Module 3.1.1 (Psychomotor Stimulants and Psychotomimetics) Flashcards
What are examples of psychomotor stimulants?
- Amphetamines
- Cocaine
- Ecstasy
- Nicotine
What are examples of psychotomimetics (hallucinogens)?
- Cannabis
- LSD
- Phencyclidine
What are examples of psychomotor depressants?
Opioids Ethanol, Barbiturates, GA, Ketamine
What is the defninition of drug addiction?
All dependence‐producing drugs including opioids, nicotine, amphetamines, ethanol and cocaine activate the mesolimbic dopaminergic pathway i.e. THE REWARD CIRCUIT
> Euphoria when taken = +ve re‐inforcement
> Dysphoria when ceased = ‐ve unpleasant experience
What is the definition of physical dependence?
Repeated doses of drug results in altered physiological state (neuroadaptive changes) which involves down regulation of receptors that the drug targets. Following neuroadaption, if drug is ceased, or dose reduced rapidly, withdrawal symptoms occur hence continued admin of drug is required to maintain normal function
What is the definition of psychological dependence?
Person is psychologically uncomfortable without the drug, have compulsion or craving for the drug, which is often associated with the avoidance of withdrawal syndrome if substance is stopped
- Dopamine released in the nucleus accumbens is the final common pathway for reinforcing drugs (and addictive behaviours).
> Cocaine and amphetamines –> direct increased release of DA in nucleus accumbens.
> Opioids, nicotine, alcohol, and marijuana –> indirect release of DA –> work via interneurons (GABAergic neurons) in the nucleus accumbens and the ventral tegmental area
What is physical dependence characterised by? What are some examples of pharmacological intervention?
Characterised by withdrawal or abstinence syndrome
- Occurs when drug is terminated abruptly in a physically dependent person. Symptoms tend to be opposite to the original effect of the drug before tolerance developed
What is the definition of tolerance? Why doesit occur?
Decrease in pharmacological effect on repeated admin of drug
- May be due to desensitisation of receptors (eg nAchR and opioid receptors)
- Develops when a drug is taken for period of time
- Becomes less effective at producing the original effect
- An increased dose is required to produce same physiological response
What are the main drugs of abuse?
what determines intensity of initial effect?
Easy: Smoking, swallowing, snorting
More intense: Injection or smoking
For stimulants, explain some properties of amphetamines. What are signs and symptoms of drug intoxication, what is the MOA?
Street drugs: NMDA or ecstasy, amphetamines (speed,uppers,pep pills), methamphetamine, dextroamphetamine
- Produce central and peripheral sympathomimetic effects
- Lethal complications include severe hyperthermia and cardiovascular effects
signs and symptoms see attached image
MOA
- Enhance release and increase concentration of catecholamines (NA, adrenaline, dopamine) at synapse
- Increase storage and release of catecholamines from vesicles
- Also inhibition of monoamine oxidase = increase in NA
What effects does the illicit use of amphetamines bring? What are some AE and what happens with prolonged use?
Produce powerful CNS stimulant action
- Feelings of euphoria, well being and increased energy
Highly re‐enforcing with repeated use
Tolerance can develop
- Adverse effects – agitation, headache, tremor, insomnia, increased BP, tremor, stroke, seizures, malnutrition, hallucination, hyperthermia
- Prolonged use = liver, kidney and lung damage
What are the two forms of drug-induced pyschosis that can occur with amphetamines?
Toxic psychosis
- after a single large dose;
- characterised by confusion and disorientation;
Amphetamine psychosis
- with chronic (long‐term) use
- characteristic behaviours
- Increased activity
> repetitive and compulsive behaviour;
> social withdrawal, delusions, suspiciousness and paranoia;
> auditory and sometimes visual hallucinations
- People who use the amphetamines intravenously have often been called “speed freaks”
What are the CNS effects, cardiovascular effects and peripheral sympathomimetic efects of amphetamines?
CNS effects
- Locomotor stimulation
- Euphoria and excitement
- Stimulant effects is followed by depression and anxiety
- Agitation, aggression, paranoid psychoses
- Anorexia – appetite suppressants
Cardiovascular
- Increase blood pressure –> hypertension
- Increase heart rate, acute pulmonary oedema
Peripheral Sympathomimetic effects (increase in NA)
- Decreased GI motility
- Mydriasis, sweating and tremor
What are the unwanted effects of amphetamines?
- hypertension
- insomnia
- anorexia
- tremors
- Amphetamine psychosis resembles schizophrenia
- Tolerance to stimulant effects develop rapid
- Risk of dependence
- Ecstasy – sudden deaths have occurred even after single moderate dose
What is the MOA of cocaine?
- Inhibits catecholamines re‐uptake by noradrenaline and dopamine transporters, as opposed to amphetamines which stimulate synaptic release
- Facilitates packaging and storage of catecholamines into vesicles like amphetamine
MOA of cannabinoids? What are two maintypes of cannabinoid (CB) receptors? What happens at high doses?
- Psychoactive drug with central sympathomimetic and antiemetic properties
- Acts on cannabinoid receptors in CNS and PNS
- Enhance dopamine release
Two main types of cannabinoid (CB) receptors
> CB1 in the brain
- cortex and hippocampus – memory and learning
- basal ganglia and cerebellum – balance & coordination
- mesolimbic dopaminergic pathways – euphoria
> CB2 in immune system
What are the toxicokinetics of cannabis?
Rapidly and completely absorbed by inhalation
- Highly protein bound, lipid soluble
- Large volume of distribution (10L/kg)
- Marked CNS effects
- Liver metabolism to active and inactive metabolites which are excreted by in urine –> 20% THC abosrbed when inhaled, 6% if orally
- Delta9‐tetrahydrocannabinol (delta9‐THC) is the major active component of cannabinoids
- Elimination half life of the metabolites – several days
What are the adverse effects of cannabis?
- In overdose THC is relatively safe
- Drowsiness and confusion
- No respiratory or cardiovascular effects that threatens life
- Safer than other drug of abuse such as opiates and ethanol
- Less liable to cause dependence
