Flashcards in Antihypertensives Deck (13):
1. Define hypertension.
Sustained systolic BP over 140 mmHg
Sustained diastolic BP over 90 mmHg
2. What is the basic underlying cause of HTN?
Increase peripheral vascular smooth muscle tone → increased arteriolar resistance and reduced capacitance of venous system
3. What are the different categories of HTN?
1. Normal (SBP/DBP, below 120/below 80)
2. Prehypertension (SBP/DBP, 120-139/80-89)
3. Stage 1 HTN (SBP/DBP, 140-159/90-99) [often controlled with a single drug]
4. Stage 2 HTN (SBP/DBP, over 160/over 100) [often requires multiple drugs]
4. Walk through the compensatory response post HTN treatment.
HTN → treatment → decreased BP →(1) increased sympathetic outflow → tachycardia → increased blood pressure
(2)increased renin release → salt and retention → increased blood pressure
5. What are the current general recommendations of treating HTN?
1. initial pharmacotherapy with single drug → ACE-inhibitor, ARB (angiotensin receptor blocker), calcium channel blocker, thiazide diuretic
2. If BP not controlled, then add another drug → select drug based on minimizing adverse effects (B-blockers, aldosterone antagonists)
3. If BP is still not controlled a third drug can be added → usually a vasodilator (loop diuretics, a-blockers, direct vasodilators, central a2-agonits, renin inhibitors)
6. Give examples of drugs that are ACE inhibitors.
**These are first-line agents – in particular for diabetics and patients with chronic kidney disease
7. What is the mode of action of ACE inhibitors?
In a normal setting, ACE cleaves angiotensin I to form angiotensin II. ACE inhibitors prevent the cleavage therefore decrease the actions of angiotensin II. Therefore there is a decrease in sodium and water retention (because lack of aldosterone secretion) and a decrease peripheral vascular resistance. There is also an increase in bradykinin levels. Bradykinin is normally metabolizes by ACE so inhibiting ACE with decrease bradykinin break down. The increase in bradykinin can cause a dry cough. There is also no reflex tachycardia to increase CO, rate or contractility.
(angiotensin II also constricts efferent arterioles of the kidney allowing for a decrease in hydrostatic pressure in the peritubular capillaries increasing sodium and water reabsorption)
8. What are the clinical applications of ACE inhibitors?
2. Preserving renal function in pts with diabetic or non-diabetic nephropathy
3. Effective in tx of chronic HF
4. Standard of care for pts following MI
9. What are the adverse effects of ACE inhibitors?
1. Dry hacking cough
5. Acute renal failure – pts with bilateral renal artery stenosis
6. Rash, fever, altered taste
10. What are the contraindications of ACE inhibitors?
1. pregnancy – risk of fetal hypotension, anuria and renal failure
2. pts with bilateral renal artery stenosis
11. What is the mechanism of ARBs (angiotensin receptor blockers)?
Blocking of angiotensin-2-type 1 receptors causing a decrease in sodium and water retention → decreasing blood pressure causing arteriolar and venous dilation. These are first line agents, esp to decrease diabetic nephrotoxicity and alternatives to ACEIs. ARDs do not increase bradykinin levels. (elevated angiotensin II)
12. What are the adverse effects of ARBs?
Same as ACEIs except there is no dry cough as the ACE enzyme is functional and can break down bradykinin. There is also a decreased risk of angioedema compared to ACEIs b/c of the lack of bradykinin vasodilatory effect.
On the good side, Losartan reduces plasma uric acid levels by inhibiting the URAT1 transporter. This decreases uric acid reabsorption and increases its excretion.