Drugs of Abuse - Bloom Flashcards
How is drug abuse defined?
What types of drugs is it most applicable to?
“The use of a drug in a manner that deviates from the approved medical patterns within a society”
This is largely directed at psycho-affective medications.
Distinguish between some of the different aspects of drug tolerance (dispositional, pharmacodynamic, etc).
Dispositional tolerance results from pharcmacokinetic causes, eg Barbiturates inducing their own metabolism.
Pharmacodynamic tolerance mostly pertains to target organ sensitivity, eg Downregulation of target receptor.
Behavioral tolerance pertains to a reduced behavioral response, eg James Bond after 3 martinis (still smooth!)
Cross-tolerance occurs between drugs of the same class.
Contrast between physical and psychological drug dependence.
Physical drug dependence refers to physical symptoms brought about by drug withdrawal (not seen with all drugs).
Psychological dependence refers to compulsive feelings of need to take the drug (also applies to things like gambling, internet gaming)
How has DSM-5 restructured the classification of substance use and -induced disorders?
Both categories have been grouped together. Substance abuse and dependence have been equivocated as “use disorders”, while intoxication/withdrawal/induced illnesses have remained more or less the same.
What criteria are needed to classify a substance use disorder?
A problematic pattern of substance use within a 12mo period manifesting as 2+ symptoms of…
Increased amount or duration of doping
Persistent desire, failure to cut down use
Excessive time spent obtaining, using, or recovering
Cessation of social, occupational, or recreational activities
Continued use despite recurrent problems, use in hazardous settings
Tolerance or withdrawal symptoms (dependence not required for diagnosis!)
When connected to a drug reservoir that is activated by a lever, for which drugs will a rat incessantly push the lever?
Stimulants, opioids, and depressants. Not hallucinogens!
What is the most commonly used drug by high schoolers?
Is it more prevalent in boys or girls?
How does it compare to cigarettes?
Marijuana.
Boys (risky behavior, novelty, etc)
Has recently exceeded cigarette use!
Cannabis contains hundreds of cannabinoid compound. Which is the primary psychoactive agent?
How much can be found in cannabis, and how does this compare to a few decades ago?
Delta-9-tetrahydrocannabinol.
Anywhere from 2-10%, much more than in years past. Note that hashish or hash oil contains even more.
How do compounds like cannabidiol or cannabinol compare to THC?
They do not bind cannabinoid receptors as well, and so have much less psychogenic effect. May be metabolites of THC.
What role does the liver play in the metabolism of THC?
How is it excreted?
How long is it detectable for?
Liver activates THC by 11-hydroxylating it. It later inactivates it by metabolizing it to a 9-carboxyl compound.
In both urine and feces.
Up to 30 days, owing to its highly lipophilic nature.
How long-acting is THC?
How does the smoked formulation compare to the eaten?
1-6hrs
Smoked reaches brain faster and is much more potent than the ingested version. However, there are some side effects as noted later…
Describe the mechanism by which cannabis causes CNS effect.
Activation of mainly the CB1 receptor, found in the cerebellum, hippocampus, and basal ganglia. This is a Gi-coupled receptor.
CB2 receptor is found in peripheral tissue, may be useful for analgesia.
Name two endogenous cannabinoids.
How were they discovered?
2-Arachidonylglycerol (2-AG) and anandamide (arachidonylethanolamide).
After the receptor was discovered in the study of cannabis, endogenous compounds were theorized to exist. The same pattern lead to the discovery of endorphins!
What effect does THC have on mood, memory, and motor function?
THC causes euphoria & mellowing, but impairment of short-term memory and motor functions (#2 substance involved in motor vehicle collisions).
What are the effects of THC on the cardiovascular system?
The pulmonary system?
Tachycardia with orthostatic hypotension. Beware in angina!
Bronchodilation, but the smoked form is irritating and may cause bronchoconstriction, decreased alveolar macrophage activity, and decreased ciliary function.
How does THC affect reproductive function?
Is it effective as a contraceptive?
Lowers testosterone level and sperm counts. Decreases LHRH release (decreasing gonadal weight), as well as prolactin release (abnormal menstrual cycles).
God no.
What are some possible negative psychiatric effects of THC?
Anxiety, paranoia (avoid use in schizophrenics), “diffuse acute brain syndrome”, and amotivational syndrome (those who are often stoned, don’t do much. Causality is unclear though)
Can tolerance & dependence be developed to THC?
What are the symptoms of withdrawal?
According to laboratory studies, yes.
Restlessness (& sleep difficulties), irritabiility, decreased appetite, nausea, and craving.
What is cannabis indicated for in Wisconsin?
Chemotherapy-induced nausea and vomiting, but only as a pill (schedule III).
Give the formulation and indication for each of the following drugs:
Dronabinol
Sativex®
Rimonabant
Dronabinol: Oral THC in sesame oil, for nausea & AIDS wasting.
Sativex®: Cannabidiol mixture, for MS & cancer pains.
Rimonabant: CB1 antagonist for weight loss (think: anti-munchies), removed from market due to increased depression & suicide.
Describe the mechanism of action of synthetic marijuanas.
Are they legal?
THC-like CB1-agonist activity.
Not DEA scheduled…yet
Describe the pharmacokinetics of Phencyclidine (PCP) and Ketamine
(they are about the same), including:
- Speed of absorption
- Plasma t1/2
- Elimination
- Rapid absorption
- t1/2 = 12-24hrs (72hrs in overdose!)
- Hydroxylation and conjugation in the liver followed by elimination in the urine
Describe the CNS effects of Ketamine and PCP.
- Complex and dose related.
- Small dose: “Drunken” state w/ extremity numbness
- Moderate dose: Analgesia & anesthesia
- The user’s psychic state crudely resembles sensory isolation except sensory impulses still reach the neocortex
-
Cataleptoid (catelepsy-like) motor phenomenons
- “trancelike level of consciousness and postural rigidity”
- Large dose: May produce convulsions
Describe the autonomic and CV effects of PCP and Ketamine.
- Tachycardia
- Hypertension
- Potentiation of catecholamines
What is the mechanism of action of Ketamine and PCP?
NMDA receptor antagonist
However, they hit other receptors as well (Various monoamines, PCP hits nicotinic ACh receptors, and ketamine hits opioid receptors)
What are the effects of a PCP overdose?
- CNS
- Anxiety
- Aggression
- Hallucinations
- Dysphoria
- Convulsions
- Delirium
- Sympathomimetic
- Tachycardia
- Hypertensive crisis
How is a PCP overdose treated?
- Support vital signs
- Gastric suction
- Acidify urine
- Diazepam / Antihypertensive agent
- Haloperidol
The indoleamine drugs, including LSD, have chemical structures similar to what endogenous neurotransmitter?
Serotonin / 5-HT
The phenethylamine drugs, including **MDMA (ecstacy**), have chemical structures similar to what endogenous neurotransmitter?
Dopamine
Describe the pharmacokinetics of LSD.
- Less than 1% crosses the BBB.
- Onset is 15-20min
- Duration is 12hrs
What are the autonomic effects of LSD?
- Sympathomimetic
- Tachycardia
- Increased BP
- Psychomotor stimulation
What are the sensory/subjective effects of LSD?
- Altered perception - particularily visual!
- Lability of mood
- Impaired judgment
What mechanism of action are the sensory effects of LSD believed to be caused by?
agonist or partial agonist of 5-HT2 receptors
What are the adverse effects of LSD toxicity / overdose?
How should it be treated?
- Hallucinations
- Anxiety
- Panic
- Depersonalization
- Lasts <24hrs
- potential Flashbacks
- days to years later
- 5-HT neuron neurotoxicity
Treat with quiet environment, BDZs for sedation
MDMA
- Typical oral dose?
- Time to onset?
- Duration of action?
- 100-150mg
- 20-40min
- 3-4 hours
What are the effects of MDMA?
- Induces feelings of “well-being and connection”
- Altered time perception
- Psychomotor stimulation, restlessness, bruxism, anorexia, sweating, tremor
What symptom is seen in MDMA “hangover”?
What neurons is MDMA potentially neurotoxic toward?
Anhedonia [interesting, right?]
5-HT neuons
What is GHB?
What is GBL?
-
GHB: A drug that is also an endogenous compound in the brain.
- Precursor and metabolite of GABA
- May have its own receptor
- Can be synthesized in the body from GBL
- GBL: Precursor to GHB
- Common in chemistry and cleaning solvents
What is a typical dose of GHB?
How long do the effects last?
1-1.5g
3hrs
What are the recreactional effects of GHB?
What about the effects of overdose?
- Typical dose
- Primarily a depressant - state of relaxation and tranquility
- Interacts with alcohol
- Primarily a depressant - state of relaxation and tranquility
- Overdose
- Drowsiness
- Ataxia
- Nausea & vomiting
- Loss of bladder control
- Temporary amnesia
- Clonus
- Seizures
Name a few volatile chemicals that can be used as inhalant drugs.
- Toluene
- Ethyl acetate
- Hexane
- Butane
- Propane
- Fluorocarbons
- Acetone
- Many others
What is the active compound and mechanism of action of Salvia Divinorum?
Duration of action?
Salvinorin-A, a Kappa opioid agonist
Duration is 20-45min
What are the sensory and autonomic effects of Salvia Divinorum?
- Creates a dream-like experience with open and closed-eyed visuals.
- Can be dissociation at high doses, with fear, panic, and perspiration.
- Many people consider its effects to be more unpleasant than pleasant.
“Bath Salts” often contain what active compound? What type of drug is this?
What herbal drug is this similar to?
Mephedrone (and other related compounds) - Stimulant
Khat, a recreational drug found in parts of Africa
