Hypertension 1: ACEI, ARBs, DRIs

Question 1

Mechanism of Action of ACE inhibitors

Answer 1

Decrease Convertion of Angiotensin I to Angiotensin II:
* Decrease VC
* Decrease Aldosterone
* Decrease Hypertrophy & remodeling of heart & BVs
* Increased Bradykinin –> VD
* Inhibits sympthetic activation

Question 2

Pharmacological Actions of ACE.Is

Answer 2

• Mixed VD, but Arterio&raquo_space; Venous
• Arterial VD –> Decrease peripheral resistance –> Decrease Afterload
• weak Venous VD –> weak Venous return —> decrease Preload
• So, Cardiac Output is maintained if not increased
• Increased renal Blood flow BUT decreases GFR by Efferent VD —> decreases Glomerular hypertension (especially in DM pateints)

Question 3

Advantages of ACEI over other antiHypertensive drugs

Answer 3

• No decrease in CO (unlike Beta blockers)
• No postural hypotension (weak veno-dilator)
• No reflex tachycardia (decreased sympathetic activity)
• No abnormality in glucose, lipids, cholesterol or uric Acid (unlike some diuretics)

Question 4

Theraputic uses of ACE.Is

Answer 4

Hypertension especially associated with:
* Diabetic nephropathy
* Heart failure
* High renin

Heart Failure:
* Decrease both preload & Afterload –> increases CO
* Decreases Secondary hyperaldosteronism

MI: decrease Hypertrophy & remodelling of Heart & BVs

Question 5

Side effects of ACE.I

Answer 5

• Dry irritant cough due to Bradykinins & PGs
• First dose hypotension (especially with Na+ depleted patients)
• Hyperkalemia (espcially with spironolactone)
• Proteinuria
• Neutropenia
• Decreased taste
• Allergic manifestations (especially S-H group Captopril) –> Angioedema

Question 6

Contraindications of ACEIs

Answer 6

• Bilateral Renal Artery stenosis –> fatal Renal failure
• 2nd - 3rd trimester of pregnency

Question 7

Drug interactions of ACE.Is

Answer 7

• Na+ depleting diuretics –> increase first dose hypotension
• K+ sparring diuretics (spironolactone) –> Hyperkalemia
• NSAIDs (asprin) block PG synthesis –> impair VD effect
• Antacids decrease ACE.I absorption

Question 8

Examples & Classification of ACE.Is

Answer 8

S-H containing:
Captopril:
* affected by food (should be taken 1-2 hours before meal)
* Short acting, so taken 2-3 times a day
* may Cause Allergy (Angio-edema)

Non S-H containing:
Lisinopril (active)
* Less side effects
* Longer duration, so taken once a day
* Not affected by food

Fosinopril –> excreted in bile instead of urine

Question 9

Members of AT1 receptor blockers/ Angiotensin II competetor (ARBs)

Answer 9

• Losartan
• Valsartan
• Candesartan
• Telmisartan
• Irbesartan

-sartan family

Question 10

Mechanism of AT1RBs

Answer 10

Compete with Angiotensin II for AT1 receptor (same effect as ACE.I):
* Decrease VC
* Decrease Aldosterone
* Decrease Hypertrophy & remodeling of heart & BVs
* Increased Bradykinin –> VD
* Inhibits sympthetic activation

Question 11

Metabolic actions of AT1RBs

Answer 11

Corrects side effect of diuretics:
* Potassium retainer –> corrects hypokalemia
* uricosuric effect –> corrects hyperuricemia
* Decreases Hyperglycemia induced by Diuretics (by helping insulin)

Question 12

Theraputic uses of AT1RBs

Answer 12

same as ACE.Is:
Hypertension especially associated with:
* Diabetic nephropathy
* Heart failure
* High renin

Heart Failure:
* Decrease both preload & Afterload –> increases CO
* Decreases Secondary hyperaldosteronism

MI: decrease Hypertrophy & remodelling of Heart & BVs

Question 13

side effects of AT1RBs

Answer 13

same as ACE.Is but less dry cough

Question 14

Example of Direct Renin inhibitor

Answer 14

Aliskiren

Question 15

Adverse effects of Aliskiren

Answer 15

• Headache
• Fatigue
• Dizziness
• Diarrhea

Question 16

precaution to take when prescribing Aliskiren

Answer 16

prescription with caution with patients with Renal dysfunction (to avoid hyperkalemia)