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Applied Pharmacology > MSK > Flashcards

MSK Flashcards

1
Q

Non-Steroidal Anti-inflammatory Drugs - Examples

A

Naproxen (low risk of CV events)
Ibuprofen (lowest GI effects)
Etoricoxib

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2
Q

NSAIDs - Indications

A

1) Mild-to-moderate pain
(alternate to paracetamol or in addition)

2) Pain related to inflammation
- Rheumatoid arthritis, severe osteoarthritis, acute gout

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3
Q

NSAIDs- MOA

A
  • NSAIDs inhibit prostaglandin synthesis from arachidonic acid by inhibiting cyclo-oxygenase (COX).

COX exists as two main isoforms:

  • COX-1 is the constitutive form. It stimulates prostaglandin synthesis that is essential to preserve integrity of the gastric mucosa; maintains renal perfusion (by dilating afferent glomerular arterioles) + inhibits thrombus formation at the vascular endothelium.
  • COX-2 is the inducible form, expressed in response to inflammatory stimuli. It stimulates production of prostaglandins that cause inflammation and pain.
  • The therapeutic benefits of NSAIDs are principally mediated by COX-2 inhibition and adverse effects by COX-1 inhibition, although there is some overlap between the two. - Selective COX-2 inhibitors (e.g. etoricoxib) were developed in an effort to reduce the adverse gastrointestinal effects of NSAIDs.
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4
Q

NSAIDs - Contraindications

A
  • Severe renal impairment
  • Heart failure
  • Liver failure
  • NSAID hypersensitivity
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5
Q

NSAIDs- Caution

A
  • Peptic ulcer disease
  • GI bleeding
  • CV disease
  • Renal impairment
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6
Q

NSAIDs - Interactions

A

Peptic ulceration:
- Low dose aspirin & corticosteroids

GI bleeding:

  • Anticoagulant - warfarin, DOAC
  • SSRIs - venlafaxine

Renal Impairment:

  • ACEi
  • Diuretics
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7
Q

NSAIDs - Prescription

A
  • Taken orally, there also topical gels, suppositories, injectable
  • Dose dependent on condition, patient choice, safety considerations
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8
Q

NSAIDs - Monitoring

A
  • Assess efficacy by enquiring about symptoms

- Monitor renal function in patients with renal impairment

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9
Q

NSAIDs - Patient Education

A
  • Help improve symptoms of pain, swelling and fever
    Most common SE is indigestion –> seek help
  • Long term use is not recommended, stop if acutely unwell or dehydrated to reduce risk of damage to kidneys.
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10
Q

NSAIDs - Adverse Effects

A
  • GI toxicity
  • Renal impairment
  • Increased risk cardiovascular events
  • Hypersensitivity reaction (bronchospasm & angioedema & fluid retention)
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11
Q

Bisphosphonates - Examples

A
  • Alendronic acid
  • Disodium pamidronate
  • Zolendronic acid
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12
Q

Bisphosphonates - Indications

A

1) 1st line for osteoporotic fragility fractures
2) Severe hypercalcaemia of malignancy –> Pamidronate & zolendronic
3) Myeloma & breast cancer with bone metastases
4) 1st line for metabolically active Paget’s disease (reduce bone turnover & pain)

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13
Q

Bisphosphonates - MOA

A
  • Bisphosphonates reduce bone turnover by inhibiting the action of osteoclasts, the cells responsible for bone resorption.
  • Bisphosphonates have a similar structure to naturally occurring pyrophosphate: hence they are readily incorporated into bone.
  • As bone is resorbed, bisphosphonates accumulate in osteoclasts, where they inhibit activity and promote apoptosis.
  • The net effect is reduction in bone loss and improvement in bone mass.
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14
Q

Bisphosphonates - Adverse Effects

A

Common:

  • Oesophagitis (oral intake)
  • Hypophosphateamia

Rare:

  • Osteonecrosis of the jaw
  • Atypical femoral fracture
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15
Q

Bisphosphonates - Contraindications

A
  • Severe renal impairement (Bisphosphonates are renally excreted)
  • Hypocalcaemia
  • Oral administration in people with active upper GI disorders
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16
Q

Bisphosphonates - Caution

A
  • Smokers

- Dental disease

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17
Q

Bisphosphonates - Interactions

A 
Bisphosphonates bind calcium. 
Their absorption is therefore reduced if taken with:
- calcium salts (including milk)
- antacids
- iron salts
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18
Q

Bisphosphonates - Prescribing

A

For osteporosis:
- alendronic acid - oral intake

For severe hypercalcaemia & bone metastases:
- pamidronate or zolendronic acid - slow IV infusion

19
Q

Bisphosphonates - Monitoring

A

Osteoporosis :

  • check & replace calcium & vit D before treatment
  • DEXA scan every 1-2 years to check bone density

Enquire about symptoms _ bone pain & complications

Safety net about oesophagitis, osteonecrosis of the jaw, atypical femoral fracture.

Monitor calicum & phosphate

20
Q

Bisphosphonates - Patient Education

A
  • Taken whole at least 30 mins before breakfast & plenty of water
  • Remain upright for 30 mins after taking to reduce GI irritation
21
Q

Allopurinol - Indications

A

1) To prevent recurrent attacks of gout.
2) To prevent uric acid and calcium oxalate renal stones.
3) To prevent hyperuricaemia and tumour lysis syndrome associated with chemotherapy.

22
Q

Allopurinol - MOA

A
  • Allopurinol is a xanthine oxidase inhibitor.
  • Xanthine oxidase metabolises xanthine (produced from purines) to uric acid.
  • Inhibition of xanthine oxidase lowers plasma uric acid concentrations and reduces precipitation of uric acid in the joints or kidneys.
23
Q

Allopurinol - Adverse Effects

A

Can trigger or worsen an acute attack of gout.
- can avoid this by co-prescription with NSAID or colchicine

Common:
- skin rash –> mild or more serious hypersensitivity reaction e.g. Stevens-Johnson syndrome or toxic epidermal necrolysis

Rare:
- Allopurinol hypersensitivity syndrome –> e.g. fever, eosinophilia, lymphadenopath

24
Q

Allopurinol - Contraindications

A
  • During acute attack of gout
  • Recurrent skin rash
  • Signs of more severe hypersensitivity to allopurinol
25
Q

Allopurinol - Caution

A

Lower dose for:

  • renal impairment
  • hepatic impairment
26
Q

Allopurinol - Interactions

A
  • The active metabolite (mercaptopurine) of the pro-drug ▴azathioprine is metabolised by xanthine oxidase. Concurrent administration increases the risk of toxicity.
  • Co-prescription of allopurinol with ▴ACE inhibitors or thiazides increases the risk of hypersensitivity reactions
  • With amoxicillin increases the risk of skin rash.
27
Q

Allopurinol - Prescribing

A
  • Orally : start low dose and titrate according to serum uric acid conc
  • For gout: prescribe with NSAID or colchicine for at least 1 month to avoid triggering acute attack (when initiating)
28
Q

Allopurinol - Monitoring

A
  • Serum acid concentration - 4 weeks after intiation or change in dose
  • Lower uric acid conc to > 300 µmol/L
  • Stop if there is a rash
  • Mild rash - reintroduced cautiously once rah resolves
29
Q

Allopurinol - Patient Education

A
  • Taken after meals, maintain good hydration with fluid intake
  • Purpose is to reduce attack of gout
  • Safety net: seek medical advise if they develop a rash
  • Do not stop if they get an acute attack of gout- can make it worse
30
Q

Colchicine - Indications

A

1) Acute Gout
2) Short-term prophylaxis during initial therapy with allopurinol
3) Prevent flare-ups of symptoms of familial Mediterranean fever (FMF) – an inherited inflammatory condition

31
Q

Colchicine - MOA

A

For gout, colchicine works by reducing the inflammation caused by crystals of uric acid in your joints. This also helps to reduce pain.

32
Q

Colchicine - Contraindications

A
  • Blood disorders
33
Q

Colchicine - Caution

A
  • Cardiac disease
  • Elderly
  • Gastro-intestinal disease
34
Q

Colchicine - Caution

A
  • Cardiac disease
  • Elderly
  • Gastro-intestinal disease
  • Renal & hepatic impairment
35
Q

Colchicine - Interactions

A
  • Amiodarone
  • Erythromycin
  • Simvastatin - rhabdomyolysis
  • Antiviral
  • Verapamil or diltiazem
36
Q

Colchicine - Monitoring

A
  • Monitor symptoms & side effects
37
Q

DMARD : Methotrexate -

Indications

A

1) As a disease-modifying treatment for rheumatoid arthritis.

38
Q

DMARD : Methotrexate -

MOA

A
  • Methotrexate also has anti-inflammatory and immunosuppressive effects.
  • These are mediated in part by inhibition of inflammatory mediators such as interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-α, although the underlying mechanisms are not fully understood.
39
Q

DMARD : Methotrexate -

Adverse Effects

A
  • Mucosal damage (sore mouth, GI upset)
  • Bone marrow suppression (neutropenia, increased risk of infection)

Rare:

  • hypersensitivity reactions (cutaneous reaction, hepatitis or pneumonitis)
  • Long- term use : hepatic cirrhosis & pulmonary fibrosis
  • Accidental overdose: if given daily
40
Q

DMARD : Methotrexate -

Contraindications

A
  • Pregnancy: methotrexate is teratogenic
  • Severe renal impairment
  • Abnormal liver function due to it causing hepatotoxicity.
41
Q

DMARD : Methotrexate -

Interactions

A

Methotrexate toxicity:
if prescribed with drugs inhibiting its renal excretion e.g. NSAIDs, penicillins

Increase risk of haematological abnormalities :
- Co prescription with other folate antagonists e.g. trimethoprim & phenytoin

Neutropenia:
- combined with clozapine

42
Q

DMARD : Methotrexate -

Prescribing

A
  • Prescribed by only specialists
  • Oral
  • Folic acid can be given to limit adverse effects.
  • Given once-weekly
43
Q

DMARD : Methotrexate -

Monitoring

A
  • Efficacy monitored by symptoms, examination & blood test (inflammatory markers)
44
Q

DMARD : Methotrexate -

Patient Education

A
  • Improve swollen painful joints -may take time for maximal effect
  • Taken ONCE A WEEK

Safety Net: seek help if:

  • sore throat or fever (infection)
  • Bruising or bleeding ,
  • Nausea, Abdo pain or dark urine (liver poisoning)
  • Breathlessness (lung toxicity)

Advice about contraception.

Patients should receive a methotrexate treatment booklet & warning card.

Applied Pharmacology (11 decks)

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