Pharmacology of Antihypertensives

Question 1

ACE Inhibitors

Answer 1

Prototype (Pril) ie. ramipril

Actions of ACE inhibitors:

• inhibit vasoconstriction
• inhibit aldosterone secretion
• inhibit NACL reabsorption
• increased vasoconstriction (bradykinin)

Result:
- decreased SVR natriuresis / diuresis

Adverse Events:

• Cough attributed to bradykinin
• Angiodedema (rare but serious)
• hypokalemia due to reduced aldosterone

Important Features:

• may delay onset of diabetic nephropathy
• reduce intraglomerular pressure dilation of arterioles)

Question 2

Ramipril

Answer 2

ACE Inhibitor

Question 3

Angiotensin Receptor Blockers (ARBs)

Answer 3

Prototype (Sartan) ie. losartan

Difference (vs Pril):
- No effect on bradykinin

Important:

They are antagonists at the AT1 receptor therefore they block the actions angiotensin 2

Question 4

Losartan

Answer 4

ARB

Question 5

Renin inhibitors

Answer 5

Prototype: Aliskiren

Note that this targets the compensatory increase seen in Prils or Sartans, however, it is yet to be proven.

Question 6

Calcium Channel Blockers (CCBs)

Answer 6

Decrease contraction by decreasing influx of Ca2+

Targets: vascular smooth myocytes (L-type calcium channels)

Subclasses:

• Dihhydropyridines (DHP)
• Non-DHP

DHP

• Prototype (AmlodIPINE)
• —> facilitator > heart (vasodilation more than contractility)

Non-DHP

• Prototype (Verapamil & Diltiazem)
• Actions - reduces heart rate, contractility, vasodilation

Question 7

Beta Antagonists

Answer 7

Prototype: Propranolol (LOL)

• large, diverse family, long history

Actions

• decrease HR, contractility (B1)
• decrease renin secretion (B1)
• decrease SNS activity (B1)

Cardioselective (B1) / Non-cardioselective (A1/B1/B2) / Partial Agonists (B1)

SE: Bronchoconstriction - B2 & fatigue

Question 8

Alpha-1 Antagonists

Answer 8

Prototype: Prazosin (ZOSIN)

• vasodilatory / ventilatory effect
• AE (orthostatic hypotension)

Question 9

Hydralzine

Answer 9

Vasodilator

MOA:
- open up K channels?

Result: Decrease TPR

Question 10

Clonidine

Answer 10

CNS Central Agent

MOA

• alpha 2 agonist
• feedback inhibition of norepinephrine release

Actions:
- decreased HR, SV, SVR

Question 11

Bosentran

Answer 11

Endothelin Antagonists (primary pulmonary hypertension)

Question 12

Omepatrilat

Answer 12

Vasopeptidase Inhibitors