General Anaesthetics

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Drugs acting on C. N. S

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Drugs Acting on C.N.S General Anaesthetics Prepared By Prof. Pratik Maske . Dept. of Pharmaceutical Chemistry, Tatyasaheb Kore College of Pharmacy, Warananagar.

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General Anaesthetics The blood circulation to C.N.S. Is very large, but only minute amount of exogenous substances can penetrate blood brain barrier. In general, the lipid soluble, non-ionising molecules can pass most readily into C.N.S. The drug which C.N.S. & produce depressant effects are called as C.N.S. depressants. General anaesthetic are the central nervous system depressant drugs which produce a partial or total loss of the sense of the pain accompanied by loss of consciousness. The state of insensibility is known as Anaesthesia . They produce anaesthesia before a surgical operation or in obstretrics .

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Stages of Anaesthesia- Analgesia which is due to depression of cortical centres. Excitement due to depression of higher motor centres. Surgical anaesthesia which includes a. Loss of spinal reflexes. b. Skeletal muscle relaxation ( this property is very essential & is useful in surgery) c. Somatic-muscle relaxation & disappearance of muscle tone. IV. The fourth stage is medullary paralysis which is due to overdose .

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Mechanism of Action-

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Meyer & Overton’s Lipid Theory-

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Classification- Inhalation anaesthetics- They includes liquids of volatile volatile nature & gaseous substance used by inhalation to produce anaesthesia. 1) Volatile liquids: a) Halogenated hydrocarbones e.g. Chloroform, Halothane, Trichloroethylene. b) Ethers- e.g. Isoflurane , Desflurane . 2) Gases: e.g. Cyclopropane, Nitrous oxide

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Intravenous anaesthetics Barbiturates- Ultra short acting barbiturates such as Methohexitone , Thiopentone sodium . II. Non Barbiturates- a) Eugenol derivatives- e.g. Propanidid . b) Phencyclidine derivative- e.g. Ketamine . c) Steroids- e.g. Althesin d) Miscellaneous- e.g. Etomidate , Propofol .

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Structure Activity Relationship- Potency of general anesthetic from n- alkane & cycloalkane class increases on lengthening carbon atom chain. The max. Carbon atom for n- alkane are 10 & for cycloalkane are 8. The replacement of hydrogen of low molecular weight ethers & hydrocarbons by halogens results in an increase in its potency with the proportional decrease in its flammability. Chlorine containing anesthetic are used clinically, bromine containing were not used clinically. e.g. Chloroform Trochloroethylene . Higher atomic mass halogen leading to increase potency. Fluorinated compound & Ethers are having less toxicity, less flammability, decreased boiling point.

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Thiobarbiturates Thiopental sodium or Thiopentone sodium It is a thiobarbiturate derivative in which C 2 -oxo group of barbiturate is replaced by thioxo group. The thioxo group is readily metabolised in the body causing desulphuration. hence, it is ultra short acting thiobarbiturate. It is 5,5-disubstituted; 1) One substituent is a branched chain, 1-methyl butyl which oxidises readily. 2) The other is the ethyl group The duration of anaesthetic action is 10 to 30 minutes. Thiopentone sodium contain 6% sodium carbonate to prevent its conversion to thiopentone by atomospheric carbon dioxide

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Uses It is very short acting thiobarbiturate. It is used as an anticonvulsant. Its used for induction of general anaesthsia . Its used for prevention & treatment of cerebral ischaemia . Pharmaceutical Formulation- Thiopentone injection. Brand Name- Pentothal sodium, Intraval sodium.

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Methohexital Sodium-

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Uses- Its use as Intravenous anesthetic. It has been commonly used to induce deep sedation. Its is used for induction of anesthesia prior to the other anesthestic agents

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Thiopental Sodium Uses- Its an ultra short acting depressant of CNS which induces hypnosis & anesthesia but not analgesia. It has been used in neurosurgical patients to reduce increased intracranial pressure. It does not produce ant excitation but has poor analgesic & muscle relaxant property

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Halothane Uses- Its is general anesthetic agent used for induction & maintenance of general anesthesia . It causes smooth induction with no stage of delirium. It reduces the blood pressure & frequently decreases the pulse rate & depresses respiration. It induces muscle relaxation & reduce pain sensitivity.

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Methoxyflurane Uses- Its is one of the most widely used potent general anesthetic agent It causes comparatively light anesthesia with deep analgesia & muscle relaxation, so its convenient for short surgical operation like obstetrics. Its a general anesthetic used for induction & maintence of general anesthesia . It induces muscle relaxation & reduce pain sensitivity

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Enflurane Uses- Its has a good muscle relaxant effect. It smoothly induces anesthesia . Sevoflurane - Uses- Its volatile anesthesia . In combination with desflurane , sevoflurane is replacing other agents in modern anesthsiology .

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Ketamine Uses - Its rapid acting general anesthetic

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Ketamine indicated as sole anesthetic agent for diagnostic & surgical procedure that don’t require skeletal muscle relaxation. Its termed as Dissociative anesthesia. It is an intravenous anesthetic agent of choice for surgical operation.

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Thank You

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