Anti-hypertensives Flashcards
Use of 2 drugs with different mechanisms of action for treatment of hypertension:
A. Is usually more effective in decreasing BP than
increasing the dose of the first drug
B. Should be considered for initial therapy in patients with a baseline BP over 20/10 mm Hg above goal
C. Often allows for lower doses of both drugs
D. All of the above
D. all the above
Which of the following antihypertensive drugs are less effective as initial therapy in blacks? A. ACEIs B. ARBs C. CCBs D. Diuretics
A. ACEIs
B. ARBs
Which of the following antihypertensive drugs can cause fetal and neonatal morbidity and death? A. ACEIs B. ARBs C. Aliskiren D. Beta blockers E. Diuretics
A. ACEIs
B. ARBs
C. Aliskiren
One advantage of ARBs over ACEIs for treatment of hypertension is that they: A. Are significantly more effective B. Are safer for use in pregnancy C. Generally have fewer side effects D. Do not cause hyperkalemia E. All of the above
C. Generally have fewer side effects
Which of the following calcium channel blockers usually cause an initial reflex tachycardia? A. Amlodipine B. Diltiazem C. Felodipine D. Nicardipine E. Nisoldipine
C. Felodipine
D. Nicardipine
E. Nisoldipine
Which of the following drugs should generally be given with a beta blocker to minimize reflex tachycardia and a diuretic to avoid fluid retention? A. Clonidine B. Hydralazine C. Prazosin D. Lisinopril E. Valsartan F. Minoxidil
B. Hydralazine
F. Minoxidil
*BB Will block reflex tachycardia caused by other classes of antihypertensive agents
BP is the product of what?
CO x SVR
Activation of baroreceptor by ____ results in ___
stretched by increased vessel tension, increased blood pressure
inhibits sympathetic discharge from medulla resulting in decreased blood pressure
What in control of moment to moment adjustments in BP and what is in control of long-term BP
Short: postural baroreceptor reflex arc
long: renal response to perfusion pressure
How do the kidneys control BP?
- Reduction in renal perfusion pressure (decreased renal blood flow) → increased Na+ and H2O reabsorption via aldosterone (released by action of angiotensin II).
- Also increase in renin production → increased angiotensin II → increased vasoconstriction (in addition to release of aldosterone)
describe the major therapeutic classifications and sites of actions for antihypertensives
- Diuretics —> kidneys (ie. thiazide)
- Vasodilators–> vessels (ie. CCBs)
- RAAS antagonists–> kidneys, BV (ie. ACEI)
- adrenergic inhibitors –> kidneys, CNS, BV, heart (ie. BB, A1 blockers, vasomotor center inhibitors)
When blood pressure is lowered by pharmacologic interventions, homeostatic mechanisms are activated to increase blood pressure - via
baroreceptor reflexes–> increase SNS outflow–> vasoconstriction, tachycardia, increased contractility= increase BP
renal perfusion reflexes: increased renin release–> Na/H20 renention = increase BP
Why does moderate-severe hypertension often have to be treated by more than 1 drug?
- rationale being that each agent acts on one of a set of interacting compensatory regulatory mechanisms for blood pressure to increase antihypertensive effect and possibly prevent toxic effect
- The hypotensive effect resulting from interference with only one mechanism may be diminished by the compensatory response of a second mechanism
What is goal blood pressure
Pts under 60, diabetes, CKD: 140/90
pts over 60: 150/90
causes of hypertension
- Unknown (essential-primary [> 90%])
2.Identifiable (secondary): renal disease, 1⁰ aldosteronism,
pheochromocytoma, Cushing’s syndrome, sleep apnea
3. Drug-Induced
-NSAIDs - COX-2 selective inhibitors
-Sympathomimetics
-Oral Contraceptives
What are the main classes of initial HTN monotherapy
- long acting CCBs
- ACEI or ARBs
- thiazide diuretic
*BB are less used due to adverse CV outcomes (ie. less protection against stroke risk)
Initial monotherapy for hypertension should be based on
age and race
- younger pts respond best to ACEI- ARBs
- Black patients and elderly patients best to thiazide diuretic or long-acting CCB
Black patients and elderly patients best respond to what hypertension monotherapy
Respond best to
- thiazide diuretic or
- long-acting CCBs as they usually have lower plasma renin activity (PRA) than younger and white patients
younger patients best respond to what hypertension monotherapy
ACEIs- ARBs
Switching to second drug has a ___% chance of normotensive response (60-80% initially controlled with a single drug)
50%
Responders to a given drug class will do so at \_\_ doses with \_\_ side effect
lower
fewer
Higher doses associated with:
- more side effects
2. without further significant reductions in blood pressure
What is indicated if not at goal BP with monotherapy
combination therapy
What is the preferred combo therapy
long acting ACEI + long acting CCB
- If treated with one as monotherapy, add the other
- If treated with thiazide diuretic, discontinue and start with ACEI and CCB combination
When should you consider 2 drugs as initial BP therapy?
over 20/10 mmHg above goal
What are lifestyle modifications that one can make to treat HTN
1 . Keep healthy eating habits: DASH diet - Mediterranean diet - AHA diet - USDA food pattern
- Limit sodium intake: no more than 1500 mg/day if BP reduction needed
- Stop smoking
- Engage in regular physical activity: 3-4 sessions per week of 40 minutes of moderate vigorous activity
- Achieve and maintain a healthy weight: if overweight or obese → set goal of 5-10% weight loss in 6 months - can reduce TGs, blood glucose, A1C, and T2DM risk
What are RAAS antagonists
ACEI and ARBs
Examples of ACEI (RAAS antagonist)
- lisinopril
- Enalapril
- Ramipril
- Benazepril
- Quinapril
- Captopril
what is the MOI of ACEI
Inhibits enzyme which converts angiotensin I to angiotensin II
- Prevents Ang II-induced vasoconstriction (increased PVR)and aldosterone secretion (increased Na+ retention)
- Decreases bradykinin inactivation, increasing its
vasodilator action
describe the absorption of ACEI
well absorbed orally– most have reduced absorption if taken with food
Most ACEI are ___ that are converted to the active metabolite by de-esterification in the liver
Prodrugs
exceptions: lisinopril and captopril
Describe the elimination and duration of action of ACEI
- Active metabolites are eliminated by the kidneys - renal dosing required
- Exceptions: moexipril and fosinopril - Duration of action generally sufficient to allow once-daily dosing for most agents
Potential SE of ACEI
- Contraindicated in pregnancy (category C/D in 2nd and 3rd trimester)
- DRY COUGH
- HYPERkalemia
- hypotension (if hypovolemic)
- acute renal failure (esp. with renal artery stenosis)
- neutropenia and proteinuria with HD captopril
- Angioedema
- Minor= altered taste sense, skin rash
first-line choice as monotherapy and combination therapy (with calcium channel blocker)
ACEI
Particularly effective in young, high-renin patients
ACEI (as w/ BB)
Can be used in asthma, diabetes, and CHF
ACEI
Clinical trials of ACEI have demonstrated favorable effects when used in patients with ___ and ___
diabetes and proteinuric chronic kidney disease
slow progression of diabetic neuropathy and reduce albuminuria
Examples of ARBs (aka AT-1 blockers)
RAAS antagonists
- Valsartan (diovan)
- Losartan (Cozaar)
- Olmesartan (Benicar)
- Irebesartan (Avapro)
What is the MOI of ARBs (aka AT-1 blockers)
selective inhibtion of angiotensin II receptor AT1
What are the advantages of ARBs vs ACEI
- More complete inhibition of angiotensin action
2. Alternative pathways to form Ang II are NOT blocked by ACEIs (uncertain significance)
What are the disadvantages of ARBs vs ACEI
- Loss of increased bradykinin actions (vasodilation) that
result from ACE inhibition - Will not block Ang II actions at non-AT-1 receptors
Describe the PK of ARBs (aka AT-1 blockers)
- All agents are effective orally with once daily dosing
except for losartan (twice daily) - Decreased losartan dose necessary in hepatic dysfxn
What are the side effects of ARBs (aka AT-1 blockers)
- similar to ACEI
1. contraindicated in pregnancy
**NO angioedema or cough (thought to be BK- mediated)
First-line choice as monotherapy and combination therapy. Role for use in hypertensive patients that have responded to ACE inhibitors but had to discontinue ACEI (mostly due to cough).
ARBs (aka AT-1 blockers)
Examples of direct renin inhibitors
- Aliskiren (Tekturna)
What are the MOI of direct renin inhibitors
a potent competitive inhibitor of renin → blocks conversion of angiotensinogen to angiotensin I.
-This results in a dose-dependent decrease in plasma renin activity (PRA) and AngI and AngII levels that is associated with a decrease in BP