SCRIPT: toxic tablets Flashcards
List some potentially dangerous oral tablets that require vigilant monitoring
- Warfarin (to a lesser extent DOACs/antiplatelets)
- Methotrexate
- Lithium
- Digoxin
- Amiodarone
Warfarin.
a) Indications
b) Contraindications
c) Pregnancy/ contraception
d) Interactions
e) Initiation - loading
f) Monitoring
a) - AF
- VTE
b) - Haemorrhagic stroke
- Significant bleeding
- Pregnancy: 1st and 3rd trimester especially
- 48 hours post-partum
- 72 hours post-surgery
- Severe renal or hepatic impairment
c) - Teratogenic risk
- Also risk of severe intrapartum bleeding - vitamin K prophylaxis if mother is on warfarin
- Women of childbearing potential should have adequate contraception and be aware of risks
d) Enzyme inducers
- (PC BRAS) - phenytoin, carbamazepine, barbiturates, rifampicin, alcohol, St John’s Wort
- reduce INR (thrombosis risk)
Enzyme inhibitors
- (AO DEVICES) - allopurinol/azole antifunfals, omeprazole, disulfiram, erythromycin/ other macrolide, valproate, isoniazid, cipro, ethanol, sweet juices (cranberry, grapefruit)
- increase INR (bleeding risk)
LOTS of other drugs (check BNF)
- Amiodarone
- Potentially antibiotics like penicillin, tetracyclines, co-trimoxazole (displaces warfarin from albumin)
Thyroid function
- Hyperthyroidism - may require lower doses
- Hypothyroidism or on carbimazole - may require higher doses
e) Loading doses:
- Slow - 3 mg daily, check INR on day 4 and adjust accordingly
- Rapid - 5-10 mg daily, check INR from day 2 and adjust accordingly
Effects of warfarin takes a few days as this is how long it takes to synthesise clotting factors
f) - INR (PT measure - extrinsic pathway [WEPT])
- Monitoring a few times per week initially, then may be spaced out once stable to monthly or longer
- Yellow Anticoagulant Book - record of INR results and dosing information
Lithium.
a) Indications
b) Contraindications
c) Pregnancy
d) Initiation
e) Monitoring
f) How should it be prescribed?
g) Patient information
a) - Bipolar disorder
- Management of mania, manic depressive illness and recurrent depression
- Treatment and control of aggression and self-mutilating behaviour
b)
c)
d) - Baseline tests:
- Initiate
- Check concentration after 4 days (takes this time to reach steady state)
e) Serum levels.
- Measure levels after 4 days* (12 hours post-dose)
- Then weekly until stable
- Then 3 monthly
*repeat after every dose adjustment
Other monitoring.
- Regular cardiac (ECG) monitoring
- U+Es/ renal function every 6/12
- Calcium every 6/12
- TFTs every 6/12
- BMI every 6/12
f) - By the BRAND name
- Note: there are 2 salts available - lithium carbonate tablets and lithium citrate liquid (they are not dose equivalent)
g) - Patient alert card
- Patient information booklet
- Education - indication, dosing, risks, toxicity, etc.
Lithium toxicity.
a) Therapeutic range
b) Adverse effects of lithium - LITHIUM
c) Toxicity - signs and symptoms
d) Toxicity - management
e) Risk factors for toxicity
a) 0.4 - 1.0:
- advise lower end for older adults
- advise higher end in acute treatment
b) - Leukocytosis
- Inspidus (nephrogenic) - polyuria, polydipsia
- Tremor
- Hypercalcaemia
- Insomnia?
- Underactive thyroid
- Mums beware - Ebstein’s anomaly
c) - Nausea, vomiting, diarrhoea
- Coarse tremor, seizures, confusion, muscle weakness, ataxia, reduced GCS
- Hypotension, dehydration, renal failure, electrolyte imbalances
d) - Stop lithium
- Fluids!
- Correct any electrolyte abnormality
- RRT may be required
- Whole bowel irrigation?
e) - Dose too high
- Dehydration
- Renal failure
- Drugs reducing renal elimination (NSAIDs, ACE inhibitors)
- Hyponatraemia
(hence risk increased on SSRIs, diuretics, etc.)
Patient on warfarin is started on erythromycin. What should you do?
- Monitor INR
- Adjust warfarin dose accordingly
- Note: erythromycin is an enzyme inhibitor so is likely to increase INR (bleeding tendency); hence warfarin dose likely needs to be reduced
Warfarin toxicity.
a) Signs
b) Management
a) - Bruising, bleeding
- Haemorrhage, eg. IC bleed, EC bleed, GI bleed
- Raised INR
b) To manage a raised INR:
1. Stop warfarin or reduce the dose
2. Reverse anticoagulation if necessary with vitamin K* +/- Prothrombin complex concentrate
3. Investigate cause (e.g. dose, drug-interaction, adherence, patient education)
4. Consider risk/benefit of continuing treatment
*Dose and route (oral or IV) will depend on how quick a response is needed and whether complete reversal is needed (only partial if metallic heart valve)
Patient information on warfarin.
a) They should know…?*
b) They should be encouraged to…?
*Should be in Yellow Book
- How warfarin works.
- Why they are taking warfarin (i.e. indication).
- The different strengths and colours of tablets available.
- The dose of warfarin to take (explain this in milligrams referring to the colours of the tablets).
- What an INR is, the importance of monitoring, and who will monitor it.
- What to do if they miss a dose, or take the wrong dose.
- The time and date of their next INR check.
- The signs of over-anticoagulation (e.g. bruising, bleeding).
- The effects of diet and alcohol on warfarin and the need to moderate intake of certain foods.
- Potential drug interactions, and the need to inform healthcare professionals when choosing to self-medicate with OTC medicines or herbal products.
- The need for contraception if they are a woman of childbearing potential.
- Duration of treatment (e.g. 3 months, 6 months, lifelong)
b) Encourage your patient to:
- Take their warfarin at the same time each day.
- Carry an anticoagulant alert card with them at all times.
- Take their record of the last six months of anticoagulant therapy to medical appointments (including the dentist) and when collecting their warfarin prescriptions.
- Obtain repeat prescriptions in advance to avoid running out of tablets.
- Seek advice (e.g. pharmacist) before buying over-the-counter medicines.
Digoxin.
a) Mechanism of action
b) Pharmacokinetics - absorption, distribution, elimination
c) Indications
d) Contraindications
e) Initiation
f) Dose changes
a) - Positive inotrope
- Negative chronotrope
b) - Absorption - oral bioavailability ~ 70%
- Metabolised in cells via p-glycoprotein efflux pump (does not use CYP450)
- High Vd (very lipid-soluble)
- Long half life: 20 - 50 hours
- Eliminated via the kidneys - hence renal function vital
c) - AF
- Heart failure
d)
e) - Loading dose (‘digitalisation’) - given either orally or IV (not a huge difference in effect)
f) Dose change will take approximately 7 - 10 days to achieve steady state concentration
Digoxin toxicity.
a) Signs
b) Risk factors
c) Therapeutic range
d) Management
a) - Hypotension and bradycardia
- Nausea, vomiting, diarrhoea
- Confusion, weakness, blurred vision, syncope
- Palpitations, arrhythmias
- AKI
b) - Renal failure
- Older age
- Hypokalaemia* (heart becomes more sensitive to arrhythmias)
- Other electrolyte abnormalities (hypomagnesaemia, hypercalcaemia, alkalosis, hypoxia, hypothyroidism)
- Interacting drugs, (eg. amiodarone, macrolides, verapamil, rifampicin, spironolactone, St John’s Wort)
*For this reason, potassium must be checked before starting anti-arrhythmics (esp. digoxin and amiodarone)
c) - 0.8 - 2.0 nanomol/litre
(toxicity generally occurs > 2.0)
d) If toxicity suspected:
1. Stop digoxin.
2. Measure plasma-digoxin concentration immediately if features of severe toxicity.
3. Obtain information regarding the dose and timing of the last dose for interpretation of serum level
4. Measure urea, electrolytes, potassium and creatinine and correct any disturbances (particularly for renal failure and hypokalaemia)
5. Monitor pulse, blood pressure and cardiac rhythm.
6. Stop any drug treatments that may affect electrolyte balance or the clearance of digoxin
7. Seek advice from National Poisons Information Service (NIPS) and their online resource TOXBASE
8. May require Digoxin binding antibody (Digibind)
Methotrexate.
a) Indications
b) Contraindications
c) Generally taken with…?
d) Baseline tests and monitoring
e) Interactions with other drugs
f) Conception/contraception advice
a) - Malignant disease
- Psoriasis
- Rheumatic disease
- Crohn’s disease
b) - Active infection*
- Immunosuppression
- Ascites, pleural effusions (risk of accumulation)
- Pregnancy
*If already on methotrexate, withhold it if you suspect sepsis (due to risk of neutropenia)
c) Folic acid:
- taken on a different day to methotrexate (otherwise will be rendered ineffective)
d) - FBC: baseline, then every 1 - 2 weeks until therapy has stabilised. Then every 2-3 months thereafter.
- LFTs - baseline, then every 1-2 weeks until therapy has stabilised, then every 2-3 months thereafter.
- Renal function - baseline, then every 1-2 weeks until therapy has stabilised, then every 2-3 months thereafter.
- Chest X-ray - on initiation, and if signs of possible pulmonary toxicity
e) - Folate antagonists: trimethoprim
- Other drugs with risk of agranulocytosis (eg. clozapine, carbimazole and many others)
- Drugs affecting renal elimination (eg. NSAIDs, aspirin)
f) Both MEN and WOMEN should use effective contraception during and for 6 months after methotrexate treatment due to teratogenic risk
What to do if patient is found to be taking daily methotrexate?
- Consult senior
- FBC, etc.
- Report incident - GP, trust and NRLS
- Educate patient on importance of weekly dosing
Methotrexate toxicity
a) Signs
b) Risk factors
c) Management
a) - Dyscrasia: lymphopenia, thrombocytopenia, anaemia, infection, etc.
- Nausea, vomiting, GI bleeding
- Dysuria/anuria
b) - Too high dose*
- Hypoalbuminaemia
- Folate deficiency
- Ascites or effusions
- Drug interactions, e.g. NSAIDs, aspirin, steroids, trimethoprim, clozapine, penicillin, cipro
*recommended to only supply methotrexate in 2.5 mg tablets (they are available in 10 mg as well - beware!)
c) 1. STOP methotrexate
2. Consult a haematologist/toxicologist
3. Give folinic acid* rescue therapy
4. Incident reporting - local, NRLS
5. Patient education
*Active folic acid
Amiodarone.
a) Indications
b) Contraindications
c) Initiation and monitoring
d) Adverse effects
e) What to do if patient develops thyroid toxicity?
a) -
b) - Thyroid dysfunction
- SA nodal/AV nodal disease (unless pacemaker)
c) - TFTs - baseline and every 6/12
- LFTs - baseline and every 6/12
- CXR - baseline
- Serum potassium - baseline (risk of arrhythmias if given amiodarone with hypokalaemia)
d)
e) - Withhold amiodarone until TFTs normalise
Patient with recent PE and diabetes has glucose of 1.9 on latest BM and is unconscious with hypoglycaemia.
They are on warfarin 4 mg OD.
a) Most appropriate management and why?
a) - 75 - 100 ml of 20% glucose given IV
- Or 150 - 200 ml of 10% glucose
(basically get 20 g glucose either way)
This is preferable to IM glucagon:
- where there is IV access and IV glucose is available
- where patients are anticoagulated (IM injections not ideal due to bleeding risk)
Patient on atorvastatin complains of muscle pains. Bloods show CK 2000 and an AKI.
a) Management
b) CK rise of what proportion indicates need to stop statin?
a) STOP the statin
- reintroduce at lower dose a later date only if symptoms resolve and CK level normalises
b) 5x normal
