Pharmacology Of Motor System

Question 1

ACh as NT

Answer 1

. Major at neuromuscular junction
. Plays role in extrapyramidal motor system
. Nicotinic receptors
. Functionally coupled w/ cation (mainly Na) channels so that binding of ACh causes depolarization of m. Cell followed by release of Ca from SR and m. Contraction
. Action terminate through hydrolysis via acetylcholinesterase

Question 2

Drugs that enhance GABA

Answer 2

. Diazepam (Valium) and related drugs

. Causes muscle relaxation from enhancing in CNS it mostly at spinal level

Question 3

Aspartate (asp) and glutamate (Glu)

Answer 3

. Excitatory
. Implicated in some seizure disorders and neurodegenerative disease
. Antiepileptic drug felbamate blacks NMDA receptors where Glu normally acts

Question 4

Tubocurarine

Answer 4

. South American plant product
. Used to be used as dart poison
. Related clinically to drug pancuronium (pavulon)
. Competitive/ non-depolarizing neuromuscular blockers
. Compete with ACh for receptor binding site

Question 5

Succinylcholine

Answer 5

. Depolarizing neuromuscular blocker
. Initially causes transient stimulation of cholinergic receptors that is later followed by desensitization of receptors
. Called depolarizing neuromuscular blockade

Question 6

Neuromuscular blocking agent effects

Answer 6

. Total paralysis
. Provided for m. Relaxation during surgery
. Agents are quaternary salts that don’t cross BBB to provide paralysis w/o loss of consciousness (until respiratory arrest occurs)

Question 7

Acetylcholinesterase inhibitors

Answer 7

. Prevent hydrolysis of ACh to raise levels at synapse
. Inc. m. Tone and spasms at low dose
. At higher doses a depolarizing blockade can occur
.examples: Neostigmine and pyridostigme treat MG, insecticides and nerve gas (m. Spasms followed by paralysis from depolarizing blockade)
. Can have effects on ANS in overdose or poisoning situations

Question 8

Centrally acting muscle relaxants

Answer 8

. Act in spinal cord and brainstem to modify reflex arcs and dec. skeletal m.
. Include benzos and baclofen

Question 9

Benzodiazepines in CNS

Answer 9

. Enhance GABA effects
. Interact w/ separate site on Cl channel that GABA is normally coupled w/ to open
. When bound to its receptor the ability fo GABA to open Cl channels is greatly enhanced
. GABA and GABA receptors must be present for benzos to work
. Effective in treating m. Spasms

Question 10

Baclofen

Answer 10

. Muscle relaxant
. Analog of GABA that acts as agonist at certain types of GABA receptors (GABAb) to inhibit release of excitatory transmitters
. Inhibits spasmogenic reflexes
. Used in treating spasticity resulting from MS and spinal cord injuries
. Adverse effects: CNS depression, hallucinations, tremors, seizures, degree of dependence w/ chronic use

Question 11

Diazepam

Answer 11

. Valium
. Treats spasticity and m. Spasms
. Enhances presynaptic inhibition by facilitating actions to GABA in spinal cord

Question 12

Muscle relaxants that have centrally mediated m. Relaxants activity similar to diazepam but are less effective

Answer 12

. Cyclobenzapine 
. Carisoprodol (SOMA)
. Methocarbamol (ROBOXIN)
. Clorzoxazone (PARAFLEX)
. Orphenadrine (NORFLEX)
. Metaxalone (SKELAXIN)

Question 13

Direct acting muscle relaxants

Answer 13

. Inhibits the release of Ca from SR (dantrolene)
. Useful for some spasticity
. Used to treat malignant hyperthermia (caused by general anesthetic in genetically suspectale people causing m. Contracture and high body temp) and neuroleptic malignant syndrome (from antipsychotics)

Question 14

Convulsive stimulants

Answer 14

. Act in spinal cord to cause seizures
. Strychnine
. Tetanus toxin
. Treatments: symptomatic support and diazepam to control seizures

Question 15

Parkinson symptoms

Answer 15

. Tremor: resting, pill-rolling movement
. Muscular rigidity: cogwheel rigidity, masked facial expressions
. Bradykinesia, akinesia: slowed purposeful movement, difficulty in initiating or stopping movement
. Postural and gait defects: simian posture, downhill walk
. Autonomic disturbances (sweating, drooling, issues swallowing)
. Apathy, social withdrawal, cognitive impairment, and dementia

Question 16

Classifications of Parkinson’s

Answer 16

. Idiopathic
. Iatrogenic: drug-induced by antipsychotics
. Post-traumatic, post-encephalitic, or atherosclerotic

Question 17

Neurologic basis of Parkinson’s

Answer 17

. Altered dopamine-ACh balance in striatum causing deficiency of dopaminergic activity in relation to ACh
. Result from death of dopamine neurons in nigrostriatal dopamine pathway
. Iatrogenic: imbalance result from blockade of dopamine receptors

Question 18

MPTP

Answer 18

. Compound found in synthetic heroin used by people that suddenly developed Parkinson’s
. MPTP is metabolized into MPP+ by MAO-B
. MPP+ accumulates in and destroys nigrostriatial dopamine neurons
. Think that MPP+ or similar agents that are present in environment may be main causative factors in development of Parkinson’s

Question 19

Pharmacologic approaches to therapy

Answer 19

. Drugs alleviate symptoms by restoring dopamine-ACh balance
.drugs that enhance dopaminergic activity (l-DOPA, seligiline/deprenyl, entacapone)
. Drugs that stimulate postsynaptic dopamine receptors (bromocryptine/Parlodel) that are moderately effective
. Drugs that stimulate release of dopamine (amantadine/symmetrel) that are moderately effective
. Drugs that reduce cholinergic activity (muscarinic antagonist benztropine/cogentin)

Question 20

I-DOPA (larodopa)

Answer 20

. Dopamine precursor that is converted into dopamine

. Most effective drug for control of symptoms

Question 21

Seligiline/deprenyl/elderpryl

Answer 21

. Inhibits metabolism of dopamine by MAO-B

. May slow progression of disease possibly by bloacking conversion of MPTP to MPP+

Question 22

Entacapone/comtan

Answer 22

. Inhibits COMT and slows metabolism of dopamine near the synaptic cleft