Stimulants - Lichtblau Flashcards
What are the CNS effects of sympathomimetics?
- Less fatigue
- More wakefulness/alertness
- Increased initiative, confidence, & ability to concentrate
- Increased motor and speech activity
- Improved athletic performance
- Increased speed performance of simple mental tasks
- Decreased food consumption
- Stimulation of medullary respiratory center
When do sympathomimetics have the greatest effect?
If performance is affected by fatigue or lack of sleep
What are the peripheral effects of sympathomimetics?
- Increased systolic and dystolic BP
- reflex decrease in HR
- due to increased NE release
- Arrhythmias (in higher doses)
In order of potency, what are the effects of sympathomimetics on neurotransmission?
- Low dose:
- Increased release of NE and DA @ jxn
- increase amount of NT that can act on post-synaptic receptors
- Increased release of NE and DA @ jxn
- Medium dose:
- Blocks NE and DA reuptake
- further increase in [NE] & [DA] levels
- Blocks NE and DA reuptake
- High dose:
- Inhibits monoamine oxidase (MAO) metabolism
- increase NT levels even higher
- Inhibits monoamine oxidase (MAO) metabolism
What are the effects of acute amphetamine toxicity?
Acute = exaggerated therapeutic effects
- Cardiovascular system
- headaches, arrhythmias, palpitations, anginal pain, circulatory collapse, and hyperthermia
- CNS
- dizziness, agitation, confusion, insomnia, seizures, coma
What do higher doses of sympathomimetics produce?
Restlessness and tremor
What are the effects of chronic amphetamine toxicity?
- Amphetamine psychosis
- vivid hallucinations, paranoid delusions and compulsions
- marked weight loss
- will have positive drug screen clinically
- symptoms will resolve in 7-10 days
What is the treatment for amphetamine caused toxicity?
- Antipsychotic
- treat psychotic symptoms
- Acidify patient’s urine
- Ammonium Chloride IV
- drugs are weak bases
What are the therapeutic uses of sympathomimetics?
- Attention deficit hyperactivity disorder (ADHD)
- Narcolepsy
(Questionable use for fatigue/weight loss)
Is amphetamine dependence primarily physical or psychological?
Psychological
(person BELIEVES that they need the drug)
What are the central effects of cocaine?
Similar to amphetamines, but more potent (1 mg of cocaine = 10 mg of amphetamine)
(awake, alert, confident, speedy, etc.)
What are the peripheral effects of cocaine?
Peripheral IV administration or smoking free-base cocaine produces a very intense pleasureable sensation known as “rush” or “flash”
What are the toxic effects of cocaine?
- cardiac arrhythmias
- coronary/cerebral thrombosis
- impairs in utero brain development leading to significantly decreased brain size and neurological manifestations
What is the potential MOA of methylxanthines?
- Translocation of intracellular Ca2+ from the sarcoplasmic reticulum
- Inhibition of phosphodiesterase
- Elevated levels of second messenger cAMP
- Nonselective adenosine receptor antagonist
- inhibits sleepiness-inducing adenosine
How is MDMA similar/different to other sympathomimetics?
- Derived from methamphetamine
- added methyl group –> increases lipophilicity
- very rapid entry into the brain
- Stimulates (CNS) release and inhibits reuptake of
- Epi
- NE
- DA
What are “bath salts”?
- Often contain various amphetamine-like chemicals
- Chemicals act in the brain like stimulants
- Toxicity associated with ingesting or snorting “bath salts”
How are “bath salts” being used?
- Chemicals act in the brain like stimulant drugs
- they are sometimes touted as cocaine substitutes
- present a high abuse and addiction liability
- oral ingestion
- snorting
- smoking
What are the clinical uses for methylxanthines?
- Cardiac stimulation in CHF (controversial)
- dilates coronary arteries –> increased coronary blood flow
- Increased inotropic and chronotropic forces
- increased O2 demand by the hear
- Paroxysmal dyspnea (associated with left heart failure)
- Analeptic
- Bronchial asthma
- Plus ergot alkaloids for migraine
- vasoconstriction of cerebral vasculature
What are the adverse effects of methylxanthines?
- Toxicity seen at doses near 1 gm
- CNS:
- insomnia, excitement, mild delirium, sensory disturbances (tinnitus)
- convulsions
- >10gm = clonic convulsions & death
- Cardiovascular
- increased HR, extra systoles, increased RR
- decreased clotting time
- Increased gastric secretions
- CNS:
Compare/contrast tolerance of amphetamines, cocaine, and caffeine.
- Amphetamine
- Develops to effects on appetite and mood
- Cocaine
- may develop
- users can take the same dose every day and get the same effect
- Caffeine
- Some (but not all) users develop tolerance to sleep-disrupting effects
Compare/contrast dependence of amphetamines, cocaine, and caffeine based on withdrawal symptoms.
- Amphetamines
- Psychological: craving for drug, prolonged sleep, fatigue, excessive eating, depression
- Cocaine
- evidence of withdrawal (physical dependence) is controversial
- Caffeine
- May appear within 12-24 hours after discontinuation of caffeine intake
- headache, irritability, inability to concentrate, drowsiness, insomnia, pain in stomach/upper body/joints
What is the MOA of Modafinil & Armodafinil?
- Monoamines
- DA
- Increase release in striatum
- Increase release in nucleus accumbens
- May block DA reuptake
- NE
- Increase release in hypothalamus
- 5HT
- Increase release in amygdala and frontal cortex
- DA
- Elevates hypothalamic histamine levels
- Activates glutamatergic circuits
- Inhibits GABAergic neurotransmission
What are common side effects of Modafinil & Armodafinil?
- Headache
- Nausea
- Insomnia
- Lack of appetite
- Dizziness
- Agitation
- Anxiety
- High BP
What are the severe side effects of Modafinil & Armodafinil?
Severe dermatologic reactions to Modafinil requiring hospitalization
