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