T41a Sedatives Flashcards
Alcohol
- o.o5: disinhibition
- o.1o: motor function
- 0.15: original legal limit driving (now o.o5/8)
- o.2o-o.25: impaired sensitivity
- o.3-o.4: unaware of surroundings alcohol is adaptive
N.B. metabolic pathway formepizole inhibits alcohol DH (also azole drugs like mtronisazole…) ethal alcohol has higher affinity to it than wood/antifreeze. Disulfiram inhibits aldehyfe dehydrogenase (asian defficiency enzyme) for abuse tx.
Tx. chronic alcoholics have induced P450 system, and B1/B6, B9 difficiency (cofactors aldehyde DH). give iv glucose with B1.
Alprazolam
benzodiazepine. potentiate GABA binding allostericly without mimetic activity (plateau/no OD). increases frequency of Cl- ligand gated channel open to ingress. BZ1 sedative, BZ2 cognitive effects.
DOA: 10-20 hrs
TX. anxiety, panic disoders, phobias
ADV: drug interactions and cross tolerance with CNS depressants.
Buspirone
partial agonist 5-HT1a. Non-classical sedative (no GABA interaction but use the same potassiu channel as GABAb). Duality of partial agonist: agonist alone, blocker with full agonist.
DOA. *effects take 7 days to establish effect*. high first pass, metabolite is alpha2 blocker.
TX. generalized anxiety. liver dysfunction may decrease tolerance anxiolytic without sedative/euphoric effect.
ADV. tachychardia, nervousness, GI distress. NO rebound anxiety/withdrawl, no potentiation with other sedatives (like alcohol), less psychomotr impairement than other sedatives.
Chloral hydrate
distinctive non-classical sedative-hypnotics p.o/rectal metabolized to trichloroethanol adv. bad taste, hepatic damage, severe withdrawl
chlordiazepoxide
benzodiazepine. potentiate GABA binding allostericly without mimetic activity (plateau/no OD). increases frequency of Cl- ligand gated channel open to ingress. BZ1 sedative, BZ2 cognitive effects.
DOA: 1-3+ days
TX.
ADV: drug interactions and cross tolerance with CNS depressants.
Clonazepam
benzodiazepine. potentiate GABA binding allostericly without mimetic activity (plateau/no OD). increases frequency of Cl- ligand gated channel open to ingress. BZ1 sedative, BZ2 cognitive effects.
DOA: 1-3 days
TX. bipolar disorder mood staibilizer in pregnancy, panic disorder
ADV: drug interactions and cross tolerance with CNS depressants.
Estazolam
benzodiazepine. potentiate GABA binding allostericly without mimetic activity (plateau/no OD). increases frequency of Cl- ligand gated channel open to ingress. BZ1 sedative, BZ2 cognitive effects.
DOA: 10 -20 hrs
TX.
ADV: drug interactions and cross tolerance with CNS depressants.
Diazepam
benzodiazepine. potentiate GABA binding allostericly without mimetic activity (plateau/no OD). increases frequency of Cl- ligand gated channel open to ingress. BZ1 sedative, BZ2 cognitive effects.
DOA: complex and long. final metabolite active oxazepam before renal excretion.
TX. anxiety, pre-op sedation, muscle relaxation, withdrawl states (IV possible)
ADV: drug interactions and cross tolerance with CNS depressants.
Flumazenil
benzodiazepine competative antagonist. both BZ1 sedative and BZ2 cognitive effects. GABA and alcohol bind seperate subunit.
DOA: 1 hr. hepatic elimination
TX. antagonis benzodiazepines, and BZ1 selective agonists (zolpidem, zaleplon, eszopiclone) in cases of overdose, respiratory depression, or post-op hastener. Caution in mixed-OD due to benzo’s protective anti-seizure effects.
ADV: agitation, confusion, anxiety, benzo withdrawl symptom
Lorazepam
benzodiazepine. potentiate GABA binding allostericly without mimetic activity (plateau/no OD). increases frequency of Cl- ligand gated channel open to ingress. BZ1 sedative, BZ2 cognitive effects.
DOA: 10-20 hours
TX. anxiety, pre-op sedation, status epilepticus (IV drug of choice for seizure)
ADV: drug interactions and cross tolerance with CNS depressants.
Flurazepam
benzodiazepine. potentiate GABA binding allostericly without mimetic activity (plateau/no OD). increases frequency of Cl- ligand gated channel open to ingress. BZ1 sedative, BZ2 cognitive effects.
DOA: 1-3+ days
TX.
ADV: drug interactions and cross tolerance with CNS depressants.
Meprobamate
distinctive non-classical sedative-hypnotics anti-anxiety agent (nighttime sedative street drug - Miltown) p.o.
Midazolam
benzodiazepine. potentiate GABA binding allostericly without mimetic activity (plateau/no OD). increases frequency of Cl- ligand gated channel open to ingress. BZ1 sedative, BZ2 cognitive effects.
DOA: 3-8 hours
TX. Pre-op sedation, anesthesia IV
ADV: drug interactions and cross tolerance with CNS depressants
Oxazepam
benzodiazepine. potentiate GABA binding allostericly without mimetic activity (plateau/no OD). increases frequency of Cl- ligand gated channel open to ingress. BZ1 sedative, BZ2 cognitive effects.
DOA: 10-20 hours (n.b. diazepam metabolite)
TX. sleep disorders, anxiety
ADV: drug interactions and cross tolerance with CNS depressants.
Phenobarbital
Barbiturate. prolong GABA activity of open Cl- and has mimetic GABA activity (overdose). Barbiturates also inhibit ETC-complex 1 which can lead to cell death (CNS damage due to decreased ATPase pp and Na+ enter cell - similar to antiarrythmics but more neurotissue selective). P450 system inducer.
DOA: Long acting. weak acid (alkalinize usring to ion trap)
TX: used in seizure disorders (in pregnancy)
ADV: paradoxical initial disinhibition. CYP450 and Pgp drug interactions
CI: porphyrias due to ALAsynthase induction (added requirement for heme in P450 induced enzymes)
Pentobarbital: ER manage seizures Phenobarbital: first line seizure disorder/status epilepticus CNS depresion (and some cardio not selective) low selectivity compaired to benzo (more sedative) powerful hepatic enzyme inducer. barbs still used as anti-epileptics, induce therapeutic coma .. but not other Adv: paradoxical excitement, CYP450 and Pgp drug interactions
