Title 21. GENERAL ANESTHETICS.pdf ✅

PHARMD GURU Page 1 General Anesthetics refer to drug-induced reversible loss of consciousness and all sensations. The features of GA are as follows: 1. Reversible loss of consciousness. 2. Reversible loss of sensation. 3. Analgesia and amnesia. 4. Muscle relaxation and abolition of reflexes. There is no single anaesthetic agent that can produce all the above effects. Hence, anaesthetic protocol includes: 1. Premedication. 2. Induction of anaesthesia (e.g. propofol). 3. Maintenance of anaesthesia (e.g. N2O " isoflurane). 4. Skeletal muscle relaxation. 5. Analgesia – as premedication, during and after the operation. 6. Use of other drugs:  To reverse neuromuscular blockade.  To reverse the residual effects of opioids (naloxone) and BZDs (flumazenil). Minimal alveolar concentration (MAC) is the minimum concentration of an anaesthetic in alveoli required to produce immobility in response to a painful stimulus in 50% patients. It indicates the potency of inhalational general anaesthetics (N2O > 100%, halothane 0.75%). MECHANISM OF ACTION OF GENERAL ANAESTHETICS: The main site of action of anaesthetics is reticular formation, which normally maintains a state of consciousness. Most anaesthetics decrease transmission in reticular formation by enhancing the activity of inhibitory transmitters like GABA (e.g. BZDs, barbiturates and propofol) and blocking the activity of excitatory transmitters (e.g. blockade of N-methyl-D-aspartate [NMDA] glutamate receptors by ketamine and nitrous oxide). GENERAL ANESTHETICS
PHARMD GURU Page 2 STAGES OF GENERAL ANESTHESIA: STAGE I: It is the state of analgesia, because sensory transmission in spino-thalamic tract is inhibited. There is no amnesia. Consciousness and sense of touch are present, while sense of hearing is enhanced. STAGE II: It is the state of excitement and delirium. The patient shows violent behaviour and is amnesic. There is irregular rise in blood pressure and respiratory rate. To avoid these symptoms, a short acting barbiturate like thiopental sodium is given intravenously before administration of inhalation anaesthetic. STAGE III: It is the stage of surgical anaesthesia. Regular respiration and relaxation of skeletal muscle occurs during this stage. It is divided in to following four planes:  Plane 1: During this plane, there are revolving movements of eye balls which while attaining plane 3 get fixed. Respiration and skeletal muscle tone are normal.  Plane 2: Most surgical procedures are performed during this plane. There is progressive loss of corneal, light and laryngeal reflexes. Respiration is slow but regular.  Plane 3: It is a plane of marked muscle relaxation. Respiration is abdominal. Eye ball movement is absent. Pupils are dilated. Light, corneal and laryngeal reflexes are absent.  Plane 4: It is a plane of complete muscle relaxation. Pupils are dilated. There is complete loss of light, corneal and laryngeal reflexes. Respiration is abdominal. STAGE IV: It is a stage of medullary paralysis. It appears due to overdose of the general anaesthetic. During this stage, there is severe depression of respiratory centre and vasomotor centre in medulla. The stage is fatal causing death of the patient. The most reliable index for attainment of stage III is loss of corneal reflex and establishment of regular respiratory pattern. A fall in BP, cardiac and respiratory depression are the signs of deep anaesthesia. As against this, resistance to insertion
PHARMD GURU Page 3 of endotracheal tube is the sign of light anaesthesia. Monitoring of vital signs reduces the dose requirement of general anaesthetic which contributes to rapid recovery from general anaesthesia. PHARMACOKINETIC PRINCIPLES: There are three factors which need attention. They are induction, maintainence and recovery. The principles of pharmacokinetics should be understood in the context of these factors. INDUCTION: It means the time interval between the administraton of anaesthetic drug and the development of stage of surgical anaesthesia. Lipophilicity is the key factor governing pharmacokinetics of inducing drugs. Being highly lipophilic, after a single intravenous bolus injection, these drugs preferentially enter in the brain. Redistribution out of CNS in to muscle, viscera and lipophilic adipose tissue are the main causes for termination of action.
PHARMD GURU Page 4 MAINTENANCE: It is the period during which the patient remains in a sustained stage of surgical anaesthesia (stage III, plane-2). During this stage, the anaesthesiologist monitors the patient’s vital signs and response to various stimuli by controlling concentration of anaesthetic to be inhaled or infused based on depth of anaesthesia. The factors which influence uptake and distribution of the anaesthetic, govern the rate at which an effective concentration of the anaesthetic reaches the brain. This requires transfer of anaesthetic from alveolar air to the blood and then to the brain. The rate of transfer depends on following factors:  Alveolar wash-in  Solubility characteristic of anaesthetic drug  Concentration of the drug in the inspired air  The pulmonary ventilation rate  Cardiac output  The partial pressure gradient of the drug between arterial and venous blood before its redistribution RECOVERY: The recovery phase starts when the anaesthetic drug is discontinued. During this phase, the anaesthesiologist has to ensure that there are no delayed toxic reactions. Frequently, oxygen is given during last few minutes of anaesthesia and in early post- anaesthetic period. Metabolism of anaesthetic is an important factor during recovery. The gradation of metabolism of anaesthetics by liver is as follows: methoxyflurane > halothane > enflurane > sevoflurane > isoflurane > desflurane > nitrous oxide. Nitrous oxide is almost totally washed out by exhalation.