Kruse DSA: Drugs of Abuse Flashcards
Opioid receptor antagonists
- Naloxone
- Naltrexone
Synthetic Opioid
methadone
Partial Mu opioid receptor agonist
-buprenorphine
Nicotinic receptor partial agonist
-Varenicline
Benzodiazepines
- oxazepam
- lorazepam
NMDA receptor antagonist
acamprosate
What is abstinence syndrome
-the signs and sx that ocur on withdrawal of a drug in a dependent person
addiction
-compulsive drug-using behavior in which the person uses the drug for personal satisfaction, often in the face of known risks to health; formerly termed psychological dependence
Controlled substance
-drug that has abuse liability that is listed on governmental schedules of controlled substances
Schedule 1
-no medical use; high addiction potential
Schedule 2
-medical use; high addiction potential
Schedule 3
- medical use
- moderate abuse potential
Schedule 4
-Medical use; low abuse potential
Dependence
-a sate characterized by signs and sx, frequently the oppostite of those caused by a drug, when it is withderawn from chronic use or when the dose is abruptly lowered
Designer drug
- a synthetic derivative of a drug, with slightly modified structure but no major change in pharmacodynamic action
- circumvention of the schedule of controlled drugs is a motivation for the illicit synthesis of designer drugs
=Tolerance
- a decreased response to a drug, necessitating larger doses toachieve the same effect
- this can result from increased disposition of the drug, an ability to compensate for the effects of a drug, or changes in receptor or effector systems involved in drug actions
Sensitization
-an increase in response with repetition of the same dose of the drug
Withdrawal
- adaptive changes that become fully apparent once drug exposure is terminated; generally due to readaptation of the CNS to the absence of the drug of dependence
- withdrawal is the evidence of physical dependence
If we knock out the D2 receptors, what did we eliminate?
-the reward properties of morphine
Is the dopaminergic pathway responsible for the positive reward AND the negative withdrawal effects?
- no!
- just the positive reward
What are the 3 classes of molecular targets that have been identified in the mesolimbic system?
- Gio coupled receptors
- ionotropic receptors
- Monoamine transporters
Which drugs get the Gio receptors?
- Opioids
- Cannabinoids
- Gamma hydroxybutyric acid
- LSD
Drugs thatbing to ionotrpic receptors and ion channels
-Nicotine
-Alcohol
-Benzos
=-Phencyclidine, ketamine
Drugs that bind to transporters of biogenic amines
- Cocaine
- Amphetamine
- Ecstasy
What are the nonaddictive drugs of abuse?
- LSD, mescaline, psilcybin
- Phencyclidine (PCP, angel dust) and ketamine (Special K)
What do drugs that activate Dio coupled receptors do?
-cause disinhibition of DA neurons
What do mu opioids do in the VTA?
-inhibit the GABA ergic inhibitory interneurons, which leads toa disinhibition of DA neurons
How do you treat the withdrawal sx of opioids?
-With naloxone!
MOA of naloxone
- pure opioid antagonist that reverses effects of a dose of opiates within minutes
- provokes an acute withdrawal syndrome in situations where a dependent person has opiates in their system (so probs make sure they’re out of there)
Methadone, buprenorphine
- long acting opioids used for substituion therapy
- tolerance and physical dependence develop more slowly in comparison to other opioids
- given with supervised intake
- abrupt discontinuation precipitates a withdrawal syndrome
What do endocannabinoids do?
-bind to presynaptic CB1 receptors and inhibit the release of either glutamate or GABA
What does THV do?
-cuases disinhibition of DA neurons by presynaptic inhibition of GABA neurons in the ventral tegmental area (VTA)
What is dronabinol?
-FDA approved THV analog used for anorexia and weight loss in AIDS pts and cancer-chemotherapy induced nausea and vomiting
What is Nabilone?
-THV analog used for the tx of refractory nausea and vomiting associated with cancer chemotherapy and as an adjunct in chronic pain management
What is Gamma hydroxybutyric acid (GHB)?
-produced during the metabolism of GABA, but the endogenous function is unknown
-GABAb receptor
-date rape drug
-hyperpolarizes DA neurons and inhibits DA release at high conc….
only inhibits GABA neurons for recreational use
What does GHB target?
-GABAb receptors on both GABA and DA neurons, but those on GABA neurons are more sensitive to GHB and lead to disinhibition of DA neurons when activated
How does THC act?
-presynaptic inhibition
MOA for nicotine
- selective agonist of the nAChR
- Neuronal nAChRs are expressed on DA neurons in the VTA; activatin fulfills the DA requirement of addictive drugs
Tx for Nicotine addiction
- gum, lozenge, inhalers, transdermal applications
- Bupropion
- Varenicline
What does Bupropion do?
- antidepressant with unknown MOA
- Used alone or in combo with nicotine-replacement therapy and/or behavioral therapy
What does Varenicline do?
- partial neuronal nAChR agonist approved for treating smoking cessation
- prevents nicotine stimulation of mesolimbic dopamine system associated with nicotine addiction
What are some examples of biogenic amine transporters?
-DAT, NET, VMAT, and SERT
Cocaine
- local anesthetic in peripheral nervous system
- Blocks the DAT and increases the DA concentration in the nucleus accumbens (rewarding)
- Blocks NET and activates the symp nervous system, high pressure, tachy, vetnricular arrhythmias, pupil dilation!
Is there an antidote for cocaine overdose?
no
MOA of ampthetamines
- cause the release of endogenus biogenic aminesby reversing the action of biogenic amine transporters at the plasma membrane
- taken up into cell by DAT
- block intracellular VMAT, depletes vesicles of NT content
- DA and other amines increase inthe cytoplasm, flow out through the DAT the other way into the synapse!!!
Ecstasy MOA
- similar to amphetamines (reverse action of biogenic amine transporters
- Preferential affinity for the SERT and increases EC concentration of serotonin
What are the acute toxic effects of MDMA (ecstasy)?
-hyperhtermia, dehydration, serotonin syndrome, and seizures
overdose effects of amphetamines and cocaine
-agitation, htn, tachycardia, delusions, hallucinations, hyperthemia, seizures, death
withdrawal sx for amphetamines and cocaine
-apathy, iritability, increased sleep time, disorientation, depression
Overdose effects for barbiturates, benzodiazepines, ethanol
-slurred speech, drunken behavior, dilated pupils, weak and rapid pulse, clammy skin, shallow respiration, coma, death
Withdrawal sx for barbiturates, benzos, and ethanol
-anxiety, insomnia, delirium, tremors, seizures, death
Overdose effects of heroin, other strong opioids?
-constricted pupils, clammy skin, nausea, drowsiness, respiratory depression, coma, death
Withdrawal sx for heroin and other strong opioids
-nausea, chills, cramps, lacrimation, rhinorrhea, yawning, hyperpnea, tremor
