Musculoskeletal pharmacology Flashcards
What effect do COX-1 prostaglandins have?
Renal homeostasis, gastric mucosal protection, platelet function.
What effect do COX-2 prostaglandins have?
Inflammatory effects - promotes pain, fever, vasodilation, block platelet aggregation
What prostaglandin is used for IOL?
Misoprostol
What are non-selective NSAIDs?
Inhibit both COX-1 and COX-2 enzymes which blocks the synthesis of prostaglandins.
What is an example of a non-selective NSAID?
Ibuprofen, naproxen
What are the ADRs of non-selective NSAID use?
- peptic ulcer due to decrease in mucus secretions
- kidney issues due to decrease in GFR
- Increased bleeding time due to platelet function decreased
What are the ADRs of selective COX-2 inhibitors?
- Increase risk of CVD complications
- dose/time dependent HTN effects
- renal insufficiency
What are 2 examples of selective COX-2 inhibitors?
Meloxicam
Celecoxib
An allergy to ________ or other NSAIDs is a contraindication for selective COX-2 inhibitor use.
Sulphonamides (OHA)
When the COX-2 enzyme is blocked the blood vessels ________, this results in ____tension
vasoconstrict, hypertension.
What are sign of decreased renal function from NSAID use?
unexplained weight gain, oedema, swelling feet or reduced urine output.
If a pt has a risk of GI issues a classic NSAID should be combined with which drug?
Anti-ulcer medication
Why do NSAIDs need to be avoided when pt is taking anticoagulants and corticosteroids?
Decreased platelet aggregation which leads to bleeding. The effects of anticoagulants and corticosteroids would be magnified.
What is a DMARD?
Disease Modifying Anti-Rheumatic Drug.
An anti-inflammatory and immunosuppressant.
What is the 1st line DMARD??
MTX (methotrexate.
What is MTX used for?
Anticancer (antineoplastic) drug and immunosuppressant so can be used for RA. It is the gold standard RA treatment.
MTX is a _____ antagonist.
folic acid.
MTX has a fast/slow onset.
fast.
How does MTX work?
Stops DNA synthesis and blocks reproduction of immune cells. It also decreases damage to the joints.
What can alleviate MTX ADRs?
folic acid.
Can MTX be taken during pregnancy?
No, as it is a folic acid antagonist it can cause neural tube defects.
Why is folic acid important?
It is a key material for RBC production.
What are the ADR of MTX?
- hepatoxicity
- stomatitis (due to folic acid antagonism)
- bone marrow suppression
- alopecia
MTX can cause ______, ______ and ______ due to bone marrow suppression.
anaemia, thrombocytopenia, infections
_____, an anti-seizure drug, cannot be co-prescribed with MTX.
Phenytoin
______, _____ and ______ function should be monitored when on MTX.
haematology, hepatic and renal
True/False: Taking folate supplement on the same day as MTX reduces ADR.
Folate should be taken on a different day
What is the antidote for MTX OD?
Leucovorin.
What is the management of OA?
- paracetamol
- NSAID + antiulcer OR COX-2 inhibitor
- short term intra-articular corticosteroid injection
What is the management of RA?
- Pain management - simple analgesics or NSAID
- DMARDs - to slow progression.
- biological DMARDs (bDMARDs)
- low dose corticosteroid therapy.
What is the second line DMARD?
Gold compound chrysotherapy - Auranofin.
What is a bDMARD?
- TNF a-antagonist: etanercept (ETN)
- Cytokine modulators: abatacept
When is bDMARD used?
severe or established RA
How does Auranofin work?
Modifies the immune response by affecting the migration of immunocompetent cells to sites of inflammation.
Why is Auranofin 2nd line treatment for RA?
It has a slower onset.
What are the 3 things that corticosteroids INCREASE?
- fluid retention
- Vasoconstriction (hypertension)
- Blood glucose levels
What are the 3 things that corticosteroids DECREASE?
- Immune suppression
- Bone density (osteoporosis)
- Potassium (hypokalaemia - CV issues)
What is an example of a corticosteroid?
Dexamethasone.
How do corticosteroids work?
- reduce infiltration and activity of inflammatory cells
- reduce synthesis of inflammatory mediators
What do corticosteroids do to blood vessels?
decrease permiability
what do corticosteroids do to immune cells, tissues and organs?
Anti-inflammatory effect
Immunosuppressant
anti-allergy
2ndary pain relief
What effect do corticosteroids have on the skin?
thinning
What effect do corticosteroids have on the metabolism?
Can produce a Cushing’s appearance.
Increase BGL, weight and fluid retention
What is the management for osteoporosis?
- Ca
- Vit D
- Bisphosphonates (Alendronate)
- Exercise
How does oestrogen effect bone density?
Oestrogen promotes osteoblasts (bone rebuilding). So reduced oestrogen can decrease bone density by throwing off the clast:blast balance.
What regulates bone metabolism?
Ca, Vit D, PTH
What affects Ca absorption?
Vit D, PTH and oxalic acid
What are the ADR of Ca?
renal calculi, GI upset
Can Ca be administered IM or SC?
Never. Can be given IV but pt must have cardiac monitoring.
What is the active form of Vitamin D?
Calcitriol
What is Calcitriol?
a fat soluble hormone formed in the kidney. The active form of Vit D.
How does Calcitriol work?
- Stimulates Ca and PO absorption from the sml intestine and REabsorption from the kidneys.
- regulates Ca levels
- regulates bone mineralisation.
How do you get Vit D?
The sun or supplementation
___ and ____ converts to Calcitriol in the liver and kidneys.
D3 or D2
True/False: D3 and D2 are active forms of Vit D
False.
Those with renal dysfunction may be at risk of ______ if given high dose of Vit D.
hypercalcaemia
What serum and urine levels should be monitored when pt is taking vit D?
Ca, K, phosphate.
What antacids need to be restricted when taking Vit D?
Mg based antacids
What are the indications or Vit D?
Rickets/osteomalacia
osteoporosis
When are bisphosphonates indicated?
Osteoporosis in post-menopausal women.
Paget’s disease.
What is an example of a bisphosphonate?
Alendronate.
How does Alendronate work?
Blocks the breakdown of bone and prevent reabsorption.
What are the ADR of alendronate?
GIT upset, oesophageal erosion, muscle/bone pain.
What is the major consideration when taking alendronate?
Take with a full glass of water and remain upright for 30mins to avoid oesophageal erosion.
What dental condition can result from alendronate?
Osteonecrosis jaw. ONJ. This can occur if dental procedures done during treatment.
What is a sign of Aspirin toxicity?
Tinitis
Which non-selective or COX-2 inhibitor NSAID have a greater adverse effect on cardiovascular system?
COX-2 inhibitor. Increase risk of CVD complications such as thrombus formation.
When taking MTX, what is a dry cough a sign of?
pneumonitis
