Vasoactive peptides and inhibitors, Antihypertensive Vasodilator Drugs 1 and 2 Flashcards
Components of blood pressure
CO (SV,HR) * SVR (PVR,RVR)
What is hypertension?
high blood pressure mostly due to sympathetic activity leading to elevated vascular resistance
Site of action: carbonic anhydrase inhibitors
proximal convoluted tubule
Site of action: thiazides
distal convoluted tubule
MOA: diuretics
na loss –> fluid loss –> reduce blood volume –> reduce CO –> reduce bp
How does the body compensate for long-term use of diuretics?
reduce plasma volume –> increase renin/aldosterone –> increase K+ loss/Na+ retention –> distal fluid reabsorption
- net effect = lower ECF volume –> lower BP even in the face of compensation
- likely secondary MOA by reduce PVR via NO
In which population do we have to be careful when prescribing thiazide diuretics and why?
elderly –> long duration of action = dehydration in older people
Who is most responsive to thiazide diuretics?
african americans and elderly –> response depends on vigor of adaptation process, response reduced in chronic renal insufficiency
Thiazide risks
sulfa allergy, hypokalemia, promotes insulin resistance by increasing plasma glucose, increase Tg/LDL cholesterol
Which tissues are most affected by calcium channel antagonists, why?
cardiac and smooth muscle –> rely on influx of extracellular calcium for depolarization
What kind of channels are blocked by most calcium channel antagonists?
L-type
2 classes of CCAs?
non dhpr, dhpr
When do nondhpr CCAs bind the L channel?
when they are open –> if frequency of stimulation is increased, (e.g. rapid arrhythmia), increased blockade
*nondphr is better in myocytes than in VSMC
When do dhpr CCAs bind the L channel?
resting state –> better binding in VSMCs
Indication for verapamil
superventricular arrhythmia and hypertension, non dhpr
Indication for diltiazem
superventricular arrhythmia + some hypertension, non dphr
Indication for nifedipine
hypertension, dphr
Danger of using DHPR
increase in HR, SVR, and RAAS as a reflex to peripheral vasodilation –> increased work of heart in those being treated for …their heart
4 stimulators of renin
- hypovolemia
- hyponatremia
- hypotension
- adrenergic activation
Rate limiting step in RAAS
renin conversion of angiotensinogen to angiotensin 1
What is the negative feedback for the action of renin?
systemic levels of angiotensin ii and amount of angiotensin ii bound to its receptors
The vasoconstrictive properties of Angiotensin II is mediated by what receptor?
AT1
Where are AT1 and AT2 receptors found?
AT1: vsm, kidney, adrenal, cortex, pituitary
AT2: uterus, fetus but can be INDUCED
Effect of binding of angiotensin ii to AT1
vasoconstriction –> aldosterone release, cell proliferation, hypertrophy, matrix deposition
