High Risk Drugs Flashcards
What side effects are associated with amiodarone? (10)
- Nausea and vomiting.
- Taste disturbances
- Pulmonary toxicity
- Tremor
- Sleep disorders
- Hypo/hyperthyroidism
- Jaundice
- Slate grey skin
- Phototoxicity.
- Corneal deposits
The half-life of amiodarone is ridiculously long so side effects may last weeks after discontinuation of the medicine - also interactions can occur weeks after the patient is no longer taking the medicine.
Why should patients taking amiodarone be advised to avoid exposure to direct sunlight or sun lamps?
Amiodarone contains iodine (hence thyroid dysfunction) and amiodarone break doen in the sunlight to cause erythema and phototoxic reactions.
What monitoring should accompany amiodarone use? (4)
- LFTs
- TFT
^at initiation and every 6 months. - Serum potassium before treatment or dose change.
- CXRay before treatment.
What is the initial dosing for amiodarone?
200mg TDS for 1 week
200mg BD for 1 week
200mg OD continued.
Amiodarone interacts with what other drugs? (4)
- Beta blockers: increased risk of bradycardia (heart block)
- Digoxin - increased plasma concentrations of digoxin so halve dose
- Lithium - increased risk of ventricular arrhythmias. (both prolong QT interval)
- Warfarin - Inhibits the metabolism of warfarin and so an enhanced coagulation effect can occur.
What is the interaction between amiodarone and beta blockers?
Increased risk of bradycardia (heart block).
What is the interaction between digoxin and amiodarone?
Increased digoxin concentraton so halve digoxin doses.
What is the interaction between amiodarone and lithium?
Increased risk of ventricular arrhythmias as both amiodarone and lithium prolong the QT interval.
What is the interacton between amiodarone and warfarin?
Amiodarone inhibits the metabolism of warfarin and so enhanced coagulation effect can occur.
What is digoxin?
A cardiac glycoside used in AF, tachycardia and heart failure.
Long half-life so once daily maintenance dosing.
How does digoxin work?
Digoxin is a positive inotrope which increases the force of the myocardial contraction and reduces conductivity within the AV node.
Is amiodarone safe for use in pegnancy or breastfeeding?
No
How does amiodarone work?
Amiodarone slows the conduction rate and prolongs the refractory period of the SA and AV nodes.
(can cause QT prolongation)
What is the desired serum concentration of digoxin?
1-2mcg/L
What is the toxicity range of digoxin?
1.5-3mcg/L.
Note: this obviously encompasses the therapeutic range of 1-2mcg/L, it has been advised that toxicity reactions are more likely to occur the closer to 3mcg/L levels are (or over).
Digoxin should be used with special care in the _____
Elderly. Elderly are more likely to have reduce renal function and renal impairment can lead to digoxin toxicity.
A reduced dose is needed if digoxin is to be used in the elderly.
What are the side effects of digoxin? (5)
- Nausea and vomiting
- Diarrhoea
- Dizziness
- Blurred vision (yellow green etc)
- Erratic heartbeat
What are the monitoring requirements of digoxin? (3)
- Serum U+E
- Renal function
- Serum levels checked with blood taken 6 hours post dose
When should serum levels of digoxin be checked?
Bloods taken 6 hours post dose, serum levels checked if potentially out of therapeutic window or suffering side effects.
What drugs does digoxin interact with? (most common not exhaustive list)
- Amiodarone - increased plasma concentration of digoxin.
- Erthryomycin - increased plasma concentration of digoxin.
- Calcium channel blockers: increased concentration of digoxin.
- Rifampicin - reduced digoxin concentration
- St Johns Wort - plasma concentration of digoxin reduced.
- Diuretics - increased plasma concentration of digoxin.
What is the interaction between amiodarone and digoxin?
Increased plasma digoxin concentration.
What is the interaction between erythromycin and digoxin?
Increased plasma erythromycin concentration.
What is the interaction between CCB and digoxin?
Increased digoxin concentration.
What is the interaction between rifampicin and digoxin?
digoxin concentrations may be reduced.
What is the interaction between st johns wort and digoxin?
digoxin concentrations may be reduced
What is the interaction between diuretics and digoxin?
Increased risk of digoxin toxicity if hypokalaemia occurs.
What are the indications of lithium?
Prophylaxis and treatment of mania, bipolar disorder, recurrent unipolar depression.
What is the generally desired serum concetration of lithium?
0.4-1.0mmol/L
Lower end for maintenance and in the elderly.
Lithium serum concentration of what or above may be toxic?
of or wbove 1.5mmol/L
A target lithium serum concentration of what should be aimed for acute episodes of mania, and for patients who have previously relapsed or have sub-syndromal symptoms?
0.8-1.0mmol/L
When should blood samples be taken following a lithium dose?
12 hours after a dose.
Routine serum-lithium monitoring should be performed weekly after initiation and after each dose change until concentrations are stable, then every how often thereafter?
3 months.
The manufacturer recommends what should be assessed prior to treatment initiation with lithium? (6)
- renal,
- cardiac,
- TFT,
- BMI,
5, U+Es - FBC
Also an ECG in patients with CVD/risk factors for CVD.
What are the toxic effects of lithium? (11)
- Blurred vision
- Gastric upset
- Muscle weakness
- Drowsiness
- Sluggishness
- Tremor
- Ataxia (co-ordination, balance etc)
- Dysarthria (speaking problems)
- Nystagmus (eye movement)
- Renal impairment
- Convulsion
How should lithium be stopped?
Reduce the dose gradually over 4 weeks, there is a risk of relapse if stopped abruptly.
Why should the use of diuretics - especially thiazides- be cautioned in people on lithium?
Lithium toxicity can occur by sodium depletion and therefore drugs which LOWER sodium should be cautioned.
Why should the use of NSAIDs be with caution by patients on lithium?
There is a risk of lithium toxicity due to reduced excretion.
Why should the use of ACEi in people on lithium be with caution?
Reduced excretion leading to toxicity.
What is the interaction between amiodarone and lithium?
Risk of ventricular arrhythmias.
What is methotrexate used to treat?
Moderate to severe active RA.
Crohn’s
Malignant disease
Severe psoriasis.
What are the side effects of methotrexate? (7)
- Blood dyscarasias: FBC before treatment and report any symptoms suggestive of blood disorders, especially sore throat, bruising or mouth ulcers.
- Anorexia
- Ab pain
- dyspepsia
- GI ucler and bleeding.
- Diarrhoea
- Mucositis
What monitoring is required with methotrexate? (3)
- Reg FBC
- RFT
- LFT
`Methotrexate can cause liver toxicity/cirrhosis. Patients should be advised to report what symptoms?
Nausea
Vomiting
Abdominal discomfort
Dark urine
Methotrexate can cause pulmonary toxicity, patients should be advised to report what symptoms?
Cough
Fever
Dyspnoea
Why should methotrexate users avoid NSAIDs?
NSAIDs reduce the excretion of MTX, patients should avoid self-medicating with nsaids.
Why is folic acid given with MTX?
To prevent methotrexate-induced mucositis or myelosuppression. Not on the same day.
Phenytoin is used in the treatment of epilsepy. What does it not treat?
Absence seizures
Status epilepticus
What is the desired serum concetrantion of pheytoin?
10-20mg/L
What monitoring is there of phenytoin?
FBC and LFTs
What side effects are there of phenytoin? (7)
- N+V
- Drowsiness
- Gingival hyperplasia
- Acne
- Hirsutism
- Diplopia
- Blood or skin disorders: report fever, rash, mouth ulcers, bruising, bleeding
How should phenytoin be taken?
With a full glass of water.
One hour before or two hours after food.
With or after food.
At night.
Take with or after food.
Could be at night if very drowsy but key point is with or after food for increased BA
What are the interactions of phenytoin? (not exhaustive, just most relevant) (4)
- Amiodarone - inhibited metabolism of phenytoin
- Warfarin - increased metablism of warfarin is caused by phenytoin.
- Fluoxetine - increased levels of phenytoin are caused by flouxetine.
- Cimetidine inhibits the metabolism of phenytoin.
What is the interaction between amiodarone and phenytoin?
Amiodarone is predicted to slightly increase the concentration of phenytoin.
Also Both amiodarone and phenytoin can increase the risk of peripheral neuropathy.
What is the interaction between warfarin and phenytoin?
Phenytoin is predicted to alter the anticoagulant effect of warfarin.
What is the interaction between fluoxetine and phenytoin?
Flouxetine is predicted to increase the concentration of phenytoin.
Same for Sertraline (and other SSRIs?)
What is the interaction between cimetidine and phenytoin?
Cimetidine increases the concentration of phenytoin.
What is theophylline?
Bronchodilator for asthma or COPD.
Metabolised in the liver and has a desired serum plasma concentration of 10-20mg/L.
How does theophylline work?
Inhibition of phosphodesterases (PDEs) in airway smooth muscle.
What is the desired serum concentration of theophylline?
10-20mg/L
The concentration of theophylline can be increased in what conditions/patient groups? (4)
Heart failure.
Hepatic impairment.
Viral infections.
The elderly.
Note: Decreases in smokers and by alcohol consumption.
What are the side effects of theophylline? (6)
Nausea + vomiting Diarhoea Palpitations. Arrhythmias Headache Convulsion.
What monitoring should accompany theophylline use? (3)
- Plasma theophylline concentrations.
- Lung function tests.
- Patient asthma symptoms etc.
What are some interactions involving theophylline? (non-exhaustive list)
- Cimetidine increases the plasma concetration of theophylline.
- Fluconazole increases the plasma concentration of theophylline.
- Quinolones cause an increased risk of convulsions when used with theophylline.
What is the interaction between Cimetidine and Theophylline?
Cimetidine increases the palsma concentration of theophylline.
What is the interaction between fluconazole and theophylline?
Fluconazole increases the plasma concentration of theopyhlline.
What is the risk of using quinolones and theophylline?
Increased risk of convulsions as both can cause convulsions as side effects/lower the seizure threshold.
What key counselling points should accompany warfarin prescribing? (3)
- Take at the same time in the evening.
- Avoid major changes in diet, especially salads and vegetables.
- Report any signs of bleeding or spontaneous bruising.
What interaction exists between warfarin and statins?
Enhanced anticoagulant effect - INR increases.
What is the interaction between NAIDS and warfarin?
Increased INR
What is the interaction between ciprofloxacin and warfarin?
Enhanced anticoagulant effect - INR increases.
Also ciprofloxacin (as a quinolone) can lower the seizure threshold so it can predispose to seizures (falls) whilst also increasing patients anticoagulation.
What is the interaction between St Johns Wort and warfarin?
Reduced anticoagulant effect: INR decreases.
What is the interaction between cranberry juice and warfarin?
Enhanced anticoagulant effect - INR increases.
What is the itneraction between warfarin and antiepileptic drugs?
Reduced INR
What is the therapeutic range of carbamazepine?
4-12mg/L
Takes 14-28 days to reach SS after starting therapy and 2-4 days after a dose change.
Samples taken predose.
How long does it take carbamazepine to reach steady state?
4-12mg/L
Takes 14-28 days to reach SS after starting therapy and 2-4 days after a dose change.
Samples taken predose.
What is the therapeutic range of digoxin?
0.8-2.0mcg/L
~7 days to SS.
Samples taken at least 6 hours post dose.
How long does it take digoxin levels to reach steady state?
0.8-2.0mcg/L
~7 days to SS.
Samples taken at least 6 hours post dose.
What is the therapeutic range of lithium?
0.4-1.0mmol/L
~4-7days SS
Samples taken at least 12 hours post evening dose.
How long does it take lithium to reach steady state?
0.4-1.0mmol/L
~4-7days SS
Samples taken at least 12 hours post evening dose.
What is the therapeutic range of phenobarbital?
15-40mg/L
~14-28 days SS,
Pre-dose sampling.
What is the therapeutic range of phenytoin?
10-20mg/L
~7-28 days SS
Pre-dose sampling.
What is the therapeutic range of theophylline?
10-20mg/l
~2 days to SS.
For M/R preps, samples taken 4-6 hours post dose.
How long does it take theophylline to reach steady state?
10-20mg/l
~2 days to SS.
For M/R preps, samples taken 4-6 hours post dose.
How should amiodarone-induced thyroid disorder be managed?
Amiodarone should be withdrawn or at least temporarily held to help achieve control.
Lithium toxicity is made worse by what electrolyte imbalance?
Sodium depletion; therefore concurrent use of diuretics - particularly thiazides, is hazardous and should be avoided.
The dose of this medicine should be halved in a patient concurrently taking digoxin:
Atenolol Bisoprolol Verapamil Sulbutamol Amiodarone Dabigatran Ramipril
Amiodarone.
Which of the following is the least appropriate anagesic for a patient taking lithium for bipolar disorder?
Codeine Ibuprofen Morphine Paracetamol Tramadol
A serious interaction between lithium and NSAIDs leading to reduced excretion of lithium and subsequent toxicity. CNS side effects of opioid analgesics are not desired but the risk of toxicity is lower. The pharmacokinetic interaction is more important than the pharmacodynamic interactions.
Both lithium and tramadol can increase the risk of serotonin syndrome.
Which ONE of the following is a toxic effect of theophylline?
Watering eyes Drowsiness Bruising Tachycardia Goitre
Tachycardia