Non-barbiturate sedatives

1- Chloral hydrate is trichlorinated derivative of acetaldehyde that is converted to trichlorethanol in the body. It induces sleep in about 30 minutes and last up to 6 hr. it is irritant to GIT and produce unpleasant taste sensation.

2- Ramelteon melatonin receptors are thought to be involved in maintaining circadian rhythms underlying the sleep-wake cycle. Ramelteon is an agonist at MT1 and MT2 melatonin receptors , useful in patients with chronic insomnia with no rebound insomnia and
withdrawal symptoms

3- Ethanol (alcohol) it has antianxiety sedative effects but its toxic potential out ways its benefits.
Ethanol is a CNS depressant producing sedation and hypnosis with increasing dose.

Absorption of alcohol taken orally is rapid, it is highly lipid soluble, presence of food delayed its absorption, maximal blood concentration depend on total dose, sex, strength of the solution, the time over which it is taken, the presence of food and speed of metabolism.

Alcohol in the systemic circulation is oxidized in the liver principally 90% by alcohol dehydrogenase to acetaldehyde and then by acetaldehyde dehydrogenase to products that enter the citric cycle. 

Alcohol metabolism by alcohol dehydrogenase follows first order kinetics in the smallest doses. Once the blood concentration exceeds about 10 mg/100 ml, the enzymatic processes are saturated and elimination rate no longer increases with increasing
concentration but become steady at 10-15 ml/ 1 hr. in occasional drinkers. 

Thus alcohol is subject to dose dependant kinetics i.e. saturation or zero order kinetics.

Actions

- Ethanol acts on CNS in a manner similar to volatile anesthetic.
- It also enhances GABA so stimulating flux of chloride ions through ion channels.
- Other possible mode of action involve inhibition of Ca-channels and inhibition of excitatory NMDA receptors.
- Ethanol has non selective CNS depressant activity.
- It causes cutaneous vasodilatation, tachycardia and myocardial depression

Halothane (Fluothane) MAC 0.76%, Blood/gas solubility ratio 2.3
- Nonflammable.
- Any depth of anesthesia can be obtained in the absence of hypoxia.
- Halothane produces a marked hypotensive effect 
- accompanies hypotension.
- Halothane “sensitizes” the ventricular conduction system in the heart to the action of catecholamines. However, ventricular arrhythmias are rare if
- respiratory acidosis, hypoxia and other causes of sympathetic stimulation are avoided.
- Respiration is depressed by all anesthetic concentrations.
- Halothane is metabolized to a significant extent and some of its metabolic produces have been shown to be hepatotoxic.
- Can produce a malignant hyperpyrexia due to an uncontrolled hypermetabolic reaction in skeletal muscle. 

Halothane is generally used with nitrous oxide, an opiate and a neuromuscular blocking drug.

Megltinides

nateglinide
repaglinide

Mechanism

binds to K+ channels on β-cells → postprandial insulin release

Clinical use
type 2 diabetes mellitus
may be used as monotherapy, or in combination with metformin

Oxyphenbutazone: one of the metabolites of  phenylbutazone. Apazone.  Similar to  phenylbutazone, but less likely to cause  agranulocytosis

Methods of general anesthesia

CIRCLE SYSTEM

*HIGH-FLOW

FRESH GAS FLOW > 3 l/min.

*LOW-FLOW

FGF ok. 1l/min.

*MINIMAL-FLOW

FGF ok. 0,5 l/min.

Estimation of the risk of anesthesia (American Society of Anesthesiologists scale)

• ASA 1: healthy patient.

• ASA 2: patient with stable, treated illness like arterial hypertension, diabetes melitus, asthma bronchiale, obesity

• ASA 3: patient with systemic illness decreasing sufficiency like heart illness, late infarct

• ASA 4: patient with serious illness influencing his state like renal insuficiency, unstable hypertension, circulatory insuficiency

• ASA 5: patient in life treatening illness

• ASA 6: brain death- potential organ donor