Hepatotoxic drugs

Mr Isoniazid is sitting at a cafe playing cards over a bottle of wine and a Guinness with his best pal Dave. Dave is taking oestrogens because he wanted a pair of breasts to complement his favourite mushroom hat, and Mr Isoniazid recently bought a plastic halo that he wears on a stick above his head, but it’s causing him to have a terrible headache. He’s also got a UTI.

Hepatotoxic drugs

  • Isoniazid
  • ACE inhibitors
  • Alcohol
  • Iron
  • Oestrogens
  • Antifungals
    • Fluconazole
    • Itraconazole
    • Ketoconazole
  • Halothane
  • Paracetamol
  • Trimethoprim

Lithium side effects 

 

Lithium is an interesting drug with some important side effects. It’s one of those drugs that has a very narrow therapeutic window (0.4-1.0mmol/L) and above 1.5mmol/L you’re at significant risk of developing toxicity.

It’s used primarily as a mood stabiliser in conditions such as Bipolar disorder and refractory depression, and it is important to remember that it’s cleared by the kidneys, so anything that interferes with kidney function can push your lithium levels up dangerously high.

Toxicity triggers:

  • Dehydration
  • Renal failure
  • Diuretics, especially anything ending in -azide
  • ACE inhibitors
  • NSAIDS
  • Metronidazole

Remember that the blood level of Lithium may be normal, but if they’ve got rubbish kidneys, they may still develop toxicity.

Contraindications:

  • Cardiac failure
  • Kidney failure
  • Untreated hypothyroidism
  • Addison’s disease (anything where the patient has low sodium)
  • Pregnancy and breast feeding – Lithium is bad for babies

Side effects:

  • Metallic taste in the mouth – classic sign, seems obvious given Lithium is a metal
  • Fine tremor
  • Weight gain and oedema
  • Abdominal pain
  • Nausea

Signs of toxicity:

  • Hyperreflexia
  • Coarse tremor*
  • Confusion
  • Seizures
  • Coma

*a fine tremor is to be expected at therapeutic levels, so don’t fret if your patient appears fine but a little shaky.

Induce or Inhibit?

Which common drugs inhibit CYP450 enzymes and which induce them?

Here’s a couple of stories to help remember them – it’s by no means a comprehensive list, but should highlight the common drugs to remember.

 

Inducers – Mr Rifampicin

Mr Rifampicin tries St John’s Wort for the first time, which causes him to have two seizures.

He then rolls over and gets caught in barbed wire, where he proceeds to stay, and passes the time by having a long drinking session.

A wandering grizzly bear then mauls him to death.

new-doc-9_1

Enzyme inducers:

  • Rifampicin
  • St John’s Wort
  • Phenytoin, Carbamazepine
  • Barbiturates
  • Chronic alcohol use
  • Griseofulvin
  • (also smoking, but via CYP1A2)

 

Inhibitors – Mrs Isoniazid

Mrs Isoniazid rolls in the New Year with a whopper of a booze binge.

This sets off her gout and causes her to vomit twice.

This then makes her feel depressed, despite the two antidepressants that she’s taking, and gives her palpitations.

She attempts to remedy the situation by having unprotected sex, which gives her HIV and a nasty infection.

She’s prescribed four separate antibiotics and two antifungals to clear everything up.

new-doc-9_2

Enzyme Inhibitors:

  • Isoniazid
  • Acute alcohol use
  • Allopurinol
  • Cimetidine, Omeprazole
  • Fluoxetine, Sertraline
  • Amiodarone
  • Ritonavir
  • Antibiotics
    • Erythromycin
    • Metronidazole
    • Ciprofloxacin
    • Quinupristin
  • Antifungals
    • Ketoconazole
    • Fluconazole

 

 

Just remember than in questions they’ll often ask something like, “which of the following drugs would increase a warfarin patient’s INR” – an increased INR implies the enzymes have been inhibited so you need to think about the inhibitors…

 

Don’t get fooled!

The DMARD pyramid

How to remember the DMARDS commonly used in rheumatoid disease?

There’s a special place, where all of the people suffering from crippling rheumatoid arthritis can go for treatment. It’s a huge golden pyramid with a log flume running down from the top.

  • Gold
  • Leflunemide (pyrimidine synthesis inhibitor)
  • pyramid also describes the therapeutic pyramid of drugs in rheumatoid arthritis

At the top is a meth addict with spina bifida who tells you when you can ride the flume. He shouts go, and turns on a huge hydro-chlorine hose that fires you down the chute. The chlorine is to keep the mosquitos away.

  • Methotrexate (folate antagonist)
  • Hydroxychloroquine (antimalarial)

At the bottom you land in a huge pit full of aspirin pills that stink of sulphur, each of which is the same size as a thigh of pure chicken.

  • Sulfasalazine (5-ASA salicylate)
  • Azathioprine (purine analogue)

It’s a suitably weird story, feel free to make up your own….

Steve can’t have NSAIDs

Steve can’t have NSAIDs. Poor Steve. Steve needs to take something else. Anything but NSAIDS. And here’s why:

Steve has a hurty, and was told to take a painkiller to make his hurty go away.

diagnosis ‘hurty’

Unfortunately for Steve, the painkiller he decided to take was an evil non-steroidal anti-inflammatory drug, which didn’t agree with him.

The NSAID made Steve’s stomach give up all hope and bleed catastrophically, resulting in quite a mess.

It totally ruined the Nativity

All of this blood loss made his kidneys and liver give up hope too, and he watched in vain as they left to search for a sunnier place to live.

This made Steve really angry, and despite his frankly incredible blood loss and dehydration, his blood pressure still managed to go so high that his heart gave up and fell out as well.

At this point, Steve thought an aspirin might help. In fact, it just sparked off his asthma and his lungs fell off too.

Ok this is just stupid now

He then had a banana. Bananas have potassium. Steve also likes bananas.

Yeah, that’ll definitely make up for the lack of vital internal organs

Absolute contraindications to NSAIDS:

  • History of sensitivity to NSAIDS
  • History of GI bleeding or ulceration
  • Severe liver dysfunction
  • Renal impairment
  • Aspirin-induced asthma
  • Uncontrolled hypertension
  • Cardiac failure
  • Dehydration
  • Hypovolaemia
  • Hyperkalaemia

Mike’s morphine toilet adventure

Mike had an absolute blinder of an evening as one beer led to another and then took the logical step toward heavily sedative opioid narcotics, as all good nights out in London do.

Yes mate

He’s now sat astride the porcelain throne, fast asleep. He tried to poo but the straining made him tired, and he’d long since given up trying to urinate. A warm aromatic pool of vomit laps gently around his toes and when he does finally wake up, he has absolutely no idea where he was or why.

Feeling an itch crawling its way up his back, he stands up to scratch it, but everything goes black and he slumps onto the floor.

#typicaltuesday

Side effects of opioid medications:

Nausea and Vomiting
Urinary retention

Pruritus
Constipation
Confusion
Sedation and respiratory depression
Hypotension