Title: Pharmacology CVS Final / Antihypertensive II

Q: MOA of vasodilators: (4)
A: 1. Work directly on arterial blood vessels, or veins.
2. Actions not antagonized by known blockers.
3. Reduce peripheral resistance, which will elicit  compensatory mechanisms leading to tolerance, resistance, or pseudo resistance.
4. Usually, other drugs are combined with vasodilators to avoid or counteract  this problem.

Q: Compensatory responses to vasodilators: (5)
A: 1. Decreased systemic vascular resistance
2. Decreased arterial pressure: which in turn leads to
3. Increased sympathetic nervvous system outflow
4. Increased renin release
5. Decreased renal sodium excretion

Q: MOAs of different vasodilators: (4)
A: 1. release of nitric oxide from drug or endothelium
2. Reduction of calcium influx
3. Hyperpolarization of smooth muscle membrane through opening of potassium channels
4. Activation of dopamine receptors

Q: Hydralazine: (8)
A: 1. Oldest vasodilator(1950s), was withdrawn and then came back.
2. Arteriolar dilator, works by release of NO.
3. Tachyphylaxis (Tolerance or Pseudo resistance).
4. Activates baroreceptor reflex.
5. Metabolized by acetylation.
6. Can cause drug-induced lupus syndrome.
7. Can be replaced by CCBs(Ca channel blockers).
8. Nowadays,used in heart failure, combined with isosorbide dinitrate

Q: Diazoxide: (8)
A: 1. Thiazide derivative, but not has no diuretic activity.
2. Potent arterial dilator, works by opening potassium channels.
3. Causes excessive hypotension.
4. Used in emergencies by rapid I.V. bolus injection.
5. Rapidly bound to albumin.
6. Onset 10-30 seconds.
7. Duration 2-4 hours.
8. Does not require constant monitoring.

Q: Sodium Nitroprusside: (8)
A: 1. Cyanide-containing molecule.
2. Useful in emergencies, during surgery, and in heart failure.
3. Relaxes both arterial and venous smooth muscle, works by release of NO.
4. No excessive reflex increase in cardiac output, but might increase C.O. if there is heart failure.
5. Short half life.
6. Action is immediate, requires constant monitoring in ICU.
7. Drug is light sensitive.
8. Can elevate thiocyanate levels and disturb acid-base balance

Q: Side effects of Sodium Nitroprusside: (6)
A: 1. Weakness
2. Nausea
3. Tinnitus
4. Flushing
5. Lactic acidosis
6. Anoxia

Q: Minoxidil: (6)
A: 1. K+ channel-opener: increases efflux leading to hyperpolarization.
2. Prolonged arterial relaxation.
3. Superior to hydralazine.
4. For severe intractable hypertension, or renal insufficiency, usually in combination with a diuretic and β blocker.
5. Hypertrichosis, so useful for baldness.
6. Can cause pericarditis.

Q: Fenoldopam: (3)
A: 1. Dopamine D1  agonist, which results in vasodilation, renal vessel dilation, and natriuresis.
2. Rapidly metabolized, short acting.
3. Used by continuous infusion in emergencies or postoperatively.

Q: What types of calcium channels are found in heart cells?
A: L and T types.
L: Long, large, high threshold
T: Short, small, low threshold

Q: Calcium channel blockers: (4)
A: 1. Primarily act to reduce PVR, aided by at least an initial diuretic effect, especially with the short-acting DHPs.
2. Effective in the elderly.
3. More effective than others, in protection against stroke.
4. Equally effective in black and nonblack patients.

Q: Side effects of calcium channels blockers: (4)
A: 1. Hypotension.
2. Headache, dizziness.
3. Flushing, especially with short acting agents.
4. Peripheral edema.
►Do not cause metabolic disturbances.

Q: Functions angiotensin-converting enzyme inhibitors: (2)
A: 1. Inhibit ACE in the lungs.
2. Inhibit kinin metabolism.

Q: Functions of Angiotensin II: (6)
A: 1. Potent vasoconstrictor by itself.
2. Facilitates release of NE.
3. Central actions to increase BP.
4. Promotes release of aldosterone.
5. Regulates tubular function.
6. Regulates intra-renal blood flow.

Q: Cardiorenal effects of ACE inhibitors: (4)
A: 1. Vasodilation (arterial & venous):
- reduce arterial & venous pressure.
- reduce ventricular afterload and preload.
2. Decrease blood volume:
- natriuretic.
- diuretic.
3. Depress sympathetic activity.
4. Inhibit cardiac and vascular hypertrophy.

Q: Types of ACEI: (6)
A: 1. Captopril (Prototype)
2. Enalapril
3. Quinapril
4. Lisinopril.
5. Benazepril
6. Fosonopril
- All are similarly effective
- Might differ in toxicity

Q: Therapeutic benefits of ACEI: (7)
A: 1. Effective in high-rennin hypertension (20%), HF and  Ischemic Heart   Disease.
2. Do not increase HR.
3.  Useful in diabetic nephropathy by  dilating efferent arterioles thus reducing intraglomerular pressure and   consequently protect against   progressive   glomerulosclerosis.
4. No need for a diuretic but a diuretic can be added.
5. Can be combined with CCBs, but should not be combined with Beta blockers.
6. No metabolic effects.
7. Contraindicated in established renal failure, pregnancy, and bilateral renal artery  stenosis.

Q: Side effects of Captopril: (5)
A: Captopril is an SH containing drug (very toxic)
1. Bone marrow suppresion
2. Dysgeusia (changed perception of taste)
3. Proteinuria
4. Allergic skin rash
5. Fever

Q: Side effects of ACEI: (4)
A: 1. Hypotension( First Dose Phenomena) especially with renovascular hypertension.
2. K+  retention, especially in the presence of renal dysfunction or when combined with K+ sparing diuretics or ARBs.
3. Cough(10% of patients).
4. Angioedema.

Q: Angiotensin
II Receptor Blockers (AT-1): (5)
A: 1. Result in more complete inhibition of angiotensin actions, with no effects on bradykinins.
2. May be only indicated when ACEI are intolerable.
3. Most expensive, but fastest growing class of antihypertensive drugs.
4. Free of side effects, especially cough.
5. May be better than ACEI in protection against stroke (activation of AT-2 receptor facilitates collateral vessels and neuronal resistance).

Q: Types of Angiotensin
II Receptor Blockers (AT-1): (6)
A: 1. Losartan.
2. Valsartan.
3. Candesartan.
4. Irbesartan.
5.Telmisartan ( additional peroxisome proliferator- activated receptor “PPR “-γ agonist activity).
6. Eprosartan.

Q: Describe "angiotensin escape": (2)
A: - Long-term treatment with ACE inhibitors is often associated with so-called “angiotensin escape,” characterized by the return of plasma angiotensin II concentration to pretreatment levels (although the beneficial effects on blood pressure usually persist).
- This rebound generation of angiotensin II occurs through the action of the serine proteases such as chymase and cathepsin G.

Q: What is the function vascular chymase: (3)
A: 1. Vascular chymase has been implicated in the ACE-independent mechanism for local angiotensin II formation in human arteries.
2. ACE-independent generation of angiotensin II plays a central role in the regulation of renal hemodynamics during the progression of diabetic nephropathy.
3. The physiologic importance of chymase is uncertain, because of the presence of natural protease inhibitors in the interstitial fluid which inhibit chymase-induced angiotensin II production.

Q: The effect of Nifedipine on (PVR, HR, CO) resepectively: (3)
A: - Decreases PVR (---)
- Reflexly increases HR (+++)
- Increases CO (++)

Q: The effect of Diltiazem on (PVR, HR, CO) resepectively: (3)
A: - Decreases PVR
- Decreases HR
- Decreases CO

Q: The effect of Verapamil on (PVR, HR, CO) resepectively: (3)
A: - Decreases PVR
- Decreases HR
- Decreases CO

Q: Aliskerin: (2)
A: - The first in the group of renin enzyme inhibitors
- Other better studied medications are typically recommended due to concerns of higher side effects and less evidence of benefit.

Q: Components of the vasomotor center: (3)
A: 1. Nucleus Tractus Solitarius
2. Nucleus Ambiguus
3. Rostral Ventral Medulla

Q: Common properties for centrally-acting antihypertensive drugs: (4)
A: 1. Cross BBB.
2. Reduce preganglionic sympathetic activity.
3. Orthostasis is unusual, due to preservation of peripheral sympathetic activity.
4. CNS side effects.

Q: Types of centrally acting antihypertensive drugs: (3)
A: 1. Propranolol
2. Reserpine
3. a- Methyl Dopa
4. Clonidine

Q: a-
Methyl Dopa: (5)
A: 1. Old drug, thought to work by forming  a pseudo transmitter  which  works peripherally.
2. Central a agonist.
3. Lowers BP but not CO or renal blood flow.
4. Can cause lactation and positive Coombs's test.
5. Safe in pregnancy.

Q: Clonidine: (4)
A: 1. Imidazoline derivative, tried initially as a nasal  decongestant.
2. Central alpha agonist.
3. When given I.V, it has a biphasic effect: peripheral then central actions.
4. Can also be given orally and as a transdermal patch (7 days)

Q: Cause of resistant hypertension: (10)
A: 1. Improper BP measurement.
2. “White  Coat Hypertension”.
3. Noncompliance.
4. Psychological stresses, secondary hypertension, sleep disorders
5. Volume overload and pseudotolerance.
6. Excess sodium intake
7. Volume retention from kidney disease.
8. Inadequate diuretic therapy.
9. Inadequate doses.
10. Inappropriate combinations .

Q: Drugs that cause resistant hypertension: (9)
A: 1. NSAID; cyclooxygenase 2 inhibitors.
2. Cocaine, amphetamines, other illicit drugs.
3. Sympathomimetics, e.g. decongestants, anorectics
4. Oral contraceptives
5. Corticosteroids
6. Cyclosporine
7. Erythropoietin
8. Licorice (including some chewing tobacco).
9. Excess alcohol intake.