Anesthetics

Prepared byChayan Dhar Clinton

B.Pharm (Hon’s) Department of pharmacy, IIUC

General Anesthetics

A drug that brings about a reversible loss of consciousness

Causes one or more of the following Pain relief Muscle relaxation Relaxation of reflexes Deep sleep

Commonly used during surgery

Pathway for general Anaesthetic

Stages of General Anesthesia

Stage I - Analgesia

Stage II - Disinhibition

Stage III - Surgical anesthesia

Stage IV - Medullary depression

Main Categories

Inhalation Anesthetics Gasses or Vapors Usually Halogenated

Intravenous Anesthetics Injections Anesthetics or induction agents

Inhalation Anesthetics

Inhaled – may be liquid or gas Nitrous oxide – gas Halothane – liquid

Several others that end with –ane

Inhaled drugs are used together with IV drugs to provide the best level of sedation for the patient & procedure = Balanced Anesthesia

Mechanisms of Action

o Activate K+ channels

o Block Na+ channels

o Disrupt membrane lipids

o In general, all general anesthetics increase

the cellular threshold for firing, thus

decreasing neuronal activity.

General Actions of Inhaled Anesthetics

Respiration Depressed respiration and response to CO2

Kidney Depression of renal blood flow and urine output

Muscle High enough concentrations will relax skeletal muscle

Cardiovascular System Generalized reduction in arterial pressure and peripheral vascular

resistance. Isoflurane maintains CO and coronary function better than other agents

Central Nervous System Increased cerebral blood flow and decreased cerebral metabolism

Intravenous Anaesthetics Commonly used IV induction agents

– Propofol– Thiopental sodium – Ketamine

Most exert their actions by potentiating GABAA receptor

GABAergic actions may be similar to those of volatile anesthetics, but act at different sites on receptor

Organ effects

Most decrease cerebral metabolism and intracranial pressure

Most cause respiratory depression

May cause apnea after induction of anesthesia

Barbiturates, benzodiazepines and propofol cause cardiovascular depression.

Thiopental sodium

rapid onset (20 sec) short-acting Effect terminated not by metabolism but by

redistribution

repeated administration or prolonged infusion approached equilibrium at redistribution sites

Build-up in adipose tissue = very long emergence from anesthesia

Propofol Short-acting agent used for the induction

maintenance of GA and sedationThe onset of its action begins after 30 s.

After a single dose patient recovers after 5 min with a clear headand no hangover.

Purpose

Overall purposes of intravenous general anaesthetic Opioid analgesic – pain relief Benzodiazepine – amnesia Anticholinergic – decreases secretions Opioid analgesics – lighter pain relief Sedative/hypnotic – lighter amnesia/sedation

Toxicity and side effects Depression of respiratory drive

Decreased CO2 drive (medullary chemoreceptor's), Takes MORE CO2 to stimulate respiration

Depressed cardiovascular drive Gaseous space enlargement by NO Fluoride-ion toxicity from methoxyflurane

Metabolized in liver = release of Fluoride ions Decreased renal function allows fluoride to accumulate =

nephrotoxicity Malignant hyperthermia

Rapidly cool the individual and administer Dantrolene to block S.R. release of Calcium.

Local Anaesthetic

• Local Anaesthetics are drugs which reversibly prevent the transmission of pain stimuli locally at their site of administration.

• The clinical uses and responses of LA s depend both on the drug selected and the site of administration.

Esters

NH2

O

O CH2 CH2 N

CH2

CH2

CH3

CH3

Amides

CH3

CH3

NH CH2 CH2 N

CH2 CH3

CH2 CH3

Procaine

Lidocaine

Mode of Action

Block ! Initiation & propagation of action potential (AP) by preventing voltage-gated Na+ channels.

Bind to specific sites on channel protein Prevent formation of open channel Inhibit influx of sodium ions into the neuron Reduce depolarization of membrane in response

to action potential Prevent propagation of action potential.

Choice of local Anaesthetic

Onset Duration Regional anesthetic technique Sensory vs. motor block Potential for toxicity

Local Anaesthetic major toxicity

Allergy CNS toxicity Cardiovascular toxicity. Excitation – anxiety, agitation, restlessness Convulsions Reduced myocardial contractility Vasodilatation

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