Slower Acting Drugs

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Chapter: Essential pharmacology : General Anaesthetics

In addition to preanaesthetic medication, BZDs are now frequently used for inducing, maintaining and supplementing anaesthesia as well as for ‘conscious sedation’. Relatively large doses (diazepam 0.2–0.3 mg/kg or equivalent) injected i.v. produce sedation, amnesia and then unconsciousness in 5–10 min.


SLOWER ACTING DRUGS

 

Benzodiazepines (BZDs)

 

In addition to preanaesthetic medication, BZDs are now frequently used for inducing, maintaining and supplementing anaesthesia as well as for ‘conscious sedation’. Relatively large doses (diazepam 0.2–0.3 mg/kg or equivalent) injected i.v. produce sedation, amnesia and then unconsciousness in 5–10 min. If no other anaesthetic or opioid is given, the patient becomes responsive in 1 hr or so due to redistribution of the drug (distribution t½ of diazepam is 15 min), but amnesia persists for 2–3 hr and sedation for 6 hr or more. Recovery is further delayed if larger doses are given. BZDs are poor analgesics : an opioid or N2O is usually added if the procedure is painful.

 

By themselves, BZDs donot markedly depress respiration, cardiac contractility or BP, but when opioids are also given these functions are considerably compromised. BZDs decrease muscle tone by central action, but require neuromuscular blocking drugs for muscle relaxation of surgical grade. They do not provoke postoperative nausea or vomiting. Involuntary movements are not stimulated.

 

BZDs are now the preferred drugs for endoscopies, cardiac catheterization, angiographies, conscious sedation during local/regional anaesthesia, fracture setting, ECT, etc. They are a frequent component of balanced anaesthesia employing several drugs. The anaesthetic action of BZDs can be rapidly reversed by flumazenil 0.5–2 mg i.v.

 

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 thrombophlebitis.

 

VALIUM, CALMPOSE 10 mg/2 ml inj.

 

Lorazepam Three times more potent, slower acting and less irritating than diazepam. It distributes more gradually—awakening may be delayed. Amnesia is more profound.

 

Dose 2–4 mg (0.04 mg/kg) i.v. CALMESE 4 mg/2 ml inj.

 

Midazolam This BZD is water soluble, nonirritating to veins, 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. Also used for sedation of intubated and mechanically ventilated patients and in other critical care anaesthesia as 0.02–0.1 mg/kg/hr continuous i.v. infusion.

 

FULSED, MEZOLAM, SHORTAL 1 mg/ml, 5 mg/ml inj.

 

Ketamine

 

It is pharmacologically related to the hallucinogen phencyclidine; induces a so called ‘dissociative anaesthesia’ characterized by profound analgesia, immobility, amnesia with light sleep and feeling of dissociation from ones own body and the surroundings. The primary site of action is in the cortex and subcortical areas; not in the reticular activating system (site of action of barbiturates).

 

Respiration is not depressed, airway reflexes are maintained, muscle tone increases; limb movements occur and eyes may remain open.

 

Heart rate, cardiac output and BP are elevated due to sympathetic stimulation. A dose of 1–3 (average 1.5) mg/kg i.v. or 5 mg/kg i.m. produces the above effects within a minute, and recovery starts after 10–15 min, but patient remains amnesic for 1–2 hr. Emergence delirium, hallucinations and involuntary movements occur in upto 50% patients during recovery; but the injection is not painful. Children tolerate the drug better. Ketamine is metabolized in the liver and has an elimination t½ of 3–4 hr.

 

Ketamine has been used for operations on the head and neck, in patients who have bled, in asthmatics (relieves bronchospasm), in those who do not want to lose consciousness and for short operations. It is good for repeated use; particularly suitable for burn dressing. Combined with diazepam, it has found use in angiographies, cardiac catheterization and trauma surgery. It may be dangerous for hypertensives, in ischaemic heart disease and in those with raised intracranial pressure (it increases cerebral blood flow), but is good for hypovolemic patients.

 

KETMIN, KETAMAX, ANEKET 50 mg/ml in 2 ml amp, 10 ml vial.

 

Fentanyl

 

This short acting (30–50 min) potent opioid analgesic related to pethidine is generally given i.v. at the beginning of painful surgical procedures. Reflex effects of painful stimuli are abolished. It is frequently used to supplement anaesthetics in balanced anaesthesia. This permits use of lower anaesthetic concentrations with better haemodynamic stability. Combined with BZDs, it can obviate the need for inhaled anaesthetics for diagnostic, endoscopic, angiographic and other minor procedures in poor risk patients, as well as for burn dressing. Anaesthetic awareness with dreadful recall is a risk.

 

After i.v. fentanyl (2–4 μg/kg) the patient remains drowsy but conscious and his cooperation can be commanded. Respiratory depression is marked, but predictable; the patient may be encouraged to breathe and assistance may be provided. Tone of chest muscles may increase with rapid fentanyl injection: a muscle relaxant is then required to facilitate mechanical ventilation. Heart rate decreases, because fentanyl stimulates vagus. Fall in BP is slight and heart is not sensitized to Adr. Supplemental doses of fentanyl are needed every 30 min or so, but recovery is prolonged after repeated doses.

 

Nausea, vomiting and itching often occurs during recovery. The opioid antagonist naloxone can be used to counteract persisting respiratory depression and mental clouding. Fentanyl is also employed as adjunct to spinal and nerve block anaesthesia, and to relieve postoperative pain.

 

TROFENTYL, FENT 50 μg/ml in 2 ml amp, 10 ml vial. In the past fentanyl was combined with the short acting neuroleptic droperidol to produce neurolept analgesia. Since the combination produces marked fall in BP, respiratory depression and occasionally cardiac arrhythmia, it is outmoded.

 

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

 

Dexmedetomidine

 

Activation of central α2 adrenergic receptors has been known to cause sedation and analgesia. Clonidine (a selective α2 agonist antihypertensive) given before surgery reduces anaesthetic requirement. Dexmedetomidine is a centrally active selective α2A agonist that has been recently introduced for sedating critically ill/ventilated patients in intensive care units. Analgesia and sedation are produced with little respiratory depression, amnesia or anaesthesia. It is administered by i.v. infusion. Side effects are similar to those with clonidine, viz. hypotension, bradycardia and dry mouth.

 

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