pharmokinetics of benzos

Question 1

t 1/2 > 100 hrs: active metabolite, oxidation pathway, intermediate rate of onset

Answer 1

chlordiazepoxide

Question 2

t 1/2 > 100 hrs: active metabolite, oxidation, VERY FAST rate of onset after oral administration

Answer 2

diazepam

Question 3

t 1/2: (5-14 hrs), (10-20 hrs), (12-15 hrs)

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Answer 3

5-14 hrs, no metabolite, conjugation, slow onset: oxazepam

10-20 hrs: no active metabolite, conjugation, intermediate speed of onset after oral admin: Lorazepam

12-15 hrs: insignificant metabolite, oxidation, fast speed of onset: alprazolam

Question 4

1.5-5 hr half life, insig metabolite, oxidation, intermed rate onset

Answer 4

triazolam

Question 5

1-4 hr half life, no active metabolite, oxidation, NA rate onset

Answer 5

midazolam

Question 6

20-50 hr half life

Answer 6

oxidation AND reduction, intermediate speed

clonazepam

Question 7

Short to intermediate acting benzos

Answer 7

ATTOM

alprazolam

Triazolam

Temazolam

oxazepam

midazolam

A > T (Tem) > O > M > T (tri)

Question 8

high lipid soluble benzos

Answer 8

Temazeopam

diazepam

midazolam

“TMD” or “DMT”

Question 9

1. Relatively short half‐lives (<6 hours), useful as hypnotics rather than sedatives
2. binds to GABAA receptors that contain the α1‐subunit
   
   1. ↑ chloride influx–> ↑ hyperpolarization–> ↓ number of ac on potentials (CNS depression)

Answer 9

the ZZZ’s

Examples:

eszopiclone (Lunesta)

zolpidem (Ambien)

zaleplon (Sonata)

Question 10

beznos as anxiolytic drugs

Advantages, Disadvantages

Answer 10

Advantages

• High therapeutic index
• antagonist available for overdose (flumazenil),
• low risk of drug‐drug interactions
• minimal effect on cardiovascular or autonomic function

Disadvantages

• Risk of dependence
• depression of CNS function
• amnestic effects
• CNS depression when combined with other drugs (ethanol)

Newer antidepressants are sometimes preferred (SSRIs)

Question 11

EtOh withdrawal characterization

Answer 11

tremors, anxiety, insomnia (delerium tremans)

Question 12

major pharamacological objective in management of of EtOh withdrawal syndrome

Answer 12

prevent arrhythmias, seizures, delirium and restore electrolytes + thiamine therapy

Question 13

drug detox tx for alcoholics

1. drugs with less dosing and built in tapering- drugs and their disadvantages
2. drugs that are rapidly converted into inactive metabolites

Answer 13

1. chlordiazepoxide, clorazepate, diazepam
   
   1. pharmacologically active metabolites may accumulate, especially in patients with compromised livers
2. lorazepam, oxazepam
   
   1. useful in patients with liver disease

Question 14

naltrexone

Answer 14

1. approved for treating Etoh and opioid dependency
2. MOA: mu-opioid receptor antagonist
   
   1. short acting
3. used for 12 wks
4. contraindicated in pts with hepatic cirrhosis or liver injury/disease
   
   1. first pass metabolism extensive
5. pt must be off opiods first or it will precipitate opioid withdrawal
6. dose related hepatocellular injury