General Anesthetics - 2

Nitrous Oxide: (N2O)

Colorless, odourless, heavier than air, noninflammable gas, Nonirritating but low potency anaesthetic; a good analgesic; Poor muscle relaxant; neuromuscular blockers are often required. Onset of N2O action is quick and smooth. Recovery is rapid: both because of its low blood solubility. Post-anaesthetic nausea is not marked. Generally used as a carrier and adjuvant to other anaesthetics. A mixture of 70% N2O + 25-30% O2 + 0.2-2% another potent anaesthetic is employed for most surgical procedures. As the sole agent, N2O has been used with O2 for dental and obstetric analgesia. Nontoxic to liver, kidney and brain, metabolism of N2O does not occur; it is quickly removed from body by lungs. Cheap and very commonly used

Ether (Diethyl ether)

Highly volatile liquid produces irritating vapours which are inflammable and explosive. Potent anaesthetic, good analgesia. Marked muscle relaxation. Recovery is slow; post-anaesthetic nausea, vomiting are marked. Not hepatotoxic, Cheap, can be given by open drop (though congestion of eye, soreness of trachea and ether burns on face can occur) without the need for any equipment, and is relatively safe even in inexperienced hands. Rarely used now because of its unpleasant and inflammable

Halothane

Volatile liquid with sweet odour. Nonirritant and noninflammable. Induction is reasonably quick and pleasant. Potent anaesthetic, not a good analgesic or muscle relaxant. Causes relatively greater depression of respiration; breathing is shallow and rapid. Urine formation is decreased during halothane anaesthesia. About 20% metabolized in the liver. Hepatitis occurs in susceptible individuals (approximately I in 10,000) especially after repeated use. A metabolite of halothane is probably involved - causes chemical or immunological injury. Smooth and quick Recovery; nause, vomiting rare. Currently one of the most popular anaesthetics because of nonirritant, nonin­flammable, pleasant and rapid action. Poor analgesia and muscle relaxation . Compensated by concomitant use of N2O or opioids and neuromuscular blockers. A genetically determined reaction malignant hyperthermia occurs rarely, due to intracellular release of Ca2+ from sarcoplasmic reticulum causing persistent muscle contraction and increased heat production. Succinylcholine accentuates the condition. external cooling, bicarbonate infusion, O2 inhalation and i.v. dantrolene are used to treat malignant hyperthermia

Enflurane

Mildly odorous, nonirritating and noninflammable liquid. Intro­duced in 1973 as a substitute for halothane. Its properties and uses are similar to that of halothane with the following differences which are mostly quantitative. Stimulates salivary and respiratory secretions slightly. Heart rate decreases little and reduction of cardiac output is less marked. Fall in BP is, however, similar to that caused by halothane: as it also decreases peripheral resistance to some extent. Does not sensitize the heart to Adrenaline, arrhythmias are rare. It has greater depressant action on respiration - assistance is generally needed to prevent acidosis. Bronchodilatation is similar to halothane. It is a better skeletal muscle relaxant. Uterine relaxation is similar to halothane. Enflurane contraindicated in epileptics. Only 3-5% of enflurane is metabolized, can give rise to fluoride as a metabolite, its quantity is insufficient to cause renal toxicity. Hepatic necrosis probably occurs with enflurane rarely. Recovery is pleasant - nausea and vomiting are infrequent. Not available in India

Isoflurane

Isomer of enflurane; has similar properties. About I-2 times more potent, more volatile and less soluble in blood. Administered through a special vaporizer, Produces rapid induction and recovery. Better adjustment of depth of anaesthesia and low toxicity. Does not provoke seizures and is preferred for neurosurgery. It is expensive: use in India is limited to few centres

Desflurane

Fluorinated congener of Isoflurane. High volatility, lower oil: gas partition coefficient and very low solubility in blood and tissues because of which induction and recovery are very fast. Less potent than isoflurane; higher concentration has to be used for induction. Irritates air passage-may induce coughing, breath holding and laryngospasm because of somewhat pungent odour of its vapours

Sevoflurane

Latest polyfluorinated anaesthetic with properties intermediate between isoflurane and Desflurane. Latest polyfluorinated anaesthetic with properties intermediate between isoflurane and Desflurane.

Inducing agents

Thiopentone sod, Methohexitone sod, Propofol, Etomidate

Slower acting drugs

Benzodiazepines, Diazepam, Lorazepam, Midazolam

Dissociative anaesthesia

Ketamine

Neurolept analgesia

Fentanyl + droperidol

Thiopentone sod

Ultrashort acting, highly soluble in water yielding a very alkaline solution, must be prepared freshly. Injected i.v. (3-5 mg/kg) as a 2.5% solution, it produces unconsciousness in 15-20 sec, consciousness is regained in 10-20 min. Hepatic disposal (elimination t1/2 is 7-10 hr). Residual CNS depression may persist for >12hr. Poor analgesic, weak muscle relaxant. Respiratory depression with large doses. BP falls after injection, but recovers rapidly. Cardiovascular collapse may occur if hypovolemia, shock or sepses are present, arrhythmias are rare

Adverse effects of Thiopentone: Laryngospasm occurs generally when respiratory secretions or other irritants are present, or when intubations is attempted while anaesthesia is light. Succinylcholine and thiopentone react chemically, should not be mixed in the same syringe. Shivering and delirium may occur during recovery. Post-operative pain induce restlessness. Postanaesthetic nausea and vomiting are uncommon

Other uses: Occasionally used for rapid control of convulsions. Gradual i.v. infusion of subanaesthetic doses can be used to facilitate verbal communi­cation with psychiatric patients: acts by knocking off guarding

PENTOTHAL®,

INTRAVAL SODIUM® 0.5, 1g powder for making fresh injectable solution

Similar to thiopentone, 3 times more potent, has a quicker and briefer action. Excitement during induction and recovery with muscular movements and restlessness is more common as is coughing and hiccup. More rapidly metabolized than thiopentone: patient may be roadworthy more quickly

Propofol

Oily liquid introduced recently as a I % emulsion for i.v. induction and short duration anaesthesia. Unconsciousness after propofol injection occurs in 15-45 sec and lasts -15 min. Distributes rapidly, elimination t1/2 (100 min) is much shorter than thiopentone due to rapid metabolism. Intermittent injection or continuous infusion has been used for total i.v. anaesthesia when supplemented by Fentanyl. It is particularly suited for out patient surgery because residual impairment is less marked and incidence of post operative nausea and vomiting is low. Induction apnoea lasting -1 min is common. Produces dose dependent respiratory depression. Pain during injection is also frequent

Dose: 2 mg/kg bolus i.v. for induction; 9 mg/kg/hr for maintenance.

PROPOVAN® 10 mg/ml and 20 mg/ml in 10, 20 ml vials

Slower Acting Anaesthetics

Benzodiazepines (BZDs)

Diazepam

0.2--0.5 mg/kg by slow undiluted injection in a running i.v. drip: this technique reduces the burning sensation in the vein and incidence of thromboflebitis

VALIUM®, CALMPOSE® 10 mg/2 ml inj.

Lorazepum

Three limes more potent, slower acting and less irritating than diazepam, distributes more gradually - awakening may be delayed. Amnesia is more profound. Dose 2-4 mg (0.04 mg/kg) i.v

CALM ESE® 4 mg/2 ml inj

Midazolam

Water soluble, nonirritating, faster and shorter acting and 3 times more potent than diazepam. It is being preferred over diazepam for anaesthetic use: 1-2.5 mg i.v. followed by 1/4th supplemental doses

PULSED®, MEZOLAM®, SHORTAL® 1mg/ml, 5 mg/ml inj

Ketamine

Pharmacologically related to the hallucinogen phencyclidine; induces 'dissociative anaesthesia' -profound analgesia, immobility, amnesia with light sleep and feeling of dissociation from ones own body and the surroundings. The primary site of action: cortex and subcortical areas; not in the reticular activating system (site of action of barbiturates). Respiration is not depressed, reflexes are not abolished and muscle tone increases, heart rate, cardiac output and BP are elevated due to sympathetic stimulation. Dose: 1-4 mg/kg i.v. or 6.5-13 mg/kg i.m. Onset 10--15 min, patient remains amnesic for 1-2 hr. Children tolerate the drug better. Used in head and neck surgery, patients with asthma. Good for repeated use; for burn dressing. Combined with diazepam, Found use in angiographies, cardiac catheterization and trauma surgery. Dangerous for hypertensives and in ischaemic heart disease but is good for hypovolemic patients

KETMIN®, KETLAR® 100 mg and 500 mg/10mI inj

Fentanyl - Droperidol combination

Fentanyl: short acting (30-50 min.), potent opioid analgesic related to pethidine

Droperidol: rapidly acting potent neuro­leptic related to haloperidol

Combination of these is injected i.v. a state of 'NEUROLEPT ANALGESIA' is produced, characterized by general quiescence, psychic indifference and intense analgesia without unconsciousness. This state lasts for 30-40 min.

A fixed ratio combination is generally used:

fentanyl 0.05 mg + droperidol 2.5 mg per ml; 4-6 ml is diluted in glucose solution and infused i.v. over 10 min. Supplemental doses of fentanyl alone may be given at 30 min intervals because it is shorter acting than Droperidol. Recovery is slow, and at this time extrapyramidal side effects of droperidol- muscle dystonia and abnormal movements may appear. Nausea and vomiting is not prominent. Psychomotor function remains depressed for many hours. Neurolept analgesia: suitable for endoscopies, angiographies, burn dressing etc. and has been used for a variety of minor surgical procedures in severely ill or otherwise poor risk patients. It can be converted to 'neurolept anaesthesia' by administering 65% N2O + 35% O2'

TROFENTYL® 50 µg/ml fentanyl citrate inj in 2 ml amp and 10 ml vial

Alfentanil and Sufentanil are still shorter acting analogues which can be used in place of fentanyl

Category: Pharmacology Notes