Exam 1, Drugs of Abuse Flashcards
physiological vs psychological dependence
Physio dependence: Neuroadaptations - abnormal behavior and physical sx (withdrawal) occur if drug is withdrawn
Psych dependence:
dysphoria and intense craving following withdrawal of drug. Occurs with or without physical dependence
What is the basis of withdrawal
adverse rxns caused by dc of drug; based on neuroadaptations of brain –> release dynorphine and GABA in nucleus accumbens (reward pathway)
What is tolerance and what forms of tolerance are there?
Tolerance = more drug needed to produce effect; dose/ response curve shifted RIGHT
Innate (genetic lack of sensitivty)
PK: increased metab
PD: receptor downregulation
Learned: adapted to degree of intoxication
Conditioned: familiar settings diminish effects, novel enhance
Acute: repeated use over short period of time
Cross: one drug produces tolerance to another
What is sensitization
increased responsiveness after repeated use
Dose/response curve shifts LEFT
define addiction related to drugs, contrasted with recreational use
compulsive, relapsing drug use in spite of adverse consequences
*recreational use: drug use to achieve pleasurable expericne
How does addiction affect the body
neural plasticity alters brain function
- typically psychological in nature
- physio dependence usually present (but this dose no mean addiction)
- abuse is generally a factor, drug is causing harm
- dev depends on individual, drug, and environment
What are some non drug related addictions that cause the same brain stimulation/pathways affected as drugs
Gambling and
Oniomania (addiction to shopping)
What are general properties of abused drugs
- cause euphoria
- easy to use
- potency & purity (need effect with small dose)
- rapid onset/short action (shroter DOA, more often need to reinforce effect, more freq use of drug, greater addiction potential)
Outline the reward pathway in the brain
aka Mesolimbic DA pathway
*VTA –> NAc (nucleus accumbens) –> prefrontal cortex
- reinforcement/reward, motivation, reinforcing effects of drugs (such as opiates)
what various drugs cause addiction by affecting DA release, specifically increasing DA levels
Amphetamine, Cocaine, Nicotine, Morphine
*all increase release of DA in nucleus accumbens
How do Addicting drugs like cocaine also have an effect on memory?
drug abuse and environmental cues activate cortical regions in brain (ie watching a cocaine video increases amygdala activity - responsible for memory)
Sites of action:
What drugs are considered Class I and where do they act
Class I: opioids, THC, GHB,
act on GPCRs in VTA
Sites of action:
What drugs are considered Class II and how/where do they act?
Class II: BZ, nicotine, EtOH
act on ion channels in VTA
Sites of action:
what drugs are considered Class III and where do they act?
Class III: cocaine, amphetamine, exstasy (MDMA)
act on monoamine transporters (ie MDMA acts on serotonin transporter, cocaine and amphetamine on dopamine) in both VTA and NAc
all addictive drugs…
increased DA in NAc
What types of drugs are considered CNS depressants? how do they work?
Alcohol: commonly abused, severe withdrawal
Sedative Hypnotics:
Barbiturate - no longer common
BZ - combined with other drugs
Work at GABAa receptor (increase GABAa receptor activity = increased CNS depression)
how do you treat alcohol abuse (a CNS depressant drug of abuse)
Naltrexone (opioid antagonist)
Disulfiram (neg SE)
Acamprosate (GABA analogue)
What drugs are considered opioids
Heroin
Morphine
Codeine
Oxycodone
How/why are opioids typically used?
Recreational use: produce sense of euphoria, reduces anxiety
*tolerance builds quickly, become physically dependent, severe withdrawal
How do you treat opioid (heroin, oxycodone, codeine, morphine) abuse?
Naltrexone (opioid antagonist)
Methadone (keeps levels constant)
What drugs of abuse are considered CNS stimulants
Amphetamines (ex Ritalin, Adderall, or Meth/ICE)
- increases release of DA, reverses DA transport through DAT (DA not able to be taken up at postsynaptic receptor)
What are therapeutic uses of CNS stimulants
Narcolepsy, ADHD (Ritalin, Adderall)
what CNS effects and peripheral effects due CNS stimulants (ampethamines, ritalin, adderall) have?
CNS:
- alertness, euphoria, excitement
- appetite suppression
- aggression, paranoia, delusions
Peripheral: increase BP, cardiac stimulation (may cause HF)
What withdrawal sx present when CNS stimulants (amphetamines) are dc
increased appetite, fatigue
Methamphetamine aka ICE, crystal meth… MOA, effect?
Increases release of DA and NE in basal ganglia
- more CNS effects that amphetamine (alert, euphorai, excitement, appetite suppression, aggression, delusions)
- may produce amphetamine psychosis
What long term/chronic effects does Meth have that are related to its addictiveness?
Chronic use may cause permanent neurotoxic damage to Noradrenergic and serotonergic neurons
- long term personality changes common
- rapid physical and psych dep
- craving in abstinence intense
- withdrawal may be severe and long lasting
What dangerous SE besides the addictive properties, does Meth have
Cardiac toxicity - Pulmonary edema and HF
seizures, organ damage, stroke, heart attack
DA transporter related SE of Meth include
meth induced loss of DA transporters (down reg DA transporters due to continuous stimulation) –> deficiency in both motor and memory
other SE of meth include
wt loss, whiter skin, odor (hyperthermia), dilated pupils, dental problems “meth mouth”, formication “meth bugs”,
What is cocaine and it’s MOA
alkaloid found in leaves of erythroxylon coca; ingredient of coca-cola until 1903
MOA: inhibits DA reuptake (blocks DAT, increases DA in cleft)–> physical and psych dependence
what effects does cocaine have? CNS, peripheral, Medical
think stimulant, SNS!
CNS stimulation: alertness, euphoria, anxiety, hyperactivity
Peripheral effects: cardiac
- tachy, vasoconstriciton, HTN, bronchodilation, hyperprexia, dilated pupils (all SNS)
Medical:
local anestheic, vascoconstrictor
Chronic cocaine use can result in
reduction in overall brain activity
- anxiety, insomnia, paranoia, hallucinations, repetitive behaviors, “cocaine bugs” (Formication)
- nasal congestion and perforated nasal septum
- intense psychological dependence (dysphoria, craving when levels drop)
- withdrawal can be severe
Describe cocaine potential OD/toxicity effects?
ventricular tachycardia and fibrillation, stroke, cerebral hemorrhage, seizures
which is worse: cocaine or meth withdrawal
meth
What is recommended tx/recovery process
detox and withdrawal
abstinence
long term support, 12 step, avoid environmental cues
Pharm: Bromocriptine to decrease cocaine craving
What drug helps with cocaine recovery
bromocription (activates DA receptors to prevent craving)
How is cocaine normally taken
intranasally (immediate onset of action)
“freebase” (can be inahled) -even faster onset
“crack lung”
“crack babies”
smoking & IV fastest
What is Nicotine MOA
activates nicotinic receptors in CNS and periphery
*increases 5-HT and DA release
CNS effects
What effects does Nicotine have on the body
CNS stimulant = mild euphoria, increased arousal, appetite suppression
- intense psych and physical dependence
- difficult withdrawal can last mths
PK of nicotine?
rapid absorption, half life 30 min, CYP450 metab, induces CYP450
how do you treat nicotine withdrawal
Bupropion
*treats craving, DA reuptake inhibitor
how does smoking effect nicotinic receptors
smokers have excess nicotinic receptors during first month of abstinence
What is MDMA and it’s MOA
3.4 Methylenedioxymethamphetamine
aka “ecstasy”
increases 5-HT activity by blocking reuptake and stimulating 5-HT receptors
*increases serotonin activity
How does MDMA affect the body
produces feelings of peacefulness, empathy, closeness and trust followed by confusion, depression, anxiety and paranoia
*increased BP and HR
SE of MDMA?
increased BP and HR, Hyperthermia, dehydration, kidney failure can lead to fatalities
Persistent memory loss may occur
outline the short term effects of MDMA
1) during excstasy, elevated mood due to increased 5-HT (blocked SERT, more serotonin in synapse)
2) After ecstasy: depression like feeling and irritability due to decreased 5-HT (down reg of serotnin receptors)
- decreased cerebral blood flow
what are long term effects of MDMA
significant decreases of serotonin present in cerebral cortex neurons (even 7 yr post ecstasy)
What is marijuana, how is it taken? pk?
delta–tetrahydrocannabinol (THC)
- smoked or eaten;
- quick absorption,
- very lipophilic, long half life
What are the effects of THC/marijuana?
Produces state of mild euphoria, well-being, altered sense of time, difficulty concentrating, introspection, tranquility
*no physical dependence; psych dependence possible
what is a unique aspect about THC?
no physical dependence or neuro adaptations
what is THC/cannabinoids MOA?
- Targets presynaptic cannabinoid (CB1) receptors
- Inhibits NT release (glutamate and ACh)
* bind CB1, and inhibits glutamate and ACh
What are adverse effects of MDMA?
- anxiety, decreased memory, impaired cognitive functioning
- amotivational “lazy” syndrome
- bronchial irritation, ^CA risk
- dec ovulation and test/sperm
- LBW, fetal malformations
What are bath salts? frequency of use?
synthetic “cannabinoid” AGONISTS
1/9 HS seniors
- psychoACTIVE effects
what effect do bath salts (CB agonists) have?
psychoactive:
paranoia, hallucinations, mood swings, aggression, outbursts
- elevated BP, HR
- not tested for human effects, high rate ER visits
what are some medical uses of marijuana
- decreased IOP (tx glaucoma) not proven to be effective
- decreased spasticity/ataxia, muscle weakness (tx MS, cerebral palsy, spinal cord injuries
- analgesic (cancer pain, post op pain, phantom limb)
- appetite stim
- antiemetic
- bronchodilation (asthma)
what are LSD, mescaline, & psilocybin?, MOA? effect?
Lysergic acid diethylamide (LSD)
- acts on 5-HT receptors in brain (not addicting, don’t stim DA pathway)
- euphoria, visual hallucinations, altered sense of time and reality, bad trips/flashbacks
- Synesthesia: one sensory modality assumes characteristics of another (colors hear or sounds seen)
what are SE of LSD
may increase BP, HR
flushing, dilated pupils
“bad trips”; flashbacks
altered sense of time, reality, synesthesia, euphoria, visual hallucinations
What are PCP, Ketamine, GHB? MOA?
Developed as general dissociate anesthetics (ketamine used as horse tranquilizer)
PCP (angel dust) and ketamine are NMDA receptor antagonists (glutamate hypothesis)
GHB is a GABA receptor weak agonist
what effects do PCP, Ketamine, and GHB have on the body?
- dissociative anesthetics, sensation of dissociation or “floating”
- PCP and ketamine may cause analgesia and aggression
- may produce amnesia and personality changes
- PCP often produces psychosis, (treat with haloperidol in ER)
- ketamine, GHB “date rape”
- increase BP, may cause coma with non reactive pupils
what are the date rape drugs
ketamine and GHB
what does PCP often cause, and how do you treat it?
PCP –> psychosis
treat with haloperidol in ER
increased BP, coma and non reactive pupils… cause?
PCP, Ketamine, GHB
what are inhalants and what effect do they have? MOA?
chem vapors (huffing)
- household cleaners, solvents, nitrates, ketones, hydrocarbons
- produce sense of euphoria
- mech unknown
- toxicity in many organs; lesions in brain’s white matter
What is nitrous oxide and how is it used
inhalant with rapid, short acting pleasurable effects
- causes peripheral neuropathy with chronic use
- OD can be fatal
- overused by dentists
what are amyl and butyl nitrite? effect?
“poppers” or “snappers”
SM relaxants
euphoria, light headedness, blurred vision, HA, nausea, hypoTN, tachycardia
