Egleton: Drug Abuse Flashcards
Cause of pleasure sensation
Mesolimbic tract
Dopamine
Cause of craving
PFC
Hippocampus
Cause of withdrawal
Hypothalamus
Brain stem
Meds with Direct effect
Cocaine
Amphetamine
Meds with Indirect effect (disinhibition)
Nicotine Alcohol Opioids Benzos Cannabinoids PCP
Severity of addiction depends on what
Dose and Duration
Opioids: MoA
Stimulate opioid receptors in mesolimbic reward circuit
Inhibit GABAergic transmission
Increased Nucleus accumbens Dopamine release
Induce Euphoria, then tranquility and drowsiness
Opioids: overdose
Decreased respiratory rate Decreased bowel sound Constricted pupils Dereased tidal volume Depressed mental status
Opioids: treatment
Ventilation
Naloxone (IV/IM)
Opioids: maitenance
Methadone maintenance (gold standard) {reduce craving and withdrawal}
Buprenorphine (partial Mu agonist, Kappa antagonist) {induce withdrawal abstinence}
Naltrexone (antagonist) {prevent relapse}Opioids: withdrawal
Pupil dilation
Yawning
Increased bowel sounds
Hypotension (by diarrhea and vomiting){loss of volume}
Dysphoria, Restlessness Rhinorreha, Lacrimation Myalgias, Arthralgias Nausea, Vomiting, Abdominal cramping, Diarrhea Hypersensitivity to pain
Oxycodone
Hillbilly heroin Delayed release formulation Longest actign pain reliever on market Cheap Combination with Acetaminophen> potential Liver problem
Heroin
Diacetylmorphine metabolized to 6-monoacetylmorphine then Morphine
High BBB penetration
Effects by 6-monoacetylmorphine and Morphine
Urine test detects 6-monoacetylmorphine specific heroin metabolites
Cheese heroin
Mixture of Black tar heroin and Tylenol PM
{liver damage!}
Krokodil
The living dead
Russian addicts
Leaves scaly skin akin to crocodile’s
Benzodiazepines {BDZ}
Generally safe in overdose {unless with Alcohol/ depressants}
Sedative/ cause CNS depression with normal vital sign
Antidote= Flumazenil
Abrupt withdrawal= Tremor, Anxiety, Perceptual disturbance, Dysphoria, Psychosis, Seiuzures
Treated with Diazepam (IV)
Flunitrazepam
Roofie drug
Date rape drug (added to drinks)
Barbituates
Sedative
Can lead to respiratory depression and death
No antidote
Propofol
In anesthesia
Short power naps for Anesthesiologists
Short term effects: Mild euphoria, Hallucination, Disinhibition
Long term effects: Addiction
Gamma-hydroxybutyrate
Sedative
Date rape drug (put into drinks)
CNS depressant, Increase release of endogenous opioids
ADR: Drowsiness, Dizziness, Nausea/ Vomiting
Toxicity: Amnesia, Seizures, Cardiopulmonary depression, Coma, Death
Alcohol
Stimulate both GABA and Opioid transmission
Antidote= Naltrexone
Antabuse= Disulfiram
Amphetamines
Directly increase levels of Dopamine in Nucleus accumbens
Metamphetamine is the most effective (BBB crossing)
Meth is better at it.
Amphetamines: MoA
Increase neurotransmission in central NE, DA and 5-HT system by their release
Low dose: NE released more
Moderate dose: NE and DA released
High dose: NE, DA, 5-HT released
{NE>DA>5-HT}
Blockade of reuptake of NE, DA, 5-HT
Inhibition of MAOMeth
Increase attention, Concentration, Focus, Talkativeness
Good for ADHD
Increase vigilance, Wakefulness
Decrease fatigue, Appetite
Increased mood, Elation, Euphoria, Self confidence, Psychomotor stimulation
Popular in college campus
Oral, nasal, IV
Rapid onset, Prolonged symptoms
Meth: ADR
{Like Schizophrenia}
Acute: Restlessness, Anxiety, Insomnia, Agitation, Aggressiveness, High dose= Convulsions
Chronic: Paranoid schizophrenia-like state, Delusions, Hallucinations
CV: Palpitations, Arrhythmias, Hypertension, Anginal pain, Circulatory collapse
GI: Anorexia, Nausea/Vomiting, Abdominal cramps, Diarrhea
Others: Meth mites, Meth mouth, etc
Headaches, chills, sweating, Fulminant hyperthermnia, DIC, Rhabdomyoslysis, Renal failure, Hepataotoxicity
Meth: Tolerance
With chronic use
Withdrawal symptoms of Mental depression, Fatigue, Hunger
Meth: Overdose
CNS stimulation (Agitation, Delirium, Acute psychosis) Tachycardia Hypertension Dilated pupils Diaphoresis Hyperthermia
Meth overdose treatment, avoid what
Beta blockers
Meth overdose treatment: meds
Benzodiazepine (Lorazepam, Diazepam) Antipsychotics (Chlorpromazine, Haloperidol, Droperidol, Ziprasidone) Stabilize airways and CV function Activated charcoal Control seizure Modify urine pH
Meth: Withdrwal
Mental depression
Fatigue
Ravenous hunger
MDMA:MoA
Amphetamine derivative
Indirect serotonergic agonist
{Increase 5-HT release, Block reuptakes}
MDMA: action
Prolonged effect up to 1wk Sympathomimetic and Psychotomimetic Increased Euphoria, Empathy Enhances pleasure Heightens sexuality Expands consciousness Positive change in self-image
MDMA toxicity
{Problem if dehydrated}
Narrow margin of safety
Cardiac arrhythmias
Hyperthermia
Convulsions
Rhabdomyolysis
renal failure
Fatalities
Psychosis
Depression (after long term use)
Chronic use= Hepatic damage
Cocaine: MoA
Blocks reuptake of NE, DA, 5-HT
Blocks Na channel
{Act as local anesthetics for eye/nasal surgeries}
Increase concentration of excitatory AA (Glutamate, Aspartate) in Nucleus accumbens
Cocaine: CNS stimulation
Increase mental awareness, Euphoria
Feeling of well being, Increaed self confidence
Hallucinations, Delusion, Pranoia
Reduction of fatigue
Restlessness, Irritability, Anxiety, Sleeplessness, Mood swings
Cause of cocaine craving
Chronic cocaine intake= DA depletion by breakdown
Cocaine: withdrawal
Fatigue, Depression, Sleep disturbance, Increased appetite
Cocaine metabolites
Active metabolite:
Cocaethylene (formed only in presence of alcohol via transesterifcication, 17%)
{Crosses BBB, block reuptake, as potent as cocaine}
Inactive metabolites:
Benzoylecgonine (spontaneous hydrolysis, 50%)
Ecgonine (plasma/ liver pseudocholinesterase 40-50%)
Norcocaine (liver P450 induced demethylation, 5%)
Cocaine: overdose toxicity
Cardiac failure (rapid elevation of blood pressure= stroke, irregular heartbeat, cardiac arrest}
Delirium, Violent behavior
Weak and irregular pulse
Tonic-clonic seizures
Malignamnt encephalopathy
Cocaine: treatment
Agitation: Benzodiazepine (Diazepam, Lorazepam}
Hypertension: Benzodiazepine, Phentolamine
MI: Aspirin, Nitroglycerin, Phentolamine
{No Beta blockers for Hypertension and MI}
Bromocriptine: DA agonist, reduces craving of drug?
Cocaine: prolonged use
Addiction and Physical dependence
Malnutrition, Weight loss, Sexual problems, Mental confusion, Anxiety
Cocaine babies
Hyperactivity, tension, Muscle stiffness, Poor reflexes, Delayed motor development
Levamisole
Anthelminthic drug used by vets in Mexico
MAOI and COMT inhibitory action
Induce Neutropenia, Agranulocytosis
Crack
Free base form of Cocaine
“Crack lips” due to hot pipe
Bath salts
Designer drugs
Metphedrone, MDPV, Methylone
{Cathionones= similar to Amphetamine}
Bath salts: MoA
Similar to Amphetamine {transporter inhibition}
Not as potent
Induce Feeling of empathy, Stimulation, Alertness, Euphoria, Mood lift, Appreciation of music/ Awareness of senses
Bath salts: ADR
Similar to Amphetamine’s
Bath salts: treatment
{Similar to Amphetamine's}
Benzodiazepine (Lorazepam, Diazepam)
Antipsychotics (Chlorpromazine, Haloperidol, Droperidol, Ziprasidone)
Stabilize airways and CV function
Activated charcoal
Control seizure
Modify urine pHKhat
East Africa, Arabian-Peninsula
From Catha edulis (flowering shrub’s shoots/ leaves)
Cathinone= active chemical
Structurally similar to Amphetamine, similar potency
90 min of action
ADR/ Withdrawal same as Amphetamine’s
Nicotine
From Nicotiana plant Lipid soluble Tertiary amine Rapidly absorbed/ distributed Cotinine= metabolite Tars in cigarette smoke accelerates metabolism of other drug
Used for smoking cessation therapy
Nicotine: MoA
Activate Cholinergic nicotinic receptors (CNS, PNS)
Initially stimulate>then block receptor
Inhibit MAO= activate DA neurotransmission (dependence)
Stimulate NE/DA release
Promote mild euhpria
Increase Arousal and Concentration
Improve memory
Suppress appetite
Nicotine pharmacokinetics
Absorption: lung, GI, skin Cross placental membrane Secreted in milk Metabolized in Lung/ Liver= Cotinine is the metabolite Urinary excretion
Nicotine: ADR
Irritability, Tremors, GI cramps, Diarrhea, Increased HP and BP
Nicotine: Toxicity
Central respiratory paralysis
Hypotension from Medullary paralysis
Nicotine: withdrawal
Irritation, Anxiety, Restlessness, Frustration, Difficulty concentrating, Headache, Insomnia
Peak 1-2 days after quitting
Decrease over weeks
Caffeine: Use
Treat idiopathic apnea of premature neonates {Caffeine citrate}
Acute Circulatory failure
Diuretics
Treat Spinal puncture headaches (Caffeine sodium benzoate}
Adjuvant for Analgesics
Caffeine: MoA
Methylxanthine
Translocation of extracellular Ca2+
Inhibit PDE> Increase cAMP, cGMP
Blockade of Adenosine receptors {induce wakefulness}
Caffeine: Effects
Decrease fatigue
Increase mental alertness
{100-200mg}
Increase anxiety and tremor (1.5g)
Increase spinal cord stimulation (2-5g) Cardiac arrhythmias (Lethal dose= 10g)
Why are kids hyper on Halloween nights?
Dark chocolates got caffeine, yo!
Caffeine: other effects
Mild diuretics
Positive inotropic/ chronotropic effects at high dose
Increase secretion of gastric HCl
Insomnia, Anxiety, Agitation at moderate doses
Emesis and Convulsions at high doses
LSD (Lysergic acid diethylamide)
5-HT1/2 agonist
Hallucinations with brilliant color {Visual hallucination}
Mood alteration
LSD: ADR
Hyperreflexia Nausea Muscle weakness Increased HP, BP Mydriasis Flashbacks (days-1yr)
Not drug of abuse
LSD: treatment
Haloperidol (block hallucinations {Neuroleptic therapy}
Ketamine and Phencyclidine (PCP)
Glutamate action antagonist
Anticholinergic
Cause dissociative anesthesia
Ketamine and Phencyclidine (PCP): ADR
Extremity numbness Staggered gait Slurred speech Muscular rigidity Increase BP/ HR Nausea/Vomiting Violent behaviors Suicidal Seizures
Hallucinogenic mushrooms
“Shroom”
Psilobycin, Psilocin
20min-6hr effects
Dilated pupils, Confusion, Vertigo
Exhilaration, Laughter, Hallucinations
Tachycardia, Hypertension
Nausea/ Vomiting
Hallucinogenic mushrooms: Treatment
Activated charcoal
Diazepam
Peyote
By Apache, Navajo, and Plains Tribes
Used in Native American Church rituals, Legal for them
Peyote= small, spineless cactus
Contain Phenethylamine alkaloids (Mescaline)
Similar to LSD, but not as potent
Marijuana
THC (delta9-tetrahydrocannabinol) metabolized to 11-OH-delta9-THC
Receptors in Basal ganglia, Hippocampus, Cerebellum
Euphoria followed by Drowsiness/ Relaxation
Impairs short-term memory and mental activity
Visual hallucinations
Delusions
Increased HR
Munchies
Tolerance, Withdrawal Addiction possible
Lipophilic
Dronabinol
THC (Tetrahydrocannibinol)
Treat severe nausea and pain by AIDS/ Cancer
Appetite stimulant
“Medical marijuana”
Marijuana vs Hashish-Hash oil
Lipophilic
NBome
5HT2A agonist
Agitation, Hallucinations
Tachycardia, Hypertension
Treat with Benzodiazepine (IV)
Prolonged periods of aggressive behavior
Inhalants
Volatile solvents
Aerosols
Gases
Nitrites
Tend to have burned mouth{b/c of solvent on their mouth and high prevalence of smoking}
Axonopathies, Hepatotoxicity, Cardiotoxicity
Alcohol high
Euphoria, Delusion, Sedation, Hallucinations
