Pharmacology of Antihypertensives Flashcards Preview

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Flashcards in Pharmacology of Antihypertensives Deck (28)
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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
  1. Diuretics
  2. Inhibitors of RAS System (ACE inhibitors, ARB’s, renin inhibitors)
  3. Calcium channel blockers
  4. Sympatholytics (beta antagonists, alpha 1 antagonists)
  5. Vasodilators
  6. 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