27926954
Description
Flashcards by Majd Fawaz, updated more than 1 year ago
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Created by Majd Fawaz
over 3 years ago
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| Question | Answer |
| Thalidomide | - Was OTC antiemetic drug (morning sickness) - Many pregnant women used it - Withdrawn from the market because of teratogenic effect - Immunosuppressive activity - Effective against advanced cancer and leprosy |
| - Buspirone - Anxiolytic with no sedation - Partial 5-HT agonist - No rebound anxiety or withdrawl symp. - Needs a week to establish effect | |
| - S-Ramelteon - 1st MT1-agonist (FDA approved) - Used to treat insomnia (initiate sleep) - Rapidly absorbed after oral admin - Extensive First Pass (2% remains) - No residual effect - No abuse potential (no tolerance/withdrawl) - No depression of cognition and memory | |
| MII is 20-100 folds better bioavailability but 17-25 fold less active in binding | |
| - Diphenhydramine (OTC) - 1st Gen antihistamine and hypnotic - Class: Ethanolamine/Amino ether - Used for acute insomnia - Cross BBB --> sedation - Tolerance to hypnotic effect - Next day sedation | |
| - Doxylamine (OTC) - 1st Gen antihistamine and hypnotic - Class: Ethanolamine/Amino ether - Used for acute insomnia - Cross BBB --> sedation - Tolerance to hypnotic effect - Next day sedation | |
| Barbiturates | - They increase the duration of opening of the chloride channel - At high doses, they acts as GABA (so no need for GABA) --> Overdose can kill - Small doses causes hyperexitation because its not enough to depress RAS - This results in a small margin of safety - Inducer of P450 liver enzymes (DDI) - Decrease sleep latency, nighttime awakening, REM sleep with increase of total sleep time |
| SAR of barbs | - The more lipophilic the substitution on C-5 --> More potent + faster onset (ex. Pento vs Butabarbital - The cyclic chain is more potent than the straight chain - More branching --> More potent + Decrease DOA - Methyl on N1 or N3 --> Increase lipophilicty --> Shorter DOA with no effect on potency - Hydrophilic groups decrease potency - Sulfuration increase lipophilicity |
| - Methohexital - Used as IV anesthetic | |
| - Phenobarbital (anticonvulsant) - Slow onset/Long DOA (longer than mephobarbital) - Oral | |
| - Mephobarbital (anticonvulsant) - Slow onset/Long DOA (shorter than phenobarbital) - Oral | |
| - Amobarbital (sedative hypnotic) - Slow onset + intermediate DOA - Oral | |
| - Butabarbital (sedative hypnotic) - Slow onset + intermediate DOA - Oral | |
| - Pentobarbital (sedative/hypnotic) - Rapid onset + Short DOA - Oral | |
| - Secobarbital (sedative/hypnotic) - Rapid onset + Short DOA - Oral | |
| - Thiopental (IV anesthesia) - Immediate onset + V.short DOA - Class: Thiobarbiturate | |
| What are the 4 pathways of Barb metabolism? | - Oxidation desulfuration - Oxidation - Aromatic hydroxylation - Glucoronidation |
| Thiopentobarbital metabolism | |
| Phenobarbital metabolism | |
| - Chloral Hydrate - Sedative-hypnotic - No analgesic activity - Barb-like drug (acts on GABA-a) - Weak acid --> Prodrug (protect GI) - DDI: alcohol - Discontinued | |
| - Chloral hydrate metabolism - Metabolite characteristics | |
| Pharmaco effects of BZD | - Reduce sleep latency - Reduce the #/duration of nighttime awakening - Inc. total sleep hours - Amnesia - Next day residual effect - Tolerance/Withdrawl |
| SAR of BDZ: Ring A | - Ring A: Benzo ring - Pi-Pi stacking interactions with receptor - e- withdrawing group on C-7 (inc. activity) - Any other sub. dec. activity |
| SAR of BDZ: Ring B | - Ring B: Diazepine (optimal binding) - R1= H or small alkyl - R3= H or OH - 4-5 imino not needed - C=O not needed - Amide not needed |
| SAR of BDZ: Ring C | - Ring C contributes to receptor binding through hydrophobic and steric interactions - R'2 = H or halogen (inc. activity) - Any other sub. dec. activity |
| - Flurazepam - Sleep inducer - Onset: 30 min - T1/2: 2Hr - Efficacious for 1-2 days after discontinuation (metabolites) --> residual next day hypnosis | |
| - N-dealkyl T1/2: 47-100 Hr - N-hydroxyethyl T1/2: 2-4 Hr and undergoes phase 2 gluc | |
| - Quazepam - Sleep inducer - Onset: 30 min - Its metabolites are active and have a long T1/2 --> residual next day hypnosis - Class: Thioamide | |
| - 2-oxoquazepam (long T1/2) - N-desalkyl-2-oxo-quazepam = N-desalkylflurazepam - Slow elemination | |
| - Estazolam - Sleep inducer - Onset: 30 min - Short DOA - Its metabolites have short T1/2 and are less/inactive (triazolo ring) - Class: Triazolobenzodiazepine | |
| - 4-Hydroxy-estazolam is less active - 4'-Hydroxy-estazolam is inactive - Both undergo Phase 2 gluco and are more hydrophilic | |
| - Triazolam - Sleep inducer (elderly) - Onset: 1-2 Hr - T1/2: 4 Hr - Its metabolite undergoes rapid glucoronidation --> urine excretion --> Short DOA | |
| - Temazepam - Sleep inducer - Onset: 1-2 hr - T1/2: 0.4-0.6hr - 3-hydroxy --> immediate gluco --> rapid excretion - No active metabolites | |
| -Diazepam - Used for endoscopy (with a seditive) - Long DOA (active metabolites) - Oxazepam (metabolite) can be a drug on its own, undergoes gluco | |
| - Flumazenil - Competitive antagonist of BDZ - Short T1/2 (<1hr) - Used to treat overdose - At low doses, used to treat dependence - At rapid administration, may cause withdrawl symptoms --> slow infusion - Given IV (1st pass metabolism) - Inactive metabolites (Acid+Demthylation) | |
| Picrotoxin | - Agent that blocks Cl channel and causes convulsion and a state of arousal |
| Z Drugs | - Selective GABA agonist - Rapid onset (oral) - Short DOA (1 hr) - Give inactive metabolites (liver) - No drug accumulation - No addiciton - No rebound insomnia - If taken with food, delays onset - Can be reversed by flumazenil |
| - Zolpidem (2hr) - Class: Imidazopyridine - Sedative-hypnotic choice for pregnant women - High binding to plasma protein | |
| - Zaleplon - Class: Pyrazolopyrmidine - Shortest DOA (1hr) - Faster onset that zolpidem | |
| - Eszopiclone (3-6Hr) - Class: Cyclopyrrolone - Racemix mixture was associated with nest day residual effect and cognitive effect - Less selective on a1 that the other 2 |
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