Drugs for HTN Flashcards
What seems to be the initiating event in chronic hypertension?
an initial increase in cardiac output causes a volume overload leading to increased TPR
OR
an increase in TPR can be the initiating event
What organs are critical in controlling BP long term?
Kidneys
“slow but ultimate regulator of BP due to their ‘infinite gain’”
What are the main causes of Primary HTN?
Low renin
normal renin
high renin
idiopathic
What is secondary HTN?
Has a primary cause and can sometimes be cured by treating cause
What are some common causes of secondary HTN?
Renal parenchymal disease
renovascular disease
primary aldosteronism
OSA
Drugs/ETOH
Pheochromocytoma
What are the main drug classes of primary agents for treating HTN?
Thiazide Diuretics
ACEi
ARB
CCB (dihydropyridines and non-dihydropyridines)
What are the drug classes for secondary agents of HTN?
Loop diuretics
K sparing Diuretics
Aldosterone antagonists
B blockers
Renin inhibitors
Alpha-1 and 2 blockers
direct vasodilators
What is the MOA of thiazides?
Block Na-Cl cotransporter in the DCT
increases Ca reabsorption in PCT because of volume contraction
Mg and K loss increased
What are the clinical applications for hydrochlorothiazide?
(thiazide)
HTN alone or in combo with others
not effective in pt’s with low GFR
used off label for calcium nephrolithiasis
What are the toxicities for HCTZ
(thiazide)
Low K, Mg, Na
Low Cl, metabolic alkalosis
Sulfa hypersensitivity
What is the MOA for Furosemide?
(loop diuretic-Lasix)
Blocks Na-K-2Cl transporter
What are the clinical applications for Furosemide?
(loop diuretic)
edema
heart failure
decreases preload, ECV
relieve dyspnea
HTN (even with low GFR)
What are the toxicities of Furosemide?
Low K, Na, Ca, Mg, Cl
metabolic alkalosis
HYPERglycemia and Hyperuricemia
OTOTOXICITY
Sulfa hypersensitivity
What is the benefit of Torsemide over furosemide?
Longer 1/2 life, better oral absorption
better for Heart Failure
What is the benefit of Bumetanide over Furosemide?
more predictable oral absorption
What is the benefit of ethacrynic acid?
non-sulfanamide
(use for sulfa allergies)
What is the MOA for K-sparing diuretics?
Amiloride blocks Na channels in collecting duct
Spironolactone blocks aldosterone receptor in collecting duct
What are the clinical applications for Amiloride?
(K sparing)
Counteracts K loss from other diuretics (used in combo)
What are the toxicity concerns with amiloride?
HyperKalemia
What is the effect of Spironolactone?
K-sparing diuretic
Antagonizes pro-fibrotic effects of aldosterone
What are the clinical applications for Spironolactone?
counteracts K loss induced by other diuretics especially in treating Heart Failure
Reduce fibrosis in HFrEF and post-MI heart failure
Off label for HFpEF, acne
When GFR decreases due to ACEi, what rises?
Creatinine
(helps preserve kidney function, but should be less than 30% increase with no associated hyperkalemia)
What is the MOA of Captopril?
How long is the half life?
What are the main toxicities?
ACEi
t1/2 = 1.7hrs, longer if renal impairment
Cough, angioedema
What is the MOA of losartan?
nonpeptide angiotensin II receptor antagonist
(binds 1000x better to AT1R than AT2R)
What is the benefit of valsartan over losartan?
What is the benefit of Candesartan over losartan?
It is not a prodrug
relatively irreversible binding
What is Aliskiren and why is it not widely used?
Direct renin inhibitor
new, expensive, and no obvious benefit with increased risks of adverse effects
(lose-lose-lose situation)
Drugs that interfere with Angiotensin II have what effects on the kidneys?
decrease AngII and increase efferent tone
can cause renal failure in pt’s with bilateral renal stenosis
can preserve renal function in DM pt’s
ACEi are contraindicated in which special population?
Pregnant Women
Should be discontinued ASAP
What is the MOA of Nifedipine?
What are is a main effect?
dihydropyridine CCB
Frequency-independent, AKA not cardioactive
What are the clinical applications for Nifedipine?
HTN
HTN emergency in pregnancy
Pulmonary HTN
What are toxicities of Nifedipine?
Flushing
Peripheral Edema
Headache
Palpitations
gingival hyperplasia
Why is amlodipine often used over nifedipine?
limited to CAD and HTN, but very widely used due to long half life (30-50hrs)
What is the MOA of Verapamil and Diltiazem?
What are there effects?
non-dihydropyridine CCB
Frequency-dependent, AKA cardioactive
Nifedipine preferentially affects depolarized tissues leading to
Verapmil and Diltiazem are use-dependent and target channels that cycle regularly, thus affecting what?
blockade that is voltage dependent in arterial blood vessels
myocardium and tachycardic hearts
HR and CO are increased by reflex SNS activation with Nifdepine why?
Because Nifedipine exerts smaller direct inotropic effects and no chronotropic effects with large vasodilatory effects
(thus causing the increased HR and CO due to reflex SNS activation)
Early Alpha Receptor Blockers such as ___ and ____ were not well tolerated due to what effects?
Phentolamine and Phenoxybenzamine
due to hypotensive episodes, orthostatic hypotension, arrhythmias, angioedema, miosis
What are the clinical applications of prazosin
(a1R blocker)
HTN
late choice because increases likelihood of stroke and CHF with doxazosin compared to chlorthalidone
What are the toxicities associated with Prazosin?
orthostatic hypotenision
“retrograde” ejaculation
What is tamsulosin, terazosin and doxasozin marketed for besides HTN?
BPH and passing kidney stones
What is the MOA and effects of Clonidine?
A2R antgonist
produces a transient increase in BP that then reduces sympathetic outflow from the CNS
What are the toxicities for Clonidine?
drowsiness, xerostomia
REBOUND HTN if dose is missed
What is the MOA and main use of a-methyldopa?
A2R antagonist
Drug of choice for gestational hypertension
What are some toxicities of a-methyldopa?
can cause a positive Coombs test and SLE-like sx
What were some of the issues with SNS and PNS blocker, Hexamethonium?
higher resting HR and BP and opposite of SLUDGE
-dry mouth, dry eyes, urinary retention, constipation, mydirasis
Difficulty maintaining CO and BP when upright
What is the MOA of reserpine?
What was the effect?
What are the adverse effects?
blocked incorporation of NE into synaptic vesicles
mild decrease in BP, no change in CO, RBF, or GFR
Severe depression and SI
what is the MOA for Guanethidine?
What is the adverse effects?
displaces NE from synaptic vesicle
decreases CO, TPR, RBF, and GFR
Severe orthostatic hypotension,
BP slowly increases throughout day
What is the MOA of propranolol and who is it contraindicated in?
Nonselective beta blocker
can cause cold extremities especially in infants and those with peripheral vascular disease
What happens if an a2 agonist or B blocker is stopped abruptly?
Unmasking the B receptors leads to excessive cardiac stimulation in response to normal SNS tone
-leads to tachycardia, HTN, angina, MI, arrhytmia
Suddenly stopping A2 agonists releases CNS brake on SNS tone leading to Rebound HTN (and death)
Why are beta blockers not used as much now?
Current data suggests that B-blockers DO NOT prevent MI, heart failure or death, as well as other therapies and, are associated with significantly higher incident of stroke
What is the MOA of hydralizine and who is it often used in?
direct vasodilator of arteriols
Used in hypertensive emergency in pregnancy
What are the toxicities of hydralizine?
(many)
Drug induced lupus-like syndrome
cardiovascular
CNC
Derm
GI/GU
Hematologic
NMS
Ocular
Resp
What is the MOA of nitroprusside?
Venous and arteriolar vasodilation
What is the MOA of minoxidil?
Concerning Toxicities?
vasodilation of arteriolar smooth muscle
Pericardial effusion with tamponade
What conditions suggest bilateral renovascular hypertension rather than primary HTN?
Flash pulmonary edema
progressive renal failure
refractory congestive heart failure
Why is renal revacularization not done now?
restoring vessel patency with surgery or stenting fails to materially recover kidney function
IE-no better than drugs to block the RAAS and statin therapy
Initial treatment of HTN includes which drug classes?
If this is not enough to lower BP, and chest pain is present, what is the next step?
What if BP goal is not met, but there is no chest pain?
B-Blockers, ACEi, ARBs
add Dihydropyridine CCBs
Add dihydropyridine CCB, thiazide and/or MRAs
In CKD with goal BP under 130/80 and albuminuria is present, what is the drug class of choice?
what if they are intolerant to that drug class?
ACEi
Treat with ARB
What is the goal BP to prevent HD in adults with HTN?
What is the goal of treating HTN in those with HFrEF?
What is teh goal of treating HTN in those with HFpEF?
What is the goal of treating HTN after renal transplant?
130/80
GDMT (BB) titrated to BP <130/80; nondihydropyridine CCB are not recommended
Diuretics for volume overload and HTN, ACEi or ARBs and BB titrated to SBP 130
BP <130/80 with calcium antagonist to improve GFR and kindey survival
How to lower BP in acute spontaneous ICH?
(within first 6 hrs)
If BP is 150-220 lower to <140
if BP is >220, lower with continuous IV infusion and close BP monitoring
Metabolic syndrome is diagnosed with three of the following five
Abdominal obesity
serum triglycerides over 150 or drug treatment for it
serum HDL <40 in men, <50 in women or drug tx for it
BP 130/85 or drug tx for it
fasting plasma glucose >100 or drug tx for it
What are some ways to increase medication compliance and improve outcomes in treating HTN?
1x day or combination pills
behavioural and motivational strategies
team-based approach
EHR
Telehealth strategies
performance measures and quality improvement strategies
HTN urgency is different from emergency, in that emergency has what?
Emergency has impending or progressing target organ dysfunction
Ex: dissecting aortic aneurysms, renal failure, ischemic stroke, eclampsia, etc
When pt’s present with hypertensive emergency, what is the next step?
If aortic dissection, (pre)-eclampsia, pr pheochromocytoma present, what is the next step?
If there is no dissection, eclampsia, etc, what is the next step?
admit to ICU
Reduce BP to <140 in first hour and then to <120 in case of dissection
Reduce BP by max 25% over first hour then to 160/100 over next several hours then to normal over 1-2 days
What happens if you drop someone’s BP too quickly?
dropping it too far too fast can mean no flow if there is chronic high BP
Nicardipine is CI in whom?
Clevicipine is CI in whom?
in those with advanced aortic stenosis
Soy allergies, egg allergies, defective lipid metabolism
Na Nitroprusside should be monitored for what effects?
NTG should be used in whom and not used in whom?
BP “overshoot”, lower doses in elderly, and CN toxicity
USein pts with ACS or acute pulmonary edema only; do not use in volume depleted pts
Hydralizine is unpredictable, thus it is not what?
Emsmolol is CI in whom?
It is not good for the first-line agent in most patients
Those with concurrent beta-blocker therapy, bradycardia, or decompensated HF; can affect lung function
Labetalol is CI in whom?
Phentolamine should be used in whom?
FEndolapam is CI in whom?
Enalaprilate is CI in whom?
those with reactive airway disease, or COPD
those with HTN emergencies from catecholamine excess
those at risk for glaucoma or increased IC pressure, sulfite allergies
CI in pregnancy and should not be used in acute MI or renal artery stenosis
