Sedative-Hypnotics (Benzos, Imidazos, Pyrrolos) Flashcards Preview

Pharmacology > Sedative-Hypnotics (Benzos, Imidazos, Pyrrolos) > Flashcards

Flashcards in Sedative-Hypnotics (Benzos, Imidazos, Pyrrolos) Deck (48):
1

What are 3 general clinical uses of the sedative hypnotic drugs?

Insomnia
Anxiety disorders
Alcohol withdrawal

2

Describe the dose dependent effects of sedative hypnotics

Increasing the dose increases the degree of sedation, which could eventually lead to coma and death

Benzodiazepines have a plateau or "tailing off" where they no longer produce sedative effects

Barbiturates are more dangerous and continually increase sedation with inc dose

3

What receptor do all the sedative hypnotic drugs work on?

GABA-A

4

Describe the GABA-A receptor. It is ___tropic. What activates it and what happens downstream?

Inotropic

Requires an alpha, beta, and gamma subtype to function

Activated by GABA> Leads to inc Cl- channel opening, leading to Cl- influx and an IPSP. Causes hyperpolarization and decreased neuron firing.

5

What determines the subtype of the GABA A receptor?

Alpha subunit

6

Describe the BZ1 subtype

a1B2y2

Can bind benzodiazepines, imidazopyridines, or pyrrolopyrazines

7

Describe the BZ2 subtype

a2B3y2 or (a3,a5)Bny2

Binds ONLY benzodiazepines

8

What part of the GABA-A receptor binds GABA?

Alpha-Beta interface

9

What part of the GABA-A receptor binds drugs (benzos, imidazos, pyrrolos)?

Alpha-Gamma interface

10

What part of the GABA-A receptor binds barbiturates?

Intracellular beta portion

11

Where does the benzodiazepine antagonist flumazenil bind the GABA A receptor?

Alpha-Gamma interface

12

What is the primary indication for flumazenil and what is one potential contraindication or drawback?

Benzodiazepine overdose, but may cause withdrawal symptoms in patients who have been on benzodiazepines for a long time

May also be used to reverse Benzodiazepine sedation after surgery

13

What is the MOA of Beta-Carbolines?

Inverse agonists --> negative allosteric modulators of GABA receptor function

Bind BZ1 or BZ2 sites and block benzo effects

Lead to decreased frequency of chloride channel opening

14

What are the basic MOAs of benzodiazepines, imidazopyridines, and pyrrolopyrazines?

Positive allosteric modulators of GABA-A receptor

They bind their sites, increase GABA's affinity for the alpha-beta receptor site, increase frequency of Cl- channel opening, IPSP, decreased neuron firing

15

What is the basic MOA of barbiturates?

Increase DURATION of Cl- channel opening in the presence of GABA

Does NOT bind BZ1 or BZ2 sites

16

Benzodiazepines
Indications

Anxiety disorders
Insomnia
EtOH withdrawal
Anticonvulsant effects
Skeletal muscle relaxation

17

List the Benzodiazepines

Midazolam
Alprazolam
Tiazolam
Estazolam

Diazepam
Lorazepam
Oxazepam
Temezepam
Clonazepam

Chlordiazepoxide
Chlorazepate

18

Benzodiazepines
Metabolism

All undergo Phase I oxidation and Phase II conjugation, except...

LOT only go through Phase II glucoronidation (Lorazepam, Oxazepam, Temazepam)

19

Benzodiazepines
Solubility and Protein binding

Lipid soluble

Highly protein bound, so drug-drug interactions are likely

20

How does the half life of benzodiazepines contribute to potential toxicity and adverse effects?

Short half life -- concentration remains pretty consistent day to day

Long half life-- drug conc accumulates to a much higher concentration, which could lead to oversedation

21

What is diazepam's active phase I metabolite? How long does it take after diazepam withdrawal for it to clear from your system?

Desmethyldiazepam is the primary metabolite

Takes 6-7 to clear from a patient's system after stopping diazepam

22

How does hepatic function affect benzodiazepine blood levels?

Tend to stay elevated longer in elderly patients with decreased hepatic function

23

Benzodiazepines
Adverse Effects

Drowsiness
Ataxia
Amnesia

Confusion
Paradoxical excitement
Dizzy

Paradoxical rage
Allergic rxn

24

Benzodiazepines
Tolerance and Dependence

Physical dependence can occur in pts who take large doses for long periods of time

Can develop tolerance to sedative effects of benzodiazepines over time, but tolerance is NOT developed to their anxiolytic effects

25

Symptoms of Benzodiazepine Withdrawal

Anxiety
Insomnia
Loss of appetite
HA
Nausea
Tremor
Muscle aches
Sweating
Irritability

Rare: Confusion, Delirium, Psychosis, Seizures, Catatonia

26

How could each of these factors increase risk for tolerance and dependence?
-T 1/2
-Time to drug onset
-Potency
-Dose
-Time length drug taken

- Low T 1/2
- Short time to drug onset
-High Potency
-High Dose
-Long time length drug taken

27

List the imidazopyridines

Zolpidem
Zaleplon

28

What is the only Pyrrolopyrazine?

Eszopiclone

29

What drug can block effects of imidazopyridines and pyrrolopyrazines?

Flumazenil (benzodiazepine antagonist)

30

Imidazopyridines and Pyrrolopyrazine Dependence Risk

Lower than for benzodiazepines, but can still be habit forming

31

Imidazopyridines and Pyrrolopyrazine
Adverse Effects

HA
Dizziness
Somnolence
Nausea
Vomiting
Diarrhea
Anterograde amnesia
Rebound insomnia

Sleep driving and sleep eating with no memory of event

32

Relative half lives of Imidazopyridines and Pyrrolopyrazine

Zolpidem- 1.5-3 hrs

Zaleplon- 1 hr

Eszopiclone- 6 hrs

33

List the Barbiturates

Phenobarbital

Methohexital

Thiopental

34

Barbiturates
MOA at low and high doses

Low doses -- bind intracellular GABA-A Beta subunit; increase DURATION of Cl- channel openings

High doses- directly activate Cl- channel opening independent of GABA

35

Barbiturates
Adverse Effects

Low therapeutic index that is lethal at 10x the hypnotic dose

Potent resp depression, esp when combined with alcohol

Can cause physical dependence and withdrawal

36

Barbiturates
Metabolism

Stimulates CYP450 activity and induces hepatic microsomal oxidases

May increase metabolism of other drugs

37

Ramelteon
MOA

Melatonin receptor (MT1 and MT2) agonist

38

What is 1st, 2nd, and 3rd line therapy for insomnia?

1st: CBT and Sleep Hygeine

2nd: Work up for underlying cause of insomnia

3rd: Sedative Hypnotic Drugs

39

Which sedative hypnotic is most commonly prescribed for insomnia treatment?

Temazepam

40

Which sedative hypnotics should be used more in elderly people? Why?

LOT = Lorazepam, Oxazepam, Temazepam

Elderly ppl have lower liver function, so it is better to give them drugs that don't require phase I oxidation via the liver

41

How are benzodiazepines dosed for insomnia treatment?

In general, you don't want them to take the drug more than 3 nights per week so they don't associate a good night's sleep with the drug

Should be used short term (1-3 months)

42

What might happen after cessation of benzodiazepine for insomnia?

Rebound insomnia -- original symptoms recur, or reoccur in greater intensity

Withdrawal

43

Herbal Preps
Valeriana officinalis
What is the active compound and its MOA?

Sesquiterpenes: mediate GABA release and inhibit GABA breakdown

Useful for 4 weeks insomnia

44

Herbal Preps
Chamomile
What is the active compound and its MOA?

Apigenin, a benzodiazepine agonist

45

What are the two currently available FDA-approved OTC sleep aids? Active compounds and general MOA?

Unisom -- contains doxylamine (antihistamine)

ZzzQuil- contains diphenhydramine (antihistamine)

46

Buspirone
MOA

5HT 1A partial agonist

47

Buspirone
Drug Interactions

DO NOT use buspirone with a MAOI
-Need to clear system of either drug entirely before starting the other, or you risk Serotonin Syndrome

48

Buspirone
Indications

Anxiety disorder(with antidepressants)

Major depression (with antidepressants)

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