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EXAM 1 > NSAIDS, MTX, LEFLUNOMIDE, CICLOSPORIN THERAPEUTICS > Flashcards

NSAIDS, MTX, LEFLUNOMIDE, CICLOSPORIN THERAPEUTICS Flashcards

1
Q

What is the oral dose for Leflunomide for RA?

A

Oral - 100 mg OD for 3 days (loading dose)
* Then, DECREASE to 10-20 mg OD

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2
Q

When would you start seeing effects for Leflunomide AND maximal effects?

A
  • The effect starts after 4-6 weeks and may further improve up to 4-6 months
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3
Q

What monitoring’s are required for Leflunomide?

A

Liver function tests (LFT), full blood count (FBC) and BP
* Prior to initiation
* Every 2 weeks for the first 6 months
* Then, every 8 weeks

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4
Q

What are the common side-effects of Leflunomide?

A
  • GI
  • Alopecia
  • Skin reactions
  • Dizziness
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5
Q

What are the SEVERE side-effects of Leflunomide?

A
  • Hepatic impairment
  • Bone marrow suppression – leucopoenia, anaemia, thrombocytopenia, pancytopenia
  • Increased BP (Common)
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6
Q

What are the contraindications (people) of Leflunomide?

A
  • Hepatic impairment – accumulation
  • Severe immunodeficiency
  • Severe infection
  • Severe hypoproteinaemia
  • Moderate to severe renal impairment – no data
  • Pregnancy
  • Breastfeeding
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7
Q

When giving Leflunomide what groups of people should be closely monitored?

A
  • Haematotoxic or hepatotoxic drugs
  • People with History of TB
  • Bone marrow suppression –
    anaemia, leucopenia, thrombocytopenia
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8
Q

What additional advice should be given to patients on Leflunomide?

A
  • Avoid live vaccines
  • Avoid alcohol (increase risk of hepatic impairment)
  • Can be taken with or without food
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9
Q

What is procedure is carried out after Leflunomide is discontinued?

A
  • Monitoring after discontinuation is required
  • Washout procedure –
  • Stop treatment
  • Give colestyramine 8 g TDS or activated charcoal 50g QDS
  • Treat for 11 days
  • The active metabolite has a long half life – 1-4 weeks
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10
Q

What class of drug is Ciclosporin?

A

Calcineurin inhibitor

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11
Q

What diseases can Ciclosporin be used for?

A
  • Inflammatory bowel disease
  • Immunosuppressive therapy in transplant patients (SOT and bone marrow)
  • Psoriasis
  • Severe atopic dermatitis
  • Rheumatoid arthritis
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12
Q

How is Ciclosporin given?

A

PO, IV

  • Doses vary greatly for the different conditions - Doses are often titrated
  • Balance between effective treatment and tolerability/adverse effects
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13
Q

What are the common side-effects of Ciclosporin?

A
  • GI, fatigue, convulsions, headache, muscle cramps, tremor,
    hyperG, hyperL, hyperK, hyperuricaemia
    hypoM, HP, hirtsutism, Hypertrichosis, hepatic impairment,
    renal impairment, leucopenia
  • Other important side effects –
  • Immunosuppression
  • Immunosuppression – lymphomas and malignancies (esp. skin)
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14
Q

Who is Ciclosporin Contraindicated in ?

A
  • Abnormal Renal function
  • Malignancy
  • Uncontrolled hypertension
  • Uncontrolled infection
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15
Q

What are the cautions for Ciclosporin?

A
  • Elderly
  • Gout
  • Hepatic impairment
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16
Q

What would be monitored when taking Ciclosporin?

A
  • Renal function
  • Hepatic function
  • BP
  • Lipids
  • Electrolytes – potassium, magnesium,
  • Uric acid
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17
Q

What are some interactions with Ciclosporin?

A
  • CYP450 inhibitors – macrolides, diltiazem, verapamil, lercanidipine, fluconazole,
    itraconazole, ketoconazole, grapefruit juice → ↑blood ciclosporin levels
  • CYP450 inducers – rifampicin, carbamazepine, phenobarbital, phenytoin, St. John Wort
    → ↓ blood ciclosporin levels
  • Statins – avoid or dose reductions
  • Nephrotoxic drugs – NSAIDs, MTX
  • Any drugs causing effects as seen with ciclosporin
  • i.e. K+ sparing diuretics
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18
Q

What is the difference in IV and Oral preparations?

A
  • The oral dose of ciclosporin is approximately 3 times that of the IV formulation

Specific information relating to the oral solution -
* Required dose should be mixed with orange or apple juice immediately before
administration

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19
Q

What advice should be given to patients taking Ciclosporin?

A
  • Twice a day preparation
  • Should be maintained on the same brand of ciclosporin
  • Consistency of administration – time of day and proximity to food
  • Avoid live vaccines
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20
Q

What is the frequency of administration for Methotrexate?

A

Once a week

  • On the same day of the week – documented in full on the prescription
  • Patient should be appropriately educated about the dosing schedule
  • Dose and frequency should be clear on the label
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21
Q

What strength should be prescribed for Methotrexate?

A

The strength of tablet should be prescribed as a single strength of tablet, only
2.5mg should be used

– low dose MTX

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22
Q

What are the different ways that Methotrexate can be given?

A

Oral (Po), intramuscular (IM), subcutaneous (SC)

  • There are slight differences in dosing for different immune diseases and when
    using different routes
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23
Q

What is the time of effect for Methotrexate?

A

Generally it will take some time for MTX to start to have it’s effect and for that effect to be at a maximum * i.e. for RA it can take 6 weeks to begin to work and 12 weeks to feel the maximum effect

  • In RA, dose escalation is required to reach the optimal dose
  • 2.5mg to 5mg increases every 1-3 weeks
  • Aim for optimal dose in 4-6 weeks
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24
Q

What is the baseline assessment for Methotrexate in starting therapy?

A
  • Full blood count (FBC)
  • Liver function test (LFT)
  • Renal function (creatinine, Cr or estimated glomerular filtration rate, eGFR)
    = every 1-2 weeks until therapy stabilised
  • Once stabilised – every 2-3 months
  • Urea and electrolytes (U&E)
  • Chest x-ray
25
Q

What monitoring’s should patients and carers carry out?

A
  • Signs of an infection i.e. sore throat, bruising, bleeding – indicating blood disorders
  • Nausea, vomiting, abdominal discomfort and dark urine – indicating liver toxicity
  • Shortness of breath – indicating respiratory effects
26
Q

What are the key side-effects of Methotrexate?

A
  • Bone marrow suppression
  • GI toxicity
  • Liver toxicity
  • Pulmonary toxicity
  • Skin reactions
27
Q

What are the key contraindications for Methotrexate?

A
  • Active infection
  • Severe renal impairment
  • Hepatic impairment
  • Bone marrow suppression
  • Immunodeficiency
  • Pregnancy and breast feeding
28
Q

What are the key cautions for taking Methotrexate?

A
  • Surgery
  • Renal impairment
  • Diarrhoea
  • Ascites
  • Peptic ulcer
29
Q

What should be co-prescribed with Methotrexate, what does it do and what is the dose?

A

Folic acid – Should be co-prescribed

5 mg OD (1 to 6 days a week, not MTX day)

Reduce the risk of hepatotoxicity and GI side effects

30
Q

What is the amount of supply, what happens if you miss a dose of Methotrexate and what vaccines are recommended?

A
  • Amount to supply – Supply only the required amount of MTX and folic acid
  • Missed doses - Dose can be taken within 2 days

pneumococcal and influenza

31
Q

What interactions are there between Methotrexate and other drugs?

A
  • Anti-folates – co-trimoxazole, trimethoprim
  • NSAIDs
  • Live vaccines
  • Ciclosporin
32
Q

Who should patients inform when taking Methotrexate?

A
  • Inform all HCP of MTX use

Patients should also receive and carry a methotrexate card with them at all times.

33
Q

What is Paracetamol used for and what are the special patient groups?

A

Mainly used for pain and as an antipyretic

Paracetamol does NOT have significant anti-inflammatory effect (although
central action on COX enzymes is postulated)

Special patient groups:
* Children
* Low body weight (<50 kg)
* Liver impairment (or those with risk factors for hepatotoxicity)

34
Q

What are the Preferred analgesic over NSAIDs for?

A
  • Elderly (need to consider weight)
  • Patients with: hypertension, CVD, renal impairment, GI issues
  • Patients on medicines interacting with NSAIDs, i.e. warfarin
35
Q

What are the available preparations for Paracetamol?

A
  • Tablet, caplet, capsule, orodispersible tablet (need to consider requirements of sale)
  • Suspension (need to consider the concentration and licensing)
  • Suppositories
  • Infusion
  • Compound preparations – co-codamol (paracetamol and codeine), co-dydramol
    (paracetamol and dihydrocodeine), OTC preparations – Lemsip etc.
36
Q

What class of drug is Aspirin and what is its loading dose?

A
  • Antiplatelet – 75 mg – 300 mg daily (loading dose dependent on indication)
  • No anti-inflammatory effect
37
Q

What is the standard dose of paracetamol as an analgesic?

A
  • Analgesic – Standard oral dose: 300-900 mg every 4 – 6 hours when required
    (max. 4 g per day)
  • Rarely used now in inflammatory conditions
38
Q

What are the special groups for Aspirin?

A
  • Contraindicated in children under 16 (except when specifically indicated - Kawasaki
    syndrome)
  • Contraindicated in patients with: previous or active peptic ulcerations, bleeding
    disorders, severe cardiac failure, previous hypersensitivity to aspirin or NSAID
  • Elderly
  • Caution in patients with: asthma
39
Q

What are the interactions of Aspirin?

A
  • Drugs that increase the risk of GI irritation and bleeding – steroids, NSAIDs, SSRI’s,
    anticoagulants
  • Drugs that increase the risk of renal side effect – Bisphosphonates
  • Drugs where aspirin can increase the toxicity of other drugs – Methotrexate
40
Q

What are the different preparations of Aspirin?

A
  • Tablet, EC, dispersible (need to consider requirements of sale)
  • Suppositories
  • Compound preparations – Beechams powders (aspirin/caffeine), codis 500
    (aspirin/codeine), Alka-seltzer (aspirin/sodium bicarbonate)
41
Q

What are the different effect times for analgesics and anti-inflammatory?

A
  • Analgesic effect starts soon after first administration and full effect obtained within a
    week
  • Anti-inflammatory effect may not be achieved for up to 3 weeks
  • The difference in anti-inflammatory effect of the NSAIDs is small
  • Considerable variation in individual response and tolerance
42
Q

How should NSAID selection be based on?

A
  • Selection of an NSAID should be based on the characteristics of the drug and
    individual patient risk factors for adverse effects
43
Q

What are the key side-effects of NSAIDs?

A
  • GI mucosa
  • Kidney
  • Cardiovascular system
44
Q

What is the most IMPORTANT things about NSAIDS in terms of dose and DOA?

A

If an NSAID is indicated, the LOWEST
effective dose should be used for the
SHORTEST duration

45
Q

What are the GI side-effects of NSAIDs?

A

Epithelial damage, ulceration and bleeding
* Caused by:

  1. Suppression of physiological homeostatic prostanoid (COX-1) inhibition
    * Reduced mucus production
    * Reduced bicarbonate production
    * Reduced mucosal blood flow
  2. Topical irritation and direct epithelial damage
46
Q

What are the Selective COX-2 agents designed to do?

A
  • Selective COX-2 agents – coxibs – designed to inhibit those prostanoids of
    COX-2 isoform (involved with inflammation and less important in GI
    homeostatic roles).
  • Lower risk of upper GI s/e than non-selective NSAIDs
47
Q

Name an example of a drug in each risk category for NSAIDs?

A
  1. Highest risk: Ketoprofen, Ketorolac, Piroxicam
    COX-2 Inhibitors, ibuprofen 2.4g or more daily (CV event)

2.Intermediate risk: Indometacin, Diclofenac, Naproxen

  1. Lowest risk: ibuprofen (low dose, up to 1.2 g)
    (Lowest risk: Coxibs)

Lowest risk agent preferred,
to start at lowest dose and
not used with another
NSAID

48
Q

What are the KEYPOINTS of GI side effects in NSAIDs?

A
  1. Lowest risk agent preferred
  2. Start at lowest dose
  3. Use for the shortest duration (review need)
  4. Do not use more than one NSAID at a time
  5. Advise medication to be taken with food to reduce contact
    irritation
  6. Co-prescribe with gastroprotection in those patients at risk of GI
    ulceration, i.e. PPI
  7. Monitor for adverse events
  8. Review patient for risk factors
49
Q

What are the interactions of NSAIDs?

A
  • Aspirin
  • NSAIDs
  • Other drugs increasing the risk of GI ulceration and bleeding – steroids, bisphosphonates
  • Other drugs increasing the risk of bleeding: serotonin reuptake inhibitors
    (SSRI’s), anticoagulants
50
Q

What are the monitoring requirements for NSAIDs?

A
  • Reported symptoms of dyspepsia/GI irritation
  • Hb
  • Signs of GI bleeding – haemoptysis, dark stools
51
Q

What drug is classed as low thrombotic risk?

A

Naproxen (1g daily)

52
Q

What are the KEYPOINTS for CV events for NSAIDs?

A
  1. NSAID selection
  2. Use lowest effective dose
  3. Use for the shortest duration (review need of long term therapy)
  4. Monitor for adverse events
  5. Review patient for risk factors
53
Q

COX-2 inhibitors, Diclofenac and high dose Ibuprofen are indicated in what disease?

A

Ischaemic heart disease

Cerebrovascular disease

Some stages of heart failure

54
Q

What interactions occur in NSAIDs for CV event?

A
  • Antihypertensives (opposite effect)
  • Antiplatelet dose aspirin (75 mg)
55
Q

What monitoring’s are required for NSAIDSs in CV event?

A
  • Increase occurrence or first occurrence of CV event
  • Risk factors for increased CV risk – BP, medical history of diabetes /hypercholesterolaemia
56
Q

When are Renal side-effects seen in patients that are taking NSAIDs?

A

Mainly seen in individuals where compensatory prostaglandins are playing a role to maintain renal function, i.e. advanced age, renal impairment, heart failure, volume depletion, liver cirrhosis

Through effects on the kidney, NSAID use can cause:
*Decrease renal blood flow and increase the risk of acute kidney injury
* Sodium and water retention – oedema and hypertension

57
Q

What drugs prescribed together can cause renal interaction side-effects?

Monitoring’s that should be carried out?

A
  • Co-prescribed nephrotoxic medicines – diuretics, ACE-inhibitors
  • Anti-hypertensive – (opposite effect)
  • Lithium and methotrexate – decreased renal elimination causing toxicity
  • Renal function – GFR, urine output, urea
  • BP
  • Electrolytes – sodium and potassium
  • Oedema (weight, visual signs)
58
Q

What are the Counselling points when taking NSAIDs?

A

Take the lowest effect dose for the shortest period
Take with or after food
Self monitor for signs of GI disturbance – report
Do not self medicate with other NSAIDs or aspirin

EXAM 1 (14 decks)

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