Pharm - stimulants, drugs of abuse

Question 0

Buproprion

Answer 0

oral atypical antidepressant also used for smoking cessation, (independent of depression Tx).
Mech: replaces 5-HT and DA,
most effective in combo w/ nicotine replacemet
SE: anxiety, seizures (rare)

Question 1

Nicotine as therapy

Answer 1

“Nicotine Replacement” for smoking cessation;
Route: intradermal (patch), oral, nasal spray, smoked.
= lower amt than cigs, “takes edge off cravings” but easier to stop.
SE: (rare) anxiety, nausea, nightmares

Question 2

Nortryptiline

Answer 2

oral tricyclic (antidepressant) also used for smoking cessation;
*NOT as effective as Buproprion*

Question 3

Varenicline

Answer 3

oral R selective partial nicotine agonist, for smoking cessation.
- agonist: nicotine-like effect (reduce cravings)
- antagonist: reduce effect of concurrent nicotine (less reward from smoking)
SE: dose-related nausea/vomiting/insomnia; RARE: MI, arrhythmia

Question 4

Nicotine (in cigarettes)

Answer 4

#1 addictive substance in tobacco (rapid uptake!), relatively safe; 	- acts on nAChRs (--> Mesolimbic/reward pathway)
Metab: by CYP2A6, induced by estrogen (F = faster metabolizers)
*fast metabolizers -- harder to quit, smoke more
* 1/2 life = 2 hrs

Question 5

methamphetamine

Answer 5

sympathomimetic stimulant; used for narcolepsy (?).
Route: oral, intranasal, smoked
Mech: evokes release of NE, DA, & 5-HT (reverse transporters)
SE: cardiac arrest, seizures, tachycardia & HTN crisis
Withdrawal: (~mild) fatigue/malaise, depression

Question 6

Dextroamphetamine

Answer 6

oral sympathomimetic stimulant, for ADHD or narcolepsy;
Mech: evoke release of NE, DA, & 5-HT (reverse transporters), - short-acting
SE: insomnia
Withdrawal: (~mild) fatigue/malaise, depression

Question 7

Methylphenidate (Ritalin)

Answer 7

oral sympathomimetic stimulant, #1 for ADHD, also for narcolepsy.
Mech: evoke release of NE, DA, & 5-HT (reverses transporters);
- short acting (or extended release)
SE: insomnia
Withdrawal: (~mild) fatigue/malaise, depression
*therapeutic use (low dose) is effective at PREVENTING drug abuse

Question 8

Cocaine

Answer 8

sympathomimetic stimulant and local anesthetic (esp. for upper respiratory tract);
Route: oral, intranasal, smoked
Mech: blocks monoamine reuptake (NE, 5-HT, esp. DA)
SE: sudden cardiac death,
Tx: benzodiazepines

Question 9

Caffeine

Answer 9

mild oral stimulant, *often w/ theobromine or aminophylline.
Use: respiratory stimulant in neonates (esp. theophylline), promote wakefulness (OTC)
Mech: adenosine R antagonist & inhibit phosphodiesterase
SE: nervousness, tachycardia, delirium (@ high doses)

Question 10

Modafinil

Answer 10

Mild oral orexigenic stimulant; for narcolepsy, shift work disorder, & daytime drowsiness w/ sleep apnea.
Mech: inhibits NE & DA transporters, potentiates Locus Ceruleus
increased wakefulness but not better motor f(x)
SE: headache, nausea, anxiety, high BP, insomnia, serious derm condition in children!, less abuse potential.

Question 11

Atomoxetine

Answer 11

oral SNRI, for ADD, esp. adults; NOT a stimulant!
Mech: inhibit NE reuptake only
SE: GI upset/nausea, insomnia, sexual dysfunction

Question 12

THC (delta-9-tetrahydracannabinol)

Answer 12

the neuroactive component of marijuana; FDA approved for: anti-emetic and appetite stimulant in AIDS/chemoTx patients.
Route: oral, smoked *low abuse liability
Mech: partial CB1R agonist
Use: euphoria/sense of well-being, increased appetite
Withdrawal: anxiety & irritability
SE: depression & suicidality

Question 13

LSD (Lysergic Acid Diethylamide)

Answer 13

oral hallucinogen (visual, auditory), + paranoia, psychosis.
Mech: 5-HT R agonist, *very potent.
SE: flashbacks (to trip), toxic psychosis, neurotoxicity (degen. 5-HT pathways)
NO withdrawal

Question 14

MDMA (ecstasy)

Answer 14

oral sympathomimetic stimulant & hallucinogen;
Mech: Reverses transport @ SERT (#1), DAT, & NET
Use: increased pleasure & energy, low need for food & sleep
OD: tachycardia, muscle tension, insomnia, anxiety, confusion
Long term: degen of serotonergic pathways

Question 15

Characteristics of substance abuse (according to DSM-V)

Answer 15

1. impaired control (cravings, unable to control use)
2. social impairment (social roles ignored)
3. risky behavior
4. pharmacological (tolerance, withdrawal)

Question 16

Factors for absorption of drug abuse (increased experience/Sxs)

Answer 16

1. rate of absorption into brain

2. highly lipophilic (crosses BBB more easily/rapidly)
   * inhalation, or IV = fastest routes if highly lipophilic.

Question 17

Actions of drugs of addiction

Answer 17

Acutely: act on mesolimbic pathway (increase DA from nucleus accumbens)
- nicotine: direct stimulation
- opioids: disinhibition
- stimulants: inhibit reuptake
Chronicly: altered protein expression –> tolerance & dependence

Question 18

Opiates

Answer 18

heroin, morphine, methadone, oxycodone, hydrocodone…
*HIGH abuse liability, chronic use = to avoid withdrawal.
Mech: opiate R agonists
use: euphoria, relaxation, apathy, slurred speech
OD: coma, resp. depression, miosis
Withdrawal: not fatal - craving, yawning, hyperalgesia, sweating…
- Tx: Methadone (long acting, decrease highs), Clonidine (decrease ANS Sxs), Naloxone causes withdrawal (detox).

Question 19

Stimulants

Answer 19

*MOST addictive. Cocaine, amphetamine, methamphetamine.
Mech: block/reverse DAT & NET
Use: euphoria, alertness, increased motor activity
OD: seizures, arrhytmias, hyperthermia, anxiety
Withdrawal: (~mild) craving, fatigue
Complications: Rhabdomyolisis, toxic psychosis