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  1. 1. DRUG DRUG INTERACTIONS INTERACTIONS IN LABOR IN LABORA PRACTICAL VIEWA PRACTICAL VIEW Dr.Mohamed El Sherbiny MD Obstetrics & Gynecology Senior Consultant Damietta General Hospital Damietta Egypt
  2. 2. Basic principles:DEFINITION ::DEFINITION Drug interaction meansDrug interaction meansmodification of the effect of amodification of the effect of adrug by concurrentdrug by concurrentadministration of other drugs.administration of other drugs.
  3. 3. ADVERSE &BENEFICIAL INTERACTIONSAdverse interaction includes:Adverse interaction includes:1-Loss of drug action1-Loss of drug action2-Unexpected increase in drug action2-Unexpected increase in drug action3-toxicity3-toxicityBeneficial interaction: e.g..Beneficial interaction: e.g..*Pethidine+ Metochlopromide(Plasil)*Pethidine+ Metochlopromide(Plasil)*Naloxone+Morphia.*Naloxone+Morphia.
  4. 4. Mechanisms Of Interactions:I-PHARMACOKINETICS:I-PHARMACOKINETICS:Everything that happensEverything that happensto the drug in the bodyto the drug in the body
  5. 5. II-PHARMACODYNAMICII-PHARMACODYNAMIC* Everything the drug* Everything the drugdoes to the bodydoes to the body N.B Interaction outside the N.B Interaction outside the body (Incompatibility )) body (Incompatibility e.g. ketamine is incompatible with barbiturate & e.g. ketamine is incompatible with barbiturate & diazepam diazepam
  6. 6. I-PHARMACOKINETICWhat happens to drugs in thebody?* Absorption * Distribution * Metabolism * Excretion* Absorption: may be interfered with e.g.Al(OH)3 In most antacid adsorb digoxinAdrenaline to local anesthesia prolong effec
  7. 7. * Distribution: affected byCompetition for plasma protein bindingE.g:Indomethacine displaces Warfarine . Free Warfarine -->anticoagulant effect* Excretion : drug clearance affected by another drug e.g NaHC3 pH of renal tubules absorption of Aspirin & Phenobarbital (weakly
  8. 8. * Metabolism Interfered with through liver enzymes: Interfered with through liver enzymes:•Induction of liver micosomal Enzyme CYTOCHROME P 450 (7-10 days) e.g.Rifampicin, Phenobarbiton, Carbamaziben (Tegretol)Phenytoin:They increase the metabolism and decreaseactivity of other drugs e.g. Theophyllin, & Valproic acid
  9. 9. * Metabolism Cont..Inhibitor of liver enzymes(a rapid effect) e.g. Cemitidin,Erthromycindecrease the metabolism andincrease activity of other drugseg.Theophyllin,Anticoagulant
  10. 10. 2-PHARMACODYNAMICSynergism1-Addition 2+2=4 e.g. B Blockers +Thiazide2-Potentiation 2+2=5 Trimethoprin+sulfmethexasolAntagonism(Opposing)B-Blockers Propanolol(Inderal) prevent the bronchodilator effectof Sulbitamol (Ventolin) or Terbutalin (Bricanyl)Indomethacine inhibits biosynthesis of Vasodilator natrureticprostaglandins -->inhibit diuretic effect of Lasix and Thiazide
  12. 12. II -DRUGS USED IN -DRUGS USED IN ORDINARY LABOR & C S. ORDINARY LABOR & C S.Analgesic &Anesthetics Antacids , H2 antagonist & antiemetisc Antibiotics Ecbolic (Oxytocics) Intravenous additives
  13. 13. Analgesic &Anesthetics Analgesic &AnestheticsOpioidsBenzodiazepins:Diazepam(Valium)&Midazolam(Dormicum)Ketamine(ketalar or Kalypsol)
  14. 14. Analgesic &Anesthetics (cont.)Analgesic &Anesthetics (cont.)No2,No2,Hydrocarbon inhalation anesthesiaHydrocarbon inhalation anesthesia Fluthane ,Triline,Fluthane ,Triline,Muscle relaxant.Muscle relaxant.Conduction AnestheticsConduction Anesthetics
  15. 15. CNS depression producing drugs commonly used during labor e.g. Anesthetics, Opioid,Magnesium sulfate ,Anticonvulsant, Metoclopromide Benszodiazepine,Promothiazine Skeletal muscle relaxant ,Barbiturate , Beta adrenergic blockers, Antihistaminic, AntidepressantsUsually they potentiate each otherUsually they potentiate each other
  16. 16. Atropine AtropineUsed for :* preanesthetic medication * fetal Bradycaredia Atropine has these effects: *Ketamin(Ketalar) : Delirium *Metoclopramide: Antagonize effect on GI motility *Opioid : Constipation &urinary retention. *Thiopental: Vagal effect *Neostigmine : Muscrinic action of Acetyle cholin
  17. 17. Opioid Morphine,pethidine,Butorphanol,Nalbuphine ,fentanyl &,tramadolInteractionsOther CNS depressants: Maternal and fetalCNC& Respiratory depression& hypotensione.Anticholinergic: Sever constipation &Paralytic ileus
  18. 18. Naloxon(Narcan)• Reverses the analgesic and respiratory effect of opioids•Withdrawal symptoms in dependents• Large dose may be required to reverse Butorphanol(Stadol)
  19. 19. Pethidine Mono amine oxidas (MAO) Inhibitors Antidepressant(Parnate) Sever fatal reaction : (Excitation,sweating,sever hypertension) Metoclopramide : Analgesia & Emetic effect. But Promethazine (Sparin): Analgesia. Oxytocine &Prostglandines : Potentiaton.Ranitidine &Metoclopramide should given tooppose the delayed gastric effect of pethidine
  20. 20. Butorphanol(Stadol)It is (k)agonist& mixed (µ)agonist and antagonist-2mg is comparable with 80mg pethidine-2mg has respiratory depression of 10mg morphine but greater doses has no further depression(ceiling)Effect is altered by :Cimetidine,Erythromycine &Thiophylline( Hepatic) Antagonizes narcotic Antagonizes narcotic effect of Pethidine effect of Pethidine
  21. 21. Nalbuphine (NUBIN)* It is a (µ) partial antagonist and( k) agonist*10mg = 10mg Morphine or 50 mg Pethidine*Higher dysphoria &fetal R. depression (So not popular)*Ceiling effect with dose > 30mgInteraction:Concurrent .or following (µ) Analgesia & Respiratory depression
  22. 22. Tramadol (Tramal) (50mg)Weak µ agonist less respiratorydepression for the fetus50mg Tramal = 40mg PethidineMay antagonize antiepilepticsCarbamazepine (Tegretol) : decreases effect of tramadol
  23. 23. Fentanyl Fentanyl (Systemic ,Spinal & Epidural) 100 times as potent as morphine. 50 ug = 50mg pethidine More maternal nausea and vomiting, Similar neonatal side effect and More naloxon need for antagonist compared to pethidine*Addition of Chloroprocaine(Nesacaine) . . . . +Fentanyl:(Epidural)Unexplained increase of post operative pain
  24. 24. KETAMINE (KETALAR OR kLAPYSOL) 50mg/ml- Obstetric analgesia0.3mg/kg& anesthesia1mg/kg or to supplement No 2- It stimulate CVS ---> hypertension,tachycardia.&increase C.output- this effect is opposed by Bezodiazepine or Volatile anesthesiaInteractions:Thyroid hormone:Hypertension &TachycardiaCNS depression producing drugs: Hypotension&R.depressionHalogonated inhalation :Delayed recoveryThiopental or diazepam : Dreams and illusion of ketamine Incompatible with barbiturate & diazepamMay produce myocardial depression with Labetalol(Trandate):
  25. 25. Antianxiety (( minor tranquilizers) Antianxiety minor tranquilizers) Benzodiazepines Benzodiazepines Diazepam Valium Midazolam (Dormicum) Should be limited to Status epilepticus&Anexity Was used for ECLAMPTIC fitsWith CNS depression drugs: Potentiate each others- Antacids delay effect of oral Diazepam- Cimitidine & Erthromycin inhibit metabolism : Increase effect Fentanyl or Thiopental Dose for induction
  26. 26. Thiopental Thiopental Used to induce sleep If used as anesthesia-:---> Marked neonatal depressionCNS depression producing agents: CNS & respiratory depression,Hypotension ,and prolong anesthesiaHypotensive agents &diuretics:Additive hypotension.Rapid or high dose Ketemine(ketalar): : Risk of hypotension& respiratory depressionMgSO4 : CNS depressant& anaesthetic effects
  27. 27. NO2 CNS depression Producing medication : Anestheticrequirement Hypotension Respiratory depression Methyledopa(Aldomet): Decrease anesthetic requirement
  28. 28. HALOTHANE (FLUOTHANE)LABETALOL:Profound hypotensionRitodrin(Yutopar): Potentiate Arrhythmia &Hypotension OXYTOCICS : Decrease uterine respondCatecholamines (Dopamin,adrenaline ,Noradrenaline ),Ephedrin or Cocaine : Risk of ventricular arrhythmia.Nitrous Oxide Concurrent use : Requirement of the otherKetamine ----->Prolonged recovery
  29. 29. Muscle relaxant SUCCINYL-CHOLINE MgSO4, Aminoglycosides ,or Ranitidine(zantac) Potentiate muscle relaxant effectDigitalis toxicity (arrhythmia):Digitalis toxicity (arrhythmia):due to shift of intracellular K due to shift of intracellular KKetamine or Clindamycine :Prolongs apneaKetamine or Clindamycine :Prolongs apnea
  30. 30. Nondepolarizing Nondepolarizing Neuromuscular Blockers Neuromuscular BlockersGallamine(Flaxidil),Atracurium(Tracrium), Pancuronium(Pavulon) •B adrenergic blockers :Prolong the effect of Flaxidil& Pavulon •Calcium salt: Reverses the blocking effect •Opioids: Additive central respiratory depression •MgSO4 or Halothane : :Enhances blockadeN.B. Atracurium(Tracrium)N.B...Atracurium(Tracrium)Has insignificant placental transfer and rapid reverse.Has insignificant placental transfer and rapid reverse.
  31. 31. Conduction (Regional)AnestheticsIncreased effect by :Adrenaline,Beta blocker, (Cemitidene, Diazipam,Ketamine and opioids,Local Infiltration:Before and after episiotomy or Emergency CS in absence of anesthetic support0.5% Lidocaine(Zylocaine) or Chloroprocaine(Nesacaine)Adrenaline will prolong the effect of Lidocaine. or Chloroprocaine
  32. 32. Conduction (Regional)Anesthetics [Contin.] Paracervical block : 1% Lidocaine. or Chloroprocaine at 3&9 O’clock Fetal bradycardia is common:No longer recommendedPudendal Block :(before Forceps or Vacuum delivery)1% Lidocaine. or Chloroprocaine. Patient under heparin may have troublesome hematoma
  33. 33. Spinal(Subarachonoid) block : Tetracaine(Pontocaine), Bupivacine(Marcaine) (duration :90:150m. minutes) Lidocaine(60:90 minutes). or Chloroprocaine The addition of 0.2 mg of Morphine improves pain control during & after delivery
  34. 34. Epidural Analgesia: For Vaginal delivery &CS.Compared with IV. Analgesia: Epidural block hasSame degree of analgesia:Longer labor Chorioamnionitis, Forceps,and CS.
  35. 35. Epidural Analgesia: Morphia ,Pethidin,or Fentanyl + smaller dose of Bupivacine (Marcaine) Rapid onset, Good pain relief Shivering Tachyphlaxis of prolonged administration But higher pruritis (less with stadol) and U.retention*0.5mg Ketamine+ 0.25% Bupivacaine (Marcaine ) :prolongs the duration of Caudal block with reduction of the dose.
  36. 36. Epidural analgesia ( Contin.) *Addition of Chloroprocaine(Nesacaine) +Fentanyl: Unexplained increase of post operative pain *Addition of Lignocaine( Xylocaine) to. Bupivacaine can precipitate toxicity-Uterine displacement+Hydration with balanced salt solution--.>Decrease incidence of hypotension after Spinal or Epidural block-Hydration with rapid infusion of 25 g Glucose:Can lead to fetal acidosis ,Hypoglycemia,&Hyperbilirubinemia.Paradoxically: Hypertension associatedwith methergin is more commonwith spinal or epidural block.
  37. 37. ANTACIDSUsed in labor for prophylaxis with analgesia or anesthesiabefore CS will neutralize gastric contents in 90%.Gastric alkalinization: The absorption & bioavailability of:Some antimascarinics,Phenothiazine,Propranolol,Atenolol,DigoxineIndomethacine.Prednisone, Phenytoin, &Ranitidine(Zantac)With Misoprostol (Cytotec ) &-PE2- :Diarrhea
  38. 38. H2 receptor Antagonist H2 receptor Antagonist Cimetidine(Tagamet) & Ranitidine (Zantac) Cimetidine(Tagamet) & Ranitidine (Zantac) Inhibits Cytochrom450&448 * Increased level of : Phenobarbiton.,Diazepam, ,Phenytoin,Tricyclic antidepressent Theophylline, ,&Lidocaine) B Blocker,C chanel Blockers * Decrease level of Metronidazol.Ranitidine (Zantac)Weak enzyme inhibitor = Less interaction than Cimetidine
  39. 39. ANTIEMETICSPhenothiazines:Promazine (Sparine) Chloropromazine(Largactil )Benzamide:Metochlopramide(Primperan,Plasil) Ondansetron (Zofran)
  40. 40. Metochlopramide (Primperan,Plasil) MUsed with opioid analgesia and preanaesthetic medication toreducegastric volume and increase the tone of L.esophageal sphincter With CNS depressant drugs:Potentiate each others Decreases absorption of Digoxine ---> Decreases its effect Decreases effectiveness of Aldomet Prolongation of action of Succinylcholine Anticholinergics :lessen GIT motility effects of primperanOpioids : Primperan antagonize the emetic effect Gastric volume & Potentiats analgesic effect.
  41. 41. Ondansetron (Zofran) Used in resistant postoperative vomitingLiver Enzymes Inhibitors( Cemitidin,Erthromycin ): Increase activity of Zofran CYTOCHROME P 450 Inducers (Rifampicin,Phenobarbiton,Carbamazepine ( Tegretol) &Phenytoin,) : Decrease activity of ( Zofran)
  42. 42. Phenothiazines: Promazine (Sparine) Chloropromazine(Largactil)They should be limited to Psychotic patients or for sever nausea or vomiting CNS depressants : Potentiate each others-Potentiate orthostatic hypotension with Thiaside-Lower seizure threshold: Decrease effect of anticonvulsant & increase theirtoxicity--Inhibit effect of Adrenaline-Potantiate effects of Anticholinergics: Potentiates respiratory depression of pethidine and decreases analgesic effect
  43. 43. ANTIBIOTICS *AMPICILLIN : Potentiate , Prednisolone,Digoxin,Thyophillin,&Ergot* PIPERACILLIN(Piprel)&Carbincellin(Pyopen) :Potentiate thrombolytic effect of Heparin & Aspirin*CEPHALOSPORINES Nephrotoxicity with Gentamycin or tobramycin(Nebcin)Cephoperazon(Cefobid): Nephrotoxicity with aminoglycosides and potentiate anticoagulant effect of thrombolytics*PEN ICILLINS or CEPHALOSPORENS ):Mixing with aminoglycosides = Mutual inactivation
  44. 44. ANTIBIOTICS (Cont.)ERYTHROMYCIN :(It is A hepatic enzyme inhibitor)--> Potantiat effects of Digoxin, vasospasm of ErgotTheophylline,&Potantiat effects of Some antiepeleptics As :(Phyntoin(Epanutin),Carbamazepine(Tegratol),&Valproic acid(Depakene) METRONIDAZOL (FLAGYL) Potentiated by Phenbarbitone and phenytoin Opposed by Cemitidine
  45. 45. ANTIBIOTICS (Cont.)AMINOGLCOSYDES1-Mutual inactivation with Penicillins or Cephalosporins2-Indomethacine --> Nephrotoxicity in premature neonates3- Potentiate ototoxicity of Vancomycin( combination for endocarditis and resistant staph) :dose monitor4-Potentiate neuromuscular blocking agent
  46. 46. OXYTOCINIV oxytocin with General Anesthesia.; Sever hypotensioneWith Hydrocarbon inhalation anesthesia:(Cyclopropan, Halothen,Enfluran &Isoflurin):Hypotension & Maternal Sinus BradycardiaHalothane,Enfluran Decrease oxytocic effectCaudal block with vasoconstritcorsPotentiate the effect of prophylactic Vasoprerssors --->severe hypertension even rupture of cerbral blood vessels
  47. 47. OXYTOCINPg E2 & Pg E1 : Additive effectNon S. Anti inflammatory: OpposingExcessive Saline :Water intoxication Maternal &Fetal convulsionsExcessive 5% dextrose ?? Neonatal hyperbilirubenemia
  48. 48. METHERGIN* With general anesthetic:Potentiate vasoconstriction *Halothane >1% : Opposes oxytocic effect -->Postpartum hemorrhage*Sympathomimetics: Hypertension & Headaches (additive)*Paradoxically Hypertension with: Spinal and Epidural anesthesia B blockers
  49. 49. PROSTAGLANDINS All Prostaglandins are potentiated with concomitant oxytocin. Combination my be used therapeutically PgE2 PgE1 &P f 2 α with methergin : of Bp. Prostaglandin E1(Misoprostol=Cytotic) The same as in Pg E 2 PgE 1 + Mag. Antacid --> DiarrheaProstaglandinF2aMay potentiate effect of vasopressorsMgSO 4 : the effect of Pf 2 α markedly
  50. 50. INTRAVENOUS ADDITIVES INTRAVENOUS ADDITIVES Guidelines: *Drugs should only be added when constant plasma concentrations are needed . *In general one drug compatible should be added *Label : Name, drug and date.*Drugs should not be added toblood products, substitutes, manitol or sodium bicarbonate
  51. 51. Continuos or intermittent drug infusion?Continuos or intermittent drug infusion?Intermittent infusion :It is used if the drug is unstableor incompatible over infusion period . In 50: 200cmm over 30 - 60 minutes
  52. 52. Continuous in dextrose 5 % or salineCalcium gluconate - Digoxine Naloxone - Magansium sulfate Diazepam (Valium) or insulin in ( glass container) Oxytocin in Dextrose: ?Hyperbilirubinemia
  53. 53. Continuous in dextrose 5 %Terbutaline (Bricanyl) - Ritordine (Yutopar) Pg E 2 Methyl dopa (Aldomet)
  54. 54. Intermittent in dextrose 5 % or saline Penicillins Aztronate (Azactam)-Gentamycin -TubramycinCeftrixone (Cefobid) Not with calcium - Ceftazidime (Fortum) Labetalol(Trandate) - Ranitidine(Zantac)
  55. 55. Continuos or intermittent infusionAtropine sulfate - Prostigmine - Adrenaline - Noradrenaline Cephradine ( Velosef ) Cimetidine( Tagamet ) Metocolpramide(Primperan )
  57. 57. PRETERM LABOR & PROMPRETERM LABOR & PROM *TOCOLYTICS 1-Beta Adreneregic Agents 2- Magnesium Sulfate 3-Calcium Channel Blockers 4- Antiprostaglandines *Clucocorticoids *Clucocorticoids *Phenobarbital *Phenobarbital *Vitamin K1(Konakion) *Vitamin K1(Konakion) *Antibiotics *Antibiotics
  58. 58. B adrenergicsRitodrine(yutopar) - Terbutaline (Bricanyl)Salbutamol(Ventolin)Ritodrine is the most effective tocolytic(Selective B2 agonist ) Pulse+ BP Rennin & Hyperglycemia
  59. 59. Ritodrine (yutopar) Interactions--G.Anesth., Pethidine,or MgSO4:Arrhythmia& hypotension-Atropine :Increase B.P.-B Blockers :Decrease tocolytic effect.-Asthmatic patients under B.Adrenergics:Tachyphlaxis(drug resistance)-Diabetic patients : Insulin Antagonist( insulin requirement)Corticosteroids or MgSO 4 : Pulmonary edema
  60. 60. Calcium channel BlockersNifedipine (Adalat, Epilat)•Inhibits the influx of Ca ionsinto . myometrial cells•Excellent for hypertensives .•Can be used for:• Diabetics,• M.valve prolapse• Mild arrhythmia.
  61. 61. Calcium channel Blockers Nifedipine (Adalat, Epilat) Cont.* Neuromuscular blockade with MgSO 4 (live threatining)*Severe hypotension with : Barbiuturat, B Blockers and with Fenanyl Anesthesia*Low dose of both Nifidipen& B adrenergics (Epilate+Yutopar): better uterine relaxation and fewer side effect
  62. 62. Calcium Gluconate or Chloride*May antagonize the effect of calcium channel blockers*Precipitate sever arrhythmia for patient taking digitalis*Opposes the neuromuscular depression of magnesium sulfate
  63. 63. Nonsteroidal Anti inflammatory Nonsteroidal Anti inflammatory drugs (NSADs) drugs (NSADs) Indomethacin(Indocid) - Diclofenac(Voltaren,Olfen), Ibuprofen(Brufen) the safest during pregnancy Naproxin(Naprosyn),&Piroxicam(Felden) The last 3 can be used during lactation .Indication: Antiinflammatory,Tocolysis. Interactions:Increase effect ofDigoxin,Aminoglycosides&antiepilepticsDecreased effect by:Prostaglandins,Diuretics&B blockersThe effect of Oxytoctics especially Prostaglandins(PP.Hg)
  64. 64. Magnesium Sulfate (used when there is contraindication to RitodrineActionAnticonvulsant Peripheral effect decreases Acetyl Choline at myoneural junction ordirect effect at the muscleCentral ? CNS depressionTocolytic: Altering calcium uptake(Little effect if cervix>2cm)
  65. 65. Magnesium Sulfate Has Antiarrhythmic and coronary protector Has Antiarrhythmic and coronary protector (Suitable for heart abnormalities )) (Suitable for heart abnormalities But with cautions of over load in valvular diseases. But with cautions of over load in valvular diseases. IncompatibilitiesCalcium, Bicarbonates Clindamycine, Hydrocortisone & SalicylatesInfusion in Dextrose (Preeclampsia)& Saline (Tocolytics)Corticosteroids or yutopar : Pulmonary edema
  66. 66. Magnesium SulfateInteractionsCalcium gluconate : AntagonistCNS depressant drugs : PotentiationDigitalis: Heart blockNifedipine: Potentiate Hypotension &neuro muscular blockBeta Adreneregics: Pulmonary edemaCorticosteroid : Pulmonary edemaPF 2 α (Enzaprost): Oppose its effect in postpartum hemorrhageNeuromuscular blockers: Potentiation & delay recovery .
  67. 67. Magnesium SulfateInteractions :: Case reports.Interactions Case reports.2 Cardiac arrest at CS for preterm labor:First:Mgso4+ Thiopental +Supine hypocavel2 nd : Mgso4 + Methergin
  68. 68. Patient under corticosteroidObstetric disordersPreterm Labor Antiphospholipid and HELLP syndromesAssociated disordersAllergic ( eg. Asthma) Hematologic disease ITP,Collagen disease (eg. SLE), Shock states,Arthritis
  69. 69. CORTICOSTEROIDS CORTICOSTEROIDS Ephedrine--> Increase metabolic clearance->less effect Hepatic enzyme inducing agents(e.g..phenytoin,Baribturates ,Carbamazepine,&Rifampicin--> Increase clearance->less effect Digitalis ---> Arrhythmia (due to hypokalemia)Nondepolarizing neuromuscular bloking agent--> Enhancing (due to hypokalemia) BUT Pancuronium(Pavulon) is inhibited (unknown)Insulin-->More insulin doseNSAIDS ( e.g. endomethacine): Potentiation of antirhumatic effect &GIT ulceration Ritodrine (Yutopar)or MgSO 4 ---> Pulmonary edema
  70. 70. Barbiturate BarbiturateInduce microsomal enzymes leading to:Induce microsomal enzymes leading to: Enhance metabolism (( effect) of :: Enhance metabolism effect) of Corticosteroids,Digitalis& ,Metronidazol Corticosteroids,Digitalis& ,Metronidazol Digoxin,Phenothiazines,Tricyclic antidepressant Digoxin,Phenothiazines,Tricyclic antidepressantHypotension with Calcium Channel BlockersHypotension with Calcium Channel Blockers
  71. 71. PREECLAMPSIA & ECLAMPSIAAntihypertensive drugsHydralzine (Aprisoline)Labetalol (Beta & Alpha blockers)(Trandate)Calcium Channel blockers(Adalat) Anticonvulsive : Mg SO4
  72. 72. Antihypertensive drugs used in chronic hypertension Diuretics Thiazids in intravascular volume expansionDrugs decreasing cardiac outputB.blockors: Nonselective : Propranolol(Inderal)B1 selective-No bronchospasm :Atenolol(Tenormin)Prazosin : α blocking(Minipress)->in Resistant casesCentrally acting Methyldopa(Aldomet)
  73. 73. HYDRALZINE(Aprisoline)*Additive hypotensive effect with : Aldomet *Drug of choice for acute control of sever pregnancy induced hypertension *May be used with Methyldopa or B blocker for chronic hypertension. *NSAID(eg Indomethacine):Reduce antihypertensive effect
  74. 74. Labetalol (Trandate) Labetalol (Trandate)A combined Alpha & Beta adrenergic blockerA combined Alpha & Beta adrenergic blockerfor control of severe pregnancy induced hypertensionfor control of severe pregnancy induced hypertensionIt may be used with thiazide for chronic hypertension.It may be used with thiazide for chronic hypertension.Additive hypotensive effect and Bradycardiawith (Reserpine)Tremor with Tricyclic antidepressant..Cimetidine decreases the effect of trandate.
  75. 75. Methyldopa (Aldomet) Methyldopa (Aldomet)*Drug of choice for essential hypertension*Additive hypotensive effect with:Hydralzine ,Beta adrenergic blockers&General anesthetics.*Reduced hypotensive effect with:TricyclicAntidepressent,Barbiturate&SympathomymeticsNSAIDs(eg Indomethacine):Reduce its antihypertensive effect.Ephedrine is less effective when used with aldometMOA inhibitoers: (Parnate) Hyperexcitability and sever hypertension .
  76. 76. Propnanolol(Inderal) Propnanolol(Inderal).. Effect by:Cimetidine,Largactil&Hydralzin(Enzymeinheritors) &Hydralzin(Enzymeinheritors),, Effect by:Phenytin,&barbirurates Effect of: Theophylline&XylocaineAdditive Toxicity: Methergin: Sever Hypertension Requirement of InsulinNifedipen:Myocardial depression
  77. 77. III- DRUGS USED IN COMMON MEDICAL DISORDERSHeparinHeparin Aspirin Aspirin Antidepressent Antidepressent Insulin Insulin Adrenaline Adrenaline Antihestaminics Antihestaminics Theophyllines Theophyllines
  78. 78. HEPARINPotentiated by Plateletaggregation inhibitors as:Dextran, NSIDs, CarbencillinAspirin,Cephoperozon”Cefobid”&, Valproic acid“Depakene”
  79. 79. ASPIRIN*Low dose Aspirin is used for prophlaxis against DVT, Antiphosplipid syndrome,prevention of Pre eclampsia *Decreased effect by Corticosteroid( metabolism). metabolism). * Requirement of Vit.K * Requirement of Heparin *Platelet aggregation inhibitors as: *Platelet aggregation inhibitors as: Dextran,, Carbencillin,Cephoperozon”Cefobid” Dextran,, Carbencillin,Cephoperozon”Cefobid” &, Valproic acid“Depakene” &, Valproic acid“Depakene” They potentiate bleeding tendency * Effec of NSIDs NSIDs
  80. 80. Antidepressants Antidepressants Tricyclics TricyclicsImpiramine (Tofranil) -- Amitriptyline (Tryptazol) Impiramine (Tofranil) Amitriptyline (Tryptazol)*Potentiate the action of ::CNS depressant D.Anticholinergics, *Potentiate the action of CNS depressant D.Anticholinergics,Antihistamines,oral anticoagulant,Antithyroids&PhenothiazineAntihistamines,oral anticoagulant,Antithyroids&Phenothiazine Monoamine Oxidase inhibitors (MAO) *Tranylcypromine(Parnate) Hypertensive crises with Pethidine or aldomet , metabolism of B Adrenergi
  81. 81. INSULIN*Hyperglycemic agents: Corticosteroid,ACTH,Diuretics,*Hyperglycemic agents: Corticosteroid,ACTH,Diuretics,Epinephrine,&Thyroid hormone:Epinephrine,&Thyroid hormone:(( Decrease the dose) Decrease the dose)*Hypoglycemic agents NSAIDs,B.blockers &Labetalol:*Hypoglycemic agents ::NSAIDs,B.blockers &Labetalol: (Increase the dose)(Increase the dose)
  82. 82. Adrenaline*Increases toxicity of Antidepressent*Increases toxicity of Antidepressent*Beta Blockers the pressor and bronchodilator effect*Beta Blockers:: the pressor and bronchodilator effect*Hydralazine :: Reduced Pressor effect of adrenaline*Hydralazine Reduced Pressor effect of adrenaline* Prolongs the effect of Local anesthetic agents* Prolongs the effect of Local anesthetic agents
  83. 83. Antihistaminics*Chlorophenramine,Dimethenedine(Fenistil):Pheneramin (Avil) Celimestin(Tavegyl),Nonsedative selective H1 antagonistAstemizol (Hismanal) & Loratidine (Claritine) Potentiate anticholinergics & CNS depressantsCa channel blockers or Phenothiazine:Increase Risk of arrhythmia with Astemizol(Hismanal)but not with Loratidine (Claritine)
  84. 84. THEOPHYLLIN E Effect By: Effect By: 1-Liver enzymes inhibitors as 1-Liver enzymes inhibitors asCemitidine,Corticosteroid,Ertromycine,ProplanololCemitidine,Corticosteroid,Ertromycine,Proplanolol 2-Additive:Ephedrine ,Ketamine&Halothen. 2-Additive:Ephedrine ,Ketamine&Halothen. Effect By:-1-Liver enzymes inducers as:Rifampicin,Barbiturates,Carbamazepin(Tegratol)Phenytoin(Epanutin)2- Antagonism : Diazepam&Metoclopramide
  85. 85. Thank You