ending of dihydropyridine (DHP) calcium channel blockers (CCBs)
-dipine
non-DHP CCBs
- diltiazem
- verapamil
K+ channel openers
- diazoxide
- minoxidil
dopamine agonist
fenoldopam
NO modulators
- hydralazine
- nitroprusside
- isosorbide dinitrate
- nitroglycerin
ending of beta-andrenergic antagonist (beta-blockers)
-lol or -olol
alpha1-adrenergic antagonists (alpha1-blockers)
- doxazosin
- prazosin
- terazosin
centrally acting sympathoplegics (alpha2-agonists)
- clonidine
- guanabenz
- guanafacine
- methyldopa
MOA: DHP CCBs
block L-type Ca receptors (vasculature > cardiac)
MOA: non-DHP CCBs
nonselective block of L-type Ca channels
PK: CCBs
orally active w/ high first-pass metabolist
CCBs given IV
- nifedipine
- clevidipine
- verapamil
- diltiazem
T1/2 most CCBs
2-12 h
T1/2 amlodipine
35-50h
AE: DHP CCBs
- xs hypotension
- dizziness
- HA
- peripheral edema
- flushing
- tachy
- rash
- gingival hyperplasia
type of DHP used to tx chronic HTN
slow-release and long-acting
AE: non-DHP CCBs
- dizziness
- HA
- periperal edema
- constipation
- AV block
- brady
- HF
- lupus-like rash (diazetam)
- pulmonary edema
- coughing and wheezing
non-DHPs causing slow HR
verapamil > dilitiazem
non-DHE CCB that esp causes constipation
verapamil
mechanism by which CCBs cause worsening HF
negative ionotropic effect
DI: DHP CCBs
other vasodilators
DI: non-DHP CCBs
other cardiac depressants and hypotensive drugs
clinical uses of CCBs
long-term out-pt therapy for HTN, HTN emergencies, angina
MOA: diazoxide
opens K channels thereby hyperpolarzing membrane and reducing contractility
DOA: diazoxide
long-acting, 4-12 hours
administration: diaoxide
3-4 injections at 5-15 minute intervals PRN
AE: diazoxide
- xs hypotension (> in renal failure and beta-blocker pts)
- hyperglycemia
- H20 + Na retantion (v rare)
CI: diazoxide
-ischemic HR: causes angina, ischemia, CF
clinical use of diazoxide
HTN emergencies
MOA: minoxidil
opens K channels in smooth m thereby allowing hypepolarization leading to decreased contractility
phys effect of minoxidil
dilation of aa, not vv; > effect than hyralazine
AE: minoxidil
- HA
- sweating
- hypertrichosis
- reflex sympathetic stim
- Na H2O retention; leads to tachy, palpitations, angina, edema
what do you NEED to use with minoxidil and why?
- beta-blocker: avoid excess sympathetic stim
- loop diuretic: avoid edema
clinical uses of minoxidil
- LT out-pt therapy of severe HTN
- topically for hair growth
MOA: fenoldopam
D1 receptor agonist
phys effects of fenyldopam
arteroilar dilator, naturetic
ROA: fenyldopam
cont IV infusion
T1/2: Fenyldopam
short - 10 min
AE: fenoldopam
- tachy
- HA
- flushing
CI: fenyldopam
glaucoma - increased intraoccular P
clinical uses of fenyldopam
HTN emergencies, peri and post-op HTN
MOA: hydralazine
release of NO from endothelium causing increased cGMP
PK: hydralazine
high first pass and therefore low bioavailability
AE: hydralazine
- HA, nausea, anorexia, palpitation, sweating, flushing
- angina and arrhythmias in some pts (ischemic heart dz, reflex tachy, symp stim)
- rare: periph neuropathy, drug F
clinical uses of hydralazine
- LT out-ppt with HTN
- frist line in preg F w/ HTN
- use with methyldopa for AA’s w/ HTN + HF
- IV for HTN emergencies
phys effects of hyralazine
- aa dilation but not vv
- reflex tachy
MOA: sodium nitroprusside
release of NO leading to increase cGMP
phys effect of sodium nitroprusside
- aa and vv dilation, dec BP
- pts with HF = increase CO too
DOA: sodium nitroprussides
-rapid onset w short duration
ROA: sodium nitroprusside
IV infusion w/ cont monitoring
AE: sodium nitroprussides
- excessive hypotension
- cyanide and thiocyanate release - potential for poisoning if used for several days
clinical uses of sodium nitroprussides
- HTN emergencies
- acute decompensated HF
organic nitrate agents
- nitroglycerin
- isosorbide dinitrate
- isosorbide mononitrate
MOA: organic nitrates
release of NO via enzymatic metabolism
phys effects of organic nitrates
- vv dilation > aa: increased venous capacity
- decreased vent preload
- reduced pulmonary vasc P
- reduces heart size
- reduced CO
ROA: organic nitrites
oral, transdermal and buccal (for longer DOA)
DOA: organic nitrates
- reach therapeudic levels w/in minutes
- effects lasts 15-30 min
limitation of organic nitrates and how to prevent it
can build tolerance, need to have nitrate-free period for at least 8 hr btwn doses
AE: organic nitrates
- orthostatic hypotension
- syncope
- throbbing HA
CI: organic nitrates
increase ICP
DI: organic nitrates
hypotension w/ PDE5 inhibitors
clinical uses of organic nitrates
- HTN emergency
- angina
- heart failure
when are sympathoplegic agents most effective?
when used with a diuretic
Beta1-blockers do what in the kidney?
inhibit renin secretion
beta-blocker not available as oral preparation
esmolol
extended release beta-blockers
- carvediol
- metoprolol
- propranolol
beta-blockers available as parenternal preparations
- atenolol
- esmolol
- labetalol
- metoprolol
- propranolol
beta-blockers that cross the BBB
- propranolol
- penbutolol
CI: beta blockers
- asthma/COPD ( benefit may outweigh risk of COPD)
- diabetes: benefits may outweigh risk in pts after MI
AE: beta blockers
- brady
- fatigue
- sexual dysfunction
- depresion
- unfavorable plasma lipid profiles (inc VLDL, dec HDL)
- rebount HTN after sudden stopping w/ possible angina and MI
DI: beta-bockers
heart block if used with verapamil or diltiazem
clinical uses of beta-blockers
- HTN
- heart failure
- ischemic heart disease
- cardiac arrythmias
- glaucoma
clinical use for beta1-selective agonist
- comorbid asthma
- DM
- peripheral vascular disease
clinical use of beta2 selective agonists
- bradyarrhythmias
- peripheral vascular disease
MOA: alpha1-blocker
reversible antagonists at alpha 1 receptors
phys effects of alpha1 blockers
- vasoconstrcitos aa and vv
- relax smooth mm in prostate
- H2O and Na retention (when used w/out beta blocker)
- no change or improvement of plasma lipid profiles
AE: alpha 1 blockers
- orthostatic hypotension
- dizziness
- palpations
- HA
- lassitude
alpha 1 blockers have less incidence of what in comparison to non-selective alpha adrenergic blockers?
reflex tachy
DI: alpha 1 blockers
most effective when used with other drugs (beta-blockers and diuretics)
clinical use of alpha 1 blockers
concurrent HTN and BPH
MOA: centrally acting agents (alpha 2 agonists)
- reduce sympathetic outflow from vasomotor centers
- retain or increase sensitivity to baroreceptor control
clinicl uses of central acting (alpha 2) agonists
- v rare use
- methyldopa is used for HTN in pregnancy
MOA: clonidine
lowers BP by reducing CO and peripheral vascular resistance
AE: clonidine
- sedation
- dry mouth
- depression
- sexual dysfunction
SAE: clonidine
abrupt w/drawal can lead to life-threatning HTN crisis
MOA: methyldopa
- lowers BP via reduction in peripheral vascular resistance
- variable reduction in HR and CO
AE: methyldopa
- sedation
- dry mouth
- lack of concentration
- sexual dysfunction