Abused Drugs Flashcards
Depressants
Ethanol, Benzos, Barbs, Solvents, GHB
Stimulants
Cocaine, Amphetamines, Me-phenidate
Opioids
Heroin, hydromorphone, oxycodone, fentanyl, methadone, W-18
Psychadelics
LSD, Mescaline, Psilocybin, Synthetics
Others
Cannabis and synthetic CBs, Bath Salts, PCP/Ketamine, Steroids, Nicotine, Caffeine
SUD Spectrum
Mild 2-3/11, Moderate 4-5/11, Severe 6+/11
Trend of Alcohol Use
Current drinking increases and binge drinking decreases with age
What is the neurobiological system of reward?
Mesotelencephalic DA system
What is the path of the Mesolimbic DA system?
VTA to NAcc
Changes in the craving state
Cues from hippocampus, amygdala, and stress from insula drive; PFC is compromised and normal executive fxn impaired –> enhances drug use behavior
Which drugs of abuse act on the VTA?
Opioids, ethanol, barbiturates, benzos
Which drugs of abuse act on the NAcc?
Amphetamines, cocaine, opioids, cannabinoids, phencyclidine
Which drugs act on GPCRs? Where?
Opioids, THC, GHB; VTA
Which drugs act on channels? Where?
Benzos, nicotine, ethanol; VTA
Which drugs act on transporters?
Cocaine, amphetamine, ecstasy
Ethanol distribution attributes
Rapid/wide in aqueous compartments, freely permeable across BBB and placenta, no protein binding/sequestration, no uptake into fat depots
Primary pathway of alcohol metabolism
Hepatic ADH (cytosolic) – NAD+ dependent (rate limiting), non inducible, some in stomach
What can block ADH?
Fomepizole
Secondary pathway of alcohol metabolism
CYP450 2E1>1A2>3A4 (MEOS – uses NADPH cofactor), high threshold, low capacity, but inducible
Acetealdehyde metabolism
ALDH – mitochondrial, NAD+ dep;
What blocks ALDH?
Disulfram
Acute actions of hydrocarbon inhalants
Rapid onset euphoria and short duration (similar to EtOH – early excitation and loss of inhibition followed by risky behavior, then dazed/drunk; later headache. bloodshot eyes(
Acute effects of nitrite inhalants
Vascular/smooth muscle dilation, hypotension, increased CBF
Adverse effects of inhaled hydrocarbons
Anxiety, decreased appetite, tinnitus, marrow & CNS pathology, tolerance, withdrawal symptoms (similar to EtOH)
Adverse effects of inhaled nitrites
Methemoglobinemia, decreased BP, HA
Effects of EtOH
Biphasic on NE/DA turnover, actions at GABA-A and NMDA-Glu receptors, action at cation channels, AC, and PI PLC
Acute psychological effects of EtOH
Dose-related excitation –>depression; alters cognitive, emotional, and behavioral functions, state dependent learning, labile affect, attention decreased and actions disorganized
Acute neurological effects of EtOH
Anterograde amnesia, positional nystagmus, EEG changes
Acute CV effects of EtOH
Myocardial depression, labile BP, arrhythmias, CVA potential, vasodilation, elevation of HDL3
Acute renal effect of EtOH
Diuresis (decreased ADH release)
Acute endocrine effects of EtOH
Increased release of CRF, ACTH, Cortisol, Oxytocin, PRL; Decreased release of GNH and GH
Attributes of pharmacodynamic tolerance
Membrane changes, GABA-R and GLU(NMDA)-R and Ca2+ channels
Attributes of metabolic tolerance
Induction of CYP450s (2E1, 3A4, 1A2)
Symptoms of EtOH abstinence syndrome
Craving, hyperirritability, anxiety, tremor, insomnia, nausea, sweating, hallucination, seizure
Delirium Tremons
Confusion, disorientation, agitation, hyperpyresis (fever, dehydration)
Tx of Alcohol OD
Supportive therapy, flumazenil if w/ benzos
Tx of methanol tox
Antagonize ADH w/ fomepizole or EtOH
Tx of withdrawal/abstinence syndrome
Sub therapy: BDZ, phenobarb
Symptomatic therapy: phenytoin, gapapentin
Supportive therapy: thiamine, NSAIDS
EtOH Recovery management
Discontinue sed/hyps, disulfram (aversive), naltrexone (anti-craving), acamprosate (anti-craving – is NMDA antagonist and GABA-A agonist)
PK of Cocaine
Liphophilic but charged; widely H2O distributed but redistributes to fat depots as well (Metabolism limited)
Metabolism of cocaine
Ester hydrolysis to polar products (cholinesterases); N-demethylation to active norocaine metabolite
Adverse effects of cocaethylene
seizures, immune system depression, hepatic damage
Cocaine excretion
Renal
Cocaine MOA
Blocks GNA (no change in RP); sypathomimetic effects indriectly by blocking presynaptic NE uptake; blocks DAT, NET, and 5HT transporters
Actions of cocaine
LA, vasoconstriction, psychomotor stimulant
Difference between amphetamine MOA and cocaine MOA
Amphetamines also block VMAT and reverse DAT so they secrete cytoplasmic rather than vesicular DA
Effects of cocaine
CV: Increased BP, HR, CO Respiration: hyperpnea Smooth M: Increased GI/UG tone Eye: mydriasis and cycloplegia Themoreg: hyperthermia Appetite: Suppression CNS: general arrousal> desynchronization> seizure
Cocaine order of events with behaviors
Euphoria –> dysphoria –> hallucinosis –> psychosis
Cocaine OD
Profound CNS excitation (hypervigilence –>extreme agitation –> seizure), cardiac arrhytmia, hypertensive crisis, respiratory paralysis
Stages of triphasic withdrawal syndrome in cocaine dependence
Crash (hours) –> subacute (days-weeks) –> extinction (months-years)
Opiate effects
CNS: euphoria (rush) –> sedation (nod), analgesia
Respiration: depression of CO2 drive/responsiveness
GI Smooth m: increased resting tone w/ decreased peristalsis/secretion
Eye: Miosis
Nausea/Emesis: stimulation of CTZ
CV: reduced TPR, orthostatic hypotension, cerebral vasodilation (increased CO2)
Opiate tox triad
Coma, respiratory depression, miosis
Acute abstinence syndrome for opioids
Mydriasis, sweating, piloerection, tachycardia, diarrhea, yawning, HTN, fever, craving, irritability, nausea, cramps, muscle/bone aches, dysphoria, insomnia –> protracted: periodic anxiety, insomnia, craving
Opiate OD Tx
Support vital fxns (esp respiration), naloxone
Opiate withdrawal tx
Methadone detox (cross dependence), clonidine detox + acetaminophen, decrease dose by 20-25%/d
Long term management of opiate abuse
Agonist maintenance: methadone (dosage issues)
Buprenorphine (+naloxone)
Antagonist tx: naltrexone
OIC Rx: MeNTX and naloxegol
MJ Absorption
Inhalation – 10-50% in circ, peak in 10-20 min
Oral – slow uptake, peak 1-3 hrs
MJ Distribution
95-99% plamsa protein bount – high distribution in lipid tissues; rapidly distributed into lipid environments (terminal t1/2 is almost a full day) – extended w chronic admin because extends half life
MJ Metabolism
Lungs and liver – lots of 1st pass; alkyl hydroxylation – active 11-OH THC (25% more potent); oxidative rxn –> inactive OH/COOH metabolisms
MJ Excretion
1/3 urine –> glucuronide and metabolites
2/3 fecal –> enterohepatic recirc
MJ Intox Syndrome
Euphoria, altered perception, intensified sensorium
—>
impaired goal-direction, lapse of attention, sedation
—>
Anterograde amnesia, narrowed visual field, poor coordination/rxn time
—>
anxiety, dysphoria, panic etc.
Acute MJ Effects on CNS
State-dependent learning, analgesia, thermoreg –> hypothermia, stimulates appetite, suppresses NV, suppresses REM sleep, decreases intraocular pressure
Acute MJ effects on CV
Tachycardia (20-100% increase in HR for 1-3hrs, dose-related), CO increase in supine position, postural hypotension
Acute MJ Effects on resipiratory, endocrine, and immune systems
Respiratory: bronchodilation, irritation of mucosa
Endocrine: less T and spermatogenesis in males, less PRL, LH, FSH, GH in females
Immune: impares cell and humoral responses (increases susceptibility)
NT and Molecular MOA for MJ
NT: catecholamines, GABA, opioids, serotonin, glutamate, ach
Molecular: AC inhibition (Gi), calcium channel inhib, K channel activation
Signs/Symptoms of MJ Dependence (Withdrawal syndrome)
Irritability, restlessness, insomnia anorexia nausea, diarrhea, sweating, increased Tb, weight loss, hand tremor, salivation, tearing, REM rebound, sleep disturbances (usually gone w/in 48 hrs)