DSA 34 Drugs for Motor Disease and Muscle Spasticity Flashcards
which drugs are used for dopamine replacement therapy?
levodopa, carbidopa
which anti-Parkinson’s drugs are direct agonists?
pramipexole, ropinirole
which anti-Parkinson’s drug is a COMT inhibitor?
entacapone
which anti-Parkinson’s drugs are antimuscarinics?
biperiden, trihexyphenidyl, benztropine
which anti-Parkinson’s drugs are MAO-B inhibitors?
selegiline, rasagiline
what is the mechanism of action of amantidine?
increases dopamine availability by increasing dopamine release and decreasing dopamine reuptake
which drugs used to treat myasthenia gravis are immunosuppressants?
azathioprine, cyclosporine, intravenous immunoglobulin
which drugs used to treat myasthenia gravis are anticholinesterases?
pyridostigmine, neostigmine
list the CNS spasmolytics.
baclofen, diazepam, tizanidine, riluzole, gabapentin, metaxalone
what class of drug is dantrolene?
PNS spasmolytic
which class of anti-Parkinson’s drugs primarily help with tremors but not bradykinesia?
anti-ACh agents
what is thought to cause the symptoms of Parkinsonism?
loss of dopamine inhibition → cholinergic excitation → symptoms of Parkinsonism
what primarily occurs in Huntington’s chorea?
GABAergic loss in the indirect pathway → loss of inhibition of thalamic activity
fill in the blank: ACh __ (>/<) DA → Parkinson’s. akinesia, tremors, rigidity.
ACh > DA
fill in the blank: ACh ___ DA (>/<) → Huntington’s. dyskinesia, choreiform movements
ACh < DA
what is the intended target for drug therapy in Parkinsonism?
nigrostrial system
what is the mechanism of action of antipsychotics? result of this action?
block DA receptors, can produce Parkinsonism and/or dystonias
why is L-DOPA not initially used in the treatment of Parkinson’s?
it has about a 5 year window of effectiveness
what is the typical strategy for the treatment of Parkinson’s?
start with MAO-B inhibitor and/or dopaminergic agonist
what is the primary isoenzyme responsible for the degradation of DA in the striatum?
MAO-B
what is a benefit of MAO-B inhibitors not affecting degradation of catecholamines in other brain regions or in the periphery?
little risk of hypertensive crisis due to accumulation of peripheral NE
what causes insomnia as a side effect for MAO-B inhibitors?
amphetamine and methamphetamine metabolites
identify: this drug’s best documented use is as an adjunctive agent to improve response to levodopa.
selegiline
why should selegiline not be given to patients taking TCAs or SSRIs?
danger for serotonin syndrome (profound sympathetic activity with hyperthemia)
why should non-selective MAOIs not be used in Parkinsonism?
would lead to hypertensive crisis when combined with L-DOPA therapy
explain how dopamine agonists have nausea/vomiting as significant untoward effect.
they stimulate D2 receptors
identify: dopamine agonist that affects D3 receptors.
pramipexole
what is the mechanism of action of anticholinergics?
centrally-acting competitive inhibitors of muscarinic cholinergic receptors
which symptom(s) of Parkinson’s is not improved by anticholinergics?
bradykinesia
what are classic side effects of anticholinergics?
dry mouth, urinary retention, constipation
what are contraindications for the use of anticholinergic agents?
prostatic hyperplasia
obstructive GI disease
glaucoma
identify: giving this class of drug will worsen dementia in patients with age- or Parkinson’s-related dementia.
anticholinergics
what are side effects of amantidine?
insomnia, restlessness, depression, GI disturbances, ataxia, livedo reticularis
what are contraindications for amantidine?
seizures disorders, congestive heart failure
explain the relationship between catecholamine neurons and L-DOPA.
L-DOPA can be converted to dopamine in catecholamine neurons via dopa decarboxylase
why is therapy with L-DOPA necessary?
dopamine itself does not penetrate the CNS
what is the function of carbidopa?
it does not cross the BBB. inhibits peripheral DA formation → allows levodopa dose to be lowered while increasing its availability to the CNS
how is L-DOPA administered?
always in combination with carbidopa
what is the benefit of giving carbidopa with levodopa?
carbidopa gets into the peripheral system and blocks transformation of some of the L-DOPA into DA. this will then limit the side effects of levodopa
what can be used to control the behavior disturbances induced by L-DOPA?
atypical antipsychotics (e.g. olanzapine)
why can L-DOPA not be used with MAO-A inhibitors?
intense peripheral vascular effects of excess DA
what are adverse effects of levodopa?
mood change, hallucinations, sleep disturbance, arrhythmia, N/V, dyskinesia
what are 3 ways in which levodopa therapy can fail?
- ) response fluctuations
- ) end of dose failure
- ) on-off phenomena
what is the clinical benefit of COMT inhibitors?
the “capones” may smooth response to levodopa and may permit lowering of levodopa dose
where is entacapone active?
only in the periphery
what is the mechanism of action of azathioprine?
converted to mercaptopurine, interferes with purine nucleic acid metabolism
what are the toxicities of azathioprine?
bone marrow suppression (leukopenia), GI signs (diarrhea, vomiting) typical of high dose
what is the mechanism of action of cyclosporine?
inhibits production of helper T cells
what are the toxicities of cyclosporine?
nephrotoxicity and hypertension
what is the benefit of IV Ig over azathioprine or cyclosporine?
much faster than either, used for immediate improvement in MG patients
what are side effects of IV Ig?
during: headache, muscle aches, chills
post-infusion: fatigue, fever, nausea
what is a main use of plasmapheresis?
relieve myasthenic crisis
identify: these drugs are quarternary salts. as such, permanently charged and cross membranes very poorly.
pyridostigmine and neostigmine
what are the benefits of quarternary salts as treatment for MG?
do not penetrate CNS → no intoxication/seizure problem
penetrate ganglia poorly → little effects on blood pressure
identify: when using these drugs, you must also use an antimuscarinic to block excess ACh in the parasympathetic nervous system.
anticholinesterases
how does the tensilon test differentiate between myasthenic crisis (under dose of AChE) and cholinergic crisis (overdose of AChE)?
by adding short acting anticholinesterase, the situation will get better (patient was under dose) or worse (patient was overdosed)
what is the mechanism of action of baclofen?
GABA-B receptor agonist → inhibits release of excitatory amino acids and substance P from IA neurons themselves
when is baclofen more effective?
spinal injury and MS
what are the untoward effects of baclofen?
drowsiness, lassitude, ataxia
muscular weakness
constipation, urinary retention
fill in the blank: diazepam is not effective in the treatment of _______.
ALS
what is the mechanism of action for diazepam?
increases GABAergic neurotransmission → enhanced presynaptic inhibition (internuncial neurons)
how do GABA-B receptors cause hyperpolization?
stimulation of GABA-B receptors increases K+ conductance
how do GABA-A receptors cause hyperpolarization?
excitation of GABA-A receptors increases Cl- conductance
identify: this drug is particularly used in peripheral neuropathies for pain reduction.
gabapentin
what is the mechanism of action for gabapentin?
increases GABA release
what are the toxicities/contraindications for gabapentin?
somnolence, dizziness, ataxia, headache, tremor
what drug has the same side effects as gabapentin?
metaxalone
identify: this drug is marketed for the relief of muscle spasm.
metaxalone
what adverse effects are seen with use of tizanidine?
alpha2 agonist effects → hypotension, drowsiness
what are the adverse effects of riluzole?
GI hemorrhage, sepsis, convulsions, neoplasm
what is the contraindication for riluzole?
lactation
identify: this drug is a skeletal muscle relaxant that interferes with release of Ca2+ from SR.
dantrolene
what are the uses for dantrolene?
cerebral spasticity (not ALS), malignant hyperthermia, external sphincter hypertonicity
fill in the blank: avoid use of dantrolene in ______ patients
ambulatory–it causes muscle weakness
in what other CNS area will anticholinergic treatment most likely produce significant unwanted effects?
hippocampus
what are the criteria for beginning L-DOPA therapy?
age >65
debilitating Parkinson’s
how does selegiline improve Parkinson’s symptoms?
blocks DA metabolism presynaptically
what is mechanism of action of ropinirole?
dopamine D2 receptor agonist
what is the most likely untoward effect of trihexyphenidyl?
dry mouth
selegiline or rasagiline are less likely than other drugs to enhance dietary effects of?
tyramine
entacapone may be started with carbidopa/L-DOPA because?
reduces rate of metabolism of L-DOPA in the periphery → longer half-life and more even uptake of the L-DOPA
to minimize unwanted side effects of pyridostigmine, it may be necessary to also administer?
muscarinic antagonist
mechanism by which anticholinesterases cause worsening of muscle strength in cholinergic crisis?
excess ACh binding at nicotinic receptors
