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13.02.14 Pharmacology - Liver

Important P450 substrates
  • Logic
    • Narrow therapeutic index
    • Therefore small changes in metabolism have a big effect
  • Examples:
    • Warfarin
    • Ciclosporin
    • Theophylline
      • Methylxanthine - PDE inhibitor / Adenosine antagonist
    • Phenytoin
    • Carbamazepine
    • Oral contraceptive


CYP inhibitors

  • Erythromycin
  • Ciprofloxacin
  • Sodium valproate
    • The only antiepileptic to inhibit rather than induce
  • Omeprazole
  • (Statins)


CYP inducers

  • Several epilepsy drugs
  • GRAP GPS
    • Carbemazepine
    • Rifamicin
    • Alcohol
    • Phenytoin
    • Griseofulvin
      • For fungal toenail infections
    • Phenobarbitone
    • Smoking


Amiodarone

  • Domestos of antiarrhythmics
  • Takes 250 days to eliminate
  • Many, many side effects
    • Deranged LFTs
    • Pulmonary fibrosis
    • Thyroid (looks similar to thyroxine)
    • Corneal deposits
    • Blue-grey skin
    • Peripheral neuropathy
    • Epididymitis


Common drugs deranging LFTs

  • Several antibiotics
  • Anti-epileptics
    • Carbemazepine
    • Phenytoin
  • Anti-TB drugs
    • Everything except ethambutol
      • => Renal damage and optic neuritis (do Ishihara test before + during)
  • Typical antipsychotics
  • Statins
  • Amiodarone
  • COCP
  • Spironolactone


Decompensated liver disease

  • Alcohol
    • Presentations
      • Wernicke's
        • Nystagmus
        • Ophthalmoplegia
        • Ataxia
      • Korsakoff's
        • Short-term memory loss
    • Treatment
      • Chlordiazepoxide, haloperidol
      • Pabrinex
  • Ascites
    • Exclude SBP
    • Sodium restriction
    • Spironolactone, furosemide
    • Ascitic drain
  • Varices
    • Acute bleed:
      • Terlipressin
      • Octreotide (somatostatin mimetic)
    • Long-term:
      • Endoscopy + banding
      • Propanolol
  • Hepatic encephalopathy
    • Diet
    • Lactulose
    • Neomycin
  • Hepatorenal syndrome
    • Terlipressin


Linked side-effects

  • Heart + brain (ion channels)
    • Effects
      • Convulsions
      • Arrhythmias
    • Drugs
      • Phenytoin
      • Lidocaine
  • Ear + kidney
    • Aminoglycosides


Enterohepatic circulation

  • BenPen is fine
    • Only given IV => Little gut penetration
    • Also means it doesn't encourage C. diff


Blood results in liver disease

  1. Is it liver? (GGT)
  2. Where in the liver? (ALT/ALP)
  3. Is liver function affected? (Albumin/INR)
  4. Is there secondary organ involvement? (Creatinine)


Ascites in liver damage

  • Reduced blood oncotic pressure
  • Portal hypertension
  • Reduced aldosterone metabolism => Raised plasma levels


Notes

  • Penicillins characteristically have a wide therapeutic range
  • Now only one level line for paracetamol
  • NAC has risk of anaphylaxis
  • In a cirrhotic liver, liver enzymes might not be that abnormal, as there aren't many cells left
  • Metronidazole is the only antibiotic you can't drink on
    • Inhibits acetaldehyde dehydrogenase (like disulfiram) and so causes SOB, nausea, headache (hangover)
  • Reserve ciprofloxacin for pseudomonas
  • CURB-65 is assessing secondary organ involvement
  • Chlorpromazine => Cholestatic jaundice


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