Downloaded 1,048 times
More Related Content
Similar to Iv anaesthetics
Iv anaesthetics
- 1.
- 2. Introduction Used IV anestheticdrugs are: 1. Propofol ,Fospropofol 2.Thiopentone, Methohexital 3.Ketamine 4.Etomidate 5.Benzodiazepines (Diazepam, midazolam, lorazepam) 6.Dexmeditomidine
- 3. Chemical Structure Propofol Thiopenton e KetamineEtomidate Benzodiazepin es Isopropyl phenol Barbiturate Replacemen t of oxygen at C2 with sulphur. Analogue of phencyclidine Carboxylat ed imidazole Benzene ring and 7 member diazepine ring.
- 4. Physio chemical properties PRPOFO L THIOPENTONEKETAMINE ETOMIDATE BENZO- DIAZEPINE Colour Emulsion *, milky white Sodium salts Clear aqueous solution Clear solution Midazolam- Clear aqueous solution. Conc. 1%, 2% soln. Medium, long chain triglycerides Yellow amorphous powder. 500mg, 1g 1%, 2%,10% solution 2mg/ml in 35% propylene glycol Lipid Solubility Only in emulsion form Highly soluble Very Lipid soluble Acidic pH lipid soluble Lipid soluble midazolam Water solubility Insoluble Readily soluble Soluble Poorly water soluble. Water soluble ph 4.5-6.4 10.5 3.5-5.5 6.9 3.5 pKa 11 7.6 7.5 4.2 6.15 Chirality Not chiral Racemic mixture Racemic Single isomer R+
- 5. PROPOFOL Neeeds an emulsifyingagent: 1% (w/v) propofol 10% soyabean oil 2.25% glycerol 1.2%purified egg phosphatide Di-sodum edetate (0.005%) Supports bacterial growth. E.Coli and Pseudomonas. Aseptic technique should be used during administration. KETAMINE Racemic mixture S+ isomer. THIOPENTONE Cannot be mixed with catecholamines, opioids and NMB drugs. Powder form stable at room temp indefinately. Refrigerated- 2weeks Room temp reconstituted- 6 days BENZODIAZEPINES: Have a reversible ring structure that opens at a pH <6 and closes at pH>6.
- 6. METABOLISM PROPOFOL THIOPENTONE KETAMINEETOMIDATE BENZO- DIAZEPINE S Liver Ring hydroxylation by CytP450 4-hydroxy propofol. CONJUGATION Glucuronidation and sulfation EXCRETED Kidney Inactive metabolite Liver Oxidation, N- dealkylation, desulfration and destruction of barbituric acid ring. EXCRETED Kidneys and bile Inactive metabolite Liver Demethylatio n of ketamine by P-450 Nor- Ketamine ACTIVE METABOLITE Hydroxylated and conjugated Water soluble glucuronide metabloite. EXCRETED Liver and plasma esterase. Hydrolysis of ethyl ester side chain. Carboxylic acid ester. EXCRETED Kidney Inactive metabolite Liver 1-hydroxy midazolam. N-dealkylation and aliphatic hydroxylation/ glucuronide conjugation. EXCRETED Kidney Phase I metabolite is active.
- 7. Pharmacokinetics PROPOFOL THIO- PENTONE KETAMINE ETOMIDATEBENZO- DIAZEPINES ONSET 15-45s <30s 45-60s 15-45s 30-90s AWAKENING 5-10mins 5-10mins 10-20mins Full orientation 60-90mins 3-12 mins 15-30mins RATE OF FALL IN PLASMA CONC. Redistribution and elimination redistribution redistribution CONTEXT SENSITIVE HALF LIFE <40mins <150mins EXTRACTION RATIO low high high
- 8. After delivery ofan IV bolus, the percentage of thiopental remaining in blood rapidly decreases as drug moves from blood to body tissues. Initially, most thiopental is taken up by the vessel-rich group (VRG) of tissues because of their high blood flow. Subsequently, drug is redistributed to muscle and to a lesser extent to fat. Throughout this period, small but substantial amounts of thiopental are removed and metabolized by the liver.
- 10. Mechanism of action PROPOFOLTHIOPENTONE KETAMINE ETOMIDATE BENZO- DIAZEPINES Selective modulator of GABAa increasing affinity for GABA. Depress RAS in brain stem. Action via GABAa receptor, increases the duration of opening of chloride channels. Non competitive binding to phencyclidine site on NMDA receptors. Weak action at GABA. Dissociates THALAMUS from LIMBIC CORTEX. Depresses RAS in the brain stem. Binds to a subunit of the GABAa receptor increasing affinity for GABA. Bind to GABAa receptor but different site. Increase the frequency of opening of the chloride ion channel.
- 11.
- 12. CENTRAL NERVOUS SYSTEM PROPOFO L THIOPENTONE KETAMNEETOMIDATE MIDAZOLAM CMRO2 CBF ICP IOP − − − DISSOCIATIVE ANESTHESIA ✕ ✗ ✔ ✕ ✗ EMERGENCE REACTION ✕ ✗ ✔ ✕ ✗ NYSTAGMUS ✕ ✗ ✔ ✕ ✗ SKELETAL MUSCLE TONE − − − − SALIVATION LACRIMATION − − − −
- 13. PROPOFOL THIOPENTONE KETAMINE NEURO- PROTECTIV E •Anti oxidant properties. • Reduced infarct size when administered immediately or 1hr after ischemic insult • Decreases oxygen demand • Preserves CPP (cerebral perfusion pressure) • Robin Hood phenomenon • Free radical scavenging • Improves perfusion in incomplete cerebral ischemia THIOPENTONE KETAMINE ETOMIDATE EEG changes • Small dose-low voltage fast wave activity • High dose-high voltage slow wave activity • Continuous infusion- isoelectric EEG • Abolotion of alpha rhythm and dominance of theta activity. • Onset of delta activity co incides with loss of consciousness. • Produces burst supression at high dose. • Similar to thiopentone but frequency of excitatory spikes is more
- 14. CVS PROPOFOL THIOPENTONE KETAMINEETOMIDATE BENZO DIAZEPINES BP 25-40% − unchange d HR Inhibits tachycardic response to hypotension . May cause bradycardia − unchange d CO − unchange d
- 15. Respiratory System PROPOFO L THIOPENTONE KETAMINEETOMIDATE BENZODIAZEPINE S APNEA ++ ++ + LARGE DOSE + RAPID INJECTION + VENTILATOR Y DRIVE BHRONCODIL ATATION ✔ ✗ ✔✔ ✗ ✗ AIRWAY REFLEXES intact intact intact intact
- 16. DOSES PROPOFOL THIOPENTO NE KETAMINE ETOMIDATEBENZO- DIAZEPINE S Induction 1-2.5 mg/kg IV 3-4mg/kg 0.5-2 mg/kg IV4-6 mg/kg IM 0.2-0.6 mg/kg IV 0.05- 0.15 mg/kg Maintainence 50- 150 µg/kg/min IV combined with N2O or an opiate 50-100mg every 10-20 mins 0.5-1 mg/kg IV with N2O 50% in O2 15- 45 µg/kg/min IV with N2O 50-70% in O2 10 µg/kg/min IV with N2O and an opiate 0.05 mg/kg prn 1 µg/kg/min Sedation 25- 75 µg/kg/min IV 0.2-0.8 mg/kg IV over 2-3 min 2-4 mg/kg IM 0.5-1 mg repeated 0.07 mg/kg IM Analgesia 0.15- 0.25 mg/kg IV. Preventive/pre emptive. Anti-emetic 10-20 mg IV, repeat every 5- 10 min or start infusion
- 17. Drug interactions PROPOFOL THIOPENTON E KETAMINEETOMIDATE BENZODIAZE PINE • Fentanyl and Alfentanyl concentration s may be increased with concurrent administratio n. • Contrast media and drugs that occupy the same protein binding sites can displace drug. • Ethanol, opioids and anti histamines potentiate the CNS depressant effect. • Interacts synergisticall y with volatile anesthetics • Midazolam attenuate ketamines cardio- stimulatory effect. • Fentanyl increases its plasma level • Opioids decrease the myoclonusch aracteristic. • Eryhtromycin inhibits metabolism of midazolam • In combination with opioids BP falls. • Reduce the MAC of volatile anesthetics as much as 30%
- 18. USES POPOFOL THIOPENTON E KETAMINE ETOMIDATEBENZODIAZE PINE INDUCTION ✔ ✔ ✔ ✔ ✔ SEDATION ✔ − ✔ ✔ ✔ MAINTAINENC E ✔✔ ✔ ✔ ✔ ✔ ANALGESIA ✗ ✗ ✔✔ ✗ ✗ PRE-EMPTIVE ANALGESIA ✗ ✗ ✔✔ ✗ ✗ ANTI EMETIC ✔✔ ✗ ✗ ✗ ✗ ANTI PRURITIC ✔ ✗ ✗ ✗ ✗ ANTI CONVULSANT ✔ ✔ ✗ − ✔ CHR. HEADACHE ✔ ✗ ✗ ✗ ✗ AMNESTIC ✔ − ✔✔ − ✔
- 19. Side Effects PROPOFOL THIOPENTO NE KETAMINEETOMIDATE BENZODIAZ EPINE Pain on injection ✔✔ ✔ ✗ ✔ ✗ Hypotension ✔✔ ✔ ✗ ✔ ✗ Bronchospas m ✗ ✔ ✗ ✗ ✗ Allergic rxn ✔ ✔ ✗ ✗ ✗ Emergence rxn ✗ ✗ ✔ ✗ ✗ Thrombophle bitis ✔ ✔✔ ✗ ✗ ✗ Hangover effect ✗ ✓ ✔ ✗ ✗ Tolerance and dependence ✔ ✔ ✔ − − Immunosuppr ession ✔ − − ✔ Neutrophil func. ✗ −
- 20. Other side effects PROPOFOL:Risk of bacterial infection Hypertriglyceridemia Pulmonary Embolism Propofol infusion syndrome: Lactic acidosis >75mcg/kg/min for >24hrs Unexpected tachycardia with increased anion gap MOA- Poisoning of ETC D/D: Hyperchloremic metabolic acidosis Diabetic Ketoacidosis
- 21. ETOMIDATE: Adrenocortical suppression, inhibitionof 11-beta hydroxylase. Lasts for 4-8hrs after induction.
- 22. KETAMINE: Emergence delirium Symptoms: Visualauditory proprioceptive and confusional illusions. Transient cortical blindness. Dreams (morbid) Hallucinations. Mechanism: Ketamine induced depression of inferior colliculus and medial geniculate body Incidence: Age>15, Female, Dose>2mg/kg, H/O personality problems Prevention: Benzodiazepines pre-operatively 5mins before induction.
- 23. DEXMEDITOMIDINE Highly selective α2adrenergic agonist. Physicochemical properties: Active S enantiomer of meditomidine. Water soluble. Pharmacokinetics: Rapid hepatic metabolism. Conjugation. Metabolites excreted through urine and bile. Clearance high, elimination half life short. Significant increase in context sensitive half time from 4mins after 10min infusion to 250 mins after 8hr infusion
- 24. Pharmacodynamics: Activation of CNSα2 receptors. Hypnosis is due to this activation in locus cerulus. Analgesia at the level of spinal cord. Sedation resembles physiologic sleep state. Decreases CBF no significant change in ICP. CVS: HR & SVR BP Heart block asystole or sever bradycardia may occur. RS: Mod decrease in tidal volume. Upper airway obstruction due to sedation possible. Uses: Short term sedation of ICU patients. Adjunct to GA. Sedation during fiberoptic intubation/ regional anesthesia. DOSE: 0.5-1mcg/kg over 10-15mins followed by infusion of 0.2- 0.7mcg/kg/hr.
- 25. References Millers 7th edition ClinicalAnesthesiology- Morgan 5th edition Stoeltings handbook of pharmacology and physiology in anesthetic practice. 4th edition Clinical Anesthesia Barash 7th edition