Drugs used in anesthesia_Pharmacology.pptx

Anesthesia_Pharmacology

1. Anesthesia and Anesthetics Anesthesia; “ loss of sensation” Anesthetics are type of medications that prevent people from feeling pain during or following surgery. There are four main categories of anesthesia: General anesthesia Local anesthesia Regional anesthesia Sedation

2. Anesthetics General anesthetics (GAs) GAs put a person into a state of controlled unconsciousness so that they do not experience pain during the procedure and do not know what is happening. Reversible state of CNS depression - causes loss of response to and perception of stimuli. Local and Regional anesthetics These agents numb the part of the body that requires numbing, allowing the patient to stay awake during the procedure Sedation   helps a person feel relaxed. Routes I njection I nhalation T opical application

3. Local Anesthetics Local anesthetics provide regional anesthesia Unlike general anesthetics, local anesthetics do not cause a person to lose consciousness. Local anesthetics stop the nerves in a part of a person’s body from sending pain signals to their brain. This prevents the person from feeling pain. Used for a variety of reasons: Treating pain : sore throat, mouth ulcers, piles Minor procedures : biopsies, tooth removal, minor skin procedures like mole removal Agents ; creams, gels, or ointments, sprays, lozenges, injections

4. Drug classification; Local Anesthetics Esters (metabolized by plasma and tissue esterases ) Procaine Benzocaine Cocaine Amides (metabolized by liver amidases ) Lidocaine or Lignocaine Bupivacaine Mepivacaine Oxethazaine

5. MoA The non-ionized form of the drug crosses the axonal membrane. Once inside the nerve, the ionized form blocks the inactivated Na+ channels. The drug slows recovery and prevents propagation of action potentials. Co-administration of α 1 agonist; Decrease LA absorption into the systemic circulation Prolong effects and decrease toxicity A/ Es Neurotoxicity CV Toxicity Allergies

6. Pharmacological Actions LAs block the transmission of pain from the nerve endings into the CNS. The primary mode of action is blockade of the fast voltage‐gated sodium channels. To achieve this effect, the unionised fraction of the drug crosses the lipid bilayer of the axoplasm and blocks the channel intracellularly . The duration and density of the block depend on both the volume and concentration of the agent used. Factors that influence the efficacy of local anaesthetics are the pH, pKa , lipid solubility, protein binding, etc. Efficacy can be augmented by use of adjuncts such as adrenaline, opioids, alpha 2‐adrenergic agonists (clonidine) and alkalinisation . Toxicity is related to the site of injection, the vascularity of the site and the injected dose. The use of vasoconstrictors may reduce toxicity due to reduction in systemic absorption.

7. Lidocaine Aka Lignocaine MoA Ref previous slide C/U Local anesthesia Advanced airway management Cardiac arrhythmia: Lidocaine is a class Ib  antiarrhythmic agent, and its use is indicated in the management of ventricular tachycardia. Adjuvant analgesic: As an adjuvant analgesic in managing acute and chronic pain.

8. A/ Es Ref the figure Precautions and C/Is Hypersensitivity reactions Abnormal hepatic functions Abnormal renal functions Heart block (second or third degree) Dose Local anesthesia (topical) LA x BID Local anesthesia ( Inj ) Max individual dose: 4 mg/kg (IV) Ventricular tachycardia 50-100 mg IV bolus, following bolus administration: 1 to 4 mg/min continuous IV infusion

9. Procaine C/U Local anesthesia Contemporary applications of procaine: Co-administration with IM penicillin for the treatment of syphilis, pneumococcal pneumonia, scarlet fever, pharyngitis, rheumatic fever, and glomerulonephritis Dental procedures such as tooth extractions, cavity fillings, and root canals  Local analgesia A/ Es Hypersensitivity reactions; urticaria , pruritus, erythema, laryngeal edema , Nausea , vomiting, dizziness , perspiration, and hyperthermia. Cardiotoxic and neurotoxic effects. Cardiac symptoms include heart block, tachycardia, hemodynamic instability, heart failure, and cardiac arrest. Neurologic symptoms include tinnitus, blurred vision, dizziness, akathisia , anxiety, tremors, seizures, coma, unconsciousness, and respiratory arrest.

10. Precautions and C/Is Hypersensitivity reactions Spinal anesthesia with procaine is contraindicated in cases of septicemia and cerebrospinal diseases such as syphilis and meningitis. Pregnancy Category C Procaine administration should be undertaken cautiously in patients with cardiac arrhythmias, asthma, sulfite sensitivity, local/systemic infection, and advanced age or debility. Dose 7-10 mg/kg body weight (not to exceed 1000 mg)

11. Oxetacaine / O xethazaine MoA It produces a reversible loss of sensation by preventing or diminishing the conduction of sensory nerve impulses near the site of its application. This also decreases the permeability of the nerve cell membrane to sodium ions (membrane stabilizing effect ). In the stomach it increases the pH and neutralizes the gastric acid, which relieves the hyperacidity problems. C/U It is administered orally (usually in combination with an  antacid) for the relief of pain associated with  PUD  or esophagitis . It is also used topically in the management of  hemorrhoid pain .

12. A/ Es Rashes Constipation, nausea , diarrhea , anorexia Thirst Headache, vertigo Sleepiness, weakness Precautions and C/Is Hypersensitivity reactions to the drug Continuous treatment with this should be avoided. Tablets are to be swallowed whole, without being crushed or chewed, in order to avoid numbness of the oral cavity. Granules are swallowed whole in order to avoid numbness of the oral cavity Used with caution in pregnancy/lactation/pediatric patients Dose Susp (combination with antacids); 2 tsp x TDS x PC Oral-Tablet: 3-8 tab (15-40mg) daily divided into three to four doses. Granules: 0.3-0.8g (15-40mg) daily divided into three to four doses.

13. General Anesthesia Stages and depth of anesthesia Induction Maintenance of anesthesia Recovery Depth of anesthesia Stages I-IV

14. Note: GA has three stages; Induction, maintenance, and recovery. Induction; the time from administration to development of anesthesia Maintenance; provides sustained anesthesia Recovery; time from discontinuation of anesthetic until consciousness and protective reflexes return. Induction of anesthesia depends on how fast effective concentrations of anesthesia reach the brain. Recovery is essentially the reverse of induction. Depth of anesthesia is the degree to which the CNS is depressed. There are four stages in the depth of anesthesia.

15. Drug Classification; General Anesthetics Inhalational agents Volatile liquids Diethyl ether Halothane, Desflurane , Sevoflurane , Enflurane , Isoflurane , Chloroform Gases Nitrous oxide Cyclopropane Intravenous anesthetics Barbiturates; Thiopental, Methohexital Benzodiazepines; Midazolam, Diazepam, Lorazepam Opioid analgesics; Fentanyl, Alfentanil Others; Ketamine, Propofol Etomidate , Dexmedetomidine

16. MoA ; General Anesthetics Increase the threshold of cells to firing, resulting in decreased activity. Decrease the rate of rise of action potential by interfering with Na + influx. Inhaled anesthetics, Propofol ; Binding of GABA is enhanced by inhalation anesthetics Resulting in greater entry of chloride ions; reduces neuronal excitability b. Nitrous oxide , Ketamine ; Activates K channels and inhibit NMDA (Glutamate; N-methyl- D - aspartate) Receptors.

17. Nitrous Oxide Not effective alone as GA, usually supplemented with opioids, thiopental and Nm blockers. Pharmacological actions CVS: Activation of SNS Increases TPR, BP, and decreases CO. Respiratory system: Bronchodilation , depresses airway mucociliary functions Decreases respiratory rate and increases tidal volume (TV)

18. Advantages Non-explosive but supports combustion Non-irritant to respiratory passages Rapid induction and recovery A/ Es Respiratory depression Inadequate muscle relaxation Diffusion hypoxia during recovery Distention of bowel, pneumocephalus , air emboli Post-operative N V Fever , pulmonary atelectasis, and infectious complications Hyperhomocysteinemia :  Nitrous oxide irreversibly oxidizes the cobalt atom of vitamin B12  and reduces the activity of vitamin B12 dependent enzymes such as methionine synthetases which can also lead to megaloblastic anemia. Subacute myeloneuropathy C/Is Hypersensitivity reactions, pregnancy, Immunosuppressed patients, pernicious anemia, severe cardiac disease Dose; For  surgical procedural sedation and dental procedures, nitrous oxide (30 to 50%) is combined with oxygen .

19. Halothane Pharmacological Actions CNS : Dilatation of cerebral BVs, Increases cerebral blood flow and CSF pressure CVS : Depresses cardiac sympathetic activity causing bradycardia, depresses myocardial contractility and arterial BP Increases cutaneous blood flow as BV dilate. Respiratory system: Respiration becomes deep and shallow Bronchodilation , Depresses airway mucociliary function Kidney ; Decreases GFR Liver ; Decreases hepatic functions Skeletal muscles ; Relaxation of skeletal muscles Triggers “Malignant Hyperthermia” Uterine smooth muscle ; Relaxes uterine smooth muscles

20. Advantages Non-inflammable and non-explosive. Non-irritant to respiratory passages. Useful in patients with asthma due to its bronchodilating action. Useful in plastic surgery to produce a “bloodless area” through inducing controlled hypotension. Safe for children. A/ Es Halothane hepatitis; fever, anorexia, vomiting, eosinophilia, and bronchial abnormalities Malignant hyperthermia; muscle rigidity, fever, and tachycardia Postoperative jaundice Hepatic necrosis Hypotension, arrhythmia, bradycardia Respiratory depression

21. C/Is Unexplained liver dysfunction following previous anesthetic exposure, heart failure (reduced ejection fraction), or pheochromocytoma Dose The induction dose varies from patient to patient. The maintenance dose varies from 0.5 to 1.5%. Halothane may be administered with either oxygen or a mixture of oxygen and nitrous oxide.

22. Ketamine Produces dissociative anesthesia NMDA receptor antagonist Pharmacological Actions CNS Increases cerebral blood flow and cerebral oxygen consumption Increases ICP CVS Stimulates SNS; increased HR, CO, arterial BP Respiratory System Decreases respiratory rate (for 2-3 mins ), maintains upper airway muscle tone

23. Advantages Good analgesic and amnesic Respiratory cycle in maintained Useful in patients with shock A/ Es Emergent delirium; recovery is accompanied by emergence delirium and psychomotor activity Hallucination Cardiovascular stimulation Increased ICP C/Is Psychiatric disorders Cerebrovascular disease Respiratory infection Dose The recommended initial IV dosage of ketamine falls within the range of 1 to 4.5 mg/kg (0.5 to 2 mg/ lb ) administered over 60 seconds for individuals aged 16 years and above. 

24. Propofol C/U Induction and maintenance of anesthesia Antiemetic Advantages; Rapid induction and recovery A/E Nausea, vomiting, and dreaming CNS depressant Cardiac depressant Muscle movement, hypotonous , and tremor Hypersensitivity reactions; hypotension, flushing, bronchospasm

25. Precautions and C/Is Hypersensitivity reactions Pregnancy and lactation The FDA cautions recommends against using propofol if allergic to eggs, egg products, soybeans, or soy products . Dose; ref leaflet (in pic)

26. Thank You