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L32: Drug-Drug Interactions (Phamacokinetic (Absorption :!: (DDIs within…

- - - - Propranolol(A) + Salbutamol(B) - Beta2 R
        
        A decreases efficacy of B
        
        Exacerbate Obstructive Airways Diseases
      - Naloxone(A) + Morphine(B)
        
        A decreases efficacy of B
        
        Naloxone: reversal agent in opioid overdose/ induce opioid withdrawal
    - - Warfarin + Vitamin K :!:
        
        Wafarin Inhibit Vit. K
        
        Consuming Vit. K can reduce efficacy of Warfarin
      - Nonsteroidal anti-inflammatory drug (NSAIDs)
        
        with Antihypertensive medication (ACE inhibitors/thiazides)
        
        diminish antihypertensive action with NSAIDs
        
        with Diuretics
        
        reduce efficacy of diuretics in chronic heart failure treatment
  - - - Warfarin
        
        with Antibiotics
        
        Antibiotics inhibit Vit. K production; increase Warfarin's anticoagulant activity.
        
        with Aspirin
        
        Increase risk of bleeding (GI Tract); Aspirin is also an anticoagulant
      - Diuretics(K+ depleting) + Digoxin :!:
        
        Hypokalaemia is induced by diuretics which can potentiate digoxin toxicity
    - - Hypertensive Crisis
        
        Mono-oxidase Inhibitors(MAOIs)-Tranylcypromine,phenelzine:!:
        
        with food containing Tyramine :forbidden: :!: - Fermented Food
        
        Death - Intracranial Haemorrhage
        
        with Food contain Sympathomimetics - Pseudoephedrine (cough & cold remedies)
        
        Hypertensive Crises
    - - 2 Serotonergic Drugs > Overdose of serotonin :forbidden:
        
        MAOIs
        
        Tricyclic Antidepressants :!:
        
        SSRIs (Selective Serotonin re-uptake Inhibitors
        
        OTC: St John's wort, Dextromethorphan (common cough suppression)
        
        Analgesics: tramadol, pethidine, fentanyl
        
        Illicit drugs: amphetamine, cocaine, ecstasy
        
        Duromine (appetite supressant)
      - Features
        
        Altered Mental Status (agitation, confusion, mad)
        
        Autonomic Dysfunction (diaphoresis, diarrhoea, fever, shiver)
        
        Neuromuscular Abnormalities
- - - - Exaggerated clinical response with CYP-dependent 'pro-drug'
        
        Rifampicin (CYP3A4 inducer)
        
        with Clopidogrel (anti-platelet drug)
      - Toxicity due to enhance production of Toxic Metabolite
        
        Carbamazepine / phenobarbitone /
        phenytoin / isoniazid / rifampicin (CYP2E1 Inducers)
        
        with Paracetamol overdose > increase toxic metabolite (NAPQI)
      - Loss of efficacy of parent drug
        
        Rifampicin (2C9 inducer)
        
        with Wafarin (2C9 substrate)
        
        Carbamazepine/Phenytoin OR Rifampicin (CYP3A4 inducer)
        
        with Combined Oral Contraceptive pill (COCP) > Contraceptive Failure
    - - Blood levels of drug exceed toxic threshold
        
        Clarithromycin :!: / Ritonavir (CYP3A4 Inhibitor)
        
        with Statins (Atorvastatin / Simvastatin) > myopathy & rhabdomyolysis**
      - Loss of 'Pro-Drug' efficacy
        
        Quinidine (CYP2D6 Inhibitor)
        
        Codeine (prodrug) :no_entry:> Morphine (analgesic)
        
        Paraxetine (CYP2D6 Inhibitor)
        
        Tramodol (prodrug) :no_entry:> O-desmethyltramadol (analgesic)
        
        Fluoxetine / Paroxetine (CYP2D6 Inhibitor)
        
        Tamoxifen :no_entry:> active metabolite
      - Blood levels of drug (low dose) increases to therapeutic levels
        
        Diltiazem (CYP3A4 Inhibitor)
        
        [Cyclosporin] increases, low dosage required
      - Xanthine Oxidase (XO) metabolises 6-MP > Non-toxic
        
        Allopurinol (XO Inhibitor)
        
        AVOID with Azathioprine/Mercaptopurine (6-MP) :forbidden: >Myelosuppression
      - Aldehyde dehydrogenase (ALDH) metabolises Ethanol > Non-toxic
        
        Metronidazole (ALDH Inhibitor)
        
        AVOID with Alcohol :forbidden:> Disulfiram Reaction
  - - - Drugs bind to another, limiting oral bioavailability
        
        Cholestyramine (Questran)
        
        Bind to
        
        Digoxin
        
        Thyroxine
        
        Warfarin
      - Drugs form Insoluble precipitate
        
        Antacids + Quinolones
        
        Calcium/Iron Ions + Tetracyclines
    - - Decrease acidity with Proton Pump Inhibitors
        
        Absorption of Drugs decrease
        
        Ketoconazole
        
        Itraconazole
        
        Erlotinib
    - - GI Absorption slowed by drugs that delay gastric emptying
        
        Atropine
        
        Opiates
      - GI absorption accelerated by drugs that stimulate gastric emptying
        
        Metoclopramide (Maxolon)
    - - P-Glycoprotein Inhibitors
        
        Block Efflux transporting function; :arrow_up:Drug Absorption
        
        P-Glycoprotein Substrates
        
        HIV protease inhibitors
        
        Cyclosporin
        
        Quinidine
        
        Digoxin :!: :no_entry:
        
        P-Glycoprotein Inhibitors
        
        Quinidine :no_entry:
        
        AVOID with Digoxin; Quinidine will increase Plasma [Digoxin] > CNS Toxicity :!: :forbidden:
        
        Cyclosporin
        
        Fluoxetine
        
        Diltiazem
        
        Itraconazole
      - P-Glycoprotein Inducers
        
        Enhance Efflux transporting function; :arrow_down:Drug Absorption
        
        P-Gp Inducers
        
        Rifampicin :!:
        
        St John's Wort :!:
        
        AVOID with Digoxin; decrease [Digoxin] :forbidden:
  - - - Probenecid (Inhibits Renal Secretion)
        
        Beneficial
        
        with Penicillin (prolong action) :check:
        
        Deleterious
        
        with Methotrexate (Increase Toxicity) :forbidden: