General Anaesthetics

Introduction to General Anaesthetics
Introduction General Anaesthetics, Stages of anaesthesia, Classification of General Anaesthetics, Mechanism of action of General Anaesthetics, Pharmacokinetics, Pharmacodynamics, Uses, Side effects
Presented by
I. Sai Reddemma
Department of Pharmacology

1. 1 A Seminar as a part of curricular requirement for I year M. Pharm I semester Presented by Ms. I. Sai Reddemma. (Reg. No. 20L81S0101) M. Pharm Department of Pharmacology. Under the guidance/Mentorship of A. Sudheer Kumar., M. Pharm. Associate Professor Department of Pharmacology. GENERAL ANAESTHETICS

2. 2 Introduction Stages of anaesthesia Classification of General Anaesthetics Mechanism of action of General Anaesthetics Pharmacokinetics Pharmacodynamics Uses Side effects References Contents

3. 3 Anaesthetics : Drugs which induce reversible loss of consciousness are known as anaesthetics. Two types of anaesthetics: 1.General anaesthetics: The drugs which makes whole body lose feeling movement and counciousness. 2. Local anaesthetics: The drugs which numb only a specific targeted area of the body. Introduction

4. 4 Properties of General Anaesthetics For Patient: - Pleasant, non-irritating and should not cause nausea or vomiting - Induction and recovery should be fast For Surgeon : - analgesia, immobility and muscle relaxation - nonexplosive and noninflammable

5. 5 Essential components of GA Cardinal Features: 1. Loss of all modalities of sensations 2. Sleep and Amnesia 3. Immobility or Muscle relaxation 4. Abolition of reflexes – somatic and autonomic

6. 6 Anaesthesia events 1. Induction: It is the period of time which begins with the administration of an anaesthetic upto the development of Surgical anaesthesia. Done by inducing agents – Thiopentone sodium. 2. Maintenance: Sustaining the state of anaesthesia. Done by Inhalation agents – Nitrous oxide and halogenated hydrocarbons. 3. Recovery : Anaesthetics stopped at the end of surgical procedure and consciousness regains

7. 7 Stage 1: Induction or Stage of analgesia Stage 2: Stage of delirium or excitement Stage 3: Surgical anaesthesia Stage 4: Medullary paralysis or Overdose Stages of general anaesthesia:

8. 8 Stage:1 Stage of analgesia Starts from beginning of anaesthetic inhalation and lasts upto the loss of consciousness . Pain is progressively abolished during this stage . Patient remains conscious, can hear and see, and feels a dream like state. Reflexes and respiration remain normal . It is difficult to maintain - use is limited to short procedures only .

9. 9 Stage:2 Stage of delirium From loss of consciousness to beginning of regular respiration Excitement - patient may shout, struggle and hold his breath Muscle tone increases, jaws are tightly closed. Breathing is jerky; vomiting may occur. Heart rate and BP may rise and pupils dilate due to sympathetic stimulation. Breath holding is commonly seen. Potentially dangerous responses can occur during this stage including vomiting, laryngospasm and uncontrolled movement.

10. 10 Stage:3 Surgical anaesthesia Extends from onset of regular respiration to cessation of spontaneous breathing. This has been divided into 4 planes: Plane 1: M oving eye balls. This plane ends when eyes become fixed. Plane 2: Loss of corneal and laryngeal reflexes. Plane 3: Pupil starts dilating and light reflex is lost. Plane 4: Intercostal paralysis, shallow abdominal respiration, dilated pupil.

11. 11 Stage:4 Medullary paralysis Cessation of breathing failure of circulatio n and death Pupils: widely dilated Muscles are totally flabby Pulse is imperceptible BP is very low.

12. 12 Classification of General Anaesthetics

13. 13 Minimal Alveolar Concentration (MAC) : Minimum alveolar concentration or MAC is the concentration of a vapour in the alveoli of the lungs that is needed to prevent movement in 50% of subjects in response to surgical stimulus. MAC is used to compare the strengths or potency of anaesthetic vapours.  Mechanism of General Anaesthetics

14. 14 GABA A  receptor agonists GABA A  receptor are chloride channels that  hyperpolarise  neurons and function as inhibitory CNS receptors. General anesthetics that agonize them are typically used to induce a state of sedation and/or unconsciousness. Examples:   Propofol   Etombidate Benzodiazepines Barbiturates 1 st group drugs mechanism

15. 15

16. 16 NMDA receptor antagonists Ketamine , an  NMDA receptor  antagonist, is used primarily for its analgesic effects and in an  off-label capacity for its anti-depressant effects. This drug, however, also alters arousal and is often used in parallel with other general anesthetics to help maintain a state of general anesthesia. Administration of ketamine alone leads to a dissociative state, in which a patient may experience auditory and visual   hallucinations. Additionally, the perception of pain is dissociated from the perception of noxious stimuli. Ketamine appears to bind preferentially to the NMDA receptors on GABAergic interneurons, which may partially explain its effects . 2 nd group drugs mechanism

17. 17

18. 18 Two-pore potassium channels (K 2P s) activation Two-pore potassium channel   (K 2P s) modulate the potassium conductance that contributes to the  resting membrane potential  in neurons. Opening of these channels therefore facilitates a  hyperpolarizing current, which reduces neuronal excitability. K 2P s have been found to b e affected by general anesthetics (esp. halogenated inhalation anesthetics) and are currently under investigation as potential targets 3 rd group drugs mechanism

19. 19

20. 20 Pharmacokinetics of I. V. Anaesthetic agents Propofol Thiopental Ketamine Etomidate Water-Soluble No Yes Yes No Half-life (initial) (min) 2 8.5 16 1 Half-life (terminal)(h) 4-7 12 3 5.4 Volume of distribution (litre kg-1) 4.6 2.4 3 5.4 Clearance (ml min kg-1) 25 11 19 18 Protein binding (%) 98 80 12 75

21. 21 Intravenous general anesthetics Induction Intravenously-delivered general anesthetics are typically small and highly lipophilic molecules. These characteristics facilitate their rapid preferential distribution into the brain and spinal cord, which are both highly vascularized and lipophilic. It is here where the actions of these drugs lead to general anesthesia induction Pharmacokinetics of I. V. GA

22. 22  Elimination Following distribution into the  C entral Nervous System (CNS), the anesthetic drug then diffuses out of the CNS into the muscles and viscera, followed by  adipose tissues. In patients given a single injection of drug, this redistribution results in termination of general anesthesia. Therefore, following administration of a single anesthetic  bolous , duration of drug effect is dependent solely upon the redistribution kinetics.

23. 23 Central Nervous System Compared to barbiturates, propofol and inhalational anaesthetics, the benzodiazepines are not able to produce the same degree of neuronal depression. At low doses the benzodiazepines have anxiolytic and anti-convulsive effects. As the dose increases, the benzodiazepines produce sedation, amnesia and finally sleep. The effect of the benzodiazepines is clearly dose-related but there seems to be a ceiling effect where increasing the dose does not increase the effect. Pharmacodynamics

24. 24 Respiration Normal oral hypnotic doses of benzodiazepines have essentially no effect on respiration in normal subjects. At higher doses, the benzodiazepines do influence respiration. The benzodiazepines affect respiration in two different ways. First, they have an effect on the muscular tone leading to an increased risk of upper airway obstruction. Thus, benzodiazepines are not recommended and are considered even contraindicated in patients suffering from obstructive sleep apnoea. Second, they also affect the ventilatory response curve to carbon dioxide by flattening the response.

25. 25 Cardiovascular System The intravenous administration of sedative or anaesthetic doses of the benzodiazepines cause a modest reduction in arterial blood pressure and increase in heart rate. These changes are mainly due to a decrease in systemic vascular resistance. In addition, they induce a minor reduction of cardiac output.

26. 26 SVR, (systemic vascular resistance), MAP, mean (arterial pressure) CBF,(cerebral blood flow) . Function Propofol Thiopental Ketamine Etomidate Heart rate Minimal effect Increased Increased No effect Contractility Reduced Reduced Increased No effect SVR Reduced Reduced Increased Minimal effect MAP Reduced Reduced Increased Minimal effect Respiratory Depression Depression Bronchodilation Minimal effect CBF Decreased Decreased Increased Decreased Adrenal cortex ------ ------ ------ Functional inhibition Systemic effects of i.v. agents:

27. 27 General anesthesia is an anesthetic used to induce unconsciousness during surgery. The medicine is either inhaled through a breathing mask or tube, or given through an intravenous (IV) line. A breathing tube may be inserted into the windpipe to maintain proper breathing during surgery. Uses of general anesthetics

28. 28 Propofol causes : Respiratory Depression, Hypotension. Barbiturates causes : Apnea, Cough, Bronchospasm. Ketamine causes : Hypertension, Tachycardia, Hypersalivation. Halothane causes : Hepatotoxicity . Side effects

29. 29 Harrison NL. General anaesthetics: mechanisms of action. In: Hemmings HC, Hopkins PM, eds. Foundations of Anesthesia, 2nd Edn. Philadelphia: Mosby Elsevier, 2006; 287– 94 Campagna J, Miller K, Forman S. Mechanisms of action of inhaled anesthetics. N Engl J Med 2003; 348: 2110– 24 Wang DS, Orser BA. Inhibition of memory and learning by general anaesthetics. Can J Anaesth 2011; 58: 167–77 Rodolf U, Antkowiak B. Molecular and neuronal substrates for general anaesthetics. Nat Rev Neurosci 2004; 5: 709–20 References

30. 30 THANK YOU