Drug consent Flashcards
Indications for methotrexate
And mechanism
Inflammatory arthritis, especially rheumatoid
Psoriasis
Some chemo eg ALL
Inhibits dihydrofolate reductase
Contraindications and interactions of methotrexate
Contraindic: men and women need to avoid pregnancy for >6 months after treatment has stopped
Interactions: trimethoprim or co-trimoxazole incr risk of marrow aplasia
High dose aspirin incr risk of methotrexate toxicity 2ndary to reduced excretion
** treatment of methotrexate toxicity is folinic acid**
Adverse effects of methotrexate
Mucositis
Myelosupression
Pneumoniitis
Pulmonary fibrosis
Liver fibrosis
Prescribing and monitoring methotrexate
Taken weekly, with folic acid 5mg once weekly coprescribed, to be taken on a different day.
FBC, U&Es and LFTs should be regularly monitored: weekly until therapy stabilised then every 2-3 months
Bisphosphonates clinical use
Inhibit osteoclasts by reducing recruitment and promoting apoptosis
Use:
- prevention and treatment of osteoporosis
- hypercalcaemia
- Paget’s disease
- pain from bone metastases
Adverse effects of bisphosphonates
Oesophagitis, oesophageal ulcers (esp with alendronate)
Osteonecrosis of the jaw (especially if IV in treatment of cancer. poor dental hygiene also a risk factor)
Incr risk atypical stress fractures of proximal femur
Acute phase following administration: fever, myalgia and arthralgia
Hypocalcaemia - usually unimportant
Advice for patients taking oral bisphosphonates
- Swallow tablets whole
- with plenty of water
- whilst sitting or standing
- on an empty stomach
- at least 30 mins before breakfast or another oral med
- stand or sit upright for 30 mins after taking
Correct hypocalcaemia/low vit D before giving bisphosphonates.
Indications for denosumab rather than oral bisphosphonates
Alendronate first line, then alternative oral eg risedronate.
Following this then only if certain criteria are met then increasing role for denosumab
Inhibits RANKL, generally well tolerated (other than dyspnoea and diarrhoea), given sc every 6 months.
Statin mechanism
Inhibit action of HMG-CoA reductase, rate limiting enzyme in hepatic cholesterol synthesis
Indications to take statin
All patients with established cardiovascular disease (stroke, TIA, ischemic heart disease, peripheral arterial disease)
Anyone with 10 year cardiovascular risk >10%
Patients with type 1 DM who were diagnosed >10 years ago or are age >40 or have established neuropathy
What statin and when
Take at night as this is when majority of cholesterol synthesis occurs. Esp Simvastatin as has shorter 1/2 life
Generally atorvastatin 20 for primary prevention
Atorvastatin 80mg for secondary prevention
Adverse effects of statins
Myopathy: myalgia, myositis, rhabdo etc. risks: increasing age, female, low BMI. more in simvastatn and atorva than pravastatin etc
Check LFTs at baseline, 3 months and 12 months for liver impairment. Discontinue if ALT rise and remain at 3x ULN
Contraindications for statins
Pregnancy
Macrolides (erythromycin/clarithromycin) potential interaction and should hold statins whwilst taking
Avoid if history intracerebral haemorrhage (mixed evidence)
, DOAC, steroid, , insulin, inhalers
Metformin mechanism
Acts via AMP-activated protein kinase
Increases insulin sensitivity, and decreases hepatic gluconeogenesis.
First line for type 2 diabetes. also used in PCOS and NAFLD
Adverse effects of metformin
GI upset common (nausea, anorexia, diarrhoea) and intolerable in 20%
Reduced vit B12 absorption - rarely a clinical problem
Lactic acidosis with severe liver disease or renal failrue - rare but important
Contraindications to metformin
Chronic kidney disease ( review when eGFR <45, and stop when <30)
Periods of tissue hypoxia, eg recent MI, sepsis, AKI and severe dehydration as incr risk lactic acidosis
Iodine containing contrast media, as incr risk provoking renal impairment
Alcohol abuse is relative contraindication
Starting metformin
Titrate up slowly to reduce incidence of GI side effects
If unacceptable SE, then consider modified release metformin
important steroid counselling re withdrawal
If on long term steriods, double dose in intercurrent illness
Longer term systemic steroids suppress natural production of endogenous. Withdrawing suddenly may precipitate Addisonian crisis
gradual withdrawal for: >40mg pred daily for >1 week, >3 weeks of treatment, or recently received repeat courses
warfarin mechanism
Oral anticoagulant
Inhibits enzyme reducing vitamin K to its active form
Vit K normally acts as cofactor in carboxylation of clotting factors II, VII, IX and X (1972), and protein C.
Indications for warfarin
Mechanical heart valves.
- mitral valves generally need higher INR than aortic
Second line after DOACs. VTE: target INR = 2.5, if recurrent = 3.5.
- AF: target INR = 2.5
Warfarin monitoring
INR ( ratio of prothrombin time for patient over normal prothrombin time)
Initially daily or alternate days until within therapeutic range.
Then twice weekly for 1-2 weeks. then weekly until at least 2 measurementts are within range
Thereafter, approx once every 3 months, depending on local protocols
How to take warfarin
Usually once a day in the evening. Take around the same time each day.
This is so if neeed to change dose after a blood test can do the same day rather than waiting until the morning
does not normally upset stomach so can take with or without food.
Things which may potentiate warfarin
liver disease
P450 enzyme inhibitors, eg amiodarone, ciprofloxacin
cranberry juice
Drugs displacing warfarin from plasma albumin eg NSAIDs
Drugs inhibiting platelet function eg NSAIDs
