Title: Pharmacology CVS / Antihypertensive Drugs

Q: What is hypertension?
A: A common, incurable, persistent, but usually asymptomatic disease whose treatment provides no immediate or obvious benefit.

Q: Benefits of lowering blood pressure: (3)
A: Antihypertensive therapy  has been associated with:
- 40% reduction in stroke incidence.
- 25% reduction in myocardial infarction.
- 50% reduction in HF.

Q: BP variations: (4)
A: 1. “White Coat” or isolated office hypertension.
2. Masked hypertension, normal at the clinic.
3. Morning surge of BP.
4. During Sleep: Two possibilities:
- “Non dipping’
- “Extreme dipping”.
--> Increased BP variability is associated with increased organ damage and cardiovascular morbidity.

Classification of hypertension on the basis of blood pressure:
< 120/80 --> Normal
120-135/80-89 --> Prehypertension
>= 140/90 -->Hypertension
140-159/90-99 --> Stage 1
>= 160/100 --> Stage 2

Q: Nonpharmacologic treatment of hypertension (lifestyle modifications): (4)
A: 1. Weight reduction
2. Diet rich in potassium and calcium and sodium reduction.
3. Dietary Approaches to Stop Hypertension (DASH) eating plan (1600-mg sodium), has effects like single drug therapy.
4. Physical activity.

Q: The goals of therapy of hypertension: (2)
A: 1. Maximal protection against cardiovascular consequences with minimal bother to the patient.
2. Stroke, coronary, and renal complications increase when BP is vigorously lowered

Q: Diuretics (Saluretics): (6)
A: 1. Widely recommended as first-line therapy, especially in the elderly, the obese, and black patients.
2. Better at reducing coronary heart disease, HF, stroke, and mortality.
3. Inexpensive.
4. Combine well with others.
5. Lower doses, with sodium restriction, cause fewer metabolic side effects, but retain antihypertensive activity.
6. All have same efficacy in lowering BP, although not  same diuretic activity.

Q: Effects of Diuretics (Saluretics): (4) ++
A: 1. Early Effects (3-4 days):
–  Diuresis lowers blood volume  and cardiac output.
–Mainly affects the systolic BP.
2. Late Effects (3-4 weeks):
–   Decreased Na+ & Cl- in blood vessels, lowers vessel contractility.  Appear  even with low doses.
3. Increase Plasma Renin
4. Side Effects: metabolic side effects(sugar, lipids, uric acid, loss of K+, Na+, Cl-,  etc…)

Q: Types of Thiazide diuretics: (4)
A: – Hydrochlorthiazide.
– Chlorthalidone: long acting.
– Bendrofluazide.
– Indapamide”Natrilex”: vasodilating and lipid neutral. Also induces regression of LVH
--> Effective in mild and moderate Ht with normal renal and heart function.

Q: Types of Loop Diuretics: (2)
A: – Furosemide: not  ideal, short acting.
– Torsemide: free of metabolic side effects.

Q: Uses of loop diuretics:
A: 1. Severe hypertension
2. Renal insufficiency
3. Heart failure
4. Cirrhosis

Q: Types of Potassium-sparing diuretics: (4)
A: – Spironolactone:
– Eplerenone.
– Ameloride.
– Triamterene
Also useful in heart failure

Q: Types of Sympatholytics
or Adrenergic Blockers: (4)
A: 1. Alpha Adrenergic Antagonists
– Non selective  Antagonists
– a1 -Selective Antagonists.
2. Beta Adrenergic Blockers
3. Adrenergic Neurone Blockers.
4. Ganglionic Blockers

Q: Nonselective alpha adrenergic antagonist: (2)
A: 1. Phentolamine
2. Phenoxybenzamine

Q: MOA of non-selective alpha adrenergic antagonists: (3)
A: –Block both a1 and a2 receptors, so  cause reflex tachycardia and increased contractility.
–Blockade of  α 2-presynaptic receptors  leads to augmented release of NE  leading to tachycardia and increased contractility of the heart.
–Used only for pheochromocytoma.

Q: Types of a1
-selective Alpha Adrenergic Antagonists: (3)
A: 1. Prazosin
2. Terazocin
3. Doxazosin

Q: a1
-selective Alpha Adrenergic Antagonists: (3)
A: 1. Selective (α 1 > α 2) blockers will lower the BP but will not cause tachycardia.
2. First - Dose Phenomenon.
3. Effective in moderate hypertension as well as benign prostatic hypertrophy.

Q: Side effects of a1
-selective Alpha Adrenergic Antagonists: (5)
A: All are free of metabolic effects, but can cause:
1. Drowsiness
2. Diarrhea
3. Postural  hypotension
4. Tachycardia
5. Tolerance due to fluid retention.

Q: Antihypertensive mechanisms of beta-adregergic blockers: (4)
A: 1.  Decrease HR, SV, and consequently C.O.
2. Decrease  Rennin Release
3.  Central Action in the vasomotor center.
4. Inhibit  NE release

Q: Therapeutic effectiveness of beta adrenergic blockers: (7)
A: 1. Effect not immediate.
2. Useful in high - rennin hypertension
3. Combination or monotherapy
4. Hyperkinetic hearts
5. Used in other cardiovascular conditions
6. Ineffective in blacks
7. No postural hypotension

Q: Side effects of beta adreneric blockers: (7)
A: 1. Bronchospasm, especially with nonselective ones.
2. Heart Failure in high doses.
3. CNS: fatigue, depression, impotence ..etc
4. Impair lipid and glucose metabolism
5. Mask hypoglycemia
6. Claudication, due to α receptor overactivity.
8. Withdrawal syndrome

Q: Types of vasodilating beta adregergic blockers: (4)
A: 1. Labetalol
2. Carvedilol
3. Esmolol
4. Nebivolol

Q: Labetalol: (2)
A: –     b, a1  (20% of b) antagonist & b2 partial agonist.
–     Useful for pheochromocytoma and emergencies.

Q: Carvedilol
A: –b, a1 (10% of b) antagonist.

Q: Esmolol: (2)
A: – b1 selective, rapidly metabolized.
– Used by continuous IV infusion.

Q: Nebivolol:
A: – b1 selective and  NO potentiating vasodilatory effect.

Q: Types of adrenergic neurone blockers:
A: 1. Guanethidine
2. Bethanedine
3. Debrisoquin
4. Guanadrel

Q: Adrenergic neuron blockers: (4)
A: 1. Hydrophilic.
2. Uptake 1.
3. Block NE release.
4. Displace NE from vesicles into the cytoplasm where it will be broken down by MAO .

Q: Reserpine (Rauwolfia Alkaloids): (6)
A: 1. Lipophilic
2. Binds to the sympathetic vesicles.
3. Prevents DA uptake into vesicles where it will be metabolized by MAO.
4. This will deplete  NE.
--> Will also deplete DA, 5HT, and ACTH.
5. Old fashioned, slow onset and offset,        very cheap.
6. Can cause depression.

Q: Types of ganglionic blockers: (3)
A: 1. Trimethaphan
2. Pentolinium
3. Mecamylamine

Q: Ganglionic blockers: (4)
A: 1. Block transmission in both sympathetic & parasympathetic systems.
2. Act immediately and are very efficacious.
3. Effect rapidly reversed, so used for short term control of BP, e.g. intraoperatively or emergency.
4. Many side effects.