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