smooth muscle Flashcards
mechanisms of smooth muscle contraction
Calcium- cell membrane and intracellular signaling mechanism
Intracellular signaling- myosin light chain kinase, rho kinase
Hormonal and paracrine factors- norepinephrine, angiotensin 2 and endothelin 1
mechanism of smooth muscle relaxation and therapeutic applications
signaling pathways that inhiibit contractile mechanisms
Paracrine factors- NO, dopamine, prostacyclin
for CV, Uterine, Gastrointestinal, pulmonary
Nitric oxide donors MOA
intracellular signaling: Cyclic GMP/protein kinase G
NO combines with the heme group of soluble guanylyl cyclase–> increase in cGMP –> activates K channels–> enhanced mmyosin light chain dephosphorylation–> relaxation
arterial and venous circulation both affected
Nitroglycerin- venous dominant dilator
Nitroprusside- arteriole and venule dilator
nitroglycerin
Relaxation of venous smooth muscle and coronary arteries
metabolized to NO via mtALDH (mito aldehyde reductase), which is high in venous smooth muscle.
Venous dilation–> decreased cardiac preload (and coronary artery dilation)–> anti-anginal actions
treatment for angina and coronary artery disease
Sublingual admin (liver inactivates NO), F for nitroglycerin is low, sub lingual gives therapy in a few minutes with a small dose
Contraindicated- elevated intracranial pressure
can develop tolerance
Toxicity- orthostatic hypotension, tachycardia, syncope, and throbbing headache
nitroprusside
Relaxes arterial and venous circulation
has iron, cyanide, and nitroso, rapidly metabolized by uptake into RBC w/ release of NO and cyanide (cyanide is metabolized to less toxic compund)
Rapid arterial pressure reduction
Nitroprusside is given IV infusion, effects gone within a few minutes, make fresh and cover with foil
No tolerance
Toxicity- hypotension, cyanide accumulation, metabolic acidosis, arrythmias
hydralazine
relaxation of arterial circulation for heart failure and hyper tension
effective in severe HTN, used in combination with nitrates
toxicity- headache, nausea, anorexia, palpitations, sweating, and flushing
minoxidil
Arterial circulation
Minoxidil sulfate- active metabolite
activates potassium channels–> hyperpolarization
used for HTN and heart failure
Toxicity- fluid and salt retention, CV effect and hypertrichosis
diazoxide
arterial circulation
activates K channels–> hyperpolarization
long acting, paternally administered
trt for: hypertensive emergencies and hypoglycemia secondary to insulinoma
Toxicity: hypotension and hyper glycemia
Ca channel blockers
toxicity
all have arterial dilatory effects but differ a little
Dihydropyridines- nifedipine, nicardipine, amlodipine
Phenylalkylamine- verapamil
Benzothiazepine- diltiazem
toxicity: Cardiac- bradycardia, AV block, cardiac arrest, and heart failure
Flushin, dizziness, nausea, constipation (verapamil) and peripheral edema
Ca channel blockers and vascular smooth muscle slecetivity
Dihydropyridines- stronger vascular effects than Cardiac effects than verapamil and diltiazem
Nicardipine- cerebral vasospasm and infarct during stroke, IV admin
Verapamil- intra-arterially administered for stroke (no cerebral affinity like nicardipine)
phosphodiesterase 3 inhibitors
milrinone and inamrinone
PDE3 inhibtion -> increase in intracellular cAMP–> PKA phosphorylation–> activates cardiac Ca channel and vascular smooth muscle K channels
positive cardiac ionotropic and vasodilator effects
used for short term heart failure IV admin
Toxicity- arrhythmias, headache, thrombocytopenia
phosphodiesterase 5 inhibitors
sildenafil, tadalafil (TADA! viagra and cialis)
PDE5 inhibition–> increase intracellular cGMP–> PKG phosphorylation
Used for erectile dysfunction and pulm HTN-> relax non vascular smooth muscle of corpora cavernosa–> inflow of blood
Toxicity- adverse effects w/ nitrates, color vision for sildenafil
fenoldopam
Dopamine D agonist
dilation of peripheral arteries and natriuresis
HTN emergencies and postop HTN-iv
Toxicity- reflex tachycardia, headach, flushing, increase intraocular pressure (cont indicated in pt w/ glaucoma)
prazosin
a-adrenergic blocker
Arterial and venous dilatior
HTN
Toxicity- reflex tachycardia, dizziness, headache
first dose orthostatic hypotension
atosiban
Oxytocin receptor antagonist- prevents preterm labor
misoprostol and alprostidl
PGE1 analog
misoprostol: stimulates uterine contractions and prevents postpartum hemmorage
Alprosidil: smooth muscle relaxant, keeps PDA open, injectable erectile dysfunction
oxytocin
uterine contraction
Ergonovine
uterine contraction
dose dependent contractions, more sensitive in late term pregnancy
metoclopramide
dopamine D2 antagonist, increases smooth muscle stimulation of upper GIT, and opens sphincter
no effects on small intestine and down
Inhibits D2 receptors in medulla–> anitemetic
used for GERD, gastric emptying, emesis
Toxicity- restlessness, drowsiness, insomina, anxiety, agitation
bethanechol
muscarinic agonist
long duration use for xerostomia, UT retention, expulsion of urine
erythromycin
stimulate motilin receptors on GIT, promote onset of migrating motor complex
IV injection for gastroperisis, (can develop tolerance)
Upper GIT hemorrage treatment
albuterol, pirbuterol, terbutaline, salmeterol, formoterol
B2 receptor antagonist for bronchodilation
Ipratropium, tiotropium
Anti cholinergic for bronchodilation
theophylline and aminophylline
bronchodilators, asthma and COPD
Theophylline- nonselective PDE inhibitor, adenosine antagonist, increases release of IL10 (antiinflammatory)
narrow therapeutc index
epoprostenol, iloprost
PGI2 analog- treatment for HTN in lung
IV and inhalation
Epo has a short half life- continuous half life
Ilo has a little longer frequent inhalations
Toxicity- flushing, headache, hypotension, nausea and diarrhea
bosentan
ETa receptor antagonist
reduces primary pulmonary HTN, IV and inhaled
Ambrisentan- orally active only ETa (ETb- dialates)
toxicity- liver toxicity, anemia, headaches, peripheral edema
