Drugs of abuse sedative hypnotics alcohol Lecture Flashcards
Benzodiazepines
- alprazolam
- chlordiazepoxide
- clonazepam
- clorazepate
- diazepam
- flurazepam
- lorazepam
- midazolam
- oxazepam
- triazolam
Benzodiazepine antagonist
-Flumazenil
Barbiturates
- Amobarbital
- butabarbital
- pentobarbital
- phenobarbital
- secobarbital
- thiopental
Misc/Newer sedative-hypnotic drugs
-Buspirone
-eszopiclone
-meprobamate
-ramelteon
-zaleplon
-zolpidem
(BEMRZZ)
Drugs for tx of acute alcohol withdrawal syndrome
- diazepam, lorazepam, oxazepam
- thiamine (Vit B1)
drugs for prevention of alcohol abuse
- acamprosate
- disulfiram
- naltrexone
drugs for tx of methanol/ethylene glycol poisoning
- ethanol
- fomepizole
drugs used to tx dependence and addiction
- opioid R antagonist- naloxone, naltrexone
- synthetic opioid- methadone
- partial u-opioid R agonist- buprenorphine
- nicotinic R partial agonist- varenicline
- benzodiazepines
- NMDA R antagonist- acamprosate
Sedative
- dec CNS activity, moderates excitement, and calms recipient
- fast acting compared to SSRIs
hypnotic
- produces drowsiness and facilitates the onset and maintenance of sleep
- recipient can be aroused easily
Benzodiazepines and barbiturates- CNS effects
- barbiturates- no plateau
- benzodiazepines- less dangerous- effects plateau!!
Benzodiazepines and barbiturates- moa
- benzodiazepines- GABAa Rs
- barbiturates- GABAa Rs
Benzodiazepines- moa
- hepatic metabolism (CYP3A4), excretion via kidney
- elimination half-lives vary- cumulative toxicity
- binds to GABAa R- enhances GABA’s effects (shifts dose response curve to left)- inc chloride influx- inc hyperpolarization- dec number of APs (CNS depression)
- diazepam, alprazolam, lorazepam
- risk of dependence, tolerance
Benzodiazepines- cumulative toxicity
-drugs w long half-lives are more likely to cause cumulative effects w mult doses!!
Barbiturates- moa
- hepatic metabolism and excretion via kidney
- binds to GABAa R and inc duration of GABA-gated channel openings- inc chloride influx- inc hyperpolarization- dec number of APs (CNS depression)
- phenobarbital, amobarbital, secobarbital
Newer hypnotics (sleep aids)- moa
- hepatic metabolism (CYP3A4) and excretion via kidney
- binds to GABAa Rs that contain the alpha1-subunit- inc chloride influx- inc hyperpolarization- dec number of APs (CNS depression)
- tx sleep disorders!!!
- eszopiclone, zolpidem, zaleplon
Tx of anxiety states
Benzodiazepines
- advantages- high therapeutic index, antagonist available: flumazenil, low risk of drug-drug interactions, minimal effect on CV or autonomic fxn
- disadvantages- risk of dependence, depression of CNS fxn, amnestic effects, CNS depression when combined w other drugs
- Newer antidepressants are sometimes preferred (SSRIs)
Tx of insomnia
- sleep aids- zolpidem, zaleplon, eszopiclone (highly effective, rapid onset w minimal hangover effects)
- Benzodiazepines can be used- but cause daytime sedation
Tx of insomnia- Ramelteon- moa
- agonist at MT1 and MT2 melatonin Rs
- oral bioavailability is < 2% (first-pass metabolism)
- metabolized by CYP1A2 to active metabolite
- avoid coadmin w fluvoxamine (SSRI and CYP1A2 inhibitor)
Buspirone
- tx generalized anxiety disorder
- anxiolytic effects may take more than 1 wk to become established
- does not cause sedation, hypnotic, anticonvulsant, or m relaxant effects
- metabolism by CYP3A4
Alcohol
- first-pass metabolism by gastric and liver ADH (alcohol dehydrogenase)
- zero-order kinetics (rate of biotransformation is indep of time and conc of ethanol- enzymes are almost immediately saturated)
- typical 70 kg adult can metabolize 7-10 g of alcohol per hour (1 drink)
Ethanol and methanol biotransformation
-ethanol, methanol–alcohol dehydrogenase–> acetaldehyde (hangovers)–aldehyde dehydrogenase (inhibited by disulfiram)
alcohol- ion channels
NMDA R (glutamate- primary EAA of CNS)
-alcohol inhibits the ability of glutamate to open the cation channel of NMDA R- inc depression of CNS
-memory loss- due to inhibition of NMDA R activation
GABA R (GABA- primary inhibitory Nt of CNS)
-alcohol enhances effects of GABA on GABAa R
alcohol- clinical pharmacology
- Acute alcohol intoxication
- chronic alcohol abuse: acute withdrawal syndrome vs alcohol dependence
Acute alcohol intoxication- tx
- monitor resp depression ad aspiration of vomit
- glucose- tx hypoglycemia and ketosis
- thiamine- protect against Wernicke-Korsakoff syndrome
Acute withdrawal syndrome- tx
- can be life threatening
- prevent seizures, delirium, arrhythmias; electrolyte rebalancing; thiamine tx
- benzodiazepines
Alcohol dependence
-psychosocial tx- primary tx!
Alcohol dependence- tx
- Naltrexone
- Acamprosate
- Disulfiram
Naltrexone- moa
- tx alcohol and opiate dependence
- u opioid R antagonist (long-acting)
- reduces craving for alcohol and rate of relapse to drinking or alcohol dependence for short term (12 wks)
- must be opioid-free b/f starting tx!!
Acamprosate- moa
- weak NMDA-R antagonist and GABAa R agonist
- reduces short-term and long-term relapse rates (> 6 months)
Disulfiram- moa
-irreversibly inhibits aldehyde dehydrogenase (build up of acetaldehyde- hangovers)- causes extreme discomfort when drink alcohol
schedule 1-IV
- I- no medical use, high addiction potential
- II- medical use, high addiction potential
- III- medical use, moderate abuse potential
- IV- medical use, low abuse potential
PSP and LSD- long term effects
- PCP- irreversible schizophrenia-like psychosis
- LSD- flashbacks of altered perception yrs after consumption
Disinhibition of DA neurons in the VTA- what drugs?
Inhibition of GABA inhibitory neurons (causes Dopamine release)
- Opioids
- THC, CBD, other cannabinoids
- GHB
drugs that bind transporters of biogenic amines
Inc conc of dopamine in synapse
- Cocaine- inhibits DA reuptake
- Amphetamine- gets taken up into vesicle so dopamine is not, so gets exported out
