Sedative: This is the class of drug which decrease the excitement and calms down the patient. There will be a decreased response to any stimulation.
Hypnotics: Hypnotics are used for inducing sleep in the patient.
- There will be all waves in EEG.
- Marked, irregular & darting eye movement.
- Dreams & nightmares occur which can be recalled.
- Heart rate & BP fluctuates.
- Respiration irregular.
- Muscles are fully relaxed.
- One sleep cycle is of 80-100 minutes then it repeats.
- There are four EEG wave ( [α - high amplitude- 8-14cps] [β - low amplitude- 15-35 cps] [ Q - low amplitude - 4-7 cps] [ δ - high amplitude .5-3 cps]
- K complex: Deep negative wave followed by positive wave.
- On the whole sleep cycle can be summarised as Stage 0------> NREM -------> REM------> NREM--------> REM ( NREM - 90 minutes & REM 20 minutes).
- α1 agonist (Methoxamine) : Decrease REM sleep.
- α antagonist: REM sleep.
- β blocker (Propanol): Insomania
- 5HT1, 5HT2 & 5HT3 agonists: Wakefulness
- 5HT2 antagonists (Ritanserin): Increase NREM sleeep.
- H2 receptors has little effect on the sleep.
|General synthesis of barbiturates|
- They were popular earlier but not used now due to toxicity.
- Dose dependent action: Sedation ----> Sleep -----> Anesthesia -----> Coma.
- Tolerance develops after sometime
- Further increasing dose, they directly increase chlorine conductance.
- This is the main difference between benzodiazepine & barbiturates where benzodiazepines act as GABA facilitating only but barbiturates can act as GABA mimetic also.
- Drug inducers: Lowers the plasma concentration of warfarin, steroids (including contraceptives), tolbutamide, griseofulvin, theophylline & Chloramphenicol.
- Additive action: Alcohol, Opoids, Antihistamines.
- Na valproate increase concentration of phenobarbitone.
- Decrease absorption of griseofulvin from the GIT.
|SAR of barbiturates|
- 5,5 disubstituted barbituric acid, 5,5 disubstituted thiobarbituric acid & 1,5,5 trisubstituted barbituric acids are active.
- Active drugs are slightly basic in nature.
- More the lipophilicity lesser will be duration of action.
- 5,5 disubstitution: Aromatic substitution decrease lipophilicity. Branching, alkyl substitution, halogen to alkyl group increase lipophilicity.
- Substitution on Nitrogen: Substitution at N1 increase lipophilicity. Large substitution at N1 gives convulsant property. N1 & N3 substitution in same drug results in inactivity.
- Modification at C2: Replacement by Sulphur of Oxygen at C2 decrease lipophilicity.
|Metabolism of barbiturates|
- They act as GABA facilitating agents with no GABA mimetic action.
- Mainly metabolized by dealkylation & Hydroxylation.
- Benzodiazepine competitive antagonist- Flumazenil.
- Benzodiazepine non-competitive antagonist- Bicculine.
- Benzodiazepine inverse agonist- β-Carboline (DMCM- Dimethyl-carbomethoxy-β-Carboline.
- Zolepon is the shortest acting among these.
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