CNS Stimulants

• CNS effects: Paradoxical sedation or dysphoria; increased performance on
  simple tasks (not necessarily fewer errors); marked euphoric flash with IV
  injection.

• MOA: Indirect thru inhibition of epinephrine and dopamine uptake;
  release of catecholamines (newly synthesized pool, alpha-methyltyrosine
  blocks amphetamine action, but reserpine does not); inhibition of MAO
  (weak); direct stimulation of 5-HT receptors.




• Therapeutic applications: ADD/ADHD (great majority show no tolerance
  to therapeutic effect); treatment of obesity (stimulation of lateral
  hypothalamic center, tolerance develops in 6-8 weeks); narcolepsy;
  antidepressant.

  
  

• Side effects: Insomnia and anorexia are most common (tolerance
  develops); growth-suppressing effect is seen early in treatment
  (dose-dependent, no deficit in adult stature); may exacerbate
  pre-existing psychoses.

• Contraindications: Tourette’s syndrome; glaucoma.




• Pharmacokinetics: Weak base; excretion enhanced by urinary
  acidification; amphetamine is resistant to metabolism my MAO and
  COMT; solid form of methamphetamine (ice/crystal) can be smoked.
  

  
  

• Toxicity: Tachycardia, hypertension, arrhythmias,
  hyperthermia, convulsions, coma; treatment is haloperidol for
  psychosis, beta blockers for hypertension, beta blockers for cardiac
  effects, diazepam for agitation, acidification of urine,
  cooling; tolerance may occur during spree; toxic psychosis
  occurs frequently with no tolerance development to this
  effect; methamphetamine is known to lesion brain 5-HT and DA
  receptors; psychosis marked by continuous touching of the fact
  and extremities (bruxism) and marked aggressiveness;
  withdrawal may be helped with TCAs.
  

  
  

• Methylphenidate (Ritalin) – Produces same effects as
  amphetamine with less peripheral action; inhibits metabolism
  of many drugs (including TCAs)
  

  
  

• Premoline – Effects similar to amphetamine; produced by
  enhancement of central actions of catecholamines; not a
  first-line therapy (liver problems).
  

  
  

• Cocaine – Inhibits catecholamine uptake by the nerve
  terminal with no increase in release in CNS. Mixture of
  cocaine, amphetamine, and an opioid is known as a
  speedball. Crack is almost pure cocaine mixed with
  baking soda and ether.
  

  
  



• Acute intoxication: Cardiac effects, seizures,
  hyperpyrexia, hallucinations, rhabdomyolosis, and
  paranoid psychosis occur. Death is generally from
  seizures and respiratory depression, but v-fib and
  hyperthermia are also causes. Treatment is similar
  to amphetamine treatment w/o use of -blockers. IV
  nitroprusside used to control hypertension.
  

  
  

• Abuse and dependence: Extremely addicting although
  degree of physical dependence is not great.
  

  
  

• Perinatal toxicity: Cocaine crosses the
  placenta.
  

  
  
  
  
  
  Methylxanthines – Caffeine, theophylline, theobromine
  

• General effects: CNS stimulation (except theobromine), diuresis,
  stimulation of cardiac muscle and relaxation of smooth muscle (especially
  bronchial muscle).
  

  
  

• Toxicity: Ringing in the ears is notable; theophylline can cause
  seizures and fatal respiratory and circulatory collapse (arrhythmias).
  

  
  

• Chronic toxicity: Symptoms resemble anxiety neurosis.
  

  
  

• MOA: Antagonism of adenosine receptors; inhibition of
  phosphodiesterase; alteration of calcium-mediated membrane
  mechanisms.
  

  
  

• Therapeutic uses: Migraine headache (with ergotamine); adjunct to
  analgesics; recurrent apnea in preterm infants; maintain
  wakefulness; theophylline for asthma.
  

  
  

Category: Pharmacology Notes