CNS Stimulants

Question 1

What are the three ways sympathomimetic stimulants can work?

Answer 1

1. increase release of NE and DA
2. Block NE and DA reuptake
3. Inhibit MAO

Question 2

What affects will sympathomimetrics have on respiration?

Answer 2

they will stimulate the medullary respiratory center and increase rate and depth

Question 3

What are the acute side effects of sympathomimetics?

Answer 3

basically exaggerated therapeutic effects:

headaches, arrhythmias, palpitations, anginal pain, hyperthermia, dizziness, agitation, confusion, insomnia, seizures and coma

Question 4

How do you treat an acute sympathetomimetic toxicity?

Answer 4

give an antipsychotic

acidify the patient’s urine

Question 5

What toxicity can develop with chromic amphetamine use?

Answer 5

amphtemine psychosis:

vivid hallucinations, paranoid delusions and compulsions

marked weight loss

Question 6

How long does it take for an amphetamine psychosis to resolve once you stop the drug?

Answer 6

7-10 days

Question 7

What will abrupt withdrawal of a sympathetomimetic cause?

Answer 7

craving for the drug, prolonged sleep, general fatigue, excessive eating and depression

Question 8

What are the 5 things we use sympathomimetics for?

Answer 8

ADHD

Narcolepsy

Chronic Fatigue

Weight loss

analeptic to reverse drug-induced depression (but we don’t do that anymore really)

Question 9

How is cocaine usually administered?

Answer 9

1. crystalline form (in hydrochloride salt) can be snorted
2. crystals can be dissolved and the base can be extracted with ether to then smoke
3. IV injection
4. indigenous populations chew the leaves and swallow saliva

Question 10

What is the potency of cocaine compared to amphetamine?

Answer 10

1 mg cocaine = 10 mg amphetamine

Question 11

What specific actions of cocaine causes the motor effects? The euphoria effects?

Answer 11

motor effects are from the blocked reuptake of NE

euphoria is from the blocked reuptake of dopamine

Question 12

How is MDMA derived from methamphetamine and why does it reach the brain more rapidly?

Answer 12

it has an addition of a methyl groups

this increases the lipophilicity, so it gains rapid entry into the brain

Question 13

What method of action does MDMA have that the amphetmaines dont?

Answer 13

it directly stimulates 5HT autoreceptors, stimulating the release of serotionin and inhibits its reuptake

(in addition to stimulating the release and inhibiting the reuptake of epinephrine, norepinephrine, and dopamine)

Question 14

What are the 3 xanthine stimulants we discussed?

Answer 14

caffeine

theobromide

theophylline

Question 15

What are the xanthine effects on the CNS in order of increasing dosage?

Answer 15

1. stimualtes cerebral cortex, so you have clearer flow of though, lower raction time and better idea associations. less fatigue and improved manual desterity in well learned tasks
2. Medullary centers affected next - stimulates respiration and vasomotor center
3. large dose will affect the spinal cord, leading to hyperreflexia

Question 16

What are the cardiac effects of the xanthines?

Answer 16

1. increased HR and increased force of cotnraction, leading to increased cardiac output
2. rapid (but transient) increase in CO for CHF patients (and diuresis)
3. arrhythmias
4. premature ventricular contractions

Question 17

What is the effect of xanthines on smooth muscle?

Answer 17

they’re smooth muscle relaxants

decreases peripheral resistance and increases cerebral fascular resistance - so may be useful for some headaches but can worsen others

Question 18

What is the proposed mechanism of action for the xanthines?

Answer 18

1. translocation of intracellular Ca2+ from sarcoplasmic reticulum
2. inhibition of phosphodiesterase, so elevated levels of cAMP
3. nonselective adenosine receptor antagonist, so inhibits sleepiness-inducing adenosine

Question 19

At what dose do you start to see cafeeine toxicity? About how many cups of coffee is this?

Answer 19

1 gm

about 80-100 cups of coffee for an average adult taken within a limited time frame

Question 20

What are the CNS toxicity symptoms for caffeine?

Answer 20

insomnia, excitement, mild delirium, sensory disturbances

followed by convulisons! Over 10 gm you get clonic convulsions and death!

Question 21

What is the toxic effect with caffeine on the GI system?

Answer 21

it increases gastric secretions

(even the decaffeinated coffee does this though)

Question 22

What are the THERAPEUTIC uses of caffeine?

Answer 22

cardiac stimulation in CHF (controversial)

paroxysmal dyspnea associated with left heart failures

analeptic

bronchial asthma

migraine (with ergot alkaloids)

Question 23

Do all caffeine users develop tolerance to the sleep-disrupting effects?

Answer 23

some do, but not all

Question 24

What are the caffeine withdrawal symptoms and how soon do they occur?

Answer 24

headache, irritability, inability to concentrate, drowsiness, insomnia, stomach pain, joint pain

may appear within 12 to 24 hours of stopping caffeine intake

Question 25

What are the clinical uses for modafinil and R-modafinil?

Answer 25

narcolepsy

shift work sleep disorder

excessive daytime sleepiness associated with obstructive sleep apnea