HIGH RISK DRUGS Flashcards
What is methotrexate indicated for?
- Severe Crohn’s disease
- Severe rheumatoid arthritis
- Neoplastic disease
- Severe psoriasis
Mode of action of methotrexate
- Inhibits dihydrofolate reductase enzyme
- Folate antagonist
When is methotrexate contraindicated?
- Active infection
- Ascites
Dosing regimen of methotrexate
Once weekly on the SAME day each week
Signs of methotrexate toxicity which need reporting to GP?
- Blood disorder
- Liver toxicity
- Respiratory
- Bone marrow suppression (Normal WBCs = 7-11 x10^9/L
- GI toxicity
Other S/E:
- Acne
- Alopecia
- Anorexia
- Change in nail/skin pigmentation
Monitoring requirements for methotrexate?
- FBC, LFTs and renal function
- Test repeatable every 1-2 weeks until stable
- Once stable, monitor every 2-3 months
Which other medications or precautions must be taken during methotrexate treatment?
- Folic acid taken on different day, to reduce S/E for non-malignant conditions
- Effective contraception required during and for 3 months after treatment in men AND women
Which drugs interact with methotrexate and increase its toxicity?
- Aspirin
- Acetazolamide
- Ciprofloxacin
- Diclofenac
- Ibuprofen
- Indomethacin
- Ketoprofen
- Meloxicam
- NSAIDs
- Naproxen
- Penicillins
- Proton pump inhibitors
Therapeutic range and signs of toxicity of lithium?
- 0.4-1 mmol/L
- GI disturbances, visual disturbances, ployuria, tremor, bradycardia, renal impairment and seizures
Therapeutic range and signs of toxicity of digoxin?
- 1-2 micrograms/L
- Nausea, vomiting, dizziness, fatigue and bradycardia
Therapeutic range and signs of toxicity of methotrexate?
- Typically 7.5-25mg weekly
- Bone marrow suppression, GI toxicity, liver toxicit
Therapeutic range and signs of toxicity of warfarin?
- Dose dependant on INR
- Haemorrhage
Therapeutic range and signs of toxicity of theophylline?
- 10-20 mg/L
- Severe vomiting, agitation, hyperglycaemia, restlessness, dilated pupils and sinus tachycardia
Therapeutic range and signs of toxicity of gentamicin?
- 5-10 mg/L (PEAK) 2 mg/L (TROUGH)
- Nephrotoxicity and irreversible ototoxicity
Therapeutic range and signs of toxicity of ciclosporin?
- Weight related dosing
- Tremor, gingival hyperplasia, hypertrichosis
Therapeutic range and signs of toxicity of phenytoin?
- 10-20 mg/L
- Nystagmus (involuntary eye movement), diplopia (double vision), slurred speech, ataxia, confusion and hyperglycaemia
Therapeutic range and signs of toxicity of vancomycin?
- 10-15 mg/L (TROUGH)
- Ototoxicity (discontinue if tinnitus occurs), “red man” syndrome, rash, blood disorders
Indications for lithium?
Treatment/ prophylaxis if mania, bipolar, recurrent depression, aggression or self-harming behaviour
Contraindications for lithium?
- Addison’s disease
- Cardiac insufficiency
- Dehydration
- Low sodium diets
- Intreated hypothyroidism
Cautions for lithium?
- Avoid abrupt withdrawal
- Cardiac disease
- Can lower seizure threshold
- Risk of toxicity with diuretic treatment
- Reduce dose for elderly
- QT prolongation
Long term risk factors for lithium?
- Thyroid disorders
- Mild cognitive and memory impairment
- Rhabdomyolysis
Pregnancy and BF considerations?
- Females of child-bearing age should use effective contraception
- Teratogenic in first trimester
- Present in breast milk
Monitoring requirements for lithium?
- Weight or BMI
- U&Es
- eGFR
- Thyroid function every 6 months
How should dose reduction be carried out with lithium?
Gradually over the course of at least 4 weeks (preferably over the course of 3 months)
Patient advice for lithium administration?
- Maintain adequate fluid intake
- Avoid dietary changes reducing or increasing sodium
- Learn to recognise toxicity symptoms
- Report episodes of diarrhoea, vomiting or forms of dehydration (sodium depletion)
Indications for digoxin?
- AF
- Flutter
- Heart failure
Where do dose changes need to be made with digoxin?
- Reduce by half with amiodarone, dronedarone or quinine
- Increase by 20-30% when switching from IV to oral
Contraindications for digoxin?
- Intermittent complete heart block
- Myocarditis
Cautions of use with digoxin?
- Risk of digitalis toxicity with hyperglycaemia
- Hypomagnesaemia
- Hypoxia
Pregnancy and BF considerations with digoxin?
- Dose may need adjusting
- Amount too small in BF to be harmful
Monitoring requirements with digoxin?
- Renal function
- U&Es (toxicity increased by electrolyte imbalance)
Indications for methotrexate?
- Crohn’s
- RA
- Neoplastic disease
- Psoriasis
Contraindications for methotrexate?
- Active infection
- Immunodeficiency syndromes
- Significant plural effusion
Cautions in methotrexate?
- Blood disorders
- Liver toxicity
- Respiratory effects
- Photosensitivity
- Stomatitis
Where is immediate withdrawal required during methotrexate therapy?
Drop in WBC or platelet count
Pregnancy and BF considerations for methotrexate?
- Effective contraception needed for duration of treatment and 3 months (male and female)
- Avoid in pregnancy as teratogenic
- Present in BF
Monitoring requirements for methotrexate?
- FBC
- Renal function
- Liver function
Repeated every 1-2 weeks until stable, and 2-3 months thereafter
Patients advised to report signs of infection, esp sore throats
What should be co-prescribed with methotrexate, and why?
*Folic acid- 5 mg weekly (on different day to methotrexate
* Decrease mucosal and GI SEs. May also prevent hepatotoxicity
Indications for warfarin?
- Prophylaxis of embolism in rheumatic heart disease and AF
- After insertion of prosthetic heart valve
- Venous thrombosis and pulmonary embolism (treatment and prophylaxis)
- Treatment of transient ischaemic attacks
Contraindications of warfarin?
- Within 48 hours post partum
- Haemorrhagic stroke
- Significant bleeding
Cautions with use of warfarin?
- History of GI bleed
- Hyper-hypothyroidism
- Uncontrolled HTN
- Recent ischaemic stroke
- Changes in diet (Vit K intake)
Pregnancy and BF considerations with warfarin?
- Danger of teratogenicity, avoid in 1st trimester (crosses the placenta)
- Safe in breastfeeding
Monitoring requirements for warfarin?
INR up to every 12 weeks
Depending on changes in patient’s clinical condition
Indications for theophylline
- Chronic asthma
- Reversible airyway obsstruction
- Severe acute asthma
Cautions to consider when prescribing theophylline
- Cardiac arrhythmias
- Elderly
- Epilepsy
- HTN
- Peptic ulcer
- Thyroid disorder
How does smoking affect theophylline therapy?
Increases clearance of theophylline
Requires greater dose
Patients stopping/starting smoking need monitoring
Signs of theophylline overdose?
- Vomiting
- Agitation
- Restlessness
- Tachycardia
- Hyperglycaemia
Ideal serum conc. of theophylline
10-20 mg/litre
Adverse effects increase over 20 mg/litre
Monitoring requirements for theophylline
Plasma conc taken 5 days after starting oral treatment
AND
At least 3 days after any dose adjustment
Extra considerations for prescribing theophylline
Maintain patients on specific brands- MR preps differ
Indications for phenytoin
Treatment of:
* Tonic clonic seizures
* Focal seizures
Prevention and treatment of seizures during or following:
* Neurosurgery or severe head injury
* Status epilepticus
Contraindications for phenytoin
- Second/third degree heart block
- Sinus bradycardia
- Stokes-Adams syndrome (sudden, brief loss of consciousness from large drop in cardiac activity)
Cautions for phenytoin use
- Heart failure
- Hypotension
- Respiratory depression
Signs and symptoms of phenytoin overdose
- Nystagmus
- Slurred speech
- Confusion
- Hyperglycaemia
Pregnancy and BF considerations for phenytoin
Increased risk of congenital malformations in pregnancy- dose adjusted depending on plasma conc.
(IF benefits outweigh the risks)
Found in breast milk but not known to be harmful
Monitoring requirements for phenytoin
- Patients of Thai or Han Chinese origins are pre-screened for HLAB*1502 allele. Increased risk of Stevens-Johnson syndrome
- Blood counts
- In IV use, ECG + BP
Indications for ciclosporin
- Keratitis
- Ulcerative colitis
- Rheumatoid arthritis
- Atopic dermatitis
- Organ/bone marrow transplant
Contraindications in ciclosporin use
- Peri-ocular infection (if used in eye)
Systemic use:
* Abnormal renal function
* Uncontrolled hypertension
Cautions in ciclosporin use
- Glaucoma (if used in eye)
Systemic use:
* Hyperuricaemia
* Malignancy
* In the elderly, monitor renal function
Pregnancy and BF considerations for ciclosporin
Avoid in both- crosses placenta and present in milk
Can be harmful
Monitoring requirements for ciclosporin
- Blood conc.
- LFTs
- Potassium
- Magnesium
- Blood lipids
- Kidney function
- BP
Reduce dose if eGFR decreases by more than 25%, dose reduction of 25-50%
Other considerations for ciclosporin use
Patients on oral ciclosporin should be maintained on the same brand due to changes in blood conc.
Indications for gentamicin
- Septicaemia
- Meningitis and other CNS infections
- Biliary-tract infections
- Acute pyelonephritis
- Endocarditis
- Pneumonia (in hospital)
- Adjunct in listerial meningitis
- Prostatitis
How is dose calculated in gentamicin use in obese patients?
Ideal body weight used for obese patients
Contraindications for gentamicin use
IV use:
* Myasthenia gravis
Use in ear:
* Patent grommet (tubes to allow airflow through eardrum)
* Perforated tympanic membrane
Cautions for gentamicin use
- Dose related SE
- Conditions with muscular weakness
- Dehydration must be corrected before treatment
Pregnancy and BF considerations for gentamicin use
Avoid due to risk of auditory and vestibular nerve damage in infant when used in 2nd and 3rd trimester
Monitoring requirements for gentamicin
- Serum conc. in renal impairment as drug is excreted renally
- Auditory and vestibular function
Indications for vancomycin use
- Complicated skin and soft tissue infections
- Bone infections
- Joint infections
- CAP + HAP
- Infective endocarditis
- Acute bacterial meningitis
- Bacteraemia
- C. diff infection
Routes of administration for vancomycin
NOT to be given orally due to lack of absorption
Only given IV and to the ear and eye
Contraindications for vancomycin use
Previous hearing loss with IV use
Cautions for vancomycin use
- Systemic absorption may be enhanced in inflammatory bowel disorders of the intestinal mucosa
Pregnancy and BF considerations for vancomycin use
- Advises only use in pregnancy if benefits outweigh the risk. Monitor blood conc.- essential to reduce risk of fetal toxicity
- Present in breast milk- significant absorption following oral admin. unlikely
Monitoring requirements for vancomycin
- Auditory function
- Blood count
- Hepatic and renal function
- Leucocyte count (risk of neutropenia or agranulocytosis with long term use)
