1 / 48

IV-induction-agents-om

it is good

bijaya1
Download Presentation

IV-induction-agents-om

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. INTRAVENOUS INDUCTION AGENTS

  2. What are i.v induction drugs? • Drugs, when given intravenously in an appropriate dose, cause rapid loss of consciousness. • Rapid onset : Often described as occurring within “ ONE ARM-BRAIN CIRCULATION TIME” • The time taken for the drug to travel from the site of injection (usually the arm) to the brain, where they have their effect.

  3. IDEAL INTRAVENOUS AGENT • Rapid onset and recovery • Analgesic • No cardiovascular or respiratory depression • No emetic effects • No excitatory phenomena • No pain on injection • No toxic effects on other organs • No allergic reaction

  4. CLASSIFICATION OF IV INDUCTION AGENTS 1) Barbiturates - Thiopental , Methohexital, Thaimylal 2) Non-barbiturates • Ketamine • Propofol • Etomidate 3) Benzodiazepines- Midazolam , Diazepam , Lorazepam 4) Opioids - Fentanyl , Pethidine , Morphine

  5. BARBITURATES • Derivatives of barbituric acid (a product of malonic acid and urea) • First clinical trial on human by Dr Ralph Waters on 1984

  6. THIOPENTAL • Sulfur atom at C2 of benzene ring : increase lipid solubility • Sodium salt in powder • Stored in nitrogen , mixed with 6 % anhydrous sodium carbonate (to increase its solubility in water) • pKa - 7.6 , 60% unionized at pH of 7.4 • pH of 2.5 % solution : 10.5 , relatively unstable (in room temp. : 24 hrs , refrigeration : 2-week shelf life) • Tautomerization : Enol form of formulation changes to keto form in blood after injection.

  7. MECHANISM OF ACTION • Mainly through interaction with inhibitory neurotransmitter – GABA in CNS • Activation of GABAA receptor  Cl- channels open increased Cl- conductance hyperpolarization of postsynaptic neurons  decreased neuronal activity

  8. PHARMACOKINETICSOF THIOPENTAL • Absorption : IV • Distribution : Highly lipid soluble - 80% protein bound - Arm-brain circulation time : 30 – 60 secs - Duration : 20-30 mins due to redistribution to the peripheral compartment - Elimination half-life : 3 – 12 hrs - Repetitive administration  saturation of peripheral compartment  redistribution cannot occur  delayed awakening duration of action more dependent on elimination THIOPENTAL SHOULD NOT BE USED TO MAINTAIN ANESTHESIA

  9. Biotransformation : Hepatic oxidation to inactive water-soluble metabolites(pentobarbital , thiobarbituric acid) • Excretion : renal FACTORS AFFECTING DOSE OF THIOPENTAL • Age of the patient • Body weight (Lean body weight preferable) • Hypovolemic shock (contracted central compartment) • Severe liver disease • Acidosis (increased unionized fraction) • Premedication with sedatives like benzodiazepines or clonidine • Hypoproteinemia

  10. EFFECTS ON ORGAN SYSTEMS CARDIOVASCULAR • Decrease in BP , increase in HR (central vagolytic effect ; reflex tachycardia) • Decreased venous return due to peripheral pooling • Maintained cardiac output : rise in HR and increased myocardial contractility from compensatory baroreceptor reflexes • In absence of compensatory response  uncompensated peripheral pooling and unmasked direct myocardial depressant effect  CO and BP fall dramatically • Slow rate of injection and adequate preoperative hydration  attenuate hemodynamic changes

  11. RESPIRATORY • Apnea usually follows an induction dose • Decreases ventilatory responses to hypercapnia and hypoxia • Decreased tidal volume and RR during awakening • Does not completely depress noxious airway reflexes • Laryngospasm and bronchospasm during airway instrumentation in light plane of anesthesia

  12. CEREBRAL • Decrease in cerebral blood flow (CBF) and intracranial pressure (ICP) secondary to cerebral vasoconstriction • Cerebral perfusion pressure (CPP) usually increased • Decreased cerebral oxygen consumption • Antianalgesic effect : lowers pain threshold • Acute tolerance and physiological dependence RENAL • Reduction in renal blood flow and GFR

  13. HEPATIC • Decreased hepatic blood flow • Induction of hepatic enzymes on chronic exposure • Induction of aminolevulinic acid synthetase  stimulates formation of porphyrin  may precipitate acute intermittent or variegate porphyria in susceptible individuals IMMUNOLOGICAL • Anaphylactic reaction due to histamine release from degranulation of mast cell and basophils

  14. USES OF THIOPENTAL • As an inducing agent • As an anticonvulsant • For barbiturate coma (massive brain swelling) • To decrease ICP • As an neuroprotective agent : used in neurosurgery • For an antioxidant effect DRUG INTERACTIONS • Precipitation if mixed with drugs such as opioids, catecholamines, and neuromuscular blocking drugs . • Contrast media , sulfonamide , aspirin increase free drug level of thiopental due to displacement from protein binding site

  15. CONTRAINDICATIONS OF THIOPENTAL • H/O idiosyncratic reaction to this drug • Septic / cardiogenic / hemorrhagic shock • Hyperesinophilia syndrome • Severe hypovolemic patient • Restrictive / dilated cardiomyopathy • Pericardial tamponade • Porphyria

  16. KETAMINE • Structural analogue of phencyclidine • Approved by FDA on 1970 • Available as a racemic mixture of two enantiomers (S-Ketamine : anesthetic effects ; R-Ketamine : the hallucinogenic effects)

  17. MECHANISM OF ACTION • An noncompetitive NMDA receptor antagonist • Also binds with opioid receptors • Provides “dissociative anesthesia” : dissociation of thalamus from the limbic cortex  clinically , the patient appears to be conscious (e.g.. eye opening , swallowing , muscle contracture) , but unable to process or respond to the sensory input

  18. PHARMACOKINETICS OF KETAMINE • Absorption : IV , IM , Oral • Distribution : Rapid brain uptake and subsequent redistribution (the distribution half life is 10-15 mins) • Biotransformation : In the liver to several metabolites among which norketamine retains anesthetic activity - Induction of hepatic enzymes due to multiple doses of ketamine may develop tolerance - Short elimination half life (2 hrs) due to extensive hepatic uptake • Excretion : Renal

  19. EFFECTS ON ORGAN SYSTEMS CARDIOVASCULAR • Indirect stimulatory effects : Increases blood pressure , heart rate , cardiac output • Secondary changes : increase in pulmonary artery pressure and myocardial work • Direct myocardial depressant effect of large doses : probably due to inhibition of calcium transients ; unmasked by sympathetic blockade or exhaustion of catecholamines stores

  20. RESPIRATORY • Ventilarory drive : minimally affected • Apnoea if rapid IV bolus or pretreatment with opioids • A potent bronchodilator • Upper airway reflexes remain intact • Increased salivation CEREBRAL • Increases cerebral oxygen consumption , CBF and ICP • Myoclonic activity • Psychotomimetic effects (e.g.,illusions , delirium)

  21. USES OF KETAMINE • As the sole anesthetic agent • For short surgical procedures • As an induction agent : Induction agent of choice in constrictive pericarditis , pericardial tamponade • To supplement analgesia (in low dose) CONTRAINDICATIONS OF KETAMINE • Intracranial space occupying lesion • Coronary artery disease • Arterial aneurysm • Hypertensive crisis • Schizophrenia

  22. DRUG INTERACTION • Potentiation of nondepolarizing NMBD by ketamine • Predisposition to seizure if combined with theophylline • Sympathetic antagonists unmask the direct myocardial depressent effect of ketamine • Myocardial depression when combined with halothane

  23. PROPOFOL • An alkylphenol derivative • Chemical name : 2,6 di-isopropyl-phenol • First clinical trials in 1977 by Kay and Rolly • 1% aqueous solution :10% soyabean oil , 2.25% glycerol and 1.2% purified egg phosphatide. • Preservatives : Disodium edenate (pH 7- 8.5) , Sodium metasulphite (pH 4.5-6.5) • Stable at room temperature , Supports the growth of bacteria; so required good sterile technique during preparation and handling

  24. MECHANISM OF ACTION OF PROPOFOL • Modulator of GABAa receptor • Does not act as spinal cord depressant

  25. PHARMACOKINETICS OF PROPOFOL • Absorption : IV • Distribution : Rapid distribution of 2-8 min • Biotransformation : Liver and lungs • Elimination half time : 0.5 - 1.5 hr • Clearance : 30-60ml/kg/min • Excretion : water soluble metabolites excreted by kidneys

  26. EFFECTS ON ORGAN SYSTEM CARDIOVASCULAR • Decrease SVR , cardiac contractility , preload : decrease in BP • Vagally mediated reflex bradycardia : usually transient CEREBRAL • Decreases CBF , ICP , cerebral oxygen consumption • Decreases intraocular pressure • Tolerance does not develop after prolong infusion

  27. RESPIRATORY • Respiratory depression – apnea • Decreases tidal volume and frequency of breathing • Decreases response to hypercarbia and inhibit hypoxic respiratory drive • Depresses upper airway reflexes • Decreases risk of laryngospasm and bronchospasm

  28. USES OF PROPOFOL • Induction of Anesthesia : 1.5 - 2.5 mg/kg • Sedation : 25 – 100 microgm/kg/min in ICU , with head injury. • Maintenance of Anesthesia : 50 – 300 microgm/kg/min • Anticonvulsant : 1mg/kg • Antipruritic : 10mg IV due to epidural opioids , cholestasis. • Antiemetic • Antioxidant property

  29. Propofol infusion syndrome : infusion of >75 microgm/kg/min for >24 hrs - Metabolic acidosis , hypophosphatemia , cardiomyopathy, skeletal myopathy , lipemia CONTRAINDICATIONS OF PROPOFOL • Hypotension • Hypovolemia • H/O Anaphylaxis • Children <3 yr DRUG INTERACTIONS • Opioids • Benzodiapines • Volatile anesthetics

  30. ETOMIDATE • Contains carboxylated imidazole ring : water solubility in acidic solution and lipid solubility at physiological pH • Preservative : Propylene glycol • Ultra short acting non barbiturate hypnotic • Causes rapid induction of anesthesia with minimal cardiovascular effects

  31. MECHANISM OF ACTION OF ETOMIDATE • Depresses the reticular activating system and mimics the inhibitory effects of GABA PHARMACOKINETICS OF ETOMIDATE • Absorption : IV • Distribution : High lipid solubility , large nonionized fraction at physiological pH • Biotransformation : hydrolysis by hepatic microsomal enzymes and plasma esterases • Excretion : Renal

  32. CARDIOVASCULAR • Minimal effect on the CVS • Slight decline in BP may be due to reduction in PVR • Unchanged myocardial contractility and cardiac output • Does not release histamine RESPIRATORY • Less affected ventilation by etomidate CEREBRAL • Decreases cerebral metabolic rate , CBF and ICP • CPP well maintained • Lacks analgesic property

  33. ENDOCRINE : • Inhibition of 11-beta hydroxylase , long term infusion leads to adrenocortical suppresion USES OF ETOMIDATE • Induction : 0.2-0.6 mg/kg given over 30-60 seconds • Maintenance : 5-20microgram /kg /minute (Haemodynamically unstable patient who cannot tolerate alternate inducing agent despite use of fluids and vasopressor agent • Sedation for diagnosis of foci of seizure (unlabelled) • Not safe for under 10 years age group

  34. METABOLISM

  35. PHARMAKOKINETICS

  36. MOA

  37. CENTRAL NERVOUS SYSTEM

  38. CARDIOVASCULAR SYSTEM

  39. RS

  40. BENZODIAZEPINES • Chemical structure : a benzene ring and a seven-member diazepine ring • Midazolam : water soluble at low pH due to imidazole ring ; becomes lipid soluble in body pH due to structural change in ring • Diazepam and lorazepam : lipid soluble , propylene glycol as a preservative • Midazolam : pKa – 6.5 , pH – 3.5

  41. PHARMACOKINETICS OF MIDAZOLAM • Absorption : Oral , IV , IM , Intranasal , buccal , sublingual . • Distribution : lipid soluble in physiological pH - Highly protein bound (90-98 %) • Biotransformation : water soluble glucoronide end products in liver - Elimination half life : 2 hrs , shortest among benzodiazepines • Excretion : renally excreted , Alpha- hydroxymidazolam causing prolong sedation in renal failure receiving midazolam

  42. EFFECTS ON ORGAN SYSTEMS CARDIOVASCULAR • Minimal cardiovascular effect • Tends to reduce BP and PVR more than diazepam • Decreased vagal tone leading to HR variability RESPIRATORY • Depress ventilatory response to hypercarbia ; insignificant unless administered IV or with other respiratory depressant CEREBRAL : Reduce cerebral oxygen consumption , CBF , ICP • Antegrade amnesia • Spinal cord mediated mild muscle relaxant • Anxiolytic and sedative effect • No direct analgesic property

  43. USES OF MIDAZOLAM • Premedication • Sedation • Induction • As an anticonvulsant • Insomnia • Schizophrenia • Short procedures DRUG INTERACTION OF MIDAZOLAM • Erythromycin inhibits metabolism of midazolam : prolongs action of midazolam • Synergistic effect with opioids • Reduces MAC value of volatile anesthetic as much as 30 % • CNS depressents potentiate effect of midazolam

  44. PETHIDINE • Synthetic morphine • Less potent analgesic • Anti cholinergic action • Less histamine release than that of morphine • pka : 7.9 , pH : 7 • 70% protein bound • Elimination half time : 3 - 5 hrs • Metabolism : in liver to normeperidine which is renally excreted

  45. FENTANYL • 75-100 times more potent than morphine and 1000 times more potent than pethidine • Highly lipid soluble • Rapid onset (peak : 7 mins) and short duration(15-30 mins) • pk=8.4 , pH=8.5 • 84% bound to plasma • Elimination half time : 3.1-6.6 hrs • Inactive metabolites , excreted renally

More Related