Medical Pharmacology Topics   

Preliminary Outline

Parenteral Anesthetics   Barbiturates          Thiopental          Thiamylal          Methohexital   Other          Propofol          Etomidate          Ketamine Inhaled Anesthetics   GC and MC activity          Mitotane          Aminoglutethimide   GC activity only          Metyrapone          Ketaconazole

General Anesthesia

Anesthesia is a state of combined analgesia (pain relief), amnesia (memory loss), loss of consciousness, and relaxation of skeletal muscles. It is a state in which there is no behavioural nor physiological response to noxious stimuli, due to the absence of sensation. Anesthesia is neither therapeutic nor diagnostic, rather it exists to create conditions favorable to perform surgery and minimize complications. When used correctly, general anesthesia will maintain homeostasis during surgery, minimize side effects of the procedure and improve the post-operative outcome.

Administration

The administration of general anesthesia can be divided into three phases: preoperative, intraoperative and postoperative. During the preoperative period, there is a patient evaluation to assess risk factors like cardiovascular, renal, pulmonary or hepatic disease, and age.  

Several pre-anesthetic medications will be administered. If a patient has any chronic conditions, normal doses of the usual medication will be administered. Anticholinergics may be used in special cases to redce secretions. Anxiolytics (benzodiazepines) or sedatives (opioids, barbiturates) will likely be administered before the general anesthetic. Questions remain whether preoperative pain relief will reduce the need for drugs after the operation.

The intraoperative period includes monitoring, induction and maintenence. Mnitoring the patient is done throughout the procedure, including EKG, heart rate, blood pressure, exhaled CO2, body temperature, and other parameters.

Induction of anesthesia is when the patient actually looses conciousness. At this point the inhalation anesthetic may decrease systemic blood pressure. Airway maintenance is critical and may be accomplished by intubation (a muscle relaxant is used to prevent the gag reflex), or by an external mask. The signs or stages of anesthesia in order of occurrence are: analgesia, delirium, and surgical anesthesia (unconciousness?).

There are two types of general anesthetics: those administered parenterally and those administered by inhalation. Inhaled anesthetics like halothane, isoflurane, sevoflurane and desflurane are organic fluoride gases with simple linear structures, some also containing chloride and/or bromide. 

Parenteral Anesthesia

Parenteral anesthetics like barbiturates, propofol, etomidate and ketamine are cyclic compounds, some with amide, amine or imidazole groups. Hydrophobicity is the key characteristic of parenteral anesthesia, allowing rapid onset. After a single IV dose, these drugs partition into the CNS and produce anesthesia, but activity is lost by redistribution as blood levels rapidly drop. In this case, the half-life with continuous infusion is termed "context-sensitive" because it varies according to the length of infusion, rate of redistribution, metabolism and storage (?).

For such lipophilic agents, as plasma concentration decreases, the concentration in brain, heart, liver and kidneys will increase. After reaching a peak concentration in these latter tissue, their concentration will decrease as anesthetic concentrations in skeletal muscle and skin increase. After reaching a peak concentration in this second set of organs, their anesthetic concentration will start to decline as the anesthetic agent accumulates in adipose tissue.

Barbiturates like thiopental, thiamylal and methohexital produce acute anesthesia for a short duration of time. Drug action is terminated by redistribution. Interestingly, neonates and infants require higher doses of barbiturates per kilogram than adults. Barbiturates also have antiseizure activity, as well as several potentially toxic side effects: decreased cerebral metabolic rate, decreased cerebral blood flow, dose-dependent decreases in blood pressure, depressed respiration, and reduction of the pai threshold. They are contraindicated in patients with porphyria.

Propofol and etomidate are parenteral anesthetics used to induce and maintain anesthesia. Propofol has a high clearance, therefore provides a more rapid recovery after continuous infusion. Its onset and duration of action, and toxic effects, are similar to the barbiturates. Etomidate is used in patients at high risk of hypertension. Side effects of etomidate include myoclonal jerks, CNS effects similar to barbiturates although with lesser respiratory depression, significant nausea and vomiting, suppression of the adrenocortical stress response and inhibition of steroidogenesis.

Ketamine is a parenteral anesthetic useful for patients at risk of hypertension or bronchospasm (is a bronchodilator). It may be administered IV, orally, rectally or intramuscular. Patients under ketamide anesthesia will have profound analgesia and amnesia but may be concious (dissociative anesthesia). Potentially toxic effects of ketamide include cataleptic state (nystagmus, mydriasis, salivation, spontaneous limb movements), increased cerebral blood flow, hallucinations and emergence delirium, and muscular rigidity.

Some therapeutic considerations when using intravenous anesthetics include: chemical stability, pain at the injection site (is it ater soluble), speed of onset, side effects, ability to produce anesthesia, speed and safety of emergence and rate of metabolism or redisribution. Clinical problems associated with intravenous anesthetics include depression of the respiratory drive (because of lower response to CO2 or to hypoxia), and depressed cardiovascular drive.

Inhaled Anesthesia

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