Module 3: Neurologic and Neuromuscular Drugs

Question 1

Types of Skeletal muscle relaxants

Answer 1

• Centrally acting: through CNS

- Direct-acting: on muscle

Question 2

Types of Neuromuscular blocking drugs

Answer 2

• Non-depolarizing

- Depolarizing

Question 3

Types of Anti-parkingsonian drugs

Answer 3

• Anti-cholinergic
• Dopaminergic
• COMT inhibitors

Question 4

Anti-migraine drugs

Answer 4

• 5-HT1-receptor agonists (triptans)

- Ergotamine preparations

Question 5

Skeletal Muscle Relaxants work to?

Name and describe the 2 Classes:
-Centrally acting?

-Direct-acting?

Answer 5

Relieve musculoskeletal pain, spasm, spasticity

• Act as CNS depressants (diazepam, baclofen, cyclobenzaprine)
• produce muscle weakness (dantrolene)

Question 6

Centrally Acting
-Mechanism?

-Adverse Effects

Answer 6

• unknown; don’t directly relax skeletal muscle or depress neuronal conduction; are CNS depressants (sedatives, anti-anxiolytics ((antianxiety))
• physical, psychological dependence; withdrawl symptoms

Question 7

Direct-acting

Drantrolene is the?

Mechanism:

Answer 7

• most commonly used
• interferes with calcium ions involved in skeletal muscle contraction➡muscle relaxation/ weakness; little effect on cardiac, smooth muscle

Question 8

Neuromuscular Blocking Drugs do what?

Name and describe the two classes:

• Non-depolarizing:
• Depolarizing:

Answer 8

• relax skeletal muscles by disrupting transmission of nerve impulses at motor end plate
• derived from curare alkaloids [atracurium, mivacurium, tubocurarine]
• [succinylcholine]

Question 9

A Motor End Plate is?

Answer 9

a terminal nerve ending that innervates muscle (instead of another nerve). Nerve impulse releases acetylcholine (ACH) into synaptic cleft to bind receptors on adjacent MUSCLE.

Question 10

Non-depolarizing blocking
-Derived from?

-Compete with acetylcholine ➡ muscle contracted prevented➡

Antidote:

Answer 10

• curare alkaloids (South American Indians used on arrow tips; paralyzes diaphragm (can’t breath, die)
• prolonged muscle relaxation…but…doesn’t cross blood-brain barrier….so remain conscious, can feel pain, just paralyzed
• anti-cholinesterase drugs [neostigmine, pyridostigmine]

Question 11

Adverse side effects of Non-depolarizing blocking

Answer 11

-non-depolarizing blockers adverse effects
apnea
hypotension
skin reactions
bronchospasm
excessive bronchial/salivary secretions

Question 12

Depolarizing Blocking
-act like acetylcholine, but not 4

• Succinylcholine:
• Adverse Effects:

Answer 12

• but not inactivated by cholinesterase
• Only therapeutic drug in this class; metabolized slower than acetylcholine➡ longer muscle paralysis
• prolonged apnea, hypotension; genetic prediposition increases risk.

Question 13

Anti-Parkinsonian Drugs:

Parkinson’s disease:

Therapy:
-Anti-cholinergic inhibit?

-Dopaminergics: enhance?

Answer 13

• dopamine deficiency, acetylcholine excess ➡ movement disorders (muscle rigidity, akinesia, temors at rest, posture/balance disturbances)
• inhibit cholinergic effects (movement disorders) [benztropine, diphenhydramine]
• enhance dopamine effects 9sustain motor activity) [levodopa, carbidopaomocriptine, amantadine]

Question 14

Parkinson’s drugs

• Anti-cholinergic(parasympatholytic) drugs inhibit?
• High acetylcholine excites?
• Adverse Effects

Answer 14

• inhibit acetylcholine action at parasympathetic receptors
• CNS causing parkinsonian termor
• confusion, restlessness, agitation and excitement, drowsiness and insomnia, tachycardia and palpitations, constipation, nausea, vomiting, urine retention, increased intraocular pressure, blurred vision, pupil dilation, photophobia

Question 15

Parkinson’s drugs: dopaminergic drugs

• Dopaminergic drugs:
• Levodopa:
• Carbidopa:

Answer 15

• act in brain to improve motor function
• inactive until crosses blood-brain-barrier and converted to dopamine
• enhances levodopa’s effectiveness by blocking peripheral conversion, increasing amount into brain.

Question 16

Dopaminergic adverse evects [levodopa]

Answer 16

• nausea, vomiting
• orthostatic hypotension
• anorexia
• neuroleptic malignant syndrome
• arrhythmias
• irritability
• confuseion

Question 17

COMT Inhibitors

COMT =

-Used as?

Adverse effects:

Liver function test required?

Answer 17

=Catechol-O-methyltransferase

• used as adjuncts to levodopa-carbidopa therapy in Parkinson patients who experience “wearing-off” symptoms at end of dosing interval
• Life-threatening acute liver failure; rapid withdrawl may lead to parkinsonian crisis
• Liver function test required every 2 weeks for 1st year, tapering thereafter.

Question 18

Anti-convulsant drugs:

Major drug names:

• phenytoin:
• phenobarbital:
• carbamazepine
• clonazepam, diazepam:
• valproate:
• Gabapentin:
• Topiramate:

Answer 18

Inhibit neuromuscular transmission; prescribed for epilepsy, seizures; numerous adverse effects

• phenytoin is a hydantoin, stabilizes nerves from over-excitement. Used to control seizures, called anticonvulsants, used after surgery to the brain or nervous system. Decreases abnormal electrical activity in the brain
• phenobarbital is a barbiturate, elevates seizure threshold by decreasing post-synaptic excitation. treats insomnia and sedating antianxiety drug.
• carbamazepine is an iminostilbene, inhibits neuromuscular transmission. treats seizures. is an anticonvulsant anti-epileptic drug
• clonazepam is a benzodiazepine, safest, fewest side effects, has sedative pro[erties
• valproate is a carboxylic acid derivative, thought to increase GABA (an inhibiory neurotransmitter). treats epilepsy and bipolar disorder and to prevent migraine headaches.
• Gabapentin is an analogue of GABA; mechanism unknown. treat partial seizures, neuropathic pain, hot flashes, and restless legs syndrome.
• topiramate thought to block voltage-dependent sodium channels, enhancing activity of GABA receptors and antagonizing glutamate receptors. control seizures, prevent migraine headache once occurs, off label to treat bulimia

Question 19

Anti-Migraine Drugs

2 types of treatment:

• Abortive:
• Prevention:

2 classes:
-5-HT1 -receptor agonists (triptans):

-Ergotamine preparations:

Answer 19

• Abortive are for after migraine starts to relieve pain
• Prevention are before migraines start
• constrict ranial vessels, inhibit neuropeptide release, reduce neurogenic inflammatory process
• less selective for 5-HT receptors; block neurogenic inflammation; effectivness increased with coffee [ergotamine]

Question 20

Triptans

• Contraindications:
• Safety?

Many?

Answer 20

• not for use in patients with ischemic heart disease (angina, myocardial infarction), cerebro-vascular syndromes (stroke), coronary artery disease (hypertension, smoking, obesity, hypercholesterolemia, diabetes)
• safety of treating 3+ migraines in 30-day period not established
• Many drug interactions