PHARMACOLOGY II DENTISTRY GENERAL & LOCAL ANESTHESIA

Dr Mohammed Shamssain

Course Contents
General & local anesthetics Sedative hypnotics & pharmacology of alcoholism Treatment of epilepsy & parkinsonism Antipsychotics, anti depressant & anxiolytics Pharmacology of pain Adrenal cortex hormones & steroidal antiinflammatory drugs

Course Contents
Thyroid hormones & anti-thyroid drugs Calcium metabolism Gonadal hormones & their antagonists Oral contraceptives Pharmacology of diabetes mellitus Antimicrobial agents Antifungal & antiviral agents Treatment of cancer & parasitic infestation

Assessment
Quiz one: one hour; 20%; date: Monday 19th March (1-2 pm) Mid-term exam: one hour; 20% Quiz two: one hour; 20%; date: Monday 14th May (1-2 pm) Final exam: two hours; 40%

General
Noradrenaline: noradrenergic transmission is important in control of mood (functional deficiency resulting depression) controlling wakefulness, and alertness Dopamine: is important in motor control (parkinsonism is due to dopamine deficiency) has behavioural effects (excessive dopamine activity is implicated in schizophrenia) hormone release (prolactin, GH) dopamine in chemoreceptor trigger zone causes nausea & vomiting

General
5-HT: physiological functions associated with 5-HT pathways include: feeding behaviour, behavioural response, control of mood and emotion, control of body temperature and vomiting Ach: has effects on arousal, on learning, and on short term memory. Dementia and parkinsonism are associated with abnormalities in cholinergic pathways. GABA (Gamma-AminoButyric Acid): is an inhibitory NT in CNS Glycine: an inhibitory NT , acts on GABA like receptor in spinal cord

Anesthetics

Ion Channels

Synapse

Anesthetic Suppression of Physiological Response to Surgery

Essential Components of Anesthesia

Analgesia- perception of pain eliminated Hypnosis- unconsciousness Depression of spinal motor reflexes Muscle relaxation

* These terms together emphasize the role of immobility and of insensibility!

Stages of Anesthesia
In general anesthesia: the patient is unconscious and has no awareness or other sensations. The relationship between the amount of general anesthetic administered and the depression of the brain's sensory usefully divided into stages to describe the depth of anesthesia.1,3,5

Mechanism of Action

General Anesthetics CNS modifying functions of ION CHANNELS modifying the electrical activity of neurons at a molecular level This may occur by

anesthetic molecules binding directly to ion channels or by their disrupting the functions of molecules that maintain ion channels.

a general anesthetic is a drug that has the ability to bring about a reversible loss of consciousness

by act on CNS via shutting off the brain from external stimuli

Anesthetics divide into 2 classes:

Inhalation Anesthetics

Intravenous Anesthetics

Gasses or Vapors Usually Halogenated

Injections Anesthetics or induction agents

What are General Anesthetics?

A drug that brings about a reversible loss of consciousness. Administered by an anesthesiologist in order to induce or maintain general anesthesia to facilitate surgery.

Pathway for General Anesthetics

Pathway for General Anesthetics

Partial Pressure in brain quickly equilibrates with partial pressure in arterial blood which has equilibrated with partial pressure perfused alveoli. DEPTH of anesthesia induced by an inhaled anesthetic depends primarily on the PARTIAL PRESSURE!!! Of the anesthetics in the brain

Pathway of General Anesthetics

Rate of induction and recovery from anesthesia depends on the rate of change of partial pressure in the brain. These drugs are small lipid-soluble molecules that cross the alveolar membrane easily. Move into and out of the blood based on the partial pressure gradient.

Variables that Control Partial Pressure in Brain

Direct Physician's Control

Solubility of agent Concentration of agent in inspired by air Magnitude of alveolar ventilation

Indirect Physicians Control

Pulmonary blood flow-function of CO Arteriovenous concentration gradient

Rate of Entry into the Brain: Influence of Blood and Lipid Solubility

Rate of Entry into the Brain

LOW solubility in blood= fast induction and recovery HIGH solubility in blood= slower induction and recovery.

General Anesthetics

General Anesthetics

General Actions of Inhaled Anesthetics

Respiration

Depressed respiration and response to CO2 Depression of renal blood flow and urine output High enough concentrations will relax skeletal muscle

Kidney

Muscle

Cont

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

Inhaled Anesthetics

Inhaled Anesthetics

Halothane Enflurane Isoflurane Desflurane

Halogenated compounds: Contain Fluorine and/or bromide Simple, small molecules

Injectable Anesthetics

Intravenous Anesthetics

Used in combination with Inhaled anesthetics to:

Supplement general anesthesia Maintain general anesthesia Provide sedation Control blood pressure Protect the brain

Adjunct Agents

Anticholinergic Drugs
Block the effects of Ach and other cholinergic drugs at cholinergic receptors of effector cells Two major types
Antinicotinics include ganglion blockers and neuromuscular blockers Anti muscarinics include tertiary amines (e.g: atropine , scopolamine, etc)

Mechanism of Action of Anesthesia

MAC:Minimum Alveolar Conc

MAC is a concept used to compare the strengths, or potency, of anaesthetic vapours Defined as the concentration of the vapour in the lungs that is needed to prevent movement (motor response) in 50% of subjects in response to surgical (pain) stimulus. A lower MAC value represents a more potent volatile anesthetic.

Overton Meyer Theory

O-M Theory: The MAC of a volatile substance is inversely proportional to its lipid solubility (oil:gas coefficient) MAC is inversely related to potency i.e. high mac equals low potency. The hypothesis correlates lipid solubility of an anaesthetic agent with potency (1/MAC) Onset of anaesthesia occurs when sufficient molecules of the anaesthetic agent have dissolved in the cell's lipid membranes, resulting in anaesthesia

Indications

Side Effects

Local Anesthetics

Types of Local Anesthetics

Parenteral Anesthetic Agents

Drug Effects

Indications

Indications

Side Effects

Neuromuscular Blocking Agents

NMBAs

NMBAs:Depolarizing Agents

NMBAs:Non-Depolarizing Agents

NMBAs

NMBAs:Indications

NMBAs: Side Effects

NMBAs: Overdose

Toxicity and Side Effects

Depression of respiratory drive

Decreased CO2 drive (medullary chemoreceptors), 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

Moderate Sedation

Dentistry Implications

Dentistry Implications

Dentistry Implications

Dentistry Implications