CNS-PART-VII-ANESTHETICS-Contd..

ANESTHETICS-Contd...

General Anesthetics-1.Inhalers:-

1.Halothane

2.Enflurane

3.Isoflurane

4.Desflurane

5.Sevoflurane

6.Nitrous Oxide

MINIMUM ALVEOLAR CONCENTRATION(MAC):-

The concept of MAC is used to define the potency of the inhaler anesthetics.

MAC is the minimum alveolar concentration of the anesthetics necessary to suppress movements among 50% of the individuals challenged by a Standardised Skin Surgical Stimulus at a steady-state(assuming at a minimum concentration for 15 minutes remained in the alveolar chamber) at 1 atmosphere (at sea level) 

The potency is calculated as an inverse proportion to the MAC. That means the greater the MAC for an agent the higher the amount of the agent needed to eliminate the movements of the individual in constant time and the lower the potency. (e.g.-Nitrous Oxide)

The MAC of a safer agent can be reduced by concomitant administration of some adjuncts such as analgesics or opioids.

1.HALOTHANE

The first generation halogenated anesthetic available in the market. Chemically it is Bromo- chlorotrifluoromethane.

It is a colorless, pleasant smelling halogenated ethane, unstable towards the light, and is stored in dark brown colored bottle mixed with thymol as a stabilizer. It is the only brominated anesthetic and because of its bromine content which increases its toxicity it is mostly replaced in developed countries by many modern inhalers.

Clinical Use:-

Because of its pleasant smell and lack of liver toxicity it is still used in pediatrics.

Kinetics and Metabolism:-

80% of the drug is eliminated in the expired air unchanged. The remaining 20% is metabolized in the liver to trifluoroacetic acid which may rarely cause (1 in 10,000) cause liver injury. Trifluoroacetic acid is excreted by the kidneys.

MAC of Halothane

MAC = 0.75%

Side Effects:-

1.Arrhythmia (by sensitizing the heart muscles to catecholamines.)

2.Decrease heart rate

3. Decrease cardiac output.

4.Hypotension with reduced peripheral resistance

5.Malignant hyperthermia-a common reaction of inhaled anesthetics composed of higher temperature, metabolic acidosis, tachycardia, and accelerated muscle contraction. Malignant Hyperthermia can be controlled by the administration of Dantrolene.

6.Liver toxicity particularly in adults (Halothane Hepatitis)

2.ENFLURANE:-

Enflurane is used to induce rapid anesthesia.

Metabolism and Kinetics

Approximately 2% of the drug is metabolized to a fluoride ion which is then excreted by the kidney.

The 98% remained is eliminated by expired air unchanged.

MAC of Enflurane

MAC = 1.6%

Side Effects:-

1.Cardio-Vascular-Decreased heart rate, Peripheral vascular resistance, and B.P.

Unlike halothane enflurane does not cause arrhythmias as it does not sensitize the myocardium to catecholamines.

2.Kidney damage by the fluoride ion after prolonged uses

Enflurane is contraindicated to those who have already kidney failure.

3.ISOFLURANE

Almost 100% of this drug is eliminated by expired air and is very safe as it does not pass into the system unless a fraction.

MAC=1.4%

Cardiovascular Effects

1.Increased heart rate

2.Decrease B.P by decreasing peripheral resistance

3.Malignant hyperthermia

Isoflurane does not sensitize the myocardium to catecholamines and hence does not cause 

arrhythmias.

4.DESFLURANE

Very similar to isoflurane this drug also 100% eliminated through expired air unless a fraction can enter into the system on prolonged use.

MAC = 6%

Side Effects:-

1. Cardiovascular effects are similar to isoflurane

2.Higher risk of Malignant Hyperthermia

5.SEVOFLURANE

Metabolism is very similar to enflurane as a small quantity can enter into the system and the remaining portion is eliminated by the expired air unchanged. But it differs from enflurane it does no cause nephrotoxicity as it is hypothesized that it is not excreted by the kidneys.

MAC=2%

Side Effects

1.Cardiovascular-Increase heart rate, lower B.P by reducing peripheral resistance,

It does not cause arrhythmias as with enflurane.

2.Malignant hyperthermia.

6.NITROUS OXIDE 

As it is a weaker anesthetic it is mostly used as an adjunct to induce anesthesia.

It can be administered either by inhalation or by I.V.

Nitrous oxide is expelled out without change as it is not metabolized.

MAC=100%, very weak as even if 100% nitrous oxide is given to the patients it does not attain the stage of surgical anesthesia.

Toxicity

1.Minimal cardiovascular effects

2.Bone marrow suppression if used for a long time

3.Neuropathies.

Contraindication

Pneumothorax-a condition in which there are closed cavities in the lung and the gas cannot escape out and will diffuse within the cavities to increase internal cavity pressure.

Precaution

The patient must be administered with sufficient oxygen during the recovery phase as nitrous oxide from the blood will diffuse into the alveoli and entirely replace the oxygen.

CNS-PART-VII-ANESTHETICS

ANESTHETICS-INTRODUCTORY

Anesthesia can be defined as a medical state which is composed of one or more of the following components of states such as analgesia(relief from the pain), state of muscle relaxation(paralysis), and loss of consciousness.

The patient who is given an anesthetic agent is said to be Anesthetized.

A nursing staff who is not a professional if give an anesthetic to a patient is known as an Anesthetist as in U.S.and North America (including Canada)

A professional who gives an anesthetic to a patient is known as Anesthesiologist.

Medical anesthesia can be divided into two types as 1. General and 2.Local.

General anesthetics are usually given by inhalation or through intravenous.

Local anesthetics are generally injected at the operative site to block the nerve conduction.

Stages of General Anesthesia

1.Analgesia or Stage of Induction:-

Loss of senses to feel pain. Consciousness is retained. The patient can talk.

2.Stage of Excitation:-

Delirium, a mental state of excitement, restlessness, incoherence with sweat.

3.Stage of Surgical Anesthesia:-

The patient is unconscious sufficiently to conduct surgery on him. Regular respiration is safely retained, with muscle paralysis and decreased vasomotor responses to painful impulses.

4.Stage of Medullary Paralysis:-

An irreversible stage if unattended, in which respiratory depression followed by coma and death occurs.

The pharmacokinetics of drugs plays an important role in attaining the different stages.

A slow-acting anesthetic like ether can give a well-distinguished stage. A fast-acting anesthetic would lead to the rapid occurring of the stages.

Induction of Anesthesia can be well defined as from the time of administration of the anesthetic 

up to the achievement of the state of surgical anesthesia.

The induction goal can be achieved as quickly as the drug reaches the central nervous system (CNS)

The complication of inducing anesthesia can be avoided by first injecting an ultra fast-acting and ultra short-lived anesthetic such as Propofol through I.V. so that the patient will rapidly progress through the first and second stages so that the anesthesia can easily enter into the state of surgical anesthesia.

The recovery from the anesthesia is the reverse process of induction. This depends on how fast the drug is removed from the CNS.

There are five factors influence the inhalation anesthesia as follows:-

1.Solubility

2.Pulmonary ventilation

3.The partial pressure of the inhaled drug

4.Alveolar blood flow.

5.Arteriovenous concentration gradient.

1. Solubility-This factor affects the rate of induction by the blood-gas partition coefficient. A low coefficient implies low solubility and a low soluble agent require fewer molecules to raise the partial pressure of the agent in the blood. Thus the equilibrium between the arterial partial pressure and the alveolar partial pressure is attained rapidly which leads to rapid induction. Recovery is similarly hastened by discontinuing the agent.

2. Pulmonary Ventilation-The rate and depth of lung ventilation (the minute ventilation) affect the rate of increase in the partial pressure of the anesthetic in the blood. An increase in minute ventilation results in an increased amount of agent and this effect is very important for agents with low solubility because they require a higher amount of the agent to attain equilibrium.

3. Partial Pressure-An increased concentration of the drug in the inhaled air mixture leads to higher concentration in the alveoli and thus increases the arterial partial pressure of the drug. Therefore a greater concentration is given initially to speed induction and then it is reduced to a maintenance level.

4. Alveolar Blood Flow-Increased blood flow causes more rapid uptake of the agent which attain quicker effect on the CNS.

5. Arterio-Venous Concentration Gradient-This depend on the tissue uptake of the drug. If more tissue uptake of the agent is there then there is a decrease venous concentration of the agent, which leads to a longer time to achieve an equilibrium between the arteriovenous concentration.

Factors Affecting Tissue Uptake Of the Anesthetics:-

1.Blood Partition Coefficient

2.Rate of blood flow to the tissue

3.Concentration Gradients between artery and vein.

Highly perfused tissues like the brain, heart, liver, and kidneys will exert greater influence on the arteriovenous concentration gradient.

Skin and skeletal muscles are low perfused and hence they exert a low influence.

Mechanism

The mechanism of action of the GA depends upon the availability of the agent in molecules. All anesthetics are assumed by acting on the action potential by nullifying them through increasing the threshold. Also acting by inhibiting the entry of sodium ion by decreasing the membrane permeability to them. The mechanism is not clear but on assumption, only.No receptors are involved inbound up with anesthetics.

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