PHRM845-FINAL EXAM Flashcards
Pharmacology of psychostimulant misuse
What are psychostimulants?
They activate the CNS resulting in alertness, excitation, and elevated mood
**3rd most used psychotherapy use
Illegal drugs that are psychostimulants that are used in the US
-Methamphetamine
-Ecstasy
-Crack
-Cocaine
Top 3 national drug-involved OD deaths
-Synthetic opioids other than methadone (fentanyl)
-Psychostimulants with abuse potential (primarily methamphetamine)
-Cocaine
**All are increasing in prevalence
80% of people that die from OD have ____
Another drug in their system
While much reference is made to an opioid crisis, we actually have a drug ____ crisis in which stimulants play a major role.
Abuse
Role of mesolimbic dopamine system
-Prefrontal cortex: planning and judgement
-Nucleus accumbens: reward
-Hippocampus: memory and learning
-Amygdala: emotion and fear
-Ventral tegmental area: stimulate DA receptors
Drugs of abuse on the dopamine reward system
Nicotine and stimulants
Nicotine MOA
-Nicotine activates nicotinic acetylcholinergic receptors
-Na+ enters the cell, K+ exits the cell –> action potential
Nicotine heterogeneity
-Heterogeneity of subunits determines how many molecules of Ach bind to the receptor
-Variation in receptor composition at different sites may influence physiological response
How many ACh binding sites are on a homomeric nicotine receptor?
5
How many ACh binding sites are on a heteromeric nicotine receptor?
2
ACh vs Nicotine
-Similarities between nicotine and ACh are charged amino groups and hydrogen bond acceptor groups
-Nicotine is membrane penetrable at physiological pH (weak base)
-Nicotine is NOT degraded by acetylcholinesterase–this means that nicotine will be in the synaptic cleft for longer time and has a longer duration of action
What is the most addictive form nicotine?
Tobacco; most patients do not become addicted, but some do
Why do a minority of people become addicted to nicotine if the pharmacology of the drug drives addiction?
Pharmacology is related to addiction, but pharmacology does NOT determine how the drug is used, the context it is used in, etc.
Partial agonist therapy
-Causes release of dopamine
-Highly addictive
-Nicotine replacement therapy is relatively ineffective alone
-Varenicline partial agonist increases quit rate success (does NOT give reward causing pt to continue smoking)
Commonly abused psychostimulants
**All have very similar structures
-MDMA (ecstasy)
-Methamphetamine (Crystal meth)
-Methylphenidate (Ritalin)
-Cocaine (fairly different; bigger molecule and may act differently than other drugs listed)
Why is pseudoephedrine kept behind the counter?
Simple chemistry can be done to create meth (Nowadays it is not the main source of meth)
**Psuedophed was reformulated to phenylephrine which is not an effective decongestant–>cannot be readily converted to meth
The effectiveness of regulating OTC pesudoephedrine is debated, the continued escalation of meth OD is not and it just continues to rise. This exemplifies that sudafed regulations ____ doing a lot.
are not
Fenethylline
-Psychostimulant
-Known as captagon and Abu Hilalai
MOA of cocaine
-Antagonist of amine transporters
1. DAT
2. SERT
3. NERT
-DAT > SERT > NERT Potency
-Prevents DA uptake
-Increases DA concentration and DA action
MOA of methamphetamine, ecstasy (XTC), and bath salts
-Carrier-mediated process (competes with endogenous substrates)
-Amphetamines/XTC/bath salts compete for reuptake
~Resembles endogenous DA, NE
~Blocks DA reuptake
~Pushes out DA from vesicles
~Increases extra-vesicular DA
~Reverse transport (gradient)
~Amphetamines are MAOi’s
-Activate trace amine-associated receptor (TAAR1)
~Phosphorylates DAT
~Induces reverse transport function (becomes an efflux transporter)
*Competes with DA for reuptake
*Increases DA efflux
Synthetic cathinones are derivatives from the ___ plant. It gives a patient ___ which is similar to ___. It is used like ___.
Khat;
mild euphoria and excitement
Strong coffee
Chewing tobacco
There is (an array/only 1) common synthetic cathinone.
An array
**Common name: bath salts, Molly
Clinical effect of methamphetamine abuse:
Neurologic
Delirium (misinterpret things in environment)
Tremor
Clinical effect of methamphetamine abuse:
Psych
Anxiety
Paranoia
Hallucinations
Delusions
Repetitive behavior
Clinical effect of methamphetamine abuse:
ENT
Profuse dental decay
Clinical effect of methamphetamine abuse:
Cardiovascular
Tachycardia
Hypertension/vasospasm
Clinical effect of methamphetamine abuse:
Skin
Diaphoresis (it is a stimulant so pt sweats)
Brian scan imaging shows more binding of meth to DA receptors making the brain more colorful.
-DA receptor changes argued as support for DA hypothesis and brain disease model
-Similar changes occur with NE and 5HT with antidepressant therapy
-Receptor downregulation believed to mediate withdrawal symptoms
-DA downregulation is not evidence of a broken brain
-Recovery of DA receptors shows ability to return to homeostasis – overstimulate receptors and get a downregulation of them.
Might substitution tx prevent return to homeostasis and full recovery?
Possibly because it is binding to the same receptors
Do addictive drugs increase brain dopamine?
Decrease in PET binding occurs as a consequence of increased competition between dopamine and tracer, and so percentage decreases in binding of tracer which reflects increased synaptic ventral striatal DA levels.
**Decreased binding = more DA released
Psychostimulants can be used as a ____ enhancer.
Cognitive
There is increasing use of stimulants with the goal of ___. This off-label use is NOT well-supported by research and can progress to ___.
Cognitive enhancement
Stimulant use disorder
Cognitive enhancement appears to be ____ and of questionable significance. Controlled studies ___ support improved attentiveness.
Marginal
DO NOT
No change from placebo
Sympathomimetic Toxidrome
**If pt OD on sympathomimetics
*Mnemonic: MATHS
M: Mydriasis
A: Agitation, arrhythmia, angina
T: Tachycardia
H: HTN, hyperthermia
S: Seizure, sweating
Examples of sympathomimetics
Ephedrine
Phenylephrine
Norepinephrine
Amphetamine
Dopamine
Cocaine
Management of Sympathomimetic toxidrome
Tx agitation, HTN, and seizures with benzos
Avoid pure BB due to unopposed alpha agonism
Tx HTN in Sympathomimetic toxidrome
Sedation so give benzo
Hyperthermia denotes a ___ prognosis
Poor; decrease in BP
BIGGEST CONCERN
Aggression and ____ are often seen, especially in hospital, and are hard to manage
paranoia
