Spasmolytic

Question 1

Progabide

Answer 1

is a GABAA and GABAB agonist and has activve metabolites, including GABA itself

Question 2

Glycine

Answer 2

Another inhibitory amino acid neurotransmitter that posesses pharmacologic activity when given orally and readily passes the blood brain barrier

Question 3

Cyclobenzaprine

Answer 3

Similar to amitriptyloine in chemical structure. Some of its effects are similar to the tricyclic antidepressants including activity, potentiation of norepinephrine, and antagonism of reserpine

Causes a great deal of sedation, confusion, and can cause visual hallucinactions due to antimuscaneric effects, also releases histamine

Relieves muscle spasms through a central action, possibly at the brain stem level

No direct action on the neuromuscular junction or the muscle

other similar agents: carisoprodol, chlorphenesin, metaxolone, methocarbamol, orphenadrine

Question 4

Tizanidine

Answer 4

A central-acting alpha2-adrenergic agonist acts presynaptically and postsynaptic within the cord

Structurally and pharmacologically related to clonidine

Decreased the release of excitatory amino acids which in turn leads to inhibition of spinal motor neurons

Produces more drowsiness and sedation than baclophen

Not associated with the muscle weakness which may occur with baclophen therapy

effect on BP?

Question 5

Riluzole and Idrocilamide

Answer 5

Rolizole is a benzothiazole- inhibits glutamate transmisson and improves energy metabolism in muscles

Inhibits release of glutamate by interfering with sodium (Na+) channels required for glutamate release

for the treatment of amytrophic lateral sclerosis (ALS) and Huntingtons disease (HD). Reduces spasms.

The altered huntington protein is believed to interfere with aerobic respiration, cells must resort to anaerobic respiration, eventually leading to cell death

Riluzole extends survival and or time to tracheostomy

Side effects: Asthenia, decreased lung function, pneumonia, veertigo, paresthesia, anorexia, and somnolence

Question 6

Direct acting spasmolytics

Answer 6

• Dantrolene (Ryanodex)
• Botulinum toxin type b (Myobloc)
• Abobotulinum toxin type a (Dysport)

Question 7

Centrally acting spasmolytics

Answer 7

• Diazepam (Valium)
• Baclofen (Lioresal)
• Cyclobenzaprine (Flexeril)
• Riluzole (Rilutek)
• Tizanidine (Zanaflex)

Question 8

Dantrolene

Answer 8

• Directly interferes with calcium ion release from sarcoplasmic reticulum within skeletal muscle cells → uncouples the excitation contraction process
• use for: malignant hypperthermia (a rare autosomal dominant disease precipitated by use of neuromuscular blocking agents)

Question 9

Botulinum Toxins (A=Botox, Dysport and Xeomin; B=Myobloc)

Answer 9

• Cleaves SNARE complex proteins (SNAP-25, synaptobrevin, syntaxin) requried for ACh vesicle fusion at neuromuscular junction
• Response is dose dependent (within 24-72 hrs, peak at 4-6 mo. lasts for 2-6 mo. Timeframe for collateral sprouting of axon)
• Produced by Clostridium botulinum
• Side effects: weakness, pain at injection site, infection, flu like syndrome, dysphagia with cervical injections, nerve injury, respiratory failure, antibody formation

Question 10

Baclofen

Answer 10

• GABA-B agonist that works at level of spinal cord to block polysynaptic afferent pathways and monosynaptic afferent pathways
• acts as inhibitory neurotransmitter itself or by hyerpolarizing the primary afferent nerve terminals which inhibits release of excitatory neurotransmitters (i.e. glutamate and aspartic acids)
• use for: spasticity, improve mobility in MS and other spinal cord lesions
• Intrathecal admin possible

Question 11

Gabapentin

Answer 11

centrally acting antiepileptic drug used in patients with MS

Question 12

Pregabalin

Answer 12

centrally acting analong of gabapentin