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- 1. DRUGS Dr .a anand ram Nri medical college
- 2. benzodiazepines • Midazolam has …. Ring in its structure IMIDAZOLE Midazolam causes ……….amnesia ANTEROGRADE Effect on cardiac output NO EFFECT i.V dose 0.02-0.03 mg/kg
- 3. • Volume of distribution 1-1.5 L/kg Ventilatory depression and apnea at doses? >0.15 mg/kg Antagaonist ? Flumazenil Which effect not reversed ? Respiratory depression.
- 5. opioids • Ultra short acting opioid ? • Remifentanyl • Mechanism of action ? • Pure mu receptor agonist • Effect on cerebral auto regulation? • No effect. • Metabolism? • Blood and tissue nonspecific esterases.
- 6. • Spinal analgesia ? • Substantia gelatinosa of dorsal horn • Supra spinal analgesia ? • Medulla,mid brain, limbic system,cerebral cortex. • Pain relief type ? • Poorly localised visceral pain is better relieved than sharp,somatic pain.
- 7. • Delayed resp depression? • With fentanyl. After a initial bolus 75% of drug is taken up by lungs. Remaining part is taken up by skeletal muscles &stomach. • TV and RR ? • RR dec more than TV • Prevention of chest rigidity ? • Priming with non depolariser, slow ,intermitent small doses ,inhalational agent. • Treatment ? • NM blockers,Naloxone.
- 8. receptors μ k δ sedation Dysphoria (psyvhomimetic effects ) Spinal anagesia Supra spinalanalgesia constipation Modulation of hormone and neuro tranmitter release. constipation Spinal analgesia Resp depression euphoria miosis
- 11. Opioid antagonists • Naloxone has greatest affinity towards • μ receptor • Dose ? • 0.5-1mcg/kg in titrated doses every 2-3 min • Renarcotization? • Seen with long acting opioids as naloxone has shorter half life (30-60min). • Advantages of naltrexone over naloxone ? • Longer acting(8-12 hrs),orally active.
- 12. Inducing agents • Drug which is used as hypnotic, inducing agent , anti convulsant • Thiopentone • Derived from? • Barbituric acid • Mechanism of action? • GABA A receptors. (increases channel opening time of Cl – channels, reduces dissociation of GABA from receptors )
- 13. • Thiopentone vs midazolam ? Regarding amnesia • Midazolam – anterograde amnesia and thiopentone – retrograde amnesia. • Onset of action? • 30 sec (one arm brain circulation time ) • Use in cardio pulmonary bypass? • Reduces neuro psychiatric complications
- 14. • Cerebral protection ? • Robin hood effect or reverse steal phenomenon (opposite of isoflurane ) • To verify wet tap in epidural ? • Precipitates with local anesthetic • Intra arterial injection treatment ? • Use 2.5% , let catheter remain in place, inject vasodilator into proximal location of artery , lidocaine , papaverine , phenoxybenzamine , stellate ganglion block , heparin if thrombosis occurs. • Contra indications ? Porphyria , Status asthmaticus
- 15. Alpha 2 agonists Complete α2a , α2b , α2c agonist Dexmeditomidine Midazolam vs dexmeditomidine in hyper baric arousal response? Dexmeditomidine preserves. Dose to prevent systemic hypotension ? 0.4 mcg/kg over 20 min.
- 16. • Icu sedation • 0.5-1 mcg/kg f/b 0.1-1 mcg /kg/hr • oral dose • 3-4 mcg/kg • I.M dose • 2.5 mcg/kg given 45 -90 min before surgery. • Maintainance of anesthesia : • 0.5-0.8mcg/kg iv bolus f/b 0.2-0.7mcg /kg/hr • Selective antagonist ? • Atipamezole
- 18. propofol • Chemical name 2-6 disopropylphenol • Contents of generic propofol 1% propofol , 2.25% glycerol ,10% soyabean oil , 1.2 %egg phosphatide • Preservative Sodium metabisulphite
- 19. • Diprivan contents 1% propofol , 2.25% glycerol , 10%soyabean oil, 1.2%egg phosfatide. Preservative is NaOH,disodium edetate • Ampofol contents 1%propofol, 0.6%egg lecitin, 0.5% soyabean oil. Preservative is none.
- 20. • Aquavan contents • It is water soluble emulsion, contains pro drug fospropofol . • 2% propofol contains • Medium and long chain fatty acids. Decreased incidence of pain on injection.
- 21. • Cns effects : • ↓ICP , CPP ,CMRO2 ; auto regulation and response to paco2 not affected ,tolerance. • Cvs effects : • ↓SBP, DBP, MAP, inhibits baroreceptor reflex,↓HR,↓C.O ,S.V. • RS effects : • Short duration apnea(30 -60sec), ↓T.V ,R.R , bronchodilation ,HPV attenuated ,laryngeal reflexes lost.
- 22. • Hepatic effects : • Prolonged infusion causes hepatocellular injury , ↑phenols in urine (green color urine ),uric acid excretion ↑, ↓ hepatic blood flow. • Ocular effects : • Potentiates occulocardiac reflex , ↓ IOP. • Metabolism : • Heptic – conjugation with glucuronide and sulfate. Hydroxylation to 4-hydroxypropofol. Extra hepatic – lungs to 2-disopropylquinol.
- 23. • Doses ? • Induction dose – 1.5-2.5 mg/kg , i.v sedation -25- 100mcg/kg/min i.v infusion, maintainance dose - 100-300mcg/kg/min • Other Uses ? • Antiemetic , antipruritic , anticonvulsant , for laryngospasm, cerebral protection. • How to prevent pain on injection ? • Inject into larger veins, pre treatment with opioids , NSAIDs, prior adm.1%lidocaine, change carrier to medium and long chain fatty acids.
- 24. • Propofol infusion syndrome dose ? • >4mg/kg/hr • Duration ? • >48hrs. • Risk factors ? • Severe CNS /respiratory Illness ,pancreatitis ,catecholamines/corticosteroid supplementation,mitochondrial disease.
- 25. • Clinical features ? • Metabolic acidosis (base deficit >10 ),lactic acidosis , hyperkalemia ,hyper lipidemia , hypertriglyceridemia, bradycardia ,sinus arrest, cardiomyopathy, cadiac failure, fatty liver, hepatomegaly, myopathy, rhabdomyolysis, acute renal failure.
- 26. • Treatment ? • Stop infusion, start alternative sedation, hemodynamic maintainance (i.v crystalloids, colloids , vasopressors , inotropes, transvenous pacing ); avoid additional lipids, add dextrose to i.v fluids, dialysis, CRRT, ECMO.
- 27. ketamine • Preservative in ketamine vial ? • Benzethonium chloride 0.01% • Derived from ? • Phencyclidine derivative. • Causes analgesia ….true or false • yes,. Even at sub anesthetic doses. • Emergence phenomenon treatment ? • Benzodiazepines, droperidol. • Airway reflexes ? • Preserved but they are not completely protective.
- 28. property thiopentone propofol chemistry Thio barbituric acid 2,6 di iso propyl phenol solubility Water soluble Fat soluble preservative 6% Na2CO3 Sodium meta bisulphite pH Alkaline (10.8) Acidic (4.5-6.5) MOA GABA A , n AchR , glutamate NMDA . Not on GABA receptors cvs tachy brady rs Bronchospasm ,laryngospasm bronchodilation hepatic Decreases blood flow Causes damage at prolonged infusions only No extra hepatic metabolism Extra hepatic metabolism in lungs and kidney.
- 29. propofol etomidate Sodium tiopentone methohxitol ketamine 2,6 di isopropyl phenol R –(+)pentyl Ethyl -1H- Imidazole -5 carboxylate sulphate. Thio barbiturates oxybarbiturat es Phencyclidin e derivative ↑transmissio n of inhibitory neurotransmi tters (GABA) Depresses RAS , mimics inhibitory effects of GABA Depresses RAS by enhancing transmission of GABA Depresses RAS by enhancing transmission of GABA Blocks polysynaptic reflexes in spinal cord ,inhibits excitatory neuro transmitter in selected areas , disosciates thalamus from limbic system,NMD A antagonist
- 30. Drug name propofol etomidate Sodium thiopentone methohexit ol ketamine Induction dose 1.5 -2.5 mg/kg 0.2- 0.6 mg/kg 3-5 mg/kg 1-1.5 mg /kg 0.5- 2 mg/kg i.v ,4-6 mg/kg i.m Sedation dose 25 -100 mcg/kg/min 5-10 mcg/kg/min 0.5 -1.5 mcg/kg 0.2 -0.4 mg/kg 0.2-0.8 mg/kg iv over 2-3 min. Maintainanc e dose 100 – 300 mcg/kg/min 10 mcg/kg/min 15- 45 mcg/kg/min metabolism Hepatic conjugation Hydrolysis by hepatic enzymes and plasma esterases Hepatic oxidation to inactive water soluble metabolites Hepatic oxidation to inactive water soluble metabolites N – demethylati on in liver to form nor ketamine.
- 31. Drug name propofol etomidate Sodium thiopentone methohexit ol ketamine onset 30 seconds < 30 seconds 10 – 30 seconds 10 -30 seconds <1 min Elimination half life (hrs) 0.5 -1.5 2 – 5 11.6 3.9 2-3 Action (cvs) ↓ b.p , ↓ PVR Slight ↓ b.p ↓b.p ↑HR,↑PVR. ↓b.p ↑HR,↑PVR. ↑b.p ,↑HR R.S apnea Apnea wit opioids Apnea ,↓TV , ↓rate Apnea ,↓TV , ↓rate Apnea ,↓TV , ↓rate CNS ↓CBF ,↓ICP ,↓ O2 consumptio n ↓CBF ,↓ICP↑CPP ,↓ O2 consumptio n ↓CBF ,↓ICP↑CPP ,↓ O2 consumptio n ↓CBF ,↑ICP ,↑ O2 consumptio n others ↓gfr ,↓ hepatic blood flow ↓gfr ,↓ hepatic blood flow
- 32. Drug name propofol etomidate Sodium thiopentone methohexitol ketamine Induction , maintainance , sedative ,antiemetic, antipruritic Induction ,maintainance , short term sedation (unstable cvs) Induction , treatment of raised ICP , cerebral protection, anti convulsant (50-100 mg iv ) induction Analgesic , induction , sedative for burns dressing. Contra indications hepatic failure Adreno cortical suppression, pain on injection,myo clonus ,allergic reactions, nausea,vomiti ng Respiratory depression , hypotension, bronchospas m in asthma pts,pain and spasm on intra arterial injection, garlic or onion taste, anaphylactic Hiccough, twitching,myo clonus , laryngospasm ,respiratory depression,hy potension. Emergence, delirium,tachy cardia ,hypertension.
- 33. Volatile agents
- 34. • Higher the blood /gas partition coefficient …….the time of induction. • Longer • Hematocrit ↑ solubility ? • Increases and slow induction.anemic pts –fast induction. • Fat content ↑ solubiity ? • Increases and slow induction. • Cardiac output ↑ rate of induction ? • Delayed. • Ventilation ↑ rate of induction ? • fastened.
- 35. • MAC def • Alveolar conc of inhalational agent that prevents movement in 50% patients in response to a surgical stimulus. • MAC awake ? • That allows pt to open eyes on verbal command during extubation. • MAC intubation ? • That allows intubation without movement or coughing. • MAC bar ? • That inibits ↑ in conc of catecholamine levels in venous blood in response to skin incision.
- 36. • Decrease MAC • Hypo/hyper thermia , old age ,acute alcohol intoxication,hypoxia ,hyponatremia ,narcotics,benzodiazepines ,barbiturates, ketamine ,local anesthetics. • Increase in MAC • Chronic alcoholism, young age (MAC max at 6 months ). • No change of MAC • Duration of anesthesia ,sex,hyper/hypo carbia.
- 37. INHALATIONAL AGENTS ether Halothan e Isoflurane sevoflura ne Desfluran e Nitrous oxide Xenon Chemical name Di ethyl eher 2-bromo- 2-chloro-1 ,1,1 - trifluroeh ane Halogenat ed methyl ethyl ether Fluorinate d methyl ethyl ether Nitrous oxide xenon Physical propertie s irritant Clear, color liquid,non irritating odour,dec omposes on exposure to light Pungent etheral odour,liqu id can be stored without a preservati ve, non corrosive Colourles s liquid,non inflamma ble,non irritanting odour,uns table in presence of sodalime Pungent odour needs a specific vaporiser as its boiling point is near room temperat ure Colourles s,sweet smelling gas ,heavier than air,non inflamma ble,stable in soda lime. Noble gas ,colourles s,odourle ss,non irritant ,4 times heavier than air,non iflammabl e,stable in sodalime.
- 38. Inhalatio nal agent ether halothan e isoflurane sevoflura ne desfluran e Nitrous oxide xenon Stored in amber colored bottles,th ymol 0.01% aded, non inflamma ble,non explosive, minimal reation with soda lime. Non inflamma ble,reacts with sodalime. Reacts with soda lime. Mol wt.(Da) 74 197.39 184.5 200.5 168.04 44 131.3 Boiling point(◦c) 35 50.2 48.5 58.5 22.8 -88 -107.1
- 39. Inhalatio nal agent ether halotha ne isofluran e sevoflur ane desflura ne Nitrous oxide xenon MAC 3.04 0.75 1.2 2.0 6.0 105 71 Blood gas solubility coefficie nt 2.4 1.4 0.65 0.42 0.47 0.115 MOA Cardiova scular stability due to release of catechol amines Modify calcium, potassiu m flux to inhibit synaptic transmis sion Modify calcium, potassiu m flux to inhibit synaptic transmis sion Modify calcium, potassiu m flux to inhibit synaptic transmis sion Modify calcium, potassiu m flux to inhibit synaptic transmis sion Second gas effect, concentr ation effect Second gas effect, concentr ation effect.
- 40. Inhalatio nal agent ether halothan e isofluran e sevoflura ne desfluran e Nitrous oxide xenon B.P maintains ↓↓ ↓↓ ↓ ↓↓ HR ↑ ↑↑ _ _or ↑ _ _ SVR _ ↓↓ ↓ ↓↓ _ _ CO _ _ _ _ _ _ _ TV ↓ ↓↓ ↓↓ ↓ ↓ ↓ ↓ RR ↑↑ ↑ ↑ ↑ ↑ ↑ ICP ↑↑ ↑ ↑ ↑ ↑ ↑ Seizures ↓ ↓ ↓ ↓ ↓ _ metabolis m 20% in liver to tri fluroaceti c acid 0.2% in liver to tri fluroaceti c acid 4% in liver 0.02% in liver 0% in liver 0% in liver
- 41. Inhalatio nal agent ether halotha ne isofluran e sevoflur ane desflura ne Nitrous oxide xenon use Previous ly used for inductio n Quick inductio n and recovery ,sweet smell- well tolerate d during inductio n,potent broncho dilator. More rapid inductio n and recovery , coronary vasodilat or,used for neurosur gery Agent of choice for inductio n,bronch odilator, no effect on ozone. Most rapid inductio n and recovery ,no effect on ozone. Used with other agent - ↓MAC ,↑its uptake, good analgesi c More potent than nitrous oxide and environ ment friendly, good analgesi c.
- 42. Inhalatio nal agent ether halothan e isoflurane sevoflura ne desfluran e Nitrous oxide xenon Side effects Irritant to airway,↑s ecretions, nausea ,vomiting Malignant hyperther mia,hepat otoxicity,t ransient ↑in liver enzymes,f ullminant heatitis,se nsitises heart to catechola mines,arr hythmias, halothane shakes. Hepatoto xicity ,pungent smell – not suitable for induction, malignant hyperther mia,shiver ing during emergenc e. Nephro toxicity,m alignant hyper thermia.
- 43. Neuro muscular blockers • Ach receptors –subunits ? α,β,γ,δ,ε • Types ? Adult/mature/junctional -2α,1β,1ε,1δ fetal/extra junctional- 2α,1β,1γ,1δ • High density of fetal receptors leads to Hypokalemia after scoline administartion.
- 44. • Atypical Pseudo cholinesterase is measured by • Dibucaine number • Dibucaine number of typical psudocholinesterase • 70-80 • Fasciculations can be blocked by ? Sub paralysing dose of non depolariser (atracurium 0.03 mg/kg ,vecuronium 0.007 mg/kg , pancuronium 0.01 mg/kg)
- 45. • Phase 2 block occurs when ? • Repeated dosing, infusion , large bolus dose (5-7 mg/kg). • Intermediate acting non depolarisers ? • Atrac , Cisatrac , vec , roc. • Histamine release is seen with ? • Benzyl isoquinolinium compounds (dTC ,atracurium, pancuronium, mivacurium, metocurine).
- 46. • Renal failure and relaxants ? • Duration prolonged -Drugs partially dependent on renal excretion (pan ,pipe ) . • Total body water ↑ .so loading dose↑ ↓plasma cholinesterase activity. (mivacurium action prolonged.) Maintainance dose ? Given at larger time intervals and smaller in amount
- 47. • Atracurium metabolite ? • Laudanosine • Drug largely dependant on liver for metabolism? • Rocuronium • Partially dependant ? • Pancuronium, vecuronium, dTC, pipercuronium, doxacurium.
- 48. • Infants and muscle relaxants ? • Large TBW and more sensitive NMJ. Both cancel each other. (loading dose same.) • Duration of action prolonged (due to immature clearance ). • Elderly ? • ↓GFR and ↓metabolising capacity of liver causes ↑duration of action of all muscle relaxants. • Ions ? Hypokalemia ,hypocalcemia, hypermagnesemia potentiate and acidosis cause ↑ duration.
- 49. • Drugs potentiating block ? • Antibiotics (aminoglycosides ,polymyxin, clindamycin,calcium channel bockers,furosemide,lithium,dantrolene ) • Drugs that cause faster recovery ? • Calcium, anticonvulsants (carbamazepine and phenytoin), theophylline,aminophylline.
- 52. Anti cholinergic drugs • M1 ,M2 ,M3 receptors ? • M1 – ganglion cells, central neurons in cortex,hippocampus,corpus striatum. M2- cardiac muscuranic receptors. M3 – visceral smooth muscle cells ,glands, vascular endothelium . (smooth muscle contraction,glandular secretions,vasodilation ).
- 53. Anti cholinergic drugs atropine glycopyrrolate Clear ,colourless solution containing 0.6mg/ml 0.2 mg/ml Chemical structure Teritary amine and an ester of tropic acid &tropine.( derived from atropa belladona ). Quaternary ammonium.it is a synthetic anticholinergic drug &mandelic acid is present in place of tropic acid. Lipid solubility good poor BBB crossing + - Vagolytic property +++ + sedation + - Anti sialogogue + ++ ↑HR +++ ++
- 54. atropine glycopyrrolate Relax smooth muscle ++ ++ Mydriasis/cycloplegia + - Prevent motion sickness + - Decrease H+ secretion + ++ ↓gastric juice volume + ++ i.V onset 1 min 2-3 min i.V duration 30-60 min 30-60 min clearance 2.3 hours 1.25 hours Excretion unchanged in urine 18% 80% dose 0.6 mg i.m adult , 15- 20mcg/kg in children 0.2mg i.m /i.v adult , 4mcg/kg in children.
- 55. atropine glycopyrrolate Indications Preanesthetic medication, cardiac vagolytic ,mydriatic, antidote for organo phosphorous poisioining. Pre anesthetic medication. Side effects Dry mouth,difficulty in swallowing ,dry flushed skin,dilated pupil, atropine fever. Dry mouth , difficulty in swallowing. Contra indications Narrow irido corneal angle , cautiously used in BPH Narrow irido corneal angle , cautiously used in BPH.
- 56. Local anesthetics • More Lipid soluble? • more potent. • High Partition coefficient .? • .more lipid soluble. • Drugs with pka close to physiological ph have? • rapid onset . • More protein binding …? • .long duration of action.
- 57. amide ester lignocaine cocaine prilocaine procaine bupivacaine chlorprocaine dibucaine tetracaine mepivacaine benzocaine etidocaine ropivacaine
- 58. • Factors affecting cardiotoxicity of L.A • Pregnancy , beta blockers, ca channel blockers, digitalis, hypoxia ,acidosis ,hypercarbia ↑. Tachycardia ↑bupivacaine toxicity .R enantiomer is more toxic. • Factors affecting cns toxicity • Bupivacaine >lignocaine (at low doses ),rate of drug adm, acidosis ,pseudocholinesterase def • Cc/cns ratio ? • Dose required to produce irreversible cardiotoxicity and the dose required to produce convulsions ..3 for bupivacaine and 7 for lignocaine.
- 59. • ? Bupivacaine more cardiotoxic than lignocaine. • Bupivacaine is fast in slow out /lignocaine is fast in and fast out drug • C/I of adrenaline as adjuvant ? • Block of digit , foot ,penis ,local infiltration of skin flap, severe hypertension, PIH.
- 61. sympathomimetics • Septic shock ? • Nor adrenaline is drug of choice . • Dopamine causes tachycardia (↓cardiac filling ). • Sepsis with depressed myocardium ? • Dobutamine+ noradernaline. • Cardiogenic shock ? • Dobutamine is DOC. (↓afterload and ↑ contractility ). • When ur ionotrope doesn’t work ? • Metabolic acidosis ,hypocalcemia ,tension pneumothorax,cardiac tamponade, steroid depleted pts.
- 63. Anti cholinesterases • Maximum dose of neostigmine can be used for reversal ? • 70mcg/kg • Edrophonium is more effective than pyridostigmine in reversal of ? • Mivacurium • Half of original dose of reversal can be given in incomplete recovery after ----- ? • 30-60 min of reversal
- 64. • Factors affecting reversal ? • Inhaled anesthetics , hypokalemia, hypothermia, respiratory acidosis, aminoglycosides, calcium channel blocker.
- 65. physostigmine neostigmine source Physostigmine the venenosum synthetic chemistry Tertiary amine derivative Quarternary ammonium compound M.O.A Inhibit the enzyme acetylcholinesterase thereby ↑conc. Of acetylcholine Inhibit the enzyme acetylcholinesterase thereby ↑conc. Of acetylcholine Oral absorption good poor Duration of action 4-6 hrs 3-4 hrs CNS actions + - Applied to eye Penetrates cornea Poor penetration Direct action on cholinoceptors absent present
- 66. use Miotic(glaucoma), in belladona poisoning Myastheniagravis ,postoperative paralytic ileus,reversal agent for non depolarising blockers. dose 0.5-1mg oral/parenteral,0.1-1% eyedrops 0.5mg/kg i.v for reversal, 0.5-2.5mg i.m/sc
- 67. Diuretics (furosemide ) • Sulphonamide derivative • 10 mg/ml injection , 40 mg tablets • Mechanism of action ? Thick ascending limb of loop of henle. • Uses : • To remove edema fluid in renal,hepatic,cardiac diseases • Acute pulmonary oedema • Hypercalcemia.
- 68. • Side effects : • Volume depletion leads to pre renal azotemia • Hypokalemia • Metabolic alkalosis • Hypocalcemia • Hypomagnesemia • Hyperuricemia • Hypersensitivity rashes &hyposensitivity. • Interstitial nephritis.
- 72. crystalloids • RL ? • Na , cl,k , lactate , calcium . • isolyte p • dextrose ,na, cl, k, phosphate , acetate , magnesium
- 75. Drugs used in obstetrics • Oxytocin : hormone from posterior pitutary. • Stimulates uterine contractions in pregnant pts. • To induce labour -10 mu /ml is used. @ 1-2 mU/min. • To treat atony – upto 40 mU/min used. • s/e : ↓ b.p , flushing , water intoxication.
- 76. • Ergometrine : • Ergot alkaloid. • Stimulates uterine contractions • Dose : 0.2-1mg i.m or 0.1-0.5 mg i.v • s/e : hypertension, acute pulmonary oedema, cerebral oedema,convulsion.
- 77. • Second most prevalent intracellular ion ,physiological antagonist of calcium • magnesium • Therapeutic range • 4-6 meq/l • Uses ? • Sub arachnoid hemorrhage ,post op shivering, antiarryhthmic(torsades de pointes,QT prolongation,intractable VT,VF,multi focal atrial tachy,SVT
- 78. • Component of cardioplegia • Treat autonomic hyper reflexia. • Reduce fasciculations of scoline • Intractable bronchospasm • Spasms with tetanus • TPN • Anti aspiration prophylaxis • Severe PIH • Hypo magnesemia • Refractory hypocalcemia • Refractory hypokalemia. • Interactions : • NM blockers to be given 30-50% of normal dose.
- 79. Magnesium toxicity Serum level Clinical features 2.5 -5 mg/dl ↓ cardiac conduction,nausea Wide qrs ↑PR interval 5-7 mg/dl Sedation &hypoventilation. ↓deep tendon reflexes Muscle weakness 7-12 mg/dl Hypotension ,brady Diffuse venous dilation Loss of DTR >12 mg/dl Areflexia,resp paralysis,coma Cardiac arres , completeheart block.
- 80. Tranexamic acid • TXA is a synthetic lysine analogue that inhibits conversion of plasminogen to plasmin by preventing plasminogen from binding to the fibrin molecule. • TXA also inhibits plasmin activity directly. • TXA inhibits fibrin cleavage, thus reducing the risk of hemorrhage. • It also blocks binding of α2-antiplasmin and inhibits inflammatory reactions. • Compared with epsilon‐aminocaproic acid (EACA), TXA is more potent by a factor of 10 [25]. • The substance can be administered orally or intravenously .
- 81. • intravenous administrationProphylaxis and treatment of bleeding due to a local or systemic hyperfibrinolysis in adults and children over the age of 1 year. • Bleeding in which hyperfibrinolysis is considered to be involved: Menorrhagia and metrorrhagia Gastrointestinal bleeding Bleeding in urinary tract infections, postoperative bleeding following prostate or urinary tract surgeryEars, nose and throat (ENT) surgery (adenoidectomy, tonsillectomy, dental extractions)Gynecological surgery or obstetric hemorrhageAbdominal and thoracic surgery and other major surgery, e. g. cardiac surgeryAs antidote in bleeding requiring immediate treatment while on fibrinolytic treatment • Oral administrationHypermenorrhea (menorrhagia)ProstatectomyEpistaxisConisation of the cervixProphylaxis of recurrent bleeding in traumatic hyphemaDental extraction and other interventions in ENT area in patients with hereditary coagulopathiesMucosal bleeding in patients with coagulopathies,Hereditary angioneurotic edema
- 82. • adverse effects of tranexamic acid : • Gastrointestinal disturbances (nausea, vomiting, diarrhea)Drop of blood pressure/dizziness following a too fast intravenous administrationIncidental allergic skin reactionsInfrequent temporal vision impairmentConvulsions.
- 83. • Contraindications : • Hypersensitivity to TXAEarly pregnancy, • in late pregnancy only when vitally indicated • Disturbances of color vision • Massive bleeding in the upper urinary tract (risk of ureter obstruction due to clot) • Acute venous or arterial thrombosis • Severe renal impairment • History of convulsionsIntrathecal and intraventricular injection, intracerebral administration (risk of cerebral edema and convulsions) • Diseminated intravascular coagulation (DIC) without severe hemorrhage
- 84. Dosage and administration • 1. Oral administration (1 tablet = 0.5 g). The recommended standard dose is 2–3 times daily 2– 3 tablets (1–1.5 g), daily dosage 2–4.5 g • 2. Intravenous administration (1 ampoule = 5 ml = 0.5 g) in fibrinolysis: The recommended standard dose is 2–3 times daily 0.5–1 g (1–2 ampoules à 5 ml) by slow intravenous injection (1 ml/min) • 3. Intravenous administration in general fibrinolysis: The recommended standard dose is 1 g (2 ampoules à 5 ml) every 6–8 h by slow intravenous injection (1 ml/min), corresponding to 15 mg/kg body weight
- 85. Corticosteroids hydrocort Both gluco and mineralo Dexamethasone &methy pred Gluco coorticoid Fludro cortisone mineralo
- 86. • Uses : • Replacement therapy (addisons). Hydrocortisone 20-30 mg /day. Major dose given in morning. • Raised ICT . Dexamethasone 4 mg i.v 6 hrly. Only due to tumor /abcess. Not effective in trauma and bleeding. • Asthma • Allergy/hypersensitivity reactions.
- 87. • Joint diseases .(rheumatoid arthritis,osteoarthritis.) • Collagen diseases( SLE ,dermatomyositis,nephrotic synd ). • Pain management
- 92. Drug interactions Drugs affecting action effect digitalis Scoline , sympathomimetic amines Ventricular arrythmias Halothane ,neostigmine Excessive bradycardia calcium Potetiate arrythmogenic effect Broad spectrum antibiotics Enhance toxicity quinidine Muscle relaxants Prolongs duration of block
- 93. Ace inhibitors Sodium nitoprusside Reduced tachyphylaxis Glyceryl trinitride Anti muscurinic agents Reduced absorption of sublingual nitrate clonidine opioids Decreased requirements Local anesthetics Potentiates effect Ganglionic blockers Neuromuscular blockers Prolong and intensify affect Calcium channel blockers carbamazepine Serum level raises bupivacaine Cardiotoxicity increases Volatile anesthetics Additive effect on conduction N.M blockers Increase potency
- 94. sics Beta blockers halothane Sudden cardiovascular collapse Warfarin,digoxin, quinidine Reduced clearance Diuretics -thiazides digitalis Increased toxicity N.M blockers Potentiates effect lithium Impaired clearance spironolactone scoline arrythmias phenothiazines barbiturates Cross tolerance Narcotics-analgesics Depolarising agents susceptible Non depolarising agents resistance
- 95. Anti convulsants ,phenytoin benzodiazepines Increased levels of phenytoin Folic acid Decreased levels phenytoin Non depolarising relaxants Resistance to actions Anti depressants ,TCA’s MAO inhibitors hypertensive crisis halothane Ventricular arrythmias MAO inhibitors Sympathomimetic drugs Exaggerated response Sedatives,hypnotics ,narcotic analgesics Cardiovascular depression ,respiratory depression, convulsion,pyrexia
- 96. antipsychotics sedatives potentiated lithium relaxants Affect potentiated Anti coagulants barbiturates Anti coagulant affect reduced Salicylates , anti microbials Affect potentiated Volatile anesthetics- halothane Adrenaline arrythmias phenobarbitone Halothane induced hepatitis Non depolarising relaxants Affect potentiated
- 97. Induction agents- thiopentone Contrast media, sulphonamides Increased free drug Ethanol,opioids, anti histamines, CNS depressants Potentiate sedative effect ketamine Non depolarising muscle relxants Potentiate effect theophylline seizures diazepam Attentuates ketamies sympathetic affects lithium Duration prolonged
- 98. etomidate fentanyl Prolongs elimination half life opioids Decreases myoclonus propofol opioids Increased conc. Of opioids