pharm stroke and spasticity
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glutamate antagonists do what?
block glutamate receptors to attenuate the neuronal damage caused by anoxia
CPP, AP-5, AP-7, PCP, MK-801
clot dissolving drug - name?
tissue plasminogen activator (TPA)
tissue plasminogen activator does what?
- dissolves clots
- good bc 80% of strokes are 2/2 blood clots
when should tissue plasminogen activator be given?
asap, or within 3 hours of onset
Ca++ channel blocking drugs - block what type of channel, and this leads to what? treats what?
treats stroke: block L-type channels so calcium can't enter the vascular smooth muscle --> less actin-myosin interaction --> vasodilation
(these drugs aren't as effective on T and N-type calcium channels)
- diltiazem and nifedipine treat angina and stroke bc by decreasing Ca++ they decrease contraction and O2 demand and alter conduction of electricity
- dantrolene limits spasticity by reducing muscle contraction
- verapamil and digitalis treat supraventricular arrhythmia
- decrease BP (no drug name)
diltiazem - type of drug? effect?
- a calcium channel blocker
- vasodilate coronary and periph vessels
- depresses electrical conduction in SA AV nodes --> bradycardia
nifedipine - type of drug? use in stroke?
- calcium channel blocker
- dilate coronary and periph vessels w/o affecting heart excitability/contractibility (they don't impact cardiac striated muscle)
also used in angina
part of dihydropyridine class
PAF antagonists - do what 2 things?
- decrease levels of arachidonic acid
- postpone neuron death
why too much calcium, glutamate, or arachidonic acid are bad
Excessive Ca++ from the glutamate cascade will activate enzymes that degrade phospholipids, --> to arachidonic acid, which when metabolized gives rise to oxygen free radicals that destroy cell membranes
- Manages Ca flow through NMDA receptor, but narrow therapeutic window and can kill you
- so not used.
baclofen - acts where? does what?
- spinal cord
- inhibits release of excitatory neurotransmitters
5mg 3x/day up to 80 mg/day
baclofen side effects
lethargy, weakness, nausea, paraesthesias, SZ w sudden withdrawal
diazepam - drug type, why it helps in spasticity
- it's GABA agonistic, mostly at spinal cord --> inhibitory
2 mg 3x/day, increasing until effective
side effects of diazepam
sedation, dependence, cognitive impairment
dantrolene - for what? what does it do basically?
- muscle relaxant
dantrolene works where?
prevents Ca++ release at sarcoplasmic reticulum
(baclofen and diazepam operate at the spinal cord)
- 25 mg/day, then do it 2x/day, 3x, etc
- if not effective in 45 days, stop
dantrolene side effects
hepatotoxicity, sedation, weakness, dizzy, paresthesia, nausea, diarrhea
doesn't cause fatigue bc it works at muscle, not at CNS
clonidine used how?
in combo with other anti-spasticity drugs (lets you reduce the dose of another drug)
it reduces symp outflow
2 GABA agonists that limit spasticity
GABA = gamma-aminobuteric acid
tizanidine (zanaflex) - for what? how?
- Stimulate presynaptic polysynaptic inhibitory pathways.
- 1/10-1/50th the potency of Clonidine in lowering BP (approved for SC and MS)
dose 4-36 mg/day
tizanidine - side effects?
dry mouth, sleepy, asthenia (weakness), dizzy, increased spasm or tone
motor point blocks
- directed at NMJ
- used less than motor nerve blocks bc too many injections would be necessary for big muscles
- treats spasticity
nerve block for spasticity
directed at the notor nerve, while motor point blocks are directed at the NMJ
what's used to do a therapeutic nerve block?
first, an anesthetic agent. If it works, more permanenet motor point or nerv blocks can be performed with phenol and alcohol solution
botulinum toxin type A = botox
treats spasticity how?
- injection into muscle
- binds to presynaptic cholinergic nerve terminals inhibiting exocytosis of acetylcholine into NMJ
timing of nerve block and botox effects?
- blocks - immediate
- botox - in a few days - lasts months
surgery for spasticity
- selective dorsal rhizotomy for CP to sever the abnormal dorsal rootlet
- intrathecal baclofen pump
anesthetic agent used for nerve block
bupivacain hydrochloride (lasts a few hours)
diazepam vs diltiazem
- diazepam: GABA agonist - used in spasticity and SZ
- diltiazem: Ca++ blocker - dilates coronary and periph vessels - used in angina and stroke
2 antihypertensive / alpha 2 adrenergic agonist drugs to treat spasticity
- clonidine (catapres)
- tizanidine (zanaflex)
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