General Anesthetics Agents are used to produce unconsciousness and loss of perception to painful surgical procedures. Physiologic state induced by general.

Slides:



Advertisements
Similar presentations
Medicinal Chemistry II 4th year Pharm Students
Advertisements

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 27 General Anesthetics.
The Use and Abuse of Nitrous Oxide: No Laughing Matter Erica Helfer LEAP Independent Study Summer 2008.
Anesthetics. Overview General anesthesia is essential to surgical practice, because it renders patients: analgesic amnesic unconscious provides muscle.
PTP 546 Module 15 Pharmacology of Anesthetics Jayne Hansche Lobert, MS, RN, ACNS-BC, NP 1Lobert.
General anesthetics Dr Sanjeewani Fonseka.
Clinical Aspect of General Anesthetics
Davis MDCH General Anesthetics Analgesia. Mild CNS depression. Suitable for surgical procedures not requiring muscle relaxation. All anesthetics.
Procedural Sedation Pharmacology Deb Updegraff R.N., P.N.P, C.N.S. Clinical Nurse Specialist LPCH Pediatric Intensive Care Unit.
Mosby items and derived items © 2007 by Mosby, Inc., an affiliate of Elsevier Inc. Chapter 12 General Anesthetics.
General Anesthetics Drugs used to induce a state of unconsciousness with the overall aim of ensuring hypnosis, amnesia, analgesia, immobility, skeletal.
CHAPTER 3 ISOFLURANE AND SEVOFLURANE (HALOGENATED COMPOUNDS) NITROUS OXIDE AND DESFLURANE ENFLURANE HALOTHANE METHOXYFLURANE DIETHYL ETHER Inhalation Anesthetics.
MCMP 407 General Anesthesia  Sleep induction  Loss of pain responses  Amnesia  Skeletal muscle relaxation  Loss of reflexes.
Inhalation Anesthetics
By PROF. Dr. Yieldez Bassiouni
CNS depressants CNS depressants
Members of the Surgical Team Surgeon Surgical assistant Anesthesiologist Certified registered nurse anesthetist Holding area nurse Circulating nurse Scrub.
Induction Recovery Concentration = Partial pressure x Solubility tissue.
Yacoub M. Irshaid, MD, PhD, ABCP Department of Pharmacology
Without reference, identify principles about Anesthesia Units with at least 70 percent accuracy.
Sedative-Hypnotic Drugs
GENERAL ANESTHETICS Tutik Juniastuti.
Lu-Tai Tien, Ph.D. School of Medicine Fu-Jen Catholic University
General Anesthesia Dr. Israa.
ANESTHETICS Dr.Shadi- Sarahroodi Pharm.D & PhD PUBLISHED BY
GENERAL ANAESTHESIA BY: DR.H.S.IMRAN-UL-HAQUE. LECTURER, PHARMACOLOGY & THERAPEUTICS
Intravenous anesthetics. Toxicity of General Anesthesia.
CNS Depressants Lab # 2.
DR. MOHD NAZAM ANSARI. Partial or complete loss of sensation with or with out loss of consciousness as a result of disease, injury, or administration.
Otto F Sabando DO FACOEP Program Director Emergency Medicine Residency St. Joseph’s Regional Medical Center Paterson NJ.
General principles of General principles of anesthesia anesthesia.
General Anesthetics Learning objectives Explain the purpose of application of GAs Classify the GAs & the typical drugs Identify the mechanism of.
Drug Interactions Critical to understand potential drug interactions, given the practice of ‘balanced anesthesia’ and the multiple drugs used to achieve.
General anesthesia General anesthesia is essential to surgical practice, because it renders patients analgesic, amnesia, and unconscious reflexes, while.
General anesthesia General anesthesia was not known until the mid-1800’s Diethylether was the first general anesthetic used for surgery General Anesthetics.
General anesthetics.
Introduction to anaesthesia
2 3  Which influence the selection of the anesthetics are  Liver & kidney – target organs for toxic effects by the release of Fluoride, Bromide.
Inhaled anesthetics By: Israa Omar.
Dr. Laila M. Matalqah Ph.D. Pharmacology PHARMACOLOGY OF CNS 3 Anesthetics General Pharmacology M212.
Local Anaesthesia and Vasoconstrictors
Definition : Anesthesia (an =without, aisthesis = sensation ) Anesthesia is medication that attempts to eliminate pain impulse from reaching the brain.
MCQ – I V INDUCTION AGENTS
Anesthetics Lecture-2. ELIMINATION The time to recovery from inhalation anesthesia depends on the rate of elimination from the brain after the inspired.
Biomedical Engineering Lecture on Drugs for sedation, general anesthesia, and other purposes.
Anxiolytic , Sedative and Hypnotic Drugs
General anaesthetics 22January2013 Batch17Year2 Pharmacology.
Dr.Arkan Jaafar , M.D. Anesthesiologist Medical college of Mosul
Med chem II tutoring Anesthetics
Anesthesia Part 3 By Alaina Darby.
HINDU COLLEGE PG COURSE.
Med Chem Tutoring - Anesthesia
GENERAL ANAESTHETIC AGENTS By Afsar fathima.
Anesthesia By Alaina Darby.
General Anesthesia.
Benzodiazepines AMD.
Anesthesia By Alaina Darby.
General anesthesia General anesthesia is essential to surgical practice, because it renders patients analgesic, amnesia, and unconscious reflexes, while.
General Anesthesia.
Department of Surgery Anesthesiology Dr. Ahmed Haki Ismael
Anesthesia In the “old days” the following were used for anesthesia.
School of Pharmacy, University of Nizwa
Introduction to Clinical Pharmacology Chapter 17 Anesthetic Drugs
CNS Depressants Lab # 2.
General anesthesia General anesthesia is essential to surgical practice, because it renders patients analgesic, amnesia, and unconscious reflexes, while.
General anesthesia General anesthesia is essential to surgical practice, because it renders patients analgesic, amnesia, and unconscious reflexes, while.
Introductory Clinical Pharmacology Chapter 21 Anesthetic Drugs
NON VOLATILE ANESTHETIC AGENTS( Intravenous Anesthetics)
Introduction to Clinical Pharmacology
Presentation transcript:

General Anesthetics Agents are used to produce unconsciousness and loss of perception to painful surgical procedures. Physiologic state induced by general anesthetics include: analgesia, amnesia, loss of consciousness, inhibition of sensory and autonomic reflexes, skeletal muscle relaxation. An ideal anesthetic would induce a smooth and rapid loss of consciousness while allowing for prompt recovery after discontinuation of administration.

General Anesthetics An ideal anesthetic would induce a smooth and rapid loss of consciousness while allowing for prompt recovery after discontinuation of administration. Possess a wide margin of safety and be free of adverse effects

General Anesthetics No agent alone has the ideal properties Most commonly the drugs are used in combination of i.v. and inhalation

General Anesthetics Intravenous Anesthetics used alone or in combination with other anesthetic and analgesics

General Anesthetics I.V. anesthetics Barbiturates The sodium salts of the ultra-short-acting barbiturates may be administered in aqueous solutions to induce anesthesia Unconsciousness is produced within seconds of injection Duration of action is about 30 minutes

General Anesthetics I.V. anesthetics Barbiturates

….Intravenous Anesthetics This intravenous group include the Na salts of ultra-short acting barbiturates (~30 min duration); administered IV in aqueous solution Administered with maintaining inhalation anesthesia Methohexital Sodium (Brevital Sodium) N-methyl barbiturate: 1-Methyl-5-allyl-5-(1-methyl-2-pentynyl) barbiturate pKa of 8.4 compared to pKa of ~7.6 for non-N-methylated cpds. Therefore higher amounts of lipid-soluble free acid form that easily penetrates the BBB. It has an accessible site for metabolic inactivation: hydroxylation at the CH2 a to the triple bond. Thiopental Sodium (Pentothal Sodium): 5-Ethyl-5-(1-methylbutyl)-2-thiobarbiturate Most widely used ultra-short acting anesthetic barbiturate. A prototype for ultra-short acting barbiturates; a standard for studying effects of structure on duration of action. Fast onset of action, the time it takes to reach the CNS. Consciousness is gained in about 30 minutes.

…General Anesthetics (Benzodiazepines) Benzodiazepines: Tend to bind to benzodiazepine recognition site that modulate the GABA binding to GABAA (a receptor which is a ligand- gated chloride ion channel) SAR: An electroneg. atom at position 7 is required for activity. No sub. in positions 6, 8 and 9. A phenyl at position 5 promotes activity. If the phenyl has ortho (2’) or diortho (2’,6’) electron attracting sub., activity is increased, para sub. decreases activity. Saturation of the 4,5 double bond or a shift of it to the 3,4 position decreases actvity. Alkyl subs. At the 3-position decrease actiity. The 3-OH are much more polar and are converted to the excreted glucoronide. Those without 3-OH, have longer half lives and undergo hepatic oxidation. Diazepam: Non polar and is rapidly absorbed (has high lipid/water partition coefficient; therefore very long acting). Known metabolism to oxazepam as shown below. Used for anxiety states, anticonvulsant and pre-medication in anesthesia.

…General Anesthetics (Benzodiazepines) Midazolam (Versed) a benzodiazepine that is CNS depressant; used IV to induce anesthesia. Midazolam has lower lipid/water partition coefficient and an improved pharmacokinetic properties. Lorazepam (generic, Ativan) – almost insoluble in water. Is also a CNS depressant, highly addictive Lorazepam

…General Anesthetics (Phenols, Ketones) Ketamine. HCl, USP (Ketalar): It is a 2-(o-chlorophenyl)-2-methylaminocyclohexanone, a structural relative of phencylidine (PCP); different mechanism than other anesthetics; blocks glutamic acid N-methyl-D-aspartate (NMDA) receptors. Causes dissociation from events being experienced followed by anesthesia, analgesia and sometimes amnesia. Incidence of hallucinations is lower than PCP.

…General Anesthetics (Phenols) Fosprofofol (Lusedra) – sedative/analgesic. Metabolized to Propofol in the liver by phosphatases. Water soluble. Propofol (Diprivan): Phenols are generally toxic (tissue destruction) but the 2,6-isopropyl groups of propofol mitigate the effect. Insoluble in water. Thus, given IV as an emulsion. Rapid BBB penetration and distribution as a product with high lipid-water partition coefficient. Used for induction and maintenance of anesthesia. Binds allosterically to GABAA receptors at non-benzodiazepine sites. Fospropofol (Lusedra)

…General Anesthetics Dexmedetomidine (Precedex) Etomidate (Amidate) Etomidate is a base. Thus, water-soluble salts are used for IV administration. A 4-carboxylic acid ester-substituted imidazole moiety and is related to the imidazolo benzodiazepines. It is a positive allosteric modulator of GABAA receptors. Has a depression of steroidogenesis as a side effect. Dexmedetomidine - is the S-enantiomer of medetomidine. It is freely soluble in water and has a pKa of 7.1 Both drugs are also sedative-hypnotics Dexmedetomidine (Precedex)

General Anesthetics Droperidol (Inapsine) Reducing nausea and vomiting during surgeries and diagnostic procedures. Inapsine is a tranquilizer. It is unknown exactly how Inapsine works. Infrequent but possibly fatal heart problems have occurred with Inapsine when used at or even below recommended doses

Inhaled Anesthetics Volatile liquids Nitrous oxide is an important adjuvant Most commonly used agents are: isoflurane, desflurane and sevoflurane Other agents are also used

…Inhalation Anesthetics Nitrous oxide: N2O, Nitrogen Monoxide, Is a gas at room temperature, but a liquid under pressure when supplied. Good analgesic at lower conc. from depressant effect on synaptic transmission of pain messages (possible effect on opioid receptors). Required to be 80% in inspired air to achieve anesthesia; (care for dangers of possible hypoxia). Given with other anesthetics. It is a positive modulator of GABA on GABAA receptors for its anesthetic action.

General Anesthetic Agents Inhalation Anesthetics: Halothane: CH(Br)Cl-CF3 Volatile (B.P. of 500 C), Nonflammable, Highly potent with low blood/gas partitioning, Mostly is excreted unmetabolized High electronegativity of F makes –CF3 group stable. Methoxyflurane (Penthrane): CHCl2CF2-O-CH3 Volatile liquid (B.P. 1050 C), it does not have a high vapor pressure, so conc. Of the inspired air is low. The compound is very soluble in lipids; thus, recovery is slow. Large blood/gas partition coefficient (slow induction of anesthesia). Produces excellent anesthesia and good muscle relaxation. 70% metabolized to form: Dichloroacetic acid, Difluoromethoxyacetic acid, Oxalic acid and Fluoride Fluoride and oxalic acid cause renal damage due to prolonged use.

…Inhalation Anesthetics Enflurane (Ethrane): HF2COCF2CHFCl, Volatile liquid; Depresses respiration, therefore mechanical ventilation and O2 supplementation.Tonic-clonic convulsive side effect (not recommended for patients with epileptic foci). 5% of drug metabolized to F- & difluoromethoxydifluoroacetic acid. Isoflurane (Forane): F3CC(H)ClOCF3 Structurally and functionally related to enflurane except: Lack of electroencephalogram and tonic-clonic activity. Only 0.2% is metabolized to F- and trifluoroacetic acid. Desflurane (Suprane): FC(H2)-O-C(H)F-C(H)F2 Sevoflurane: FC(H2)-O-CH(CH3)2: Rapidly taken up and rapidly eliminated