MSK pharmacology Flashcards
Allopurinol
Common indications
Mechanism of action
Important adverse effects
Warnings
Important interactions
Allopurinol
Common indications
- Gout-CKD, uric acid stones, tophi
- tumour lysis syndrome-side effect of chemotherapy to prevent hyperuricaemia
Mechanism of action
- xanthine oxidase inhibitor-inhibit conversion of xanthine into uric acid
Important adverse effects
- skin reactions like steven johnson’s syndrome, toxic epidermal necrosis
- drug hypersensitivity reactions-fever, eosinophilia, lymphadenopathy and organ dysfunction
- worsen acute attack of gout
Warnings
- not to be given in those with recurrent skin reactions
- not to be given in those with known hypersensitivity reactions
- not to be given in acute attacks
- drug dose lowered in hepatic and renal impairment
Important interactions
- not given with azathioprine and mercaptopurine (both metabolised by xanthine oxidase)-> azathioprine and allopurinol can cause bone marrow suppression
- not to be given with amoxicillin-> trigger skin reaction
- not to be given with ACE inhibitors or thiazides-> trigger drug hypersensitivity reaction
Aminosalicylates
Common indications
Mechanism of action
Important adverse effects
Warnings
Important interactions
Aminosalicylates (mesalazine and sulfasalazine)
Common indications
- mesalazine used in ulcerative colitis (topical)
- rheumatoid arthritis as DMARD
Mechanism of action
- broken down to release 5ASA (5-aminosalicylate acid) which is anti-inflammatory and immunosuppressive, therefore given topically instead of systemically
Important adverse effects
sulfasalazine has more side effects than mesalazine
- GI side effects like nausea, vomiting, dyspepsia
- headache
- haem-leucopenia, thrombocytopenia
- renal impairment
- oligospermia (sulfasalazine)
- serious hypersensitivity reaction causing fever, rash, liver impairment
Warnings
- not to be given with those with aspirin hypersensitivity (aspirin is also a salicylate acid)
Important interactions
- mesalazine has a pH sensitive coating hence if patient is on PPIs (increase pH)-> premature breakdown of mesalazine
methotrexate
Common indications
Mechanism of action
Important adverse effects
Warnings
Important interactions
methotrexate
Common indications
- rheumatoid arthritis (w prednisolone)
- cancers-leukemias, lymphomas etc
Mechanism of action
- inhibit dihydrofolate reductase that converts folic acid into tetrahydrofolate acid-> DNA and protein synthesis-> needed for cell replication hence used in cancers
- anti-inflammatory-> used in rheumatoid arthritis
Important adverse effects
- GI side effects (mucositis-damage to mucosa in GI tract)
- pulmonary fibrosis and hepatic cirrhosis
- drug hypersensitivity reactions like pneumonitis, hepatitis
- dangerous in overdose-> cause seizures and hepatic/renal impairment. Person should be given folinic acid which can be converted into folate.
Warnings
- not to be given in pregnancy since it is highly teratogenic-> stop 6 months before
- not to be given in renal/hepatic impairment
Important interactions
- not to be given with NSAIDs/penicillins-> inhibit renal excretion
- not to be given with other folate antagonists like trimethroprim
- not to be given with clozapine due to risk of neutropenia
NSAIDS (ibuprofen, naproxen)
Common indications
Mechanism of action
Important adverse effects
Warnings
Important interactions
NSAIDs (ibuprofen, naproxen)
Common indications
- mild to moderate pain-alternative to paracetamol
- acute inflammatory reactions-osteoarthritis, rheumatoid arthritis, acute gout
Mechanism of action
- inhibit cyclo-oxgenase-COX1 (protecting gastric mucosa); COX2 (inflammation)
Important adverse effects
- renal impairment
- GI toxicity; GI peptic ulcers and bleeding
- Cardiovascular events like MI and stroke
- NSAID hypersensitivity reactions like angiooedema
- Fluid retention
Warnings
- Not to be given in renal impairment
- not to be given in Hepatic impairment
- or hypersensitivity reactions
- not to be given with that w hypertension or heart failure due to risk of fluid retention
Important interactions
- aspirin and corticosteroids worsen GI effects
- ACE inhibitors worsen renal effects
Quinine sulfate
Common indications
Mechanism of action
Important adverse effects
Warnings
Important interactions
Quinine sulfate
Common indications
- leg cramps
- plasmodium falciparum malaria
Mechanism of action
- inhibit acetylcholine stimulation at motor end plate
- kills plasmodium falciparum parasite
Important adverse effects
- tinnitus, hearing loss, blindness
- GI upset
- hypersensitivity reactions
- G6PD reactions
- prolong QT interval
- hypoglycaemia
Warnings
- not to be given in pregnancy as it is highly teratogenic
- not to be given in those with G6PD/long QT syndrome
- or those with hearing/visual loss
Important interactions
- not to be given in those with drugs that prolong QT interval
A 66-year-old woman with severe chronic pain takes amitriptyline, ibuprofen, morphine, omeprazole and senna.
Which of her medications acts by enzyme inhibition?
- amitryptiline
- ibuprofen
- morphine
- omeprazole
- senna
- Ibuprofen (NSAID inhibit COX)
A 63-year-old man with gout, hypertension and hypercholesterolaemia complains of swelling and pain in his left big toe. His GP makes a diagnosis of acute gout. His regular medications are allopurinol, amlodipine, indapamide, ramipril and simvastatin.
What drug could be stopped or substituted to reduce the risk of future attacks of gout?
- allopurinol
- amlodipine
- indapamide
- ramipril
- simvastatin
- Indapamide
33.
A 63-year-old woman, who is an inpatient, complains of headache, nausea and sore mouth. She was admitted 2 weeks ago with a fracture of her left femoral neck. She has a past medical history of rheumatoid arthritis.
Blood tests reveal new renal and liver impairment and pancytopenia. Reviewing her drug chart, you notice that her methotrexate has been prescribed daily instead of weekly.
What is the most appropriate immediate treatment for her methotrexate toxicity?
- activated charcoal
- folic acid
- folinic acid
- granulocyte stimulating factor
- haemodialysis
- Folinic acid which can be converted to TH4. methotrexate often inhibits dihydrofolate reductase
C. Folinic acid. Methotrexate inhibits the enzyme dihydrofolate reductase, which converts dietary folic acid to tetrahydrofolate (FH4). FH4 is required for DNA and protein synthesis. Folinic acid is readily converted to FH4 (without the need for dihydrofolate reductase) and is therefore useful in methotrexate toxicity. Folic acid cannot be used as in the absence of dihydrofolate reductase activity, it cannot be converted to FH4 and is therefore not metabolically useful.
Activated charcoal is only useful where poisons have been recently ingested (e.g. within 1 hour). Toxicity in this case has occurred over weeks. Haemodialysis is not useful in removing methotrexate from the circulation, although may be necessary when managing the associated renal failure. Granulocyte colony stimulating factor (G-CSF) has been used in the treatment of neutropenia due to methotrexate toxicity, but is not routinely part of initial management.
Methotrexate toxicity may be very serious and its management is complex. Advice should be sought from a poisons centre.
