PHRM845-FINAL EXAM

Question 1

What are psychostimulants?

Answer 1

They activate the CNS resulting in alertness, excitation, and elevated mood
**3rd most used psychotherapy use

Question 2

Illegal drugs that are psychostimulants that are used in the US

Answer 2

-Methamphetamine
-Ecstasy
-Crack
-Cocaine

Question 3

Top 3 national drug-involved OD deaths

Answer 3

-Synthetic opioids other than methadone (fentanyl)
-Psychostimulants with abuse potential (primarily methamphetamine)
-Cocaine

**All are increasing in prevalence

Question 4

80% of people that die from OD have ____

Answer 4

Another drug in their system

Question 5

While much reference is made to an opioid crisis, we actually have a drug ____ crisis in which stimulants play a major role.

Answer 5

Abuse

Question 6

Role of mesolimbic dopamine system

Answer 6

-Prefrontal cortex: planning and judgement
-Nucleus accumbens: reward
-Hippocampus: memory and learning
-Amygdala: emotion and fear
-Ventral tegmental area: stimulate DA receptors

Question 7

Drugs of abuse on the dopamine reward system

Answer 7

Nicotine and stimulants

Question 8

Nicotine MOA

Answer 8

-Nicotine activates nicotinic acetylcholinergic receptors
-Na+ enters the cell, K+ exits the cell –> action potential

Question 9

Nicotine heterogeneity

Answer 9

-Heterogeneity of subunits determines how many molecules of Ach bind to the receptor
-Variation in receptor composition at different sites may influence physiological response

Question 10

How many ACh binding sites are on a homomeric nicotine receptor?

Answer 10

5

Question 11

How many ACh binding sites are on a heteromeric nicotine receptor?

Answer 11

2

Question 12

ACh vs Nicotine

Answer 12

-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

Question 13

What is the most addictive form nicotine?

Answer 13

Tobacco; most patients do not become addicted, but some do

Question 14

Why do a minority of people become addicted to nicotine if the pharmacology of the drug drives addiction?

Answer 14

Pharmacology is related to addiction, but pharmacology does NOT determine how the drug is used, the context it is used in, etc.

Question 15

Partial agonist therapy

Answer 15

-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)

Question 16

Commonly abused psychostimulants

Answer 16

**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)

Question 17

Why is pseudoephedrine kept behind the counter?

Answer 17

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

Question 18

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.

Answer 18

are not

Question 19

Fenethylline

Answer 19

-Psychostimulant
-Known as captagon and Abu Hilalai

Question 20

MOA of cocaine

Answer 20

-Antagonist of amine transporters
1. DAT
2. SERT
3. NERT
-DAT > SERT > NERT Potency
-Prevents DA uptake
-Increases DA concentration and DA action

Question 21

MOA of methamphetamine, ecstasy (XTC), and bath salts

Answer 21

-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

Question 22

Synthetic cathinones are derivatives from the ___ plant. It gives a patient ___ which is similar to ___. It is used like ___.

Answer 22

Khat;
mild euphoria and excitement
Strong coffee
Chewing tobacco

Question 23

There is (an array/only 1) common synthetic cathinone.

Answer 23

An array
**Common name: bath salts, Molly

Question 24

Clinical effect of methamphetamine abuse:
Neurologic

Answer 24

Delirium (misinterpret things in environment)
Tremor

Question 25

Clinical effect of methamphetamine abuse:
Psych

Answer 25

Anxiety
Paranoia
Hallucinations
Delusions
Repetitive behavior

Question 26

Clinical effect of methamphetamine abuse:
ENT

Answer 26

Profuse dental decay

Question 27

Clinical effect of methamphetamine abuse:
Cardiovascular

Answer 27

Tachycardia
Hypertension/vasospasm

Question 28

Clinical effect of methamphetamine abuse:
Skin

Answer 28

Diaphoresis (it is a stimulant so pt sweats)

Question 29

Brian scan imaging shows more binding of meth to DA receptors making the brain more colorful.

Answer 29

-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.

Question 30

Might substitution tx prevent return to homeostasis and full recovery?

Answer 30

Possibly because it is binding to the same receptors

Question 31

Do addictive drugs increase brain dopamine?

Answer 31

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

Question 32

Psychostimulants can be used as a ____ enhancer.

Answer 32

Cognitive

Question 33

There is increasing use of stimulants with the goal of ___. This off-label use is NOT well-supported by research and can progress to ___.

Answer 33

Cognitive enhancement
Stimulant use disorder

Question 34

Cognitive enhancement appears to be ____ and of questionable significance. Controlled studies ___ support improved attentiveness.

Answer 34

Marginal
DO NOT
No change from placebo

Question 35

Sympathomimetic Toxidrome
**If pt OD on sympathomimetics

Answer 35

*Mnemonic: MATHS
M: Mydriasis
A: Agitation, arrhythmia, angina
T: Tachycardia
H: HTN, hyperthermia
S: Seizure, sweating

Question 36

Examples of sympathomimetics

Answer 36

Ephedrine
Phenylephrine
Norepinephrine
Amphetamine
Dopamine
Cocaine

Question 37

Management of Sympathomimetic toxidrome

Answer 37

Tx agitation, HTN, and seizures with benzos
Avoid pure BB due to unopposed alpha agonism

Question 38

Tx HTN in Sympathomimetic toxidrome

Answer 38

Sedation so give benzo

Question 39

Hyperthermia denotes a ___ prognosis

Answer 39

Poor; decrease in BP
BIGGEST CONCERN

Question 40

Aggression and ____ are often seen, especially in hospital, and are hard to manage

Answer 40

paranoia