Kruse: Intro to drugs of abuse sedative-hypnotics, alcohol Flashcards
What is a sedative
-a drug that decreases CNS activity, moderates excitement, and calms the recipient
What is a hypnotic
-a drug that produces drowsiness and facilitates the onset and maintenance of sleep and from which the recipient can be aroused easily
Why are benzodiazepines better than barbiturates?
- barbiturates keep going up with the higher dose in CNS effects
- Barbiturates will plateu
Benzodiazepenes
- Act on GABA a receptors
- cause sedation, hynotic effects, muscle relaxation, anxiolytic and anticonvulsant effects
Barbiturates
- Act on GABAa receptors
- cause a wide spectrum of effects: mild sedation to anesthesia
MOA for Benzos
- bind to GABAa receptors and enhances GABA’s effects
- increased chloride influx, hyperpolarization, decreased number of action potentials
What enzyme will metabolize the benzos
- liver
- CYP3A4 and glucuronidation (phase 2)
- cumulative toxicity
What excretes the benzos
Kidneys
Barbiturates metabolism
- hepatic
- excretion via kidney
- Phenobarbital excreted unchanges
- elimination half lives long and can lead to toxicity
- can induce CYP450 enzymes
MOA for Barbiturates
- binds to GABAa receptor
- increases the duration of GABA-gated channel openings
what are benzos used for?
- anxiety sometimes
- high therapeutic index, antagonist available for overdose
- risk of dependence, depression of CNS function, amnestic effects, CNS depression when combined with other drugs
Which drugs are good for insomnia
-zolpidem, zaleplon, and eszopiclone
Ramelteon
- MOA: agonist at MT1 and MT2 melatonin receptors
- metabolized by CYP1A2 to active metabolite
- dont give with fluvoxamine
adverse effects of Ramelteon
-dizziness, somnolence, fatigue, and endocrine changes
Buspirone
-good for generalized anxiety disorder
-anxiolytic effects may take more than a week to become established
-no sedation
-metabolized by CYP3A4 a lot
-
What do we have to know about alcohol?
- high first pass metabolism by ADH
- zero order inetics
- 70kg adult can metabolize 7-10 g of alcohol per hour… one drink
What enzyme will give us a hangover if it doesn’t work?
- aldehyde dehydrogenase
- gets rid of acetaldehyde
What do we do for acute alcohol intoxication
- monitor respiratory depression and aspiration of vomitus
- glc can treat metabolic alterations such as hypoglycemia and ketosis
- thiamine to protect against wernicke-korsakoff syndrome
Naltrexone
- tx for alcohol and opiate dependence
- MOA: mu opiod receptor antagonist
- reduces craving for alcohol and the rate of relapse to either drinking or alcohol dependence for the short term
- cant be on opioids before starting this therapy
Acamprosate
- MOA: weak NMDA-receptor antagonist and GABAa receptor agonist
- reduces short-term and long term relapse rates (more than 6 months)
Disulfiram
- MOA: irreversibly inhibits aldehyde dehydrogenase and causes extreme discomfort in pts who drink alcoholic beverages
- pts must be highly motivated
What does cocaine and amphetamines do?
-keep dopamine concentration high in the synapse
What does Alcohol dehydrogenase do?
- metabolizes ethanol into things
- acetaldehyde is the bad one that gives us hangovers
What CYP enzyme degrades alcohol?
- CYP2E1
- turns it into Acetaldehyde
What is an NMDA receptor
- subtype of glutamate receptor
- that is the primary excitatory NT in the CNS
- learning and memory
- glutamate binds and then a cation channel opends… good for CNS
What does alcohol do to the NMDA?
- inhibits the ability of glutamate to open the cation channel of the NMDA receptor
- leads to and increased depression of the CNS
- this is why memory loss occurs with alcohol consumption
What do we give for acute withdrawal syndrome
-benzos
What does aldehyde dehydrogenase do?
-turns acetaldehyde into other things like formic acid and whatnot
With the schedule class thing, what does the numbers 1-4 mean?
- 1 is the most addictive, no medical use
- 4 is the least addictive
What is disinhibitio fo DA neurons in the VTA
- inhibition of GABA inhibitory neurons
- opioids do this
- THC and other cannabinoids do this
- and so does gamma hydroxybutyric acid (GHB)
