Antihypertensives Flashcards
10-15% of hypertension is caused by…
A specific cause
Examples: Renal artery constriction Coarctation of the aorta Pheochromocytoma Cushings Primary aldosteronism
What’s the difference between Stage 1 and Stage 2 HTN?
Stage 1 (130-139/80-89) only needs 1 med
Stage 2 (≥140/90) requires two meds
Blood pressure is directly proportional to …
CO and vascular resistance
What is the key to treatment of HTN?
Lifestyle modifications before or combined with drug therapy
Examples: Increased physical activity/exercise Weight reduction Moderation of dietary salt, fats, EtOH Avoid/reduce smoking
What is the most common cause of HTN treatment failure?
Non-compliance
The drugs have a lot of side effects so people don’t like to take them
HTN drug treatment OR lifestyle mods can reduce BP by…
~15 mmHg
Why do we use drug combos for HTN rather than maxing out the dose of a single drug?
Can reduce side effects produced by single drugs
Reduce doses by using different mechanisms to reduce BP
Cause synergism between drugs
Main goals of HTN treatment are…
Reduce BP and keep it normal
Reduce CV risk
Produce minimal side effects without reducing quality of life
What are the four groups of HTN agents?
Diuretics
Sympathoplegic agents
Direct vasodilators
Angiotensin inhibitors
________ diuretics are used to treat mild to moderate hypertension, reducing BP in 40-60% of patients
Thiazide diuretics
Lower BP by 10-15 mmHg
How do thiazides lower BP?
Short term by reducing CO
Long term by reducing peripheral vascular resistance
Thiazide diuretic that is also a direct vasodilator
Indapamide (has the most pronounced effect)
Common side effects of diuretics
Impotence Gout Increased renin (baroreflex) Hypokalemia ***Reduced glucose tolerance ***Increased plasma lipid concentration
Most can be avoided by lowering doses
HTN doses of diuretics are _______ than those used for diuresis
Much lower
Thiazide diuretics are most effective at lowering BP in …
African Americans
Elderly
When are Loop Diuretics used for HTN management?
In severe cases (renal insufficiency, HF)
Sympatholytics reduce BP by…
Reducing sympathetic vasomotor tone —> reducing peripheral resistance
Activate baroreflexes and generally cause Na and H2O retention but DO NOT cause reflex tachycardia
Best when combined with a diuretic
Examples of central acting sympatholytics
Clonidine
Methyldopa
MOA for central acting sympatholytics
Stimulate medullary a2 adrenergic receptors —> reduced peripheral sympathetic nerve activity —> reduced renin and reduced BP
Clonidine will reduce HR and CO more than methyldopa
Both given orally, but clonidine can also be used as a patch
Which central acting sympatholytics can safely be used to treat HTN in pregnancy?
Methyldopa
Adverse effects of Central Acting Sympatholytics?
SEDATION and other CNS effects
XEROSTOMIA
ED
Methyldopa —> hemolytic anemia with a (+) Coombs test, hepatotoxicity, GYNECOMASTIA/lactation
Why don’t you want to suddenly withdraw clonidine?
Can induce hypertensive crisis
What drugs can inhibit clonidine’s therapeutic action?
Tricyclic antidepressants
Yohimbine (b/c it’s an a2 antagonist)
What drugs are a1 adrenergic antagonists?
The “-zosins”
PRAZOSIN, Terazosin, Doxazosin
MOA for the zosins
Specifically block a1-adrenergic receptors —> reducing NE vasoconstriction —> vasodilation
Reduces peripheral resistance —> lower BP
What are the main benefits of using a1 adrenergic antagonists to lower BP?
Do not adversely effect plasma lipids
Beneficial in BPH**
What is the “first dose phenomenon”?
Postural hypotension pronounced with the first dose of an a1 antagonist (zosin)
Besides first dose phenomenon, what are some other adverse effects of a1 antagonists?
Na and H2O retention (increased renin) - so maybe combine with a diuretic)
Reflex tachycardia
***What is the only beta blocker that is a vasodilator?
Nebivolol (b/c it increases NO release)
What are the non-selective beta blockers?
Propranolol
Nadolol
Timolol
Which are the selective B1 blockers?
Metoprolol
Atenolol
Nebivolol
Acebutolol
MOA for beta blockers in HTN
Reduce BP by blocking beta adrenergic receptors:
• In heart to reduce CO
• In kidneys to reduce renin
• In CNS to reduce sympathetic vasomotor tone
***Not direct vasodilators (except Nebivolol)
Beta blockers work best in what population?
Young white males
Beta blockers are combined with other drugs to..
Counteract reflex tachycardia and increase renin secretion
No longer recommended for monotherapy
Beta blockers are the preferred drug for patients with…
Angina
Post MI
Migraine
Nebivolol —> those with ED
Beta blockers are the least preferred drug for patients with…
High physical activity African heritage ***Asthma*** DM Hypercholesterolemia Peripheral vascular disease
Contraindications for beta blockers
DM End-stage HF Severe bradycardia Heart block Asthma
Which drugs are combined a1 and beta blockers?
Carvedilol - good for patients with both HTN and HF, especially after MI
Labetalol - used for hypertensive emergencies and in pregnancy (stronger than methyldopa, but some hepatotoxicity so not used long term)
Adverse effects of combined a1/B blockers (Carvedilol/Labetalol)
Orthostatic hypotension (worse than beta blockers)
Bronchospasm
Hepatotoxicity (that’s why Labetalol is for emergency use only)
All vasodilators relax arterial smooth muscle but sodium nitroprusside preferentially relaxes…
Veins
Why do the effects of vasodilators diminish with time?
Reflex tachycardia and increased renin secretion
Hypotension from any vasodilator may be accompanied by:
Reflex tachycardia and increased myocardial contraction
Increased renin secretion
Fluid retention
Headaches, flushing
Palpitations, dizziness
Which vasodilator is one of the HIP drugs —> SLE?
Hydralazine
Hydralazine dilates ______ but not ______
Arterioles
Used in chronic therapy of severe hypertension or hypertensive emergencies in pregnancy
What is the MOA for sodium nitroprusside (Nitropress)
Rapidly lowers BP in minutes by venodilation
Effect disappears in minutes after d/c
Used for emergency hypertensive situations - IV infusion only
Adverse effects of sodium nitroprusside
Cyanide accumulation (b/c metabolized in liver to thiocyanate before excreted by kidneys)
Metabolic acidosis, arrhythmias, excessive hypotension, death (esp in patients with severe liver disease)
Topical minoxidil stimulates hair growth but orally it reduces BP by…
Opening the potassium channels and stabilizing membrane
Used for severe hypertension that is refractory to other drugs
Can cause tachycardia, palpitations, angina, etc but also HYPERTRICHOSIS
What is the MOA for Fenoldopam?
Specific D1 agonist
Postsynaptic D1 receptor stimulation relaxes arteriolar smooth muscle
Used for emergency hypertensive situations
IV administration with short half-life
Which drugs are dihyropyridine calcium channel blockers?
NIFEDIPINE
Nimodipine
(Amlodipine - has a longer half life)
Which drugs are non-dihydropyridine CCBs?
Diltiazem
Verapamil
What is the MOA for CCBs?
Orally active, bind to L-type channels in the myocardium to reduce cardiac contractility, automaticity, and conduction
Bind to calcium channels in vascular smooth muscles —> vasodilation
(Vascular smooth muscle most sensitive but affects ALL smooth muscles)
Which CCB is best for relaxing vascular smooth muscle?
Nifedipine»_space; Diltiazem»_space; Verapamil
Which CCB works most specifically on cardiac muscle?
Verapamil»_space; Diltiazem»_space; Nifedipine
Major cardiac effects of CCBs
Negative inotropy (contractility)
Negative chronotropy (SA node impulse generation)
Negative dromotropy (av node conduction)
Nifedipine will _____ HR while Verapamil with _____ HR
Nifedipine increases
Verapamil decreases
Which CCB is used for reducing HTN during pregnancy?
Nifedipine
Which CCB is most likely to produce reflex tachycardia?
Nifedipine (highest vasodilation)
Verapamil and diltiazem are weaker vasodilators so they are less likely to elicit reflex tachycardia
Which CCBs are more likely to depress SA and AV node function?
Verapamil and Diltiazem
Which antihypertensive is known to cause gingival hyperplasia?
The “-dipines” - Dihyropyridine CCBs
________ is the most common side effect of verapamil
Constipation
Contraindications for CCBs
Verapamil and diltiazem contraindicated in patients with SA or AV node abnormalities, beta blockers, and in HF
Dihydropyridines should be used cautiously in hypertensive patients with HF
Why are ACE’s so awesome?
Lower BP without compromising heart, brain, or kidneys
Mild and fewer side effects, no lipid changes
Do not cause reflex sympathetic activation or tachycardia b/c of baroreceptor resetting
Effective orally and can be used for monotherapy
ACE inhibitors are most effective in what population?
Young and middle-aged caucasians
ACEIs are the definitive DOC for HTN in patients with…
DM (esp for preventing DM nephropathy)
CKD
HFrEF
Adverse effects of ACEIs
Orthostatic hypotension and dizziness
Dry, hacking, non-productive COUGH
Angioneurotic edema
May cause hyperkalemia
Acute renal failure in patients with BL renal artery stenosis
When are ACE/ARBs absolutely contraindicated?
Pregnancy (teratogenic)
ARBs are similar to ACEs except
Don’t have the cough/angioedema (b/c no effect on bradykinin)
What HTN drug should you pick:
Age over 65
Diuretic
ACE/ARB
CCB
NO Central acting agonists
What HTN drug should you pick:
African heritage
Diuretic
CCB
NO BBs
What HTN drug should you pick:
Pregnant
Methyldopa
Nifedipine
Labetalol (emergency IV only)
NO ACE/ARBs
What HTN drug should you pick:
Angina pectorals
BB
CCB
No: Hydralazine, minoxidil
What HTN drug should you pick:
Post MI/Clinical CAD
ACE/ARB
BB
What HTN drug should you pick:
HF
ACE/ARB + BB + diuretic + aldosterone antagonist
No CCB
What HTN drug should you pick:
Recurrent stroke prevention
Diuretic
ACE/ARB
What HTN drug should you pick:
CKD
ACE/ARB
What HTN drug should you pick:
DM
ACE/ARB
CCB
NO Diuretic or BB
What HTN drug should you pick:
Asthma
CCB
ACEI
NO BB
What HTN drug should you pick:
BPH
Alpha blocker
What HTN drug should you pick:
Migraines
BB
CCB
What HTN drug should you pick:
Osteoporosis
Diuretic
