Exercise 1

Study section 2.7a

1. What is the mechanism of action of colchicine in the treatment of gouty arthritis?

• Selective inhibitor of micro-tubules and spindle formation in macrophages and leukocytes (thus inhibiting mitosis)
• Also inhibits chemotaxis
• Decreases leukocyte metabolism, thus reducing lactic acid formation and increasing pH.

2. What are the indications for colchicine’s use, its side-effects and dose? Especially ensure that you know precisely how colchicine must be used during an acute gout attack.

Indications: acute gout arthritis

Side effects: GIT discomfort, diarrhea, nausea, abdominal pain, Gastric bleeding at high dose, Liver damage, Kidney damage, Bone marrow suppression, Peripheral neuritis, Alopecia

Dose: 0.5 – 1 mg immediately, followed by 0.5 mg every 6 hours until pain relief or gastric discomfort is reached. Max: 2.5 mg in first 24 hours • No more than 6 mg over 4 days • Course may not be repeated within 3 days

3. Which other drugs can be used for the treatment of an acute gout attack?

• NSAID’s= Indomethacin, Diclofenac, Piroxicam, Naproxen
• Glucocorticoids =Prednisone, Betamethasone

4. To which group of drugs does probenecid belong?  How does this group of drugs act?

Uricosuric drugs . It act by increasing uric acid secretion.

5. How does allopurinol act; what are its indications, precautions and important interactions?

Irreversible Xanthine oxidase inhibitors • Reduces the conversion of xanthine to uric acid, thus reducing the production of uric acid • Allopurinol therefore increases [xanthine] and [hypoxanthine], both of which are more water soluble than uric acid • Precursors therefore easily excreted and lower [uric acid]

Avoid in acute gout attack

 

Exercise 2

Study section 2.7b

1. Which vascular changes can be observed before and during migraines?

Before migraines their is vasoconstriction and after migration their is vasodilation.

2. What is the role of serotonin in migraine headaches?

• Activation of 5-HT1B receptors causes vasoconstriction of cranial arteries that are painfully dilated during acute migraines.
• Activates 5HT1D receptors on presynaptic trigeminal nerve endings to inhibit neuroactive vasopeptide release and block the transmission of pain impulses to the brain

3. How is ergotamine used during a migraine attack?

acute treatment. Only effective if taken with first signs of migraine. 5-HT1D partial agonist, causes direct vasoconstriction (especially of intracranial arteries)

4. Which side-effects are experienced with ergotamine use? Which contra‑indications exist for using ergotamine?

Side effects: • Nausea and vomiting • Diarrhea • Hallucinations and confusion • Gangrene • Retroperitoneal fibrosis • Tachycardia / bradycardia, angina pain • Regular headache back pain • Contraindications: • Coronary, cerebral and peripheral vascular diseases • Uncontrolled hypertension • Hepatic and renal impairment • Pregnancy • Combination with triptans

5. Which other drugs can be used for an acute migraine attack?  What is the action of all of these drugs?

Analgesia: Paracetamol, NSAID’s, Aspirin • Anti-emetics: Metoclopramide, Domperidone, Cyclizine • Ergotamine • 5-HT1D agonist: Sumatriptan, Zolmitriptan, Eletriptan, Naratriptan, Rizatriptan • Sedative drugs: Diazepam

6. Name the drugs which can be used for migraine prophylaxis, as well as their specific side effects and precautions

Betablockers: Propranolol • α2- agonist: Clonidine • Ca2+ blockers: Flunarizine, • Tricyclic antidepressants: Amitriptyline • Anticonvulsant: Valproate, Topiramate • 5-HT2 antagonist: Pizotifen