Flashcards in Anti-hypertensive and Vasodilator Drugs Deck (41):
If you lower BP with a drug, how will the body try to reverse those changes?
With sympathetic activation, RAAS, etc.
Where do thiozide diuretics have their site of activity?
On the distal convoluted tubule.
(more on this in renal...)
How do diuretics work acutely? Long term?
Acutely, they cause natriuresis and diuresis (...depending on the diuretic).
Long-term, the body compensates for those changes, but for some people, the diuretics continue to lower BP... perhaps by decreasing SVR somehow via NO.
(In other words, you see a restoration of volume, but not BP.)
Why must you be careful using thiazide diuretics in the elderly?
Thiazides are excreted renally.
Elderly people tend to have reduced renal function, so it's easy to get a buildup of the drug.
Combined with elderly people tending to be dehydrated to begin with, this can be bad.
What racial/ethnic group responds particularly well to thiazide diuretics?
4 notable toxicities of thiazide diuretics?
Promotes insulin resistance
Increases LDL and TGs
What cardiac parameters do calcium channel blockers (CCBs) modify?
They mainly decrease SVR, but also decrease HR.
Which calcium channels do CCBs block?
Which molecule binds to Ca++ to activate contractile elements in vascular smooth muscle? In cardiac myocytes?
In vascular smooth muscle: calmodulin
Cardiac muscle: troponin
Why don't CCBs paralyze your skeletal muscles?
Skeletal muscles aren't as dependent on extracellular Ca++, so CCBs don't inhibit their contraction significantly.
Functionally, what is the difference between dihydropyridine (DHP) and non-DHP CCBs?
DHPs: bind Ca++ channel in resting state.
Non-DHPs: bind Ca++ channel in active state, thus these drugs more avidly block rapidly firing (e.g. tachycardic) myocytes.
2 non-DHP CCBs to remember?
1 DHP CCB to remember?
Ideal use of a non-DHP CCB?
Supraventricular tachycardia in a patient with pre-existing HTN or angina.
(these also dilate coronary vessels)
Are vascular smooth muscle cells frequently depolarized to maintain tone? Thus what kind of CCB would you choose to make them relax?
Vascular SMCs do not frequently depolarize.
Thus a CCB that targets resting cells, i.e. a DHP CCB like nifedipine, would be a good choice to make these guys relax.
Most notable side effect of verapamil?
Constipation (makes sense. inhibition of GI smooth muscle)
Which CCB would you use to treat SVT without HTN?
Diltiazem - doesn't cause much vasodilation.
What can often happen as a response to the drop in SVR caused by DHP CCBs (such as nifedipine)?
Reflex tachycardia and increased contractility. (this can be bad in someone with CHF, high risk for MI, angina, etc.... can be countered by giving a beta blocker concurrently)
Do peripheral vasodilators act through known receptors? Is the vasodilation dependent on innervation?
Nope and nope.
3 sites of action of peripheral vasodilators? Example(s) of a drug that does each?
Venous - nitrates
Arterial - hydralazine, minoxidil (Rogaine)
Venous and arterial - nitroprusside
DHP vasodilators (e.g. nifedipine) produce reflex tachycardia and increased contractility. Does this happen with peripheral vasodilators?
Yes. Peripheral vasodilators provoke a 10x greater response, including... sympathetic vasoconstriction, increased HR and contractility, and activation of RAAS.
Does hydralazine have a preference for dilating any arteries?
Yes - mostly affects renal, peripheral, splanchnic, and coronary arteries.
2 toxicities of hydralazine?
Too much vasodilation w. sympathetic reaction. (hypotension, flushing, sweating, palpitations, angina)
Can cause SLE (lupus)-like syndrome.
What's the known MoA of minoxidil?
Activates ATP-modulated K+ channels (apparently, preferentially in arterial smooth muscle). K+ leaves cells, making them hyperpolarized.
(but this probably isn't the whole story)
Notable side effect of minoxidil?
Hypertrichosis - i.e. excessive hair growth.
Topical minoxidil = Rogaine.
How does sodium nitroprusside work?
Vascular SMCs metabolize it into NO.
What's the byproduct of sodium nitroprusside metabolism? How is this dealt with?
Cyanide is produced (by breakdown in RBCs).
Mitochondria can break this down with rhodanase to thiocyanate, using the limiting cofactor sodium thiosulfate.
Sodium thiosulfate is administered with sodium nitroprusside.
Unusual thing you have to do with sodium nitroprusside preparations?
Cover them in foil, because it's unstable in sunlight.
What's the "drug of choice" for hypertensive emergencies?
You all know about beta blockers.
Sure do. All about them.
What are 3 prototypical alpha-antagonists and their specificities?
Prazosin - alpha-1 and alpha-2 antagonist
Doxazosin and Terazosin - pure alpha-1 antagonists.
Can you use alpha-antagonists for HTN?
Yes, but it's really not preferred. Maybe if someone has benign prostatic hypertrophy and also HTN...
What's the deal with centrally acting alpha agonists? Where do they work, and why do they do what they do?
These act in the medulla on pre-ganglionic alpha-2 receptors.
These reduce sympathetic outflow -> unopposed vagal tone.
2 examples of centrally acting alpha agonist?
Major problem with methyldopa?
Causes CNS depression - lassitude, drowsiness.
For which patients is clonidine particularly good?
Diabetics with HTN and peripheral neuropathy, because it helps prevent autonomic fluctuations.
Most adverse effects of central alpha agonism are related to what?
Too much vagal tone -> dry mouth, orthostatic hypotension, bradycardia, somnolence, etc.
How do reserpine and guanethidine work? Why aren't they used?
They deplete NE from synapses.
In the CNS, this effect causes severe depression and suicidality.
How low should you try to lower blood pressure?
For pts with concomitant renal disease and/or diabetes, for example, you should aim lower.
Should lifestyle modifications be tried first to treat HTN?