General Anaesthetic, Sedatives & Hypnotics, Antiepileptic, Alcohol & Disulfiram.pptx

General Anaesthetic, Sedatives & Hypnotics, Antiepileptic, Alcohol & Disulfiram.pptx

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  PREPARED BY Prof. ASHISHN. UMALE M. PHARM IN PHARMACOLOGY ASSISTANT PROFESSOR SHRADDHA INSTITUTE OF PHARMACY, WASHIM- 444505 PHARMACOLOGY-I
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  General Anesthetics General anestheticsare drugs that produce a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation, allowing surgical procedures to be performed safely. The process of anesthesia occurs in stages, beginning with analgesia, followed by excitement, surgical anesthesia, and finally medullary depression if overdose occurs. Classification 1. Inhalational Anesthetics These agents are administered through inhalation and are absorbed via alveoli into the bloodstream. Gases: Nitrous oxide Volatile liquids: Halothane, Isoflurane, Sevoflurane, Desflurane
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  2. Intravenous Anesthetics Thesedrugs are administered intravenously and are mainly used for induction of anesthesia. Ultra-short acting barbiturate: Thiopentone sodium Non-barbiturate: Propofol, Etomidate Dissociative anesthetic: Ketamine Mechanism of Action General anesthetics act primarily by enhancing inhibitory neurotransmission mediated by GABA-A receptors, leading to increased chloride ion influx and neuronal hyperpolarization. At the same time, they inhibit excitatory neurotransmission mediated by NMDA receptors, particularly in the case of ketamine and nitrous oxide. The combined effect results in generalized CNS depression.
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  Pharmacokinetics (Inhalational Agents) Inhalationalanesthetics are absorbed through alveoli, and their onset depends on blood-gas solubility. Drugs with low solubility produce rapid induction and recovery. Intravenous anesthetics are highly lipid-soluble and rapidly cross the blood-brain barrier, producing quick onset of action. Most agents are metabolized in the liver and eliminated through lungs or kidneys. Pharmacological Effects General anesthetics produce depression of the CNS in a graded manner, leading to loss of consciousness, suppression of reflexes, analgesia, and skeletal muscle relaxation. They also depress respiration and cardiovascular function depending on dose.
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  Adverse Effects Adverse effectsinclude respiratory depression, hypotension due to myocardial depression, arrhythmias, postoperative nausea and vomiting, and in rare cases, malignant hyperthermia. Important drug examples 1. Propofol Propofol is a short-acting intravenous anesthetic that produces rapid induction and smooth recovery. It enhances GABA-A receptor activity, leading to CNS depression. It is highly lipid-soluble, rapidly distributed, and metabolized in the liver. It is used for induction & maintenance of anesthesia and sedation. It may cause hypotension, respiratory depression, and pain at the injection site.
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  2. Ketamine Ketamine producesanesthesia by blocking NMDA receptors, thereby inhibiting excitatory neurotransmission. It has rapid onset and provides strong analgesia. It is particularly useful in emergency settings and in asthmatic patients due to bronchodilation. Adverse effects include hallucinations, increased blood pressure, and emergence delirium.
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  Pre-Anesthetic Medication Pre-anesthetic drugsare administered before anesthesia to reduce anxiety, decrease secretions, prevent reflex responses, and improve the overall safety and effectiveness of anesthesia Classification with Pharmacological Basis Sedatives and anxiolytics (Benzodiazepines) such as diazepam are used to reduce anxiety and produce amnesia by enhancing GABA activity. Anticholinergics such as atropine reduce salivary and bronchial secretions and prevent bradycardia by blocking muscarinic receptors. Opioid analgesics such as morphine provide preoperative analgesia by acting on opioid receptors in CNS. Antiemetics such as ondansetron act on 5-HT3 receptors to prevent nausea and vomiting.
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  Sedatives, Hypnotics andCentrally Acting Muscle Relaxants Sedatives and Hypnotics Sedatives are drugs that reduce excitement and anxiety, whereas hypnotics induce sleep resembling natural sleep. The same drug can act as a sedative at low doses and as a hypnotic at higher doses. Classification 1. Benzodiazepines Examples include diazepam, lorazepam, alprazolam, and nitrazepam. 2. Barbiturates Examples include phenobarbitone and thiopentone. 3. Non-benzodiazepine hypnotics Examples include zolpidem and zopiclone.
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  Mechanism of Action Benzodiazepinesbind to specific sites on the GABA-A receptor complex & increase the frequency of chloride channel opening, thereby enhancing inhibitory neurotransmission. Barbiturates increase the duration of chloride channel opening. Non-benzodiazepines act selectively on certain subtypes of GABA receptors. Pharmacokinetics They are generally well absorbed orally and are lipid-soluble, allowing easy penetration into the brain. Many are metabolized in the liver, and some have active metabolites that prolong their action.
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  Pharmacological Effects These drugsproduce sedation, hypnosis, anxiolysis, muscle relaxation, and anticonvulsant effects depending on dose. Adverse Effects Adverse effects include drowsiness, impaired coordination, tolerance, dependence, and withdrawal symptoms. Barbiturates have a narrow therapeutic index and can cause severe respiratory depression.
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  Important drug examples 1.Diazepam Diazepam is a benzodiazepine that enhances GABA-A receptor activity by increasing chloride channel opening frequency. It is used in anxiety, insomnia, seizures, and muscle spasms. It has a long duration due to active metabolites and may cause sedation, dependence, and withdrawal symptoms. 2. Phenobarbitone Phenobarbitone is a barbiturate that enhances GABA action by increasing chloride channel opening duration. It is mainly used as an antiepileptic drug. It has a long half-life and induces liver enzymes, leading to drug interactions. It may cause sedation, dependence, and respiratory depression.
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  Centrally Acting MuscleRelaxants Centrally acting muscle relaxants reduce muscle spasm by acting on the CNS rather than directly on muscle fibers. Classification Common drugs include baclofen, tizanidine, and diazepam. Mechanism of Action Baclofen acts as a GABA-B receptor agonist, reducing excitatory neurotransmitter release. Tizanidine acts as an alpha-2 adrenergic agonist, inhibiting motor neuron activity. Diazepam enhances GABA-mediated inhibition.
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  Uses They are usedin conditions such as spasticity (muscle stiffness, spasms i.e. muscle contraction) due to spinal cord injury, multiple sclerosis, and cerebral palsy Adverse Effects Common adverse effects include sedation, dizziness, muscle weakness, and hypotension. Important drug example Baclofen acts on GABA-B receptors to reduce muscle tone and spasticity. It is well absorbed and excreted via kidneys. It is used in spasticity disorders and may cause sedation and withdrawal-related seizures if stopped abruptly.
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  Anti-Epileptics (Anti-Seizure Drugs) Antiepilepticdrugs are used to prevent or reduce the frequency of seizures by stabilizing neuronal membranes and suppressing abnormal electrical activity in the brain. Classification Based on Mechanism 1. Sodium Channel Blockers  Phenytoin and carbamazepine act by prolonging the inactivated state of sodium channels, thereby reducing repetitive neuronal firing. 2. GABA Enhancers  Valproate and benzodiazepines increase GABA levels or enhance its action, leading to increased inhibition.
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  3. Calcium ChannelBlockers  Ethosuximide blocks T-type calcium channels in thalamic neurons and is particularly useful in absence seizures. 4. Drugs with Multiple Mechanisms  Valproate and lamotrigine act through multiple pathways, including sodium channel blockade & enhancement of GABA. Pharmacokinetics Most antiepileptic drugs are well absorbed orally and undergo hepatic metabolism. Some drugs like phenytoin show nonlinear kinetics. Uses These drugs are used in the management of various types of epilepsy, tonic-clonic seizures, absence seizures, and partial seizures.
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  Adverse Effects Common adverseeffects include sedation, ataxia, cognitive impairment, and hypersensitivity reactions. Specific effects include gingival hyperplasia with phenytoin and hepatotoxicity with valproate. Important drug examples 1. Phenytoin Phenytoin blocks sodium channels and stabilizes neuronal membranes. It is used in tonic-clonic seizures and has nonlinear kinetics. It may cause gingival hyperplasia, hirsutism, and ataxia. 2. Sodium Valproate Valproate increases GABA levels and blocks sodium and calcium channels. It is effective in multiple seizure types. It may cause liver toxicity, weight gain, and teratogenicity.
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  Alcohols and Disulfiram Alcohol(Ethanol) Ethanol is a CNS depressant that produces dose-dependent effects ranging from mild euphoria to deep coma. Mechanism of Action Ethanol enhances GABA-mediated inhibition & inhibits NMDA receptor-mediated excitation, leading to CNS depression. It also increases dopamine release, contributing to its addictive properties.
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  Pharmacokinetics Ethanol is rapidlyabsorbed from the gastrointestinal tract and is metabolized in the liver by alcohol dehydrogenase to acetaldehyde, which is further metabolized by aldehyde dehydrogenase.  Effects At low doses, ethanol produces disinhibition (failure to control of brain impulse) and euphoria (strong feeling of happiness, excitement). At higher doses, it causes sedation, impaired coordination, and respiratory depression.
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  Disulfiram Disulfiram inhibits theenzyme aldehyde dehydrogenase, resulting in accumulation of acetaldehyde when alcohol is consumed. Effect The accumulation of acetaldehyde produces unpleasant symptoms such as flushing, headache, nausea, vomiting, and palpitations, which discourage alcohol intake.  Therapeutic Use Disulfiram is used as a deterrent therapy in chronic alcohol dependence. Precautions Patients must be warned to avoid alcohol in all forms, including medications and food products containing alcohol.