Spasticity

Question 1

Activation of the GABAa receptors is inhibitory via an increase in ______ ______

Answer 1

chloride conductance (diazepam)

Question 2

Describe the two types of GABAb receptors and how they are inhibitory

Answer 2

1. Presynaptic receptors are inhibitory by mediating a decrease in Ca2+ conductance
2. Postsynaptic receptors are inhibitory by increasing K+ conductance when activated.

Baclofen

Question 3

Baclofen acts on which receptors:

Answer 3

GABA B (recall presynaptic Ca2+ and postsynaptic K+)

May also reduce substance P in the spinal cord

Question 4

Max dose of baclofen

Answer 4

80mg/day is FDAs recommended max. Up to 300mg/day have been reported.

Question 5

Diazepam acts on which receptors:

Answer 5

not substitute for GABA but rather facilitates GABA’s effects on the GABA A receptor (results in membrane hyperpolarization.

Increases chloride conductance.

Question 6

Overdose of valium can be treated with what

Answer 6

Flumazenil

Question 7

Dantrolene MOA

Answer 7

acts peripherally in the striated muscle by blocking the release of Ca2+ from the sarcoplasmic reticulum.

Fast twitch motor units are more sensitive that slow twitch

Question 8

Max dose dantrium

Answer 8

400mg/day

Question 9

Clonidine MOA

Answer 9

(AKA catapres)

Central acting alpha2-adrenergic agonist with effects in the locus ceruleus. In the spinal cord, provides presynaptic inhibition of sensory afferents.

Question 10

Clonidine can impair _____ tachycardia. What complication arises?

Answer 10

hypoglycemia-induced tachycardia in diabetics – thus delaying the diagnosis of clinically significant hypoglycemia in this population.

Question 11

Max dose clonidine

Answer 11

start with 0.05mg BID and increase up to 0.4mg/day

Question 12

Tizanidine MOA

Answer 12

Central acting Alpha-2 adrenergic agonist, chemically related to clonidine.

Binds to alpha 2 receptors both spinally and supraspinally.

thought to act by enhancing presynaptic inhibitory modulation of spinal reflexes.

Less potent than clonidine in regards to BP.

Question 13

Tizanidine is contraindicated with which IV medication? Why?

Answer 13

IV ciprofolxacin – due to inhibition of cytochrome P450

Question 14

Max dose tizanidine

Answer 14

36mg/day

Question 15

Cyproheptadine MOA

Answer 15

(Periactin) – nonselective histamine and serotonin antagonist. Some trial has demonstrated comparable anti-spasticity effects to baclofen and clonidine. Primarily used in SCI population.

Question 16

How do local anesthetics work during diagnostic nerve blocks

Answer 16

They work by blocking the voltage-gated sodium channels in the axon. This prevents depolarization of the axon membrane an interrupts transition of the signal along the axon.

Question 17

Chemoneurolysis agents:

How do they work?

Answer 17

Phenol, ethyl alcohol

Induce demyelination and axonal destruction via protein denaturation and axonal necrosis.

Question 18

Phenol: common concentrations used for chemoneurolysis?

Answer 18

2-7%

for chemical denervation, higher concentrations (>5%) are required.

The effects of this increased concentration are neurolytic due to axonal destruction, typically lasting >6 months.

Question 19

Ethyl Alcohol: common concentrations for chemoneurolysis?

Answer 19

45-100%

Less commonly used than phenol for neurolysis but is less toxic.

Question 20

What is the dose limit of phenol?

Answer 20

20-30mL of 5%.

8.5grams of phenol can be a lethal dose, causing convulsions, CNS depression, and cardiovascular collapse.

Patient can also get skin sloughing with phenol.

Question 21

How does all botox work (generally?)

Answer 21

all seven serotypes affect the NMJ where they produce denervation by blocking the presynaptic release (but not the production) of acetylcholine primarily at the terminal portion of the motor nerve.

Question 22

Name the 7 types of botox and which part of the snare complex they cleave

Answer 22

A,C,E: snap-25
B,D,F,G: synaptobrevin
C: also does syntaxin

Question 23

Botox should not be performed if patient is taking ____ or ____ abx

Answer 23

aminoglycoside or spectinomycin

Question 24

Initial safe dose of botox:

Answer 24

400U total or 6U/kg for an adult.

In kids, doses of 4-8U/kg are commonly used (400 units considered as max body dose)

Question 25

The ratio of baclofen concentration at the level of the spinal cord for intrathecally administered baclofen compared to orally administered baclofen is approximately:

Answer 25

100:1

Question 26

Typical starting dose for pump?

Answer 26

double the effective trial dose.

Question 27

____ may be given to reverse the respiratory depression caused by baclofen overdose

Answer 27

anticholinesterase physostigmine (2mg IV)