KG - Pharm 2 Exam 2, Antihypertensive Agents Flashcards
why use a combo of drugs?
increases efficacy and may decrease toxicity (synergism)
DOC HTN?
thiazides
when to use thiazides for HTN?
- mild to moderate HTN
- lowers BP by 10-15 mmHg
which thiazide diuretic is a DIRECT vasodilator?
indapamide (acts as a CCB)
side effects diuretics?
- impotence
- gout (hyperurecemia)
- increased renin secretion
- K+ depletion (cramps, vent arrythm., ischemia vent fib)
- REDUCED GLUCOSE INTOLERANCE
- INCREASED LIPIDS
how can diuretic side effects be avoided?
use lower dose than those needed for diuresis
except impotence in elderly not always solved…
in combo therapy how do thiazides work?
counteract Na+ and H2O retention in combo therapy (w/ vasodilators, ACEI, Beta blockers)
when should thiazides NOT be used?
- sulfa allergy
- liver metabolism (indapamide)
in which pt populations are thiazides most effective?
- African American > whites
- elderly > younger
when should loop diuretics be used instead of thiazides?
- severe cases HTN (renal insufficiency, CHF)
when should K+ sparing diuretics be used in HTN?
- use w/ loops or thiazides to minimize loss K+
- avoid in combo with other K+ sparing drugs
when to use sympatholytics?
combined w/ a diuretic
action of sympatholytics?
- activate baroreflexes & cause Na+/H2O retention
- lower BP by reducing sympathetic vasomotor tone
clonidine/methyldopa MOA?
- stimulate medullary alpha 2 adrenergic receptors, which decreases periph symp nerve activity
clonidine/methyldopa therapeutic effects?
- decreased sympathetic flow
- decreased renin secretion
HTN DOC in pregnancy?
methyldopa
which drug lowers HR and CO more - clonidine or methyldopa?
clonidine
clonidine/methyldopa adverse effects?
- SEDATION, CNS effects
- xerostomia
methyldopa-specific adverse effects?
- HEMOLYTIC ANEMIA w/ POSITIVE COOMBS TEST
- hepatotoxic
- incr prolactin secretion
- gynecomastia, lactation
clonidine/methyldopa contraindications/precautions?
- not rec for mono therapy
- SUDDEN WITHDRAWL CLONIDINE = HTN CRISIS
- antidepressants can inhibit clonidine’s actions
list alpha 1 adrenergic antagonists
prazosin, terazosin, doxazosin
prazosin, terazosin, doxazosin - MOA?
block alpha 1 without affecting alpha 2 receptors
prazosin, terazosin, doxazosin - indications/therapeutic effects?
- reduce NE vasoconstriction, dilate arteries and veins
- BP down
- DO NOT AFFECT LIPIDS!
- BENEFICIAL IN BPH (relaxes smooth muscle)
prazosin, terazosin, doxazosin - adverse effects?
- postural hypotension w/ first dose = FIRST DOSE PHENOMENON
- Na+/H2O retention
- reflex tachy
- drowsiness, dizziness, palpitations, HA, fatigue sometimes
list non-selective B-blockers
propranolol
nadolol
timolol
list selective B1 blockers
metoprolol
atenolol
nebivolol
acebutolol
list B-blockers w/ ISA
acebutolol
pindolol
how to B-blockers lower BP?
block adrenergic receptors in:
- heart to reduce CO
- kidneys to reduce renin secretion
- CNS to reduce SNS vasomotor tone
populations that work best w/ b-blockers?
white > black
young > old
mono therapy ONLY in young, white males
when are B-blockers combined with other drugs?
- to counteract tachycardia
- increase renin secretion
when are B-blockers the preferred drug for HTN?
for pts with:
- angina
- post MI
- migraine
when are b-blockers the least preferred drug for HTN?
- high phys activity
- African American
- asthma
- DM
- hypercholesterolemia
- peripheral vascular dz
which drugs are contraindicated in pregnancy?
thiazides, beta blockers
list combined alpha 1 and b-blocker?
carvedilol
labetalol
labetalol - indications?
- lower BP in HTN emergencies
- pregnancy (emergencies, maintenance stronger than methyldopa)
- lipid neutral
carvedilol - indications?
- HTN, CHF, after MI
- lipid neutral
carvediolol/labetolol - adverse effects?
- orthostatic HTN
- bronchospasm
- hepatotoxicity (labetalol = emer only!)
reason to use vasodilators for HTN?
ALL VASODILATORS relax smooth muscle
which vasodilator also relaxes VEINS?
sodium nitroprusside
why do the effects of vasodilators diminish with time?
- reflex tachycardia
- increased renin secretion
why should you use vasodilators in combo w/ other drugs?
to oppose compensatory responses (ie: reflex tachycardia)
which vasodilators (and other drugs) are used for CHRONIC ORAL treatment?
- hydralazine
- minoxidil
- CCBs
which vasodilators (and other drugs) are used as IVs IN EMERGENCIES?
- nitroprusside
- fenoldopam
- some CCBs
hypotension from vasodilators can also have ___.
- reflex tachycardia
- increased myocardial contraction
- increased renin secretion
- fluid retention
- HA, flushing
- palpitations, dizziness
when should you prescribe Hydralazine?
- used in CHRONIC THERAPY of SEVERE HTN
- only used when other treatments failed
- combined w/ other agents only
- used in severe hypertension or htn emergencies in pregnancy
which drug should be given in HYPERTENSIVE EMERGENCIES in PREGNANCY?
hydralazine
which vasodilator used for SEVERE HTN?
hydralazine
hydralazine - adverse effects?
- HA, nausea, anorexia, palpitations, sweating, flushing
- angina, ischemic arrhythmias
- SLE IN SLOW ACETYLATORS!
which drugs can cause SLE?
hydralazine
isoniazid
procainamide
which drug is used in HTN emergency situations?
sodium nitroprusside
sodium nitroprusside - indications/therapeutic effects?
- rapidly lowers BP (minutes) and effect disappears quickly, too
- HTN emergencies
sodium nitroprusside - pharmacokinetics
- IV ONLY
- metabolized to thiocyanate rapidly
- excreted by kidney
sodium nitroprusside - adverse effects?
- cyanide accumulation
- met. acidosis
- arrhythmias
- excessive hypotension
- death (in its w/ def in cyanide metabolism)
minoxidil - MOA
- opens K+ channels and stabilizes membranes
- DILATES ARTERIOLES BUT NOT VEINS
minoxidil - pharmacokinetics
- oral
- liver metabolism
- active metabolite
- 1/2 life 4 hrs, effects last 24 hrs
minoxidil - adverse effects?
- tachycardia, palpitations, angina, edema
- HA, sweating
- HYPERTRICHOSIS
what is topical minoxidil known as?
ROGAINE!
fenoldopam - MOA?
- SPECIFIC AGONIST ON D1 RECEPTORS
- post synaptic D1 receptor stim relaxes arteriolar smooth muscle
fenoldopam - indications/therapeutic effects?
HTN emergencies
fenoldopam - pharmacokinetics?
- IV
- liver metabolism
- 1/2 life = 5 min
fenoldopam - adverse effects?
reflex tachycardia, HA, flushing
list calcium channel blockers (dihydropiridines)
nifedipine
nimodipine
other -dipines
list calcium channel blockers (others)
verapamil
diltiazem
CCBs - MOA
- bind to L type channels in myocardium and vasc. smooth muscle
- closes calcium channels
- cause decrease in Ca2+ current, long lasting relaxation of vasc smooth muscle, decr cardiac contractility/conduction
which types of muscles do CCBs relax?
all smooth muscles that depends on calcium for resting tone/contraction
which type of muscle is most sensitive to CCBs?
VASC SMOOTH MUSCLE but bronchiolar, GI, uterine also relaxed
which are more sensitive to CCBs: arterioles or veins?
ARTERIOLES are more sensitive than veins
major cardiac effects of CCBs?
- neg inotropic effects (less contractility)
- reduced impulse generation in SA node
- slowed AV node conduction
which is the strongest vasodilator of the CCBs?
NIFEDIPINE
which has the strongest cardiac effects of the CCBs?
VERAPAMIL
which drug is the most moderate CCB?
DILTIAZEM
What are the differences in TISSUE SELECTIVITY between CCBs?
Nifedipine: increased HR
Verapamil: decreased HR
CCBs pharmacokinetics?
- oral
- first pass effect
- (could be IV if needed)
- renal excretion mostly
- 1/2 life 3-5 hrs
which CCB is most likely to produce reflex tachycardia?
NIFEDIPINE:
highest vasodilation –> marked hypotension –> reflex tachycardia
what are verapamil and diltiazem less likely to elicit reflex tachycardia?
- have direct inhibition on heart
- weak dilation
- directly depress SA/AN node function
“-dipines” adverse effect?
gingival hyperplasia
dihydropyridines adverse effects?
- VASCULAR side effects (ie: HA, flushing, dizziness, peripheral edema)
most common side effect of VERAPAMIL?
CONSTIPATION
which CCBs may cause bradycardia in pts w/ SA node dysfunction?
verapamil
diltiazem
CCBs contraindications/precautions?
- not for pts w/ LVH
- contraindicated w/ SA or AV node abnormalities
- CHF
if a pt has high renin, to which two classes of drugs will he/she probably respond?
beta blockers and/or inhibitors of RAS (ACEI, ARBs)
ACE inhibitors MOA?
- inhibit ACE
- lower ATII
- lower BP by reducing vasoconstriction by ATII & release of Aldo
how do ACE inhibitors lower BP? (pros?)
- without compromising heart/brain/kidneys
- no lipid changes
- no reflex sympathetic activation/tachycardia bc baroreceptor resetting
in what group of ppl are ACE inhibitors most effective as MONOTHERAPY?
young/middle age > old
less effective in elderly african americans
ACE inhibitors are the DOC treatment for HTN for ___
- diabetes
- chronic renal dz
- LVH
benefits of ACE inhibitors?
- ENHANCE ANTIHYPERTENSIVE EFFECTS OF DIURETIC DRUGS
- BALANCE ADVERSE EFFECTS OF DIURETICS
which group of diuretics do you NOT use ACE inhibitors w/?
potassium sparing diuretics
ACE inhibitors pharmacokinetics?
- oral, parenteral
- liver metabolism
- urinary/fecal excretion
ACE inhibitors adverse effects?
- hypotension in HYPOVOLEMIC pts
- dry hacking COUGH
- ANGIONEUROTIC EDEMA (incr bradykinin)
- hyperkalemia
- ACUTE RENAL FAILURE in its w/ bilateral renal artery stenosis
ACE inhibitors contraindications/precautions?
- TERATOGENIC! not in 2nd/3rd sem pregnancy!
- do not use w/ K+ sparing diuretics
- do not use w/ NSAID COMBO (CAUSES DECREASED VASODILATION)
ARBs MOA
- block AT1 receptors selectively w/out affecting AT2 receptors
what do ACE inhibitors cause that ARBs do not cause?
- cough, angioedema
when is the only time you don’t reach for a thiazide first for HTN?
diabetes
