Kruse- Intro to Drugs of Abuse Sedative-Hypnotics Alcohol Flashcards
Sedatives do what?
-decrease CNS activity, moderate excitement, and calms the recipient
Hypnotics do what?
-produces drowsiness and facilitates the onset and maintenance of sleep and from which the recipient can be aroused easily
Where/How do Benzodiazpines work?
- Act on ligand gated ion channels aka GABAa receptors
- cause sedation, hypnotic effects, muscle relaxation, anxiolytic and anticonvulsant effects
- makes receptor more active in lower concentrations of GABA
- so you need BOTH a BENZO and GABA receptor presents
Where/How do Barbiturates work?
- Act on GABAa receptors
- cause a wide spectrum of effects: mild sedation to anesthesia
- Keep receptor open for longer period of time
Where do Benzodiazepines distribute?
-CNS, Placenta, and Breast-milk
How are Benzodiazepines processed?
- CYP34A phase 1
- Glucuridation phase 2
Do Benzodiazepines have a risk of dependence and tolerance?
-yes
Benzodiazepines examples?
- Diazepam (Valium)
- alprazolam (Xanax)
- lorazepam (Ativan)
Half life and onset of Chlordiazepoxide? active metabolites?
- greater than 100 hours
- intermediate onset
- yes
Half life and onset of Diazepam? Active metabolites?
- greater than 100 hours
- very fast
- yes
Half life and onset of Oxazepam? Active metabolites?
- 5-14 hours
- Slow
- none
Half life and onset Lorazepam? Active metabolites?
- 10-20 hours
- intermediate
- none
Use of Midazolam?
- rapid on and rapid off
- dentists use this to induce anesthesia or in other quick surgery settings
Intermediate to lond acting Benzodiazepines are?
- Diazepam
- Lorazepam
- Clonozepam
Short acting benzodiazepines are?
- Midazolam
- Oxazepam
- Alprazolam
- Temazepam
- Triazolam
How do Barbiturates work?
What are examples?
risk of dependence and tolerance?
- binding to GABA a receptor and increase duration of time the channel is actually open
- —“arbitals”
- yes, risk of both but not all people have risk or dependence. all people build tolerance
How do Benzodiazepines work?
-Causes GABA receptors to be activated at lower concentrations
Barbiturates are mostly used for what? examples?
-sleep aids
-Eszopiclone
-Zolpidem
-Zaleplon
“Sleep Ezzy with barbiurates”
Sedative-hypnotics are used to treat what?
-anxiety, insomnia, epilepsy, siezures, control withdrawals
Benzo Drugs to treat anxiety?
How high is the theraputic index? What is the antagonist (antidote) to overdose?
What are the disadvantages?
- Clonazepam
- Lorazepam
- Alprazolam
- Diazepam
- high
- Flumazenil treats OD
-disadvantages are dependence risk, CNS depression, SSRIs are preferred for these reasons
Benzo drugs used for insomnia? side effect?
-Eszopiclone (long half life)
-Zolpidem (2 sustain sleep)
-Zaleplon (both Zol and Zal act rapidly)
EZZy Sleep
-sleep shopping and sleep driving
Ramelteon is used to treat what?
MOA?
bioavailability?
Metabolized by?
- insomnia
- agonist at MT1 and MT 2 melatonin receptors
- low bioavailability
- CYP1A2
Buspirone is used to treat what? how long to take affect? Does it cause sedation, hypnotic, euphoric, etc? MOA? Metabolized for?
- general anxiety
- takes a full week
- no it does not
- unknown
- CYP3A4
What is responsible for breaking down alcohol?
How high is it’s first pass?
How much metabolized per hour?
- alcohol dehydrogenase (ADH)
- alcohol had zero order kinetics meaning as soon as you start drinking all the enzymes used in its biotransformation are maxed out
- 7-10gs per hour should take 1 drink per hour
What causes hangovers?
pathway?
why are fewer asains alcoholics?
- acetaldehyde build up
- alcohol–> acetaldehyde–>acetic acid
- higher concentration of people with polymorphisms of alcohol dehydrogenase
What is the primary excitatory NT in the CNS?
what does alcohol do to it?
whats the major inhibitor in the CNS?
- NMDA glutamate receptors
- alcohol inhibits this
- GABA receptor
what is acute alcohol intoxication? what should you do?
- drunk person
- monitor breathing and inhaling of vomit
- treat w/ glucose and thiamine to prevent korsakoff syndrome
what is chronic alcohol abuse?
how to treat?
- alcoholics
- avoid withdrawal symptoms w/ BENZOs
what are withdrawal symptoms?
-seizures, delirium, and arrhythmias
what treatment does alcohol dependence require?
-psycosocial therapy first and drugs second
what drugs for alcoholism?
-Naltrexone
What is Naltrexone?
what is it used for?
MOA?
what must patients be before starting therapy?
- treatment of alcohol/opiate dependence and reduces craving
- mu opioid receptor antagonist (long-acting)
- patients must be alcohol and opioid free b/c if not you trigger alcohol withdrawal syndrome
What is Acamprosate?
MOA?
- treat alcohol/opiate
- weak NMDA antagonist and GABA receptor agonist mimicking the effects of alcohol in the body
- reduces relapse rates
What is Disulfiram?
MOA?
what must the patient be?
- for alcohol dependence
- irreversibly inhibits aldehyde dehydrogenase causing build up of acetaldehyde
- makes people feel shitty when they drink
- the patient must be highly compliant because they could easily just not take the pill
What are ethanol and Fomepizole used to treat?
What is the toxic build up?
MOA?
- methanol OD seen with antifreeze, windshield washer fluid,
- formaldehyde
- ADH has higher affinity for ethanol than it does for methanol. allowing methanol to be cleared form the body unchanged
Do schedule 1 drugs have medical use?
addictive?
examples?
- no
- strong opioids
- highest addictive
- rohypnol (date rape) Heroin, PCP, MDMA, LSD
Schedule 4 drugs use?
addictive?
examples
- medical use
- least addictive
- BENZOs and weak opioids
Are phencyclidine and ketamine addictive?
-no that are rated a 1 on his chart meaning they are not addictive
What receptors do addictive drugs commonly target?
-activate GPCRs
ie opiates, weed, GHB, LSD
BENZOs, Nicotine, and alcohol bind to what receptors?
-ionotropic receptors and ion channels
Are LSD, psilocybin, PCP., and mescaline addictive?
-no
Long term effects of:
PCP?
LSD?
PCP= irreversible schizophrenia pshchosis
LSD= flashbacks and altered perception
The Opioids— Naloxone, Naltrexone, and Methadone— inhibit what?
-inhibition of GABA inhibitory neurons
Which of these acts longer?
Naloxone vs Naltrexone
-Naltrexone is the long acting antagonist
Is Methadone a long acting antagonist or agonist?
-agonist
Agitation, HTN, tachycardia, delusions, hallucinations, death, hyperthermia…….What did the patient OD on?
-Amphetamines and cocaine
Slurred speech, drunk behavior, dilated pupils, clammy skin, coma, weak rapid pulse…..what did the patient OD on?
-Barbiturates, BENZOs, alcohol
constricted pupils, clammy skin, nausea, drowsiness, respiratory depression, coma, death…..what did the patient OD on?
-Heroin or other opioids
apathy, irritable, more sleep, disorientation, depression…..what are they withdrawaling from?
-Amphetamines and cocaine
anxiety, insomnia, delirium, tremors, seizures……what are thy withdrawaling from?
-Barbiturates, BENZOs, alcohol
Nausea, chills, cramps, lacrimation, rhinorrhea, yawning, hyperpnea, tremor….what are they withdrawaling from?
-Heroin and other opioids
What are the only two conjugated BENZOs?
- Oxazepam (slow and short acting)
- Lorazepam (intermediate and long acting)
T/F: GABA neurons synapsing on dopamine neurons can shut off the dopamine neurons?
-True
Cocaine blocks
-reuptake of dopamine
= more dopamine in the synapse
Amphetamines works by
-fill up the vesicles keeping dopamine out of the vesicles causing cytoplasmic reverse of dopamine transporter leading to dopamine being pump against its gradient
=more dopamine in the synapse
What’s a good BENZO to give an addict in order to avoid the dopamine reward pathway?
Oxazepam works because it has a slow onset
