Sedative hypnotics Flashcards
issues of Barbituates/mechanism
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)
Benzo therapeutic effects based on Drug Class
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
Benzodiazapam mechanism
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
Name the 4 Benzodiazepine
1) Alprazolam (xanax)
2) Diazepam (valium)
3) Lorazepam
4) Midazolam
Sleep wakefulness cycle: Melatonin (1/2)
Melatonin: regulate Circadian Rhythm, energy balance and Insulin
Sleep Wakefulness cycle: Orexin (2/2)
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
Benzodiazepine effect on sleep
-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
1) Alprazolam (xanax)
2) Diazepam (valium)
3) Lorazepam
4) Midazolam
ALL work through same mech
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
Flumezanil (benzo ANTagonist)
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
Benzos SIDE EFFECTS (idk why tf this fat bitch made so much shit for this)
-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
Benzos to use in people who have impair liver
Lorazepam and Oxazepam used because they skip phase 1 oxidation
(she didn’t really explain the oxidation she just said u remember this right)
Diazapam (benzo)
CNS muscle relaxant
-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
Sedative Hypnotics/ Sleep aids name the 4
1) Suvorexant (new sedative drug)
2) Melatonin
3) Eszopiclone
4) Zolpidem
name the 2 Barbituates
1) Phenobarbital
2) Methohexital
Miscellaneous Anxiolytics and Sedative hypnotics (3)
1) Hydroxyzine
2) Promethazine
3) Propranolol
Centrally acting Muscle relaxants (4)
1) Diazepam
2) Baclofen
3) Cyclobenzaprin
4)tizanidine
Zolpidem (sedative hypnotic)
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
Melatonin (sedative hypnotic)
- Agonist at melatonin receptor
- OTC
-beware of patients who have impair hepatic function because of metabolite buildup overtime
-AE drowsiness
Suvorexant (new sedative hypnotics)
- 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
Barbiturate chemistry (IDK if need to know)
-derivitives of Barbituric acid
- Sulfure on carbon 2 increases solubility and decreases duration
- Duration also decreases as number of carbons at Carbon 5 increase
Phenobarbital (barbiturate)
- 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)
Methohexital (Barbiturate)
-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)
Barbiturate Pharmacokinetics/ Redistribution
-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
Barbiturate side effects
-**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
Hydroxyzine (H1)
- Inverse agonist? at histamine H1 receptor (stupid bitch didn’t explain)
- USE: Alternative anxiolytic drug
- AE: drowsiness
Propranolol (b1)
- 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
Baclofen (Gaba B receptor agonist)
(CNS muscle relaxant)
- hyper polarization of afferent terminals prevents muscle spasticity
- used in muscle spasticity in Multiple sclerosis
-AE: CNS depression and dependency
Cyclobenzaprine
(CNS muscle relaxant)
- 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
Tizanidine (CNS muscle relaxant)
- an alpha 2 adrenergic agonist used as a SKELETAL muscle relaxant
- reduces spasticity by inhibiting presynaptic motor neurons
-AE: hypotension and sedation bc a2
