Jorvig - Tricyclic Antidepressants

Pharmaceutical Sciences 1.6 with Chakraborty at Roseman University of Health Sciences

About this deck

By: Jon Warta
Created: 2011-11-15
Size: 45 flashcards
Views: 18

About StudyBlue

STUDYBLUE makes things that make you better at school. Things like online flashcards with photos and audio. Things like personalized quizzes and friendly reminders about when (and what) to study next. Think of it as a digital backpack™: access to all of your study materials online and on your phone. STUDYBLUE exists to make studying efficient and effective for every student, for free. Join us.

“I have used this website for three exams, and I see a huge difference in my test results.”
Naj

Sign up (free) to study this.

What are thymoleptics?

the old name for antidepressants

First TCA

imipramine

Another old TCA still in the top 200

amitriptyline (Elavil)

What's a neuroleptic?

antipsychotic

Most neuroleptics have __________ structures

relatively flat ring

Most TCAs have ____________ structures

skewed or bent ring

Serendipitously discovered drugs generally have:

multiple mechanisms of action

very potent effects

more side effects

Rationally designed drugs generally have

very specific mechanism of action

less side effects

narrower clinical applicability

Which method of drug design is most suited for complex disease states?

serendipitous drug discovery

TCAs were created through which method of drug creation?

serendipitous drug discovery

Metabolite of amitriptyline that is more potent that amitriptyline

nortriptyline (2ndary amine), also in top 200

TCAs generally take __________ before effects are evident

1-3 weeks

high initial dose does not speed onset of action

this is not a pharmacokinetic or structural effect, because side effects are present within a day

What is responsible for the antidepressant effects of TCAs?

inhibition of the NE and serotonin transporters

activity at other receptors causes side effects

Function of barbiturates

depress CNS, skeletal, smooth, and cardiac muscle activity

sedation

hypnosis

anesthesia

What do sedatives do?

produce mild CNS depression, calm anxiety and excitation

What do hypnotics do?

compel sleep, stronger form of CNS depression

What do anesthetics do?

Very strong CNS depression (surgical anesthesia)

Barbiturates mechanism of action

decrease excitatory synaptic transmission

increase inhibitory synaptic transmission

prolong effects of GABA

at high concentrations, effect GABA_A receptors directly

decrease cholinergic, glutaminergic transmission

Where do barbiturates bind to GABA_A receptors?

at a unique site

enhance binding of either GABA or benzodiazepines

prolong time periods of bursts of channel opening ----> more bursts

All barbiturates are based on

barbituric acid

active compounds must be a weak acid and have moderate lipophilicity

What are the active barbiturates?

5,5-disub barbs

5,5-disub thiobarbs

1,5,5 trisub barbs

What is the point of substitution on barbiturates?

more substitution ----> less acidity ----> more ionization ----> can cross the BBB

More lipophilicity =

more BBB penetration

more oral absorption

more metabolism

More lipophilicity means less

water solubility

kidney excretion

A measure of lipophilicity

Partition Coefficient

More lipophilic barbiturates will have

quicker onset

greater activity

shorter duration of action

The lipophilicity of barbiturates must be

within certain limits

nembutal vs. thiopental: which acts faster?

thiopental; more lipophilic

Exception to the lipophilic = shorter onset, duration rule:

Phenyl groups (slowly oxidized)

Problems with barbiturate use

pain induction

after effects (lingering CNS depression)

enzyme induction (lotsa drug interactions)

low therapeutic index (suicide)

tolerance and dependence

paradoxical effects

Barbiturates were developed by which method of drug creation?

serenditipous drug discovery

Benzodiazepine still on top 200

diazepam (Valium)

Therapeutic uses of benzodiazepines

hypnotics

anticonvulsants

anxiolytics

muscle relaxants

Which are stronger anxiolytics and muscle relaxants: barbs or benzos?

benzos

Major advantage of benzodiazepines

safety - overdose is rare

because they do not directly activate GABA receptor and do not have much effect on cholinergic system

Which cause more enzyme induction: barbs or benzos?

barbs - but still metabolized by CYP450 enzymes

Major disadvantage of benzodiazepines

after effects - may last 3-4 days, barbiturates only 1 or so

Benzodiazepines mechanism of action

increase activity of GABA at the GABA_A receptor

increase frequency of channel opening bursts

interaction with different subtypes of GABA receptor subunits may cause the different benzo effect

cannot directly activate GABA_A receptors

What is priviliged structure?

substitution virtually anywhere will give an active compound

All benzodiazepines have

high partition coefficients (very lipophilic)

essentially completely absorbed

What are the redistribution effect of benzodiazepines?

rapid uptake into highly perfused areas like brain

redistributed to fat cells, slowly released into bloodstream

result of high lipophilicity

Benzodiazepines are metabolized to

longer-acting metabolites

several stages of metabolism ----> stages of drug effect

duration of action has little to do with half-life

Problems with benzodiazepines

tolerance and dependence

withdrawal symptoms

paradoxical effects

pulmonary effects

amnesiac effects (high doses)

dysinhibition

Date-rape drug banned in US

Rohypnol

Two drugs that act only as hypnotics

zolpidem (Ambien)

eszopiclone (Lunesta)

About this deck

By: Jon Warta
Created: 2011-11-15
Size: 45 flashcards
Views: 18

About StudyBlue

“I have used this website for three exams, and I see a huge difference in my test results.”
Naj