Pharmacology of Antihypertensives Flashcards
1
Q
Basic Equation
A
BP = CO x SVR
2
Q
CO Equation
A
CO = HR x SV
3
Q
Factors that affect SV
A
- excretion of fluids and electrolytes through kidneys and intake of fluids and electrolytes determines ECFV
- ECFV affects intravascular volume
- intravascular volume and venous tone determine venous return
- venous return and contractility determine stroke volume
4
Q
Antihypertensive Classes (6)
A
- Diuretics
- Inhibitors of RAS System (ACE inhibitors, ARB’s, renin inhibitors)
- Calcium channel blockers
- Sympatholytics (beta antagonists, alpha 1 antagonists)
- Vasodilators
- CNS agents
5
Q
Diuretics
A
- old, cheap, safe way to treat HTN
- affect excretion of K+ and Na+
- produce effects through natriuresis and diuresis
- antihypertensive activity not proportional to level of diuresis
- also produce vasodilation, mechanism unclear
6
Q
Diuretic Types (3)
A
- Thiazides (Hydrochlorothiazide)
- Loop Diuretics (Furosemide, eg. Lasix)
- potent
- K+ sparing diuretics (Spironolactone)
7
Q
Renin Angiotensin System
A
- beta 1 andrenergic stimulation produces renin
- renin converts angiotensinogen to angiotensin 1
- ACE converts angiotensin 1 to angiotensin 2
- ACE degrades bradykinin (bradykinin is vasodilator, causes vasoconstriction by degrading it)
- angiotensin II causes vasoconstriction and stimulates aldosterone release
- aldosterone causes sodium retention
8
Q
Targets in RAS System
A
- inhibit beta 1 receptor
- inhibit renin
- inhibit ACE
- inhibit AII receptor (AT1)
- inhibit aldosterone receptor
9
Q
Angiotensin II Effects
A
- binds AT1 receptor
- causes vasoconstriction (potent)
- causes NaCl reabsorption
- stimulates aldosterone synthesis and secretion
10
Q
ACE Inhibitors
A
- prototype: ramipril (-pril)
- effects: inhibit vasoconstriction, inhibit aldosterone production, inhibit NaCl reabsorption, increased vasodilation (reduced bradykinin breakdown)
- overall effects: decreased SVR, natriuresis, diuresis
11
Q
ACE Inhibitors and Diabetes
A
- AII causes vasoconstriction of the efferent arteriole to maintain filtration pressure at the glomerulus
- AII is a good drug to use in HTN + diabetes because it vasodilates the efferent arteriole, reducing the intraglomerular pressure and delaying onset of diabetic nephropathy
12
Q
ACE Inhibitors Side Effects
A
- cough (due to bradykinin)
- angioedema (swelling in oral cavity, rare but serious)
- hyperkalemia (reduced aldosterone production, usually only occurs when another potassium sparing agent is present)
- renal dysfunction (reduced efferent arteriole vasoconstriction, can’t maintain intraglomerular pressure)
13
Q
Angiotensin Receptor Blockers
A
- prototype: losartan (-sartan)
- no effect on bradykinin
- less cough
- less angioedema
- less vasodilation
14
Q
Renin Inhibitors
A
- prototype: aliskiren
- advantage over ACE inhibitors: with ACEi’s, can over express renin and and produce lots of AI, AI then gets converted to AII via non-ACE pathways and overcome effects of ACEi’s, this can’t occur with renin inhibitors
15
Q
Calcium Channel Blockers
A
- decrease contraction by decreasing calcium influx
- produces reduced constriction of vascular smooth muscle and cardiac myocytes
16
Q
CCB Sub classes
A
- Dihydropyridines
- Non-dihydropiridines (Diltiazem, Verapamil)
17
Q
Dihydropyridines
A
- prototype: amlodipine
- act on vasculature more than heart
- produce vasodilation strongly, weakly reduce contractility of heart
- adverse effects: reflex tachycardia (particularly with fast-acting dihydropyridines)
18
Q
Non-dihydropyridines
A
- prototype: diltiazem, verapamil
- greater activity on heart, moderate activity on vasculature
- reduce heart rate and contractility
- vasodilation
- adverse effects: cardiodepressants
19
Q
Beta blockers
A
- prototype: propanolol (-lol)
- actions: inhibit SNS, inhibit renin secretion, reduce HR and contractility
- heterogenous group
20
Q
Heterogeneity in Beta blockers
A
- cardioselective (metoprolol) (beta 1)
- non-cardioselective (propanolol (beta 1 and 2), carvedilol (alpha 1, beta 1, beta 2)
- partial agonists (acebutolol (partial agonist at beta 1)
21
Q
Adverse Effects of Beta blockers
A
- bronchoconstriction (due to beta 2 antagonism), contraindicated in asthma
- fatigue (reduced cardiac output)
22
Q
Alpha 1 Antagonism
A
- prototype: prazosin (-zosin)
- vasodilation and ventilation
- adverse effects: orthostatic hypotension
- not commonly used for HTN
23
Q
Vasodilators
A
- prototype: hydralazine
- vasodilates by unknown mechanism
- decreases systemic resistance
- rarely used for HTN
24
Q
Central Agonists
A
- prototype: clonidine
- feeds back and inhibits norepinephrine release
- decreases HR, SVR, SR
- rarely used
25
Q
Combo therapy
A
- eg. diuretics cause increased SNS activation which causes increased RAS activity, good to pair with ACEi’s
- allows maximal efficacy with minimal toxicity
26
Q
In development
A
- bosentan (-entan)
- endothelin antagnosist, causes vasodilation, good for primary pulmonary hypertension
- omepatrilat
- vasopeptidase inhibitor
- concerns over angioedema
27
Q
ALLHAT
A
- Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial
- double blind randomized control trial
- 33000 subjects, 5 year follow
- using four drugs (chlorthalidone, lisinopril, amlodipine, doxazosin)
- stopped doxazosin arm early because of increased CV morbidity
28
Q
Results of ALLHAT
A
- looking at mortality, CV events, safety/tolerability
- all three drugs performed same for deaths
- all three drugs performed same for coronary artery disease
- thiazides had lower incidence of stroke vs. ACEi
- thiazides and ACEi had lower incidence of heart failure vs. CCB
- fewer withdrawals due to adverse effects with thiazides and CCB vs. ACEi
- all three drugs and DASH diet (reduced sodium) performed the same in lowering blood pressure
