volume by increasing the rate of urine excretion.
- There are several types of diuretics,
and they can be divided into separate classes based on their mechanism
and site of action.

Question 2

i- Thiazide Diuretics

Answer 2

Hydrochlorothiazide, Indapamide, Metolazone

Question 3

Mechanism of action of Thiazide Diuretics

Answer 3

• Inhibit Na -Cl cotransport, thereby blocking Na+
  and Cl reabsorption in
  the DISTAL convoluted tubule.
  -They also increase Ca2+ reabsorption.

Question 4

Site of action & uses of Thiazide Diuretics

Answer 4

Early distal convoluted tubule.
uses:
1- First line for mild to moderate hypertension
2-Mild CHF
3-Nephrogenic diabetes insipidus,
4-Nephrolithiasis secondary to idiopathic hypercalciuria.

Question 5

Side effects of th.

Answer 5

Hypokalemia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia, sulfa allergy (hydrochlorothiazide), and impotence.

Question 6

ii-Loop Diuretic

Answer 6

Furosemide, Ethacrynic acid, Bumetanide.
Mechanism of action Inhibit Na+ -K+ -2Cl channel in the thick ascending limb of the loop of Henle.
- By preventing Na+ and K+ reabsorption into the renal medulla, they abolish the hypertonicity of the medulla.
They also increase Ca2+ excretion.

Question 7

site of action of loop diuretics

Answer 7

Thick ascending limb of loop of Henle.
- Uses
1-The most efficacious diuretics, used for edema (CHF, cirrhosis, nephrotic syndrome)
2-Acute pulmonary edema
3- Hypertensive crisis and hypertension in presence of renal dysfunction
4-Hypercalcemia
5-Hyperkalemia.

Question 8

Side effects of loop diu.

Answer 8

Ototoxicity (especially in combination with aminoglycoside), hypokalemia, hypercalciuria, hypocalcemia, dehydration, allergy to sulfa (furosemide, not ethacrynic acid), nephritis, gout.

Question 9

iii-Potassium-Sparing Diuretics

Answer 9

-As Spironolactone, Triamterene, Amiloride, and Eplerenone

Question 10

Spironolactone and eplerenone:

Answer 10

Competitive antagonists at the aldosterone receptor in the collecting tubule (indirectly inhibit Na+ reabsorption).

Question 11

Triamterene and amiloride:

Answer 11

Triamterene and amiloride: Directly block Na+ channels in the collecting tubule..

Question 12

Reasons for the K-sparing properties of this class:

Answer 12

■ Less K+ secretion occurs due to inhibition of Na+ reabsorption in the distal tubule (Na+ reabsorption and K+ secretion are coupled in this segment of the nephron).
■ Because they are not active in the proximal portions of the tubules, these agents do not greatly increase tubular flow (high flow rates through the tubules increase secretion of K+).

Question 13

Site of action & uses of k-sparing

Answer 13

Site of action Collecting tubule and collecting duct
Uses
1-Primarily used in combination with more efficacious diuretics (eg, loop and thiazide diuretics) to prevent associated K+ wasting (used in treatment of edema and hypertension).
2-Spironolactone has been proven to increase survival in patients with CHF.
3- Spironolactone used to treat ascites in patients with cirrhosis. 4-The antiandrogen effect of K+-sparing diuretics (mainly spironolactone not with Eplerenone) is useful for treating hirsutism in polycystic ovarian syndrome (PCOS).
Side effects Hyperkalemia; spironolactone causes gynecomastia and impotence.

Question 14

II- Sympatholytics

Answer 14

..

Question 15

i- β-Adrenergic Receptor Antagonists

Answer 15

β-Blockers as Propranolol, Atenolol, Metoprolol, Esmolol, Carvedilol

Question 16

Nonselective β-receptor (β1 and β2) antagonists (propranolol,
nadolol, pindolol, timolol)

Answer 16

Mechanism of action:■
Reduce HR by blocking β1 effects.
■ Reduce contractility by blocking β1 effects.
■ Inhibit renin production by blocking β1 effects.
■ More side effects because of their action on β2-receptors

Question 17

Selective β1-receptor antagonists

Answer 17

s (atenolol, metoprolol, esmolol,
acebutalol, betaxolol):
■ Same as above due to β1-blockade
■ Fewer side effects

Question 18

Mixed α- and β-receptor antagonists (carvedilol, labetalol):

Answer 18

Same as above due to β1-blockade

■ Plus decreased SVR due to α-blockade

Question 19

i- β-Adrenergic Receptor Antagonists..

Side effects, Uses, Site of action

Answer 19

Site of action
β1-Receptors on heart and kidney, β2-receptors on arterioles.
Uses
Hypertension, angina, patients with previous MI, CHF. ESMOLOL is an
ultrashort-acting agent used in acute hypertensive emergencies.
Side effects
■ Bradycardia
■ Bronchoconstriction and asthma exacerbation (especially nonselective
agents with β2 antagonism).
■ Blunted response to hypoglycemia. May be especially dangerous in
diabetics on insulin therapy. Hypoglycemic episodes are marked by
pallor, trembling, diaphoresis, and tachycardia (all mediated by increased
β-receptor activity). With β-blockade, these important clues of
hypoglycemia may be absent.
■ Other: Impotence, CNS adverse effects. Avoid in cocaine users owing
to unopposed α-agonist activity

Question 20

ii- α-Adrenergic Receptor Antagonists

Answer 20

α-Blockers as Prazosin, Doxazosin, Terazosin

Question 21

Mechanism of action and site OF ii- α-Adrenergic Receptor Antagonists

Answer 21

Selective α1-receptor antagonists; α1-blockade decreases SVR by preventing arteriolar vasoconstriction. The result is decreased BP.

Site of action.
Primarily α1-receptors on arterioles. Of note, also blocks α1-receptors at the bladder sphincter

Question 22

Uses.

Answer 22

1-Mild to moderate hypertension.
2-Most common use of α1-blockers is to treat urinary hesitancy for
patients with prostatic hypertrophy (by preventing bladder sphincter
contraction).

Question 23

Side effects.

Answer 23

First-dose hypotension, reflex tachycardia, secondary Na+ retention in
kidney (use in combination with diuretic), orthostatic hypotension. Be
careful when combining with another vasodilator (eg, nitrates, sildenafil).

Question 24

iii- Centrally Acting Sympatholytics..

Answer 24

Methyldopa, Clonidine

Question 25

Mechanism of action.

Answer 25

Selective α2-agonists. By activating α2-receptors in the brain stem, these
agents reduce central sympathetic outflow.

Question 26

Site of action.

Answer 26

Brain stem.

Question 27

Uses.

Answer 27

Rarely used for hypertension due to poor side effect profile, but
methyldopa is traditionally considered the drug of choice for
hypertension in pregnant patients.

Question 28

Side effects

Answer 28

■ Methyldopa: Sedation, positive Coombs test in 10% of patients
(reversible upon discontinuation of drug).
■ Clonidine: Sedation, dry mouth, severe rebound hypertension with
abrupt discontinuation (should not be used in patients who may have
difficulty obtaining/taking medication as directed).

Question 29

III- Vasodilator Drugs

Answer 29

Vasodilators decrease systemic vascular resistance (SVR) by relaxing
smooth muscle in arteriole walls through a number of different
mechanisms

Question 30

i- Calcium Channel Blockers

Answer 30

Dihydropyridines as Nifedipine, Amlodipine ..
- Non-dihydropyridines as Verapamil, Diltiazem
The most commonly used class is the dihydropyridines

Question 31

Mechanism of action

-

Answer 31

Block L-type Ca2+ channels, inhibiting entry of Ca2+ into arteriolar
smooth muscle; this action results in arteriole dilation and reduced SVR.
- Also inhibit entry of Ca2+ into heart leading to decrease all properties
of the heart as decrease heart rate, conduction of A-V node and contraction

Question 32

i- Direct vasodilators

Answer 32

1- Sodium Nitroprusside

Question 33

Mechanism of action

Answer 33

Spontaneously releases nitric oxide, which increase cGMP, causing
relaxation of both arterial and venous smooth muscle. This action results
in rapid reduction of SVR and BP.

Question 34

Uses

Answer 34

Hypertensive emergencies
Drug of choice due rapid, strong and controllable effect
Given by I.V. infusion route using infusion pump
Very sensitive to light, so must be freshly prepared and kept from light

Question 35

Side effects

Answer 35

1-By-products of metabolism include cyanide (increased in hepatic
failure) and thiocyanate (increased in renal failure),
The antidote is sodium thiosulfate.
2- Excessive hypotension and reflex tachycardia.
3-Manifestations of excessive vasodilation as headache, dizziness and
flushing

Question 36

2-Hydralazine

Answer 36

Mechanism of action
Exact mechanism unknown.
Vasodilator of arterioles more than veins.
Site of action
Arteriolar smooth muscle.
Uses
1-Severe hypertension but used with diuretic and beta-blocker to avoid
tachyphylaxis (caused by stimulation of sympathetic, increase renin
secretion and salt retention), can be used orally or I.V.
2-Treatment of hypertension during pregnancy
3-Treatment of CHF (but better to be combined with venodilator as

Question 37

Side effects

Answer 37

1- Excessive hypotension and reflex tachycardia.
2-Manifestations of excessive vasodilation as headache, dizziness and
flushing
3-SLE like syndrome
4-Tachyphylaxis……

Question 38

3-Minoxidil

Answer 38

Mechanism of action.
Opens K+ channels, causing hyperpolarization of smooth muscle cells
and arteriolar dilation.

Question 39

Uses

Answer 39

1-Moderate to severe hypertension but used with diuretic and betablocker to avoid tachyphylaxis (caused by stimulation of sympathetic,
increase renin secretion and salt retention), used orally.
2-Treatment of baldness and hair loss, used topically to the scalp

Question 40

Side effects

Answer 40

1- Excessive hypotension and reflex tachycardia.
2-Manifestations of excessive vasodilation as headache, dizziness and
flushing
3-Tachyphylaxis…….
4-Hirsutism, or excessive hairiness (minoxidil is the main ingredient in
Rogaine, which is used for the treatment of alopecia, or hair loss)