Anti-hypertensive agents. Vasodilators

Question 1

Anti-hypertensive agents

Answer 1

1. Direct vasodilators - relax smooth muscles
2. Sympathoplegic agents - reduce peripheral vascular resistance, reduce cardiac output, increase venous pooling capacitance vessels
3. Diuretics - depleting the body of sodium and reducing blood volume
4. Agents that block production/action of angiotensin - reduce peripheral vascular resistance and blood volume

Question 2

Compensatory responses to decreased blood pressure when treating hypertension

Answer 2

1. Compensatory increased sympathetic outflow –> use beta blockers
2. Compensatory increased renin recretion –> use diuretics, ACE inhibitors

Question 3

Anti-hypertensive agents

-names and types

Answer 3

1. Direct vasodilators - calcium antagonists (nifedipine, diltiazem, verapamil), potassium channel activators (minoxidil), increase cGMP (nitroglycerin, nitroprusside)
2. Indirect vasodilators - a1-adrenoreceptor antagonists (prazosin, doxazosin, tamsulosin), a2-adrenoreceptor antagonists (clonidine), renin inhibitors (aliskiren), ACEi (captopril, enalapril), ARB (valsartan)
3. Miscellaneous drugs - hydralazine

Question 4

Renin-angiotensin system

Answer 4

1. Sympathetic stimulation, hypotension, decrease Na+ delivery
2. Kidney releases renin
3. Renin + Angiotensinogen
4. Angiotensin I
5. Angiotensin I + ACE
6. Angiotensin II
7. Angiotensin II –> adrenal cortex –> aldosterone
8. Renal sodium and fluid retention = increased blood volume

Angiotensin II –> causes systemic vasoconstriction

Question 5

Renin, ACEi, ARB and aldosterone inhibitors

Answer 5

1. Angiotensinogen
   - -> Renin inhibitors
2. Angiotensin I
   - -> ACE inhibitors
3. Angiotensin II
   - -> AT1 receptor blockers
   - -> ARBs –> block aldosterone secretion and vasoconstriction
4. AT1 receptor

Question 6

Angiotensin-converting enzyme inhibitors (ACEi)

• names
• effect

Answer 6

-CAPTOPRIL, ENALAPRIL, VALSARTAN

• inhibit RAS and stimulate Kallikrein-kinin system (increase bradykinin levels)
• increased bradykinin levels have a better efficacy and cause vasodilation. But it could cause more side effects such as coughing and edema

Question 7

Angiotensin-converting enzyme inhibitors (ACEi)

• unwanted effects
• contraindications

Answer 7

• Captopril - rashes, taste disturbances, neutropenia, proteinuria
• severe hypotension
• acute renal failure - monitoring is necessary
• hyperkalemia
• dry cough
• angioedema

-pregnancy

Question 8

Angiotensin receptor blocking drugs (ARB) comparison with ACEi (4)

Answer 8

• no effect on bradykinin metabolism
• more complete inhibition of angiotensin action because enzymes other than ACE are able of producing angiotensin II
• benefits and adverse effects are similar
• usually used in patients with adverse reactions to ACEi

Question 9

a2 adrenoreceptor agonists

• name
• indications
• unwanted effects
• contraindications

Answer 9

• CLONIDINE
• hypertension, glaucoma, as adjunctive during drug withdrawal in addicts
• sedation, bradycardia, sexual dysfunction
• depression, bradycardia, ischemic heart disease

Question 10

Non-selective a1 and a2 adrenoreceptor antagonists

• names
• indications
• unwanted effects
• contraindications

Answer 10

• PRAZOSIN, DOXAZOSIN, TAMSULOZIN
• hypertension, benign prostatic hypertrophy, phaechromocytoma
• hypotension, tachycardia, nasal congestion, impotence, failure to ejaculate
• intraoperative floppy iris syndrome, painful erection

Question 11

Angiotensin-converting enzyme inhibitors (ACEi)

-indications

Answer 11

• useful in chronic kidney disease –> diminish proteinuria and stabilize renal function, decrease glomerular efferent arteriolar resistance, decrease intraglomerular capillary pressure
• hypertension, heart failure, following MI, high risk of ischemic heart disease, diabetic nephropathy, progressive renal insufficiency
• Nephroprotective agents –> protect kidneys from long term hypertensive diseases

Question 12

Direct vs. Indirect vasodilators

Answer 12

Direct

• act on things inside the cells
• directly acts on blood vessels smooth muscles
• Ca2+ blockers (decrease Ca2+ = relaxation), K+ channels activators (hyperpolarization), Nitrates (increase cGMP)

Indirect

• act on everything that is outside of t he cell
• alpha-2-adrenoreceptors are found in vasomotor centers and it’s activation causes the lowering of sympathetic system activity