Drug interactions

An interaction is said to occur when the effects of one drug are changed by the presence of another drug

 Fentanyl and propofol  Object precipitant  Fentanyl morphine  Object, precipitant

As anaesthesiologists

 Anesthesiologists usually combine drugs to get better action and benefits  Yes -- we combine drugs -- but what’s the problem ??

 pharmaceutical interaction  pharmacokinetic interaction  pharmacodynamic interaction (direction and intensity)  1. antagonistic = 0  2. additive 1+1 = 2  3. synergic 1+1 = 3

 A pharmaceutical interaction is a chemical or physical interaction that occurs before a drug is administered or absorbed systemically.  A pharmacokinetic interaction occurs when one drug alters the absorption, distribution, metabolism, or elimination of another.  A pharmacodynamic interaction occurs when one drug alters the sensitivity of a target receptor or tissue to the effects of a second drug.

 WTG morton  Ether day  ether by itself could produce hypnosis, reasonable levels of analgesia, and muscle relaxation  Guedel’ s stages

 No mask induction  Pain free  Quick recovery  No delirium  No vomiting

 IV Agents  Narcotics  Muscle relaxants  So what happened to Guedel stages ??

 Agents with low safety margins  warfarin, digoxin, and theophylline  Conscious sedation  Pethidine and MAOI  Can we think like this ??  If a drugs fails to act - is it due to a drug interaction ??

 Combination therapy can reduce toxicity   atenolol and hydralazine  Drugs for Malignancy  Drugs for Seizures

 Thio and scoline in the IV line  Fortwin and taxim  Bupivacaine and sodabicarb  Adrenaline and soda bicarb

 Heparin and hydrocortisone  Inactivation of heparin  Gentamicin and hydrocortisone  Inactivation of gentamicin

 Older anaesthetists  Trilene and sodalime  Younger ones  Sevoflurane and sodalime

 Absorption  distribution,  metabolism,  elimination of another drug

Oral tetracycline can be inactivated by chelation if it is given together with antacids containing polyvalent cations such as Mg 2+, Ca 2+, or Al 3+. Morphine delays gastric emptying Small gut drugs like para ??

 Adrenaline and local anaesthetics  Second gas effect

 Possible depression of cardiac function  Propofol  Agent  VRG

 Thyrotoxicosis  Fever  aspirin

 Neostigmine and scoline  Ecothiophate and scoline

 sympathetic neurotransmission:  CNS transmission  Separate topic

 Hepatic blood flow  Agents decrease hepatic blood flow  Extraction  High  Lidocaine and propranolol  Low-extraction drugs such as diazepam, alfentanil, or mepivacaine have ERs of 0.3 or less.

 etomidate, blocks the synthesis of cortisol and aldosterone by inhibiting the P450-dependent mitochondrial enzymes, 17α-hydroxylase and 11β-hydroxylase.  Protease inhibitors such as saquinavir and ritonavir can inhibit the metabolism of midazolam and fentanyl,

 propofol competitively inhibits CYP3A4, and it can reduce the clearance of midazolam by 37%  Co administration of cimetidine and diazepam causes clinically significant elevations in diazepam  Alfentanil and erythromycin are both metabolized by CYP3A4, and the antibiotic greatly prolongs the effect of the opioid.

 Probenecid and penicillin  Quinidine and digoxin  The cation system handles the elimination of atropine, isoproterenol, neostigmine, and meperidine

 Direction and intensity  1. antagonistic = 0  2. additive 1+1 = 2  3. synergic 1+1 = 3 

 Rocuronium and vecuronium  Nitrous oxide with volatile anesthetics is additive  Two benzodiazepines  likely to occur when drugs with identical mechanisms are combined

 potentiation of opioids by NSAIDs  potentiation of nondepolarizing relaxants by the various volatile anesthetics  supra-additive interaction occurs between aminosteroid and benzylisoquinolines

 neostigmine, naloxone, or flumazenil.  An antagonistic interaction occurs between succinylcholine and the nondepolarizing relaxants.  drug combination may simultaneously be synergistic and antagonistic for different effects.  When butorphanol is combined with midazolam, the mixture increases sedation but has less anterograde amnestic effect than midazolam alone

 Pharmacodynamic Interactions Affecting Hemodynamics

 Rapid-acting β 2 agonists (albuterol, terbutaline),  anticholinergics (ipratropium)  phosphodiesterase inhibitors (theophylline).  increased risk for tachydysrhythmias and ectopic rhythms.  Similar considerations apply to the patient receiving the IV β 2 agonist, ritodrine, for premature labor.

 minimize the use of pancuronium, halothane, ketamine  Prone for arrhythmias  TCADs induced hypotension ???

 Patients with chronic cocaine intoxication are less of a problem, (THAN ACUTE) but they are still at risk for dysrhythmias (avoiding halothane, pancuronium, atropine, and sympathomimetics)  Increase MAC – halothane

Pharmacodynamic Interactions Affecting Analgesia or Hypnosis

 THIOPENTONE –  FENTANYL – THEN THIPENTONE  fentanyl and midazolam are combined for conscious sedation, the opioid is producing sleep as well as analgesia.

 Thiopental–midazolam interaction has been studied in humans, and the combination was found to have 1.8 times the expected potency of the individual agents  PROPOFOL AND MIDAZ

 IV lignocaine  Clonidine.  Midaz

 Opioid  Benzodiazepines  Agents

 Agonist and antagonist

Three-Way Interactions

HerbalAgentsOpioids

 Adrenaline and local anaesthetics  Prevent absorption----- pharmacokinetic  Alpha 2 agonist action --- pharmacodynamic

 Sodabicarb and local anaethetics  Precipitation = pharmacoceutical  Increased absorption – pharmacokinetic

 Sedation  Antanalgesic effect  Pharmacodynamic

 Thank you all