Sedative & Hypnotics Flashcards
What are the 5 main types of CNS depressants?
Alcohol
General anesthetics
Barbiturates
Non - barbiturates
Benzodiazepines
Is ethanol a general CNS depressant w/ full spectrum?
Yes
-> from anti - anxiety to anesthesia / death
Where is ethanol absorbed?
Stomach
Intestine
Why is ethanol used to treat methanol intoxicated?
Compete with methanol for the enzyme
-> Alcohol dehydrogenase
Diuretic
-> promotes excretion of methanol
What are the mechanism of Disulfiram that allows it to be used as treat chronic alcoholism?
Disulfiram inhibits aldehyde dehydrogenase
-> increased acetaldehyde conc.
–> causes Acetaldehyde syndrome
—> extremely uncomfortable
Is thio - barbiturates longer acting than oxy - barbiturates in general?
No
Generally
-> oxy - barbiturates is longer acting than thio - barbiturates
If oxy - barbiturates is longer acting than thio - barbiturates, does that mean thiopental is shorter acting than methohexital?
No
-> Methohexital is kind of an exception
Provide 1 example of barbiturates with ultra short lasting, short lasting and long lasting effects
Ultra short lasting
-> Thiopental
Short lasting
-> Pentobarbital
Long lasting
-> Phenobarbital
What is the main function of Thiopental?
Anesthesia
What is the main function(s) of Pentobarbital?
Anesthetics
Hypnotic
Anticonvulsant
What is the main function(s) of Phenobarbital?
Anticonvulsant
What is the main neurotransmitter(s) for Presynaptic inhibition?
GABA
-> gamma - aminobutyric acid
–> (G)amma - (A)mino(B)utyric (A)cid
What is the main neurotransmitter(s) for Postsynaptic inhibition?
Glycine
Opioids
GABA
What type of channel is GABA(A) receptor?
Ligand - gated Cl- channel
How many subunits does GABA(A) receptor have?
What are they?
What could bind to it?
5 subunits
-> Alpha x 2
–> binding of GABA molecules for activation
-> Beta x 2
–> binding of Barbiturate
-> Gamma x 1
–> binding of Benzodiazepine
What happens when Barbiturate binds GABA(A) receptor?
Increases [Open time] of Cl- channel
High doses
-> directly activate GABA(A)
–> w/ or w/o GABA molecule on Alpha binding site for activation
—> causes CNS depression / death
What happens when Benzodiazepine binds to GABA(A) receptor?
Increases [Open frequency] of Cl- channel
Always requires GABA activation
-> does not cause severe CNS depression
Is barbiturate a full spectrum drug?
Yes
What is Therapeutic Index?
Ratio of
-> dose of a drug that produces a therapeutic effect
-> dose of a drug that produces toxicity
Equation
Median Lethal dose (LD50)
Therapeutic Index (TI) = —————————————–
Median Effective dose (ED50)
The lower the TI, the harder it is to grasp the amount of drugs needed to produce a therapeutic effect w/o causing toxicity
Can phenobarbital be administered orally and still be well absorbed?
Yes
What are the 3 main clinical uses of Barbiturates?
Anesthesia
Anticonvulsant
Euthanasia ( Small lab animals )
Is Barbiturate IV anesthesia used for induction or maintenance, or both?
Induction only
Can barbiturate used for pain control?
Nope
-> not analgesic
How is Chloral hydrate administered?
IV
PO
What is chloral hydrate mainly used for for large animals? and why?
Pre med
-> reduce dosage needed for anesthesia
-> smoother induction of general anesthesia
Is Benzodiazepine full spectrum?
Nope
-> non anesthetic
-> at most hypnotic only
Does BZD or barbiturate has less acute toxicity?
BZD has way less acute toxicity
-> LD50
–> Diazepam > Pentobarbital
Which of the following means the same as “ Major tranquilizer “
a) Neuroleptics
b) Antipsychotics
c) Antischizophrenics
d) Benzodiazepine
a) Neuroleptics
b) Antipsychotics
c) Antischizophrenics
Which of the following are clinical uses of BZD?
a) Insomnia
b) Anxiety disorder
c) Skeletal muscle relaxation
d) Alcohol withdrawal
e) Anticonvulsant
f) Pre med
All
Is Diazepam long - acting, intermediate - acting or short - acting?
Long - acting
What effects does it have in dogs & cats and are therefore used as behavior modification drugs?
Anxiolytic effects
Can both BZD and barbiturate cause addiction?
Yes
At hypnotic doses, does BZD affect respiration?
No
Can pregnancy exposure to BZD cause prenatal toxicity?
Yes
What happens to da babi if early pregnancy exposure to BZD in rodents?
Teratogenesis
What happens to da babi if late pregnancy exposure to BZD in women?
Floppy baby syndrome
Could diazepam cause serious hepatic necrosis in dogs due to toxic intermediate metabolites called nordiazepam?
No
-> cats though yes
What are 3 examples of other drugs whose CNS depressant effect can be potentiated by BZD?
Barbiturates
Ethanol
Ketamine
What are 4 difference between BZD and barbiturate?
- In terms of development of tolerance and addiction
-> Barbiturate > BZD - Barbiturate induces significant drug - drug interaction
-> Cytochrome P450 induction - Barbiturate could produce life - threatening withdrawal reactions
-> regular use could lead to dependence - In terms of pharmacological effects on CNS depression
-> Barbiturate = full spectrum
–> could cause death
-> BZD
–> hypnosis at most
Is ‘BZD’ or ‘barbiturate’ in general a safer drug? And if so, in what occasion would we use the non safer drug?
BZD is generally a safer drug
Barbiturate is still used
-> Short - acting barbiturate
–> Anesthesia
-> Long - acting barbiturate
–> Anticonvulsant
What is the BZD antagonist?
And its mechanism?
Flumazenil
-> competes for GABA(A) receptor
–> but no intrinsic efficacy
—> meaning it does not produce a pharmacological effect when bound to the receptor
What is the non BZD anxiolytic drug that falls under the category of Azapirones?
And its mechanism?
Buspirone
-> Partial agonist 5-HT(1A) receptor
–> No side ( adverse ) effects at all
