DSA 34 Drugs for Motor Disease and Muscle Spasticity

Question 1

which drugs are used for dopamine replacement therapy?

Answer 1

levodopa, carbidopa

Question 2

which anti-Parkinson’s drugs are direct agonists?

Answer 2

pramipexole, ropinirole

Question 3

which anti-Parkinson’s drug is a COMT inhibitor?

Answer 3

entacapone

Question 4

which anti-Parkinson’s drugs are antimuscarinics?

Answer 4

biperiden, trihexyphenidyl, benztropine

Question 5

which anti-Parkinson’s drugs are MAO-B inhibitors?

Answer 5

selegiline, rasagiline

Question 6

what is the mechanism of action of amantidine?

Answer 6

increases dopamine availability by increasing dopamine release and decreasing dopamine reuptake

Question 7

which drugs used to treat myasthenia gravis are immunosuppressants?

Answer 7

azathioprine, cyclosporine, intravenous immunoglobulin

Question 8

which drugs used to treat myasthenia gravis are anticholinesterases?

Answer 8

pyridostigmine, neostigmine

Question 9

list the CNS spasmolytics.

Answer 9

baclofen, diazepam, tizanidine, riluzole, gabapentin, metaxalone

Question 10

what class of drug is dantrolene?

Answer 10

PNS spasmolytic

Question 11

which class of anti-Parkinson’s drugs primarily help with tremors but not bradykinesia?

Answer 11

anti-ACh agents

Question 12

what is thought to cause the symptoms of Parkinsonism?

Answer 12

loss of dopamine inhibition → cholinergic excitation → symptoms of Parkinsonism

Question 13

what primarily occurs in Huntington’s chorea?

Answer 13

GABAergic loss in the indirect pathway → loss of inhibition of thalamic activity

Question 14

fill in the blank: ACh __ (>/<) DA → Parkinson’s. akinesia, tremors, rigidity.

Answer 14

ACh > DA

Question 15

fill in the blank: ACh ___ DA (>/<) → Huntington’s. dyskinesia, choreiform movements

Answer 15

ACh < DA

Question 16

what is the intended target for drug therapy in Parkinsonism?

Answer 16

nigrostrial system

Question 17

what is the mechanism of action of antipsychotics? result of this action?

Answer 17

block DA receptors, can produce Parkinsonism and/or dystonias

Question 18

why is L-DOPA not initially used in the treatment of Parkinson’s?

Answer 18

it has about a 5 year window of effectiveness

Question 19

what is the typical strategy for the treatment of Parkinson’s?

Answer 19

start with MAO-B inhibitor and/or dopaminergic agonist

Question 20

what is the primary isoenzyme responsible for the degradation of DA in the striatum?

Answer 20

MAO-B

Question 21

what is a benefit of MAO-B inhibitors not affecting degradation of catecholamines in other brain regions or in the periphery?

Answer 21

little risk of hypertensive crisis due to accumulation of peripheral NE

Question 22

what causes insomnia as a side effect for MAO-B inhibitors?

Answer 22

amphetamine and methamphetamine metabolites

Question 23

identify: this drug’s best documented use is as an adjunctive agent to improve response to levodopa.

Answer 23

selegiline

Question 24

why should selegiline not be given to patients taking TCAs or SSRIs?

Answer 24

danger for serotonin syndrome (profound sympathetic activity with hyperthemia)

Question 25

why should non-selective MAOIs not be used in Parkinsonism?

Answer 25

would lead to hypertensive crisis when combined with L-DOPA therapy

Question 26

explain how dopamine agonists have nausea/vomiting as significant untoward effect.

Answer 26

they stimulate D2 receptors

Question 27

identify: dopamine agonist that affects D3 receptors.

Answer 27

pramipexole

Question 28

what is the mechanism of action of anticholinergics?

Answer 28

centrally-acting competitive inhibitors of muscarinic cholinergic receptors

Question 29

which symptom(s) of Parkinson's is not improved by anticholinergics?

Answer 29

bradykinesia

Question 30

what are classic side effects of anticholinergics?

Answer 30

dry mouth, urinary retention, constipation

Question 31

what are contraindications for the use of anticholinergic agents?

Answer 31

prostatic hyperplasia obstructive GI disease glaucoma

Question 32

identify: giving this class of drug will worsen dementia in patients with age- or Parkinson's-related dementia.

Answer 32

anticholinergics

Question 33

what are side effects of amantidine?

Answer 33

insomnia, restlessness, depression, GI disturbances, ataxia, livedo reticularis

Question 34

what are contraindications for amantidine?

Answer 34

seizures disorders, congestive heart failure

Question 35

explain the relationship between catecholamine neurons and L-DOPA.

Answer 35

L-DOPA can be converted to dopamine in catecholamine neurons via dopa decarboxylase

Question 36

why is therapy with L-DOPA necessary?

Answer 36

dopamine itself does not penetrate the CNS

Question 37

what is the function of carbidopa?

Answer 37

it does not cross the BBB. inhibits peripheral DA formation → allows levodopa dose to be lowered while increasing its availability to the CNS

Question 38

how is L-DOPA administered?

Answer 38

_always_ in combination with carbidopa

Question 39

what is the benefit of giving carbidopa with levodopa?

Answer 39

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

Question 40

what can be used to control the behavior disturbances induced by L-DOPA?

Answer 40

atypical antipsychotics (e.g. olanzapine)

Question 41

why can L-DOPA *not* be used with MAO-A inhibitors?

Answer 41

intense peripheral vascular effects of excess DA

Question 42

what are adverse effects of levodopa?

Answer 42

mood change, hallucinations, sleep disturbance, arrhythmia, N/V, dyskinesia

Question 43

what are 3 ways in which levodopa therapy can fail?

Answer 43

1. ) response fluctuations 2. ) end of dose failure 3. ) on-off phenomena

Question 44

what is the clinical benefit of COMT inhibitors?

Answer 44

the "capones" may smooth response to levodopa and may permit lowering of levodopa dose

Question 45

where is entacapone active?

Answer 45

only in the periphery

Question 46

what is the mechanism of action of azathioprine?

Answer 46

converted to mercaptopurine, interferes with purine nucleic acid metabolism

Question 47

what are the toxicities of azathioprine?

Answer 47

bone marrow suppression (leukopenia), GI signs (diarrhea, vomiting) typical of high dose

Question 48

what is the mechanism of action of cyclosporine?

Answer 48

inhibits production of helper T cells

Question 49

what are the toxicities of cyclosporine?

Answer 49

nephrotoxicity and hypertension

Question 50

what is the benefit of IV Ig over azathioprine or cyclosporine?

Answer 50

much faster than either, used for immediate improvement in MG patients

Question 51

what are side effects of IV Ig?

Answer 51

during: headache, muscle aches, chills post-infusion: fatigue, fever, nausea

Question 52

what is a main use of plasmapheresis?

Answer 52

relieve myasthenic crisis

Question 53

identify: these drugs are quarternary salts. as such, permanently charged and cross membranes very poorly.

Answer 53

pyridostigmine and neostigmine

Question 54

what are the benefits of quarternary salts as treatment for MG?

Answer 54

do not penetrate CNS → no intoxication/seizure problem penetrate ganglia poorly → little effects on blood pressure

Question 55

identify: when using these drugs, you *must* also use an antimuscarinic to block excess ACh in the parasympathetic nervous system.

Answer 55

anticholinesterases

Question 56

how does the tensilon test differentiate between myasthenic crisis (under dose of AChE) and cholinergic crisis (overdose of AChE)?

Answer 56

by adding short acting anticholinesterase, the situation will get better (patient was under dose) or worse (patient was overdosed)

Question 57

what is the mechanism of action of baclofen?

Answer 57

GABA-B receptor agonist → inhibits release of excitatory amino acids and substance P from IA neurons themselves

Question 58

when is baclofen more effective?

Answer 58

spinal injury and MS

Question 59

what are the untoward effects of baclofen?

Answer 59

drowsiness, lassitude, ataxia muscular weakness constipation, urinary retention

Question 60

fill in the blank: diazepam is not effective in the treatment of \_\_\_\_\_\_\_.

Answer 60

ALS

Question 61

what is the mechanism of action for diazepam?

Answer 61

increases GABAergic neurotransmission → enhanced presynaptic inhibition (internuncial neurons)

Question 62

how do GABA-B receptors cause hyperpolization?

Answer 62

stimulation of GABA-B receptors increases K⁺ conductance

Question 63

how do GABA-A receptors cause hyperpolarization?

Answer 63

excitation of GABA-A receptors increases Cl^- conductance

Question 64

identify: this drug is particularly used in peripheral neuropathies for pain reduction.

Answer 64

gabapentin

Question 65

what is the mechanism of action for gabapentin?

Answer 65

increases GABA release

Question 66

what are the toxicities/contraindications for gabapentin?

Answer 66

somnolence, dizziness, ataxia, headache, tremor

Question 67

what drug has the same side effects as gabapentin?

Answer 67

metaxalone

Question 68

identify: this drug is marketed for the relief of muscle spasm.

Answer 68

metaxalone

Question 69

what adverse effects are seen with use of tizanidine?

Answer 69

alpha2 agonist effects → hypotension, drowsiness

Question 70

what are the adverse effects of riluzole?

Answer 70

GI hemorrhage, sepsis, convulsions, neoplasm

Question 71

what is the contraindication for riluzole?

Answer 71

lactation

Question 72

identify: this drug is a skeletal muscle relaxant that interferes with release of Ca²⁺ from SR.

Answer 72

dantrolene

Question 73

what are the uses for dantrolene?

Answer 73

cerebral spasticity (not ALS), malignant hyperthermia, external sphincter hypertonicity

Question 74

fill in the blank: avoid use of dantrolene in ______ patients

Answer 74

ambulatory--it causes muscle weakness

Question 75

in what other CNS area will anticholinergic treatment most likely produce significant unwanted effects?

Answer 75

hippocampus

Question 76

what are the criteria for beginning L-DOPA therapy?

Answer 76

age \>65 debilitating Parkinson's

Question 77

how does selegiline improve Parkinson's symptoms?

Answer 77

blocks DA metabolism presynaptically

Question 78

what is mechanism of action of ropinirole?

Answer 78

dopamine D2 receptor agonist

Question 79

what is the most likely untoward effect of trihexyphenidyl?

Answer 79

dry mouth

Question 80

selegiline or rasagiline are less likely than other drugs to enhance dietary effects of?

Answer 80

tyramine

Question 81

entacapone may be started with carbidopa/L-DOPA because?

Answer 81

reduces rate of metabolism of L-DOPA in the periphery → longer half-life and more even uptake of the L-DOPA

Question 82

to minimize unwanted side effects of pyridostigmine, it may be necessary to also administer?

Answer 82

muscarinic antagonist

Question 83

mechanism by which anticholinesterases cause worsening of muscle strength in cholinergic crisis?

Answer 83

excess ACh binding at nicotinic receptors