Drugs of Abuse 2 Flashcards
What are sedative hypnotics?
CNS depressant that has a range of magnitude depending on the dose from anti-anxiety to sedation to hypnosis and finally, general anesthesia
Sedative Hypnotic method of action
increases inhibitory signals from GABA neurons which decreases glutamate signals; GABA causes inhibition by selectively opening chloride channels resulting in hyperpolarization and decreased ability for post-synaptic neuron transmission; sedative hypnotics bind to different parts of chloride channels in CNS and modulate their activity
Examples of sedative hypnotics
Benzodiazepines, Flumazenil, Zolpidem and the Z drugs, Barbituates, Gamma-hydroxybutyric acid (GHB), Buspirone
Benzodiazepines and their pharmacology
among the most widely prescribed drugs in the world and activates the benzodiazepine receptor which increases the frequency of the opening of the chloride ion channel; normally taken as tablet or capsule (sometimes IV) and have a high therapeutic index
Short-term effects of Benzodiazepines
CNS- relaxation, calmness, relief from anxiety and tension, and drowsiness, lethargy, fatigue, impairment of thinking and memory
Lungs- respiratory depression
Motor- skeletal muscle relaxation and impairment of motor coordination
minimal REM suppression and anti-convulsion
Long-term effects of Benzodiazepines
varies btwn individuals; some can demonstrate symptoms of chronic sedative-hypnotic intoxication (impaired thinking, poor memory and judgment, disorientation, slurred speech, incoordination)
Pregnancy and elderly considerations with Benzodiazepines
crosses placenta and secretes into milk causing fetal abnormalities and sedation/death
metabolized slower in elderly leading to cognitive dysfunction and over-sedation
Abuse potential and dependence with Benzodiazepines
low abuse liability and inherent harmfulness due to high therapeutic index (leads to a lot of overdose w out death), some tolerance and a high degree of cross tolerance, low dependence and addiction can occur
Flumazenil
benzodiazepine receptor antagonist that blocks the effects of benzos and used as an antidote for benzo overdose
Zolpidem and the Z drugs
bind to subset of GABA receptors causing sedation and disturb REM sleep even less
Barbiturates and their pharmacology
activates barbiturate receptor and increases the duration of opening of chloride channel and can be long-acting (phenobarbital), short-acting (secobarbital) and ultrashort-acting (thiopental); have low TI, demonstrates a full spectrum of CNS depression, suppress REM sleep and suppresses respiratory and cardiovascular system
Short-term effects of Barbiturates
tranquility, mild euphoria, relaxation,
Long-term effects of Barbiturates
chronic inebriation, impairment of thinking, judgment, and memory, hostility and mood swings
Abuse potential and dependence of Barbiturates
high abuse liability, high inherent harmfulness due to risk of death from respiratory depression and withdrawal, rapid tolerance to sleep and mood effects but slower for motor impairments, high dependence measured by severe withdrawal syndrome, addition occurs
Gamma-hydroxybutyric acid (GHB)
antagonist to GABA receptors causing sedation and anesthesia; causes euphoria first and has been implicated as a date rape drug; not clinically used in North America
Buspirone
acts on serotonin receptor instead of GABA and used in generalized anxiety states because it doesn’t have an additive effect with other sedative-hypnotics
ADME of alcohol
A- rapidly absorbed from stomach and upper intestines
D- distributes all over body; readily gains access to brain and crosses placenta
M- converted to acetaldehyde (which produces unpleasant effects) by ADH, then to acetate by ALDH that is then broken down into CO2 and H2O
E- most eliminated by biotransformation in the liver and the rest excreted in breath, urine and sweat
Pharmacology of Alcohol
CNS depressant that binds chloride channel and enhances GABA-mediated inhibition
Short-term Effects of Alcohol
Lose dose: vasodilation of vessels to the skin, increased gastric secretion
high dose: arrhythmia, irritation of GI tract causing vomiting and ulcers, can inhibit glucose production, can lead to blackouts, impaired judgment, violence and respiratory depression
Long-term Effects of Alcohol
mental disorders, cardiomyopathy, hypertension and stroke, fatty liver to hepatitis to cirrhosis
Abuse potential and dependence of Alcohol
significant reinforcing properties and moderate dependence liability, tolerance can develop to chronic use, dependence and addiction occurs
Cross-tolerance with alcohol
increased doses of sedative hypnotics and general anesthetics needed for someone with tolerance to alcohol (bc it can increase activity of metabolic enzymes in the liver)
Alcohol Treatment
Disulfram- inhibits ADH so perceived adverse effects occur to deter user
Naltrexone- opioid antagonist that blocks activation of reward pathways
Acomprosate- ethanol susbtitute that acts as a GABA activator
MOA and Administration of Cannabis (THC)
bind to CB1 receptors in the brain that inhibits the release of excitatory neurotransmitters; when inhaled the absorption is rapid and onset of action is immediate, after oral administration absorption is slow and incomplete with delayed onset of action; slowly metabolized
Short-term effects of Cannabis
relaxation, drowsiness, euphoria, impaired motor coordination and judgment, pseudo-hallucinations, increased HR and blood flow to extremities, increased appetite and dry mouth, reduces sex drive and disruption of ovarian cycle
Long-term effects of Cannabis
significant mental impairment can occur but disappears upon cessation, increase HR and bp that are reversible,, lung disease and lung cancers if smoked, decreased fertility and can cause defects in fetus
Medical uses of Cannabis
prevention of nausea and vomiting associated with anti-cancers, increased appetite in anti-HIV drugs, neuropathic pain relief
Abuse potential and dependence of Cannabis
dependence liability is low to moderate bc euphoria is less reinforcing, low inherent harmfulness, tolerance to psychoactive, cardiovascular effects and impairment of functions, dependence can occur w high doses, and addition can occur
Narcotic Analgesics: Opioids and Opiates
opium comes from palaver somniferum, opiates are drugs derived from opium like codeine and morphine and opioids are any substances that exert actions on the body similar to those produced by morphine
Opioid MOA
block pain pathways in the CNS through activation of primarily mu receptors (but also kappa and delta) that reduce presynaptic release transmitters from pain impulses, block their post-synaptic effect, activated inhibitory pathways to block pain input and reduce the emotional reaction to pain
Short-term effects of Opioids
producing indifference to pain, sedation and hypnosis, suppression of cough centre, respiratory depression, reduces the release of sex hormones (reduced libido and menstrual irregularities), mioisis (pupil constriction), irregular HR, low body temp, constipation
Long-term effects of Opioids
mood instability, pupillary constriction (impaired nigh vision), constipation, reduced libido, menstrual irregularity and respiratory impairment
Therapeutic uses of Opioids
uses for morphine but not as much for heroin relief of severe pain, treatment of diarrhea, cough suppression
Abuse potential and dependence of Opioids
high abuse potential, low inherent harmfulness for low doses but can be deadly in high doses bc respiratory suppression can lead to death, hazards with injecting, dependence and addiction develop to euphoric effects
Opioid dependence treatment
oral methadone replaces opioid drug and dose is reduced slowly over time, the dose is not reduced but it substitutes it (risk-reduction bc availably orally), naxolone used to treat an overdose
