Sedative hypnotics

Question 1

issues of Barbituates/mechanism

Answer 1

1) OD with barbiturates dangerous because theres nothing you can do remove it from system
2) They can lead to medullary depression, death and coma
3) This occurs because Barbiturates can act without GABA present and keep Chloride channel open
4) They still bind to same GABA (A) receptors but at a different location than usual (lower down)

Question 3

Benzo therapeutic effects based on Drug Class

Answer 3

Class:
1)Sedative: decreased patient activity, reduced excitement and calmnesss
2) Hypnotic: drowsiness and facilitates onset of sleep from which patient can be aroused
3) Anticonvulsant: reduced seizures activity in CNS
4) Muscle relaxant: act on CNS and used to TX spasm and spasticisty of muscles

Question 4

Benzodiazapam mechanism

Answer 4

1) enhance inhib. effect of Gaba on Gaba (A) receptor
2) this causes influx CL-, hyperpolarizing cell thus decreasing neuronal firing
3) If someone ODs FLUMEZANIL can be administered and competes at same GABA receptor
4) Give orally or IV rarely IM
5) Lipid solubility = passage through BBB
6) hepatic metabolic oxidation but do not form drug induced enzymes

Question 5

Name the 4 Benzodiazepine

Answer 5

1) Alprazolam (xanax)
2) Diazepam (valium)
3) Lorazepam
4) Midazolam

Question 6

Sleep wakefulness cycle: Melatonin (1/2)

Answer 6

Melatonin: regulate Circadian Rhythm, energy balance and Insulin

Question 7

Sleep Wakefulness cycle: Orexin (2/2)

Answer 7

Orexin: Regulates Wakefulness, food intake, energy/glucose metabolism
Wakefulness: 1) orexin activates arousal center 2) Arousal center inhibits sleep center

Sleep: Sleep center inhibits orexin and arousal center

Question 8

Benzodiazepine effect on sleep

Answer 8

-decrease latency of sleep (fall sleep faster)
- increased duration of stage 2 NREM slep (diff from REM)
- Decreased duration of stage 3 and 4
-decreased awakening in night
- decreased duration of REM but not as much as barbiturates
- *** REM rebound occurs from abrupt cessation of drug causing intense dreams and nightmares

Question 9

1) Alprazolam (xanax)
2) Diazepam (valium)
3) Lorazepam
4) Midazolam
ALL work through same mech

Answer 9

Use: Anxiety breakthrough, panic, Muscle relax and seizures
** Diazepam and Alprolazam specifically used for Status Elipticus (seizure)
**Midazolam used in Operating room, as anxiolytic dental

Kinetics/toxic: Hepatic metabolism, CNS depression, tolerance and dependance

Question 10

Flumezanil (benzo ANTagonist)

Answer 10

1) Mech: antagonist to benzos at GABA (A) receptor
2) Used for OD
3) *** reversal of Midazolam after dental procedure like if someone had to drive
4) 20 min reversal with Flumezanil vs 3hrs without
** Beware of short half life when used to TX OD
** patients can be miserable from withdrawal syndrome related to drug used to get high

Question 11

Benzos SIDE EFFECTS (idk why tf this fat bitch made so much shit for this)

Answer 11

-sedation drowsiness
- DRUNK like symptoms mental cloudiness, confusion psychomotor impairment, slurred speech
-anterograde amnesia
-Disinhibition of suppressed behavior like cursing
-Rebound anxiety = cycle of going back to use and dependance
- Avoid in pregnancy
-cross tolerance to barbiturates and alcohol to to same action at GABA

Question 12

Benzos to use in people who have impair liver

Answer 12

Lorazepam and Oxazepam used because they skip phase 1 oxidation
(she didn’t really explain the oxidation she just said u remember this right)

Question 13

Diazapam (benzo)

CNS muscle relaxant

Answer 13

-facilitates gaba
- Muscle relaxant for short term spasm
- Redistribution important for termination bc of Dimethyldiazapam metabolite (40hr 1/2 life)
- Side effects include withdrawal syndrome

Question 14

Sedative Hypnotics/ Sleep aids name the 4

Answer 14

1) Suvorexant (new sedative drug)
2) Melatonin
3) Eszopiclone
4) Zolpidem

Question 15

name the 2 Barbituates

Answer 15

1) Phenobarbital
2) Methohexital

Question 16

Miscellaneous Anxiolytics and Sedative hypnotics (3)

Answer 16

1) Hydroxyzine
2) Promethazine
3) Propranolol

Question 17

Centrally acting Muscle relaxants (4)

Answer 17

1) Diazepam
2) Baclofen
3) Cyclobenzaprin
4)tizanidine

Question 18

Zolpidem (sedative hypnotic)

Answer 18

1) Binding same sight as Benzos enhancing gaba
2) used as sedative for insomnia
3) **Has 6-8 hr half life so you need to make sure you are getting at least 6-8 hours of sleep otherwise when you wakeup it can cause extreme drowsiness which is impairing. (going to job @ am)
4) AE: Hypotension and sedation

Question 19

Melatonin (sedative hypnotic)

Answer 19

• Agonist at melatonin receptor
• OTC
  -beware of patients who have impair hepatic function because of metabolite buildup overtime
  -AE drowsiness

Question 20

Suvorexant (new sedative hypnotics)

Answer 20

• inhibits orexin 1 and 2 receptors
• decreases sleep latency and enhances sleep maintainence
  -* Schedule 4 drug and take with at least 7h projection of waking up
• AE: ** drowsiness in day and SUICIDal ideation/ depressoin

Question 21

Barbiturate chemistry (IDK if need to know)

Answer 21

-derivitives of Barbituric acid
- Sulfure on carbon 2 increases solubility and decreases duration
- Duration also decreases as number of carbons at Carbon 5 increase

Question 22

Phenobarbital (barbiturate)

Answer 22

• Binds GABA (A) and opens CL- channel (diff site than benzo)
• **most commonly used for seizure disorders
  -oral to hepatic metabolism induces enzymes reducing efficacy of warfarin
• AE: extension of CNS depressing actions, tolerance and dependance
  -Termination of drug based on redistribution (explained on other card)

Question 23

Methohexital (Barbiturate)

Answer 23

-Binds GABA (A) and opens CL- channel (diff site than benzo)
- **most commonly used for Anesthesia
-oral to hepatic metabolism induces enzymes reducing efficacy of warfarin
- AE: extension of CNS depressing actions, tolerance and dependance
-Termination of drug based on redistribution (explained on other card)

Question 24

Barbiturate Pharmacokinetics/ Redistribution

Answer 24

-Lipid soluble = pass through BBB
- Redistribution for Drug Termination: (1) Drug first actions on BRAIN (2) drug moves to LEAN TISSUE as next site which is first sight of loss (3) Drug then moves to FAT
- Metabolism by microsomal hepatic system
a. beware of patients with impaired liver and drug interactions by microsomal enzymes and competition

Question 25

Barbiturate side effects

Answer 25

-**Withdrawal syndrome is DEADly emergyecyb
- ** Respiratory depression @ high dose (NO antidote) bc binds at diff gaba(A) site lower down
-sedation, drowsiness, lethargic, hangover effect
-Disinhibition of suppressed behavior (acting out)
- Nausea GI symptoms
- Allergic rxn skin Steven Johnsons syndrome (SJS)
-agrevation of acute intermittent porphyria

Question 26

Hydroxyzine (H1)

Answer 26

• Inverse agonist? at histamine H1 receptor (stupid bitch didn’t explain)
• USE: Alternative anxiolytic drug
• AE: drowsiness

Question 27

Propranolol (b1)

Answer 27

• comp antagonist at B1 adrenergic in heart
• used for situational/ performance anxiety (not cock)
• extensive 1st past metabolism
• AE: Sleep issues, tiredness, drowsiness, GI (poopy), nausea and yakking

Question 28

Baclofen (Gaba B receptor agonist)

(CNS muscle relaxant)

Answer 28

• hyper polarization of afferent terminals prevents muscle spasticity
• used in muscle spasticity in Multiple sclerosis
  -AE: CNS depression and dependency

Question 29

Cyclobenzaprine
(CNS muscle relaxant)

Answer 29

• inhibits both gamma and alpha motor systems making it useful in local muscle spasm
  (for example upper back muscle spasm after playing bball or sports)
  -structurally related to trycyclic antidepressants
• AE: CNS depression and anticholinergic effects

Question 30

Tizanidine (CNS muscle relaxant)

Answer 30

• an alpha 2 adrenergic agonist used as a SKELETAL muscle relaxant
• reduces spasticity by inhibiting presynaptic motor neurons
  -AE: hypotension and sedation bc a2