Muscle Spasticity

Question 1

What are the drugs used for muscle spasticity?

Answer 1

Tizanidine (covered in Muscle relaxers), Baclofen, Dantrolene, and Botulinum Toxin

Question 2

What is Baclofen used for?

Answer 2

Oral; MS, spasm, spasticity, spinal cord trauma

Question 3

Baclofen MOA?

Answer 3

Complex: acts as GABAb agonist at multiple levels in spinal cord, producing inhibitory signals or hyperpolarizing and reducing excitatory pathways (aspartate and glutamate)

Question 4

What is pain relief provided by with Baclofen?

Answer 4

By inhibition of supstance P action

Question 5

What happens in high doses of Baclofen? What does this mean?

Answer 5

Sedation, not as effectively as Diazepam; some drug activity is derived from supraspinal actions

Question 6

Baclofen Met/elim?

Answer 6

Orally active and renal slim; renal failure = accumulation with encephalopathy, seizures, resp depression, and abdominal pain from tox

Question 7

Baclofen ADEs?

Answer 7

Abrupt discontinuation should be avoided (Leads to BBW rebound CNS AE’s like seizures, confusion, hallucination, and psychosis)/(increased spasticity leading to rhabdo = organ failure = death) so taper for at least 2 weeks. Additive CNS depression and Hypotension, increase blood glucose, drowsiness (MCADE), asthenia, confusion, dizziness, fatigue, headache

Question 8

Dantrolene uses?

Answer 8

Oral/IV (IV with surfactant and water, very alkaline = thrombophlebitis), Need for reconstitution delays immediate use. Indicated for spasticity, MS, neuroleptic malignant syndrome, and Malignant Hyperthermia (combine with CCBs)

Question 9

Dantrolene MOA?

Answer 9

Inhibits Ryanodine Receptors on SR so no Ca2+ release even with T-tubule excitation; It has little effect on cardiac or smooth muscle at skeletal muscle relaxation doses

Question 10

Dantrolene met/elim?

Answer 10

Hepatic met, crosses placenta and causes floppy child syndrome during C-section

Question 11

Dantrolene ADE’s?

Answer 11

Hepatitis (maybe), additive CNS depression, muscle weakness, IV Dantrolene w/ CCBs for malignant hyperthermia = VFib and HF

Question 12

Dantrolene monitoring?

Answer 12

LFTs

Question 13

Botulinum Toxin derived from?

Answer 13

Clostridium Botulinum

Question 14

Botulinum Toxin MOA?

Answer 14

Heave chain binds cell membrane => endocytosed => light chain cleaves Snare protein SNAP25 so Ach vesicle can no longer fuse; blocks pain neuropeptides

Question 15

How can Botulinum Toxin be overcome?

Answer 15

New nerve endings sprout and re-establish connection

Question 16

What does Botulinum Toxin cause?

Answer 16

Injection causes block of muscarinic and nicotinic receptors and causes muscular relaxation = wrinkles

Question 17

What has BT been approved for in regards to the head?

Answer 17

Migraines

Question 18

BT ADEs?

Answer 18

BBW can cause systemic botulism (systemic paralysis w/ respiratory arrest/death). Typical anticholinergic ADEs (SLUDGEBBB opposites)