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
- 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
- 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
- Hepatorenal syndrome
Linked side-effects
- Heart + brain (ion channels)
- Ear + kidney
Enterohepatic circulation
- BenPen is fine
- Only given IV => Little gut penetration
- Also means it doesn't encourage C. diff
Blood results in liver disease
- Is it liver? (GGT)
- Where in the liver? (ALT/ALP)
- Is liver function affected? (Albumin/INR)
- 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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