L10 Stimulants and Muscle Relaxers

Question 1

Where does Baclofen act? What does it do?

Answer 1

Agonist of GABAb receptors (not GABAa), linked to Gi that decreases cAMP which inhibits presynaptic Ca++ terminals and opens post synaptic K+ channels (hyperpolarizes to decrease muscle firing).

Also inhibits pain by releasing substance P in spinal cord.

Used in chronic spasticity

Question 2

Kinetics and side effects of baclofen

Answer 2

complete, rapid absorption when taken orally

plasma t1/2 of 3-4h

Intrathecal administration can reduce peripheral side effects.

side effects: drowsiness, muscle weakness, may increase seizure activity in epileptics.

Question 3

Which benzo is used as a muscle relaxer?

Answer 3

Valium, at doses high enough to cause sedation.

Acts on GABAa receptors in spinal cord to treat local muscle trauma.

Question 4

Which muscle relaxer is an a2 agonist?

Uses?

Side effects?

Answer 4

Tinanidine (Zanaflex), analogue of clonidine.

Used in chronic and acute muscle spasms

causes significant sedation

may produce significant hypotension if combined with antihypertensive drugs (careful with elderly)

also causes drowsiness, sedation, dry mouth, muscle weakness

Question 5

Which sedative muscle relaxer might cause confusion and visual hallucinations?

What type of activity does it produce?

What drug type is it structurally similar to?

Answer 5

Cyclobenzaprine (flexeril)

Structurally similar to the tricyclic antidepressants, and has anticholinergic activity

Used for temporary relief of muscle spasms

Question 6

The metabolite of which muscle relaxer acts similarly to barbituates?

Answer 6

Carisoprodol (Soma) is metabolized to meprobamate which acts similarly to barbiturates and has addiction potential.

Drug of abuse

Don’t give to recovering alcoholics

Induces hepatic microsomal enzymes like barbituates do

Question 7

Which muscle relaxer is used to treat malignant hyperthermia and neuroleptic malignant syndrome?

Where does it act?

Answer 7

Dantrolene acts in the muscle and interferes with Ca++ release from the sarcoplasmic reticulum to prevent muscle contraction.

Greater effect on rapidly contracting (skeletal) muscle than cardiac or smooth muscle.

Malignant hyperthermia may be induced by anesthetics.

Antipsychotic induced neuroleptic malignant syndrome is also treated with dantrolene.

Question 8

Which muscle relaxer inhibits ACh release, how?

Uses?

Answer 8

Botulinum toxin inhibits ACh release by degrading the fusion proteins, toxic in large concentration.

Used for muscle spasms and neurological problems, treats sweaty palms, Local shots

Used non medically to reduce wrinkles.

Can regenerate nerves in places you don’t want

Question 9

Which GABA analogous are used as muscle relaxers?

Answer 9

Gabapentin and pregabalin

Bind to and blocks presynaptic N-type Ca++ channels to prevent neuropathic pain and spasticity.

Pregabalin is approved for fibromyalgia.

Both used in TMJ pain.

Excreted by kidney, no drug interactions.

side effects are sleepiness, ataxia, headache

Question 10

What are the peripheral effects of amphetamine/amphetamine like drugs?

Central effects?

Side effects?

Answer 10

They are sypmpathomimetic (mimic NE) and increase heart rate and blood pressure.

Centrally cause euphoria, alertness, reduced fatigue, increased energy, decreased appetite

side effects: anxiety, insomnia, irritability, psychosis

High abuse potential

Question 11

Mechanism of amphetamines

Answer 11

Amphetamines reverse dopamine transporters to continuously release dopamine, cocaine inhibits the reuptake of dopamine

Not specific, also effects NE peripherally

Question 12

Amphetamine low dose effects:

Answer 12

Increased blood pressure, slowed heart rate (reflex bradycardia), bronchial relaxation

Euphoria and excitement

Increased alertness, wakefulness and reduced fatigue

Loss of appetite

Increased motor and speech activity

Question 13

Amphetamine moderate dose effects:

Answer 13

All low dose effects plus:

stimulation of respiration

slight tremor

greater increase in motor activity, restlessness and agitation

Question 14

Amphetamine high dose effects:

Answer 14

All low and moderate dose effects plus:

continual, purposeless, repetitive tasks

severe anorexia and weight loss

paranoia, delusions, hallucinations

sudden outbursts of aggression and violence

behavioral fixations/behavioral repetition: counting corn flakes, tiles on the ceiling

Amphetamine Psychosis - paranoia, delusions, hallucinations, violence, mood swings

Question 15

Why are amphetamines dangerous?

Answer 15

The dopamine feels good in the mesolimbic reward system. EUPHORIA

High abuse potential, they change the setpoint for dopamine and NE in the brain.

Tolerance develops rapidly so more and more is needed to feel normal or high

Withdrawals are less dangerous than CNS depressants but can produce depression/suicidal thoughts

Antipsychotics can be used during detox

Question 16

Besides the amphetamines what drugs are used for narcolepsy?

Answer 16

Modafinil (Provigil) and armodafinil (Nuvigil), the R-enantiomer of modafinil, increase glutamatergic transmission in thalamus and hippocampus.

less likely to cause addiction, don’t promote weight loss, no withdrawal symptoms

side effects include headache, nausea and vomiting, nervousness, anxiety, and insomnia; combination with other stimulants may cause nervousness, irritability, insomnia, or cardiac arrhythmias

Question 17

What is targeted in the treatment of ADD and ADHD?

Answer 17

Increasing dopamine and NE in the prefrontal cortext.

If DA and NE are too low, they may fail to modulate GABAergic and glutamatergic transmission appropriately.

Modest increases in DA and/or NE appear to improve the “tuning” in this area, whereas higher levels may make symptoms worse or cause hyperactivity and impulsivity to occur.

Question 18

What drugs are used to treat ADD/ADHD?

Answer 18

Methylphenidate (Ritalin®) is commonly used, short t1/2

Longer acting preparations, such as ConcertaTM, have been developed to address this problem. There is also a transdermal patch available.

Pemoline (Cylert) = longer t1/2, less effective, less abuse

Amphetamine (Adderall) and d-amphetamine (Dexedrine), used occasionally, by people without a prescription (not pointing fingers) because if you’re wearing a onesie and you’ve already smoked, drank, and taken xanax, you might as well pop an adderall so you don’t pass out in your onesie on your deck with your ta-tas hanging out.

Question 19

What non amphetamine-like drug is approved for ADHD treatment?

Answer 19

Atomoxetine (Strattera) is a selective norepinephrine reuptake inhibitor (SNRI) approved for attention-deficit hyperactivity disorder.

Cardiovascular effects of beta-agonists, such as increased heart rate and blood pressure,
are potentiated by atomoxetine. Should also not be used with vasopressors such as epinephrine, midodrine, norepinephrine or phenylephrine due to increases in blood pressure.

Use with MAOIs is contraindicated.

Safe age 6 and older

Common adverse effects are nausea, vomiting, anorexia, and dizziness

Question 20

What stimulants are used to treat obesity?

Answer 20

Amphetamine-like drugs no longer used because of side effects.

New Drugs used:

naltrexone/bupropion (Contrave)
- Reduces craving, side effect of anxiety

phentermine/topiramate (Qysmia)
- causes cognitive impairmant, has serotonin effects

Lorcaserin (Belviq)

• 5HT-2c agonist, hope that it will cause weight loss without other serotenergic side effects
• only 3% weightloss shown

Question 21

What is caffeine’s mechanism?

Answer 21

Blocks adenosine receptors in the CNS and also increases cAMP by inhibiting its metabolism by phosphodiesterase.

Adenosine causes sedation, dilates cerebral and coronary blood vessels, causes some bronchospasm, and may decrease the release of many neurotransmitters.

Caffeine will inhibit these effects of adenosine.

Rapidly absorbed orally, and has a short half life

Question 22

What are the effects of caffeine?

Answer 22

 Effects include increased mental alertness, faster and clearer thought, wakefulness, restlessness
 Slight stimulant action on the heart, increases cardiac contractility and dilates coronary arteries – may trigger cardiac arrhythmias in susceptible people
 Constricts cerebral blood vessels- effective in treating headache
 Moderate bronchodilation
 Increased secretion of gastric acid (may aggravate ulcers)
 Diuresis (increased renal blood flow and decreased ADH secretion)

 Moderate consumption has health benefits.
 Very large doses, 5-10 cups of coffee per day, can cause anxiety, insomnia, and mood
changes, including psychosis. Those with a history of panic attacks are especially sensitive.
 Peripheral effects are tachycardia, hypertension, cardiac arrhythmias and GI disturbances.
 Some tolerance and dependence is seen with caffeine.
 Withdrawal syndrome includes headache, drowsiness, fatigue, and bad mood.

Question 23

Why are energy drinks dangerous?

Answer 23

Too much awesome can kill you.

Or it might be that guarana is similar to amphetamine, taurine effects aren’t known and they have too much caffeine.

Also people combine them with alcohol.