Muscle Relaxants

Question 1

Baclofen (lioresal)

Answer 1

GABAb agonist (GABAb linked to Gi and dec cAMP, inhibits presyn Ca and postsyn K-hyperpolarization). Used in chronic spasticity, may reduce pain by inhib sub P release, used for severe back pain and migraines. Rapidly/completely absorbed after oral admin, t1/2 of 3-4 hrs, intrathecal admin via pump is best. Tolerance occurs over months and dose may need to be inc. SE: drows, muscle wkns, inc seasure act in epilectics.

Question 2

Diazepam (valium)

Answer 2

Acts on GABAa in spinal cord to reduce spasticity. Dose required to reduce spasticity is significantly sedating, used for spasms assoc w/local muscle trauma, may also be used as adjunct tx in chronic muscle spasticity.

Question 3

Tizanidine (zanaflex)

Answer 3

Analogue of clonidine that reduces muscle spasm by acting as A2 agonist. Reinforces pre/postsyn inhibition in spinal cord and also inhibits pain tranmission in dorsal horn by stim A2. Used to reduce chronic muscle spaz due to spinal cord injury, useful in acute muscle spaz. Significantly sedating, hypotension if combined w/antihypertensives. SE: Drowsiness, hypotension, dry mouth, muscle wkns esp in elderly.

Question 4

Cyclobenzaprine (Flexeril)

Answer 4

Sedative at level of brain stem, structure similar to TCAs and has anticholinergic activity. Used for temp relief of acute muscle spaz caused by trauma or sprain. Significantly sedating and may produce confusion and transient visual hallucinations.

Question 5

Carisoprodol (Soma)

Answer 5

Metabolized rapidly to meprobamate (approved in 1955 for short term anxiety tx, acts similarly to benzos and has addiction potential). Carisoprodol is very popularly abused drug and is poor choice for recovering addicts/alcoholics. Induces hepatic microsomal enzymes.

Question 6

Dantrolene (Dantrium)

Answer 6

Does not act in CNS, affects excitation-contraction coupling in muscle-interferes w/release of Ca in sarcoplasmic reticulum. Rapidly contracting muscles more sensitive than contracting ones so there is little effect on cardiac or smooth muscle. Tx for malignant hyperthermia that is a result of general anesthetics w/NM blocking agents. Antipsychotics can produce similar rxn, neuroleptic malignant syn, which is tx w/dantrolene.

Question 7

Botulinum Toxin (Botox)

Answer 7

Blocks release of ACh from presyn nerves, toxic in large concentration, extremely small amts injected to control local muscle spaz due to neuro injury/stroke, injected intramuscularly/intradermally. Useful in many types of dystonias/muslce spaz, also may be injected to decrease sweating in palms, also promoted to remove wrinkles/lines.

Question 8

Gabapentin and Pregabalin

Answer 8

GABA analogues that act by binding to presyn N-type Ca channels. Blockade of these channels very effective in tx neuropathic pain, also effective for spaz in pts w/multiple sclerosis and other similar conditions. Pregabalin for fibromyalgia. Both used to tx TMJ pain, both excreted directly by kidney and have no drug interactions. SE: sleepiness, dizziness, ataxia, HA.

Question 9

Amphetamines and amphetamine-like drugs

Answer 9

Inhibit reuptake/incr release of NE and DA: inc HR, euphoria, alerness, reduced fatigue, inc energy, dec appetite. MOA: inhibit DAT of VMAT, brain particularly affected. Amphetamines have a very high abuse potential, physical dependence occurs readily, tolerance occurs rapidly.

Question 10

Methylphenidate (Ritalin)

Answer 10

Causes less CNS stimulation. Now being abused and combined with MDMA (ectasy). Used in Narcolepsy, ADHD. Short t1/2 so given in morning and lunch (insomnia if at night), can produce rebound in hyperactive behavior. Concerta is long acting version.

Question 11

Dextroamphetamine (Dexedrine)

Answer 11

CNS stimulant, used in narcolepsy

Question 12

Methamphetamine (Methedrine)

Answer 12

CNS stimulant, used in narcolepsy

Question 13

Modafinil (Provigil) and Armodafinil (Nuvigil)

Answer 13

Armodafinil is R-enantiomer of modafinal, both inc glutaminergic transmission in thalamus and hippocampus. Used in Narcolepsy. Less likely to cause addiction that d-amphetamine, do not promote wt loss, no withdrawal symptoms. SE: nervousness/anxiety/insomnia. When combined w/other stimulants may cause nervousness, irritabiltiy, insomnia, cardiac arrhythmias.

Question 14

Pemoline (Cylert)

Answer 14

CNS stimulant, used in ADHD, long t1/2 given once a day. Thought to be less effective but lower abuse potential. Can cause reversible liver damage.

Question 15

Amphetamine (Adderall) and d-amphetamine (Dexedrine)

Answer 15

CNS stimulants, used occasionally for ADAD, amphetamine has more cardiac effects but is approved for younger kids than methylphenidate.

Question 16

Atomoxetine (Strattera)

Answer 16

NE reuptake inhibitor used for ADHD. Cardiovascular effects of beta-agonists (inc HR/BP), don’t combine w/epinephrine, midodrine, NE, or phenylephrine. Don’t use with MAOI. Safe and effective in adolescents and children and adults.

Question 17

Caffeine

Answer 17

Blocks adenosine receptors in CNS and also inc cAMP by inhibiting its metabolism by PDE (adenosine is sedating, dilates cerebral aa, and coronary BVs). Rapidly absorved orally and has short t1/2. Inc mental alertnesss, faster and clearer thought, wakefulness, restlessness. Slight stimulant action on the heart-may cause arrhythmias in suscetible ppl. Constricts cerebral BVs-used to tx HA. Bronchodilation, inc gastric acid, diuresis. Some tolerance and dependence is seen.

Question 18

Guarana

Answer 18

combined w/caffeine in many energy drinks, may have similar effects but also may stim release of Ne and DA similar to amphetamine.