Gout, Migraine

Question 1

Rheumatoid arthritis

• disease
• treatment

Answer 1

• auto-immune disease = + immune cells active = + cytokines needed to communicate with them
• count number of inflamed joints before and after treatment to see if it was effective
• treatment: act on immune cells directly
• Traditional DMARs - monotherapy (leflunomide) or combination therapy
• Glucocorticoids combined with DMARDs

Question 2

Anti-rheumatic drugs

Answer 2

• NSAIDs
• Non-biologic disease modifying anti-rheumatic drugs (DMARDs) – methotrexate, leflunomide, sulfasalazine, gold salts
• Biologic disease modifying anti-rheumatic drugs (DMARDs) - abatacept, rituximab, tocilizumab, anakinra, adalimumab, etanercept, infliximab

Question 3

Methotrexate

-mechanism of action (4)

Answer 3

• inhibits enzymes involved in the purine metabolism, leading to accumulation of Adenosine, which is a inhibitor of inflammation
• DNA and RNA synthesis is inhibited
• Anti-folic agents –> use folic acid to decrease side effects
• inhibit dihydrofolate reductase = affect lymphocytes and macrophages function

Question 4

Methotrexate

• pharmacokinetics (4)
• indications (6)
• adverse effects (3)

Answer 4

• Non-biologic disease modifying anti-rheumatic drug
• 70% is absorbed after oral administration
• 1/2 life is 6-9 hours
• Excreted principally in the urine

-rheumatoid arthritis, psoriasis, Wegener’s granulomatosis, giant cell arteritis, lupus, vasculitis

• nausea, mucosal ulcers
• leukopenia, anemia, stomatitis, GI ulcerations, alopecia
• contraindicated in pregnancy

Question 5

TNF inhibitors

• names (3)
• adverse effects

Answer 5

-adalimumab, etanercept, infliximab

• injection site reactions (adalimumab, etanercept)
• infusion reactions (infliximab)
• infectious complications (tuberculosis)
• development of blocking antibodies
• other –> lymphomas, vasculitis, congestive heart failure

Question 6

Gout

• disease
• treatment

Answer 6

-too much uric acid = some drugs decrease uric acid production and some increase uric acid elimination

• acute gout attacks - NSAID, corticosteroids, Colchine
• Prevent episodes - allopurinol, febuxostat
• urate lithiasis - probenecid, pegloticase

Question 7

Colchine

-mechanism of action

Answer 7

• used to treat acute between gout attacks
• relieves the pain and inflammation in 12-24h without other analgesic effects

1. bind to intracellular protein tubulin
2. prevents its polymerization into microtubules
3. leads to inhibition of leukocyte migration and phagocytosis

-it also inhibits the formation of some leukotrienes

Question 8

Colchine

-adverse effects (4)

Answer 8

• diarrhea, nausea, vomiting, abdominal pain
• hepatic necrosis
• acute renal failure
• hair loss, bone marrow depression, peripheral neuritis

Question 9

Allopurinol

• pharmacokinetics
• mechanism of action

Answer 9

• used between gout attacks
• 80% absorbed (oral)
• long duration of action - given only once a day

-uric acid is produced from xanthine –> allopuriol inhibits xanthine oxidase = decrease uric acid production

Question 10

Allopurinol

• indications (2)
• adverse effects (5)

Answer 10

• chronic gout in period between attacks
• when starting, colchine or NSAID should be used until steady state of uric acid is normalized and they should be co-administered for 6 months or longer
• GI intolerance
• bone marrow depression
• aplastic anemia
• hepato-toxicitiy
• cataracts

Question 11

Febuxostat

Answer 11

we dont need to know

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Question 12

Uricosuric drugs

• name
• mechanism of action
• contraindication

Answer 12

• Probenecid
• inhibit active transport site for re-absorption and secretion in proximal renal tubule = net reabsorption of uric acid in the proximal tubule is decreased = high amount will be eliminated in the urine
• patients with renal failure

Question 13

Why shouldn’t aspirin be used for the analgesia of gout?

Answer 13

Because it causes the net retention of uric acid by inhibiting the secretory transporter

Question 14

Uricosuric drugs

• name
• indications
• adverse effects

Answer 14

• Probenecid
• in gouty patients with under excretion of uric acid when other drugs are contraindicated. Should not be started until 2-3 weeks after an acute attack
• GI irritation, rash, nephrotic syndrome, aplastic anemia

Question 15

Pathogenesis of migraine

Answer 15

1. initiating event may be abnormal neuronal discharge
2. Localized spreading depression - aura
3. Sensitization of central pain pathways
4. aura = constriction of blood vessels - partial ischemia
5. acute migraine attack
6. vessels are dilated (by serotonin), Trigeminal nerve endings are activated

Question 16

Pathogenesis of migraine

-Cortical spreading depression (CSD) and Neurogenic theory

Answer 16

1. propagating wave of depolarization of neurons and glial cells
2. this wave activates trigeminal nerve
3. causing a neurogenic inflammation via the release of neuropeptides
4. creating migraine

Question 17

Clinical presentation of migraine

Answer 17

• symptoms may vary between patients
• headache pain, aura + combination of other symptoms
• nausea, phonophobia (aversion to sound), photophobia (aversion to light)
• aura - visual disturbances (most of times)
• neck pain, nasal congestion, fatigue…

Question 18

Migraine treatment

-Acute attacks

Answer 18

• 5-HT1D partial agonists - Ergotamine

- Triptans - Sumatriptan, Naratriptan

Question 19

Triptans

-mechanism of action

Answer 19

• induce vasoconstriction in cranial blood vessels
• inhibit the release of neuropeptides
• direct inhibition of neuronal activation, reducing central pain transmission via activation of 5-HT1D and 5-HT1F receptors

Question 20

Triptans

• names
• indications
• contraindication
• adverse effects

Answer 20

• sumatriptan, naratriptan
• acute migraine attacks
• coronary heart disease, not controlled hypertension
• coronary vasoconstriction, arrhythmias