Pharmacology Flashcards
What are the clinical features of myasthenia graves in the following muscles?
Ocular muscle: fluctuating ptosis and/or diplopia
Bulbar muscle: dysarthria, painless dysphagia, dysphonia
Facial muscle: weakness, no firm eye closure and drooling of saliva
Axial muscular: flexion or extension of the neck
Limb muscle: weakness involving the arms more than the legs
Respiratory muscle: breathing effort, orthopnea, dyspnea
What type of therapy can be used to treat myasthenia gravis ?
According to degree of myasthenia Gravis:
Symptomatic : reversible Ach E inhibitors
Causative:
Chronic immunomodulation:
-Corticosteroids
-Non-selective conventional response modifiers
-Selective biologics
Rapid immunomodulation:
-Plasma exchange (plasmapheresis)
-IV. Immunoglobulins
Surgical: thymectomy
What type of treatment can be administered for rheumatoid arthritis?
Symptomatic:
Non-narcotic analgesics: relieve pain, swelling and fatigue
Causative:
Corticosteroids and other disease modifiers:
-Control disease activity/stop joint damage
-Preserve joint function and prevent disability
-Conventional
-Biological
-Targeted synthetic
Education + physiotherapy + surgery:
Maximise quality of life and minimise morbidity
What drugs cause hyperuricemia as a consequence of intake?
-Salicytes (less than 2g per day)
-Thiazides and loop diuretics
-Ethambutol and pyrazinamide
(Anti-tuberculous)
-Nicotinic acid (niacin) (anti-hyperlipidemic)
-Cyclosporine (immunosuppressant)
What is the classification of drugs used in treatment of gout?
Drugs for acute gouty arthritis:
-Non-steroidal anti-inflammatory drugs (NSAIDS)
-Corticosteroids
-Colchine
-Interleukin-1 inhibitors
Drugs for prevention of recurrent attacks:
-Uricostatic drugs: Xanthine oxidase inhibitors: Allopurinol
-Uricosuric drugs: Probeneceid
-Recombinant uricases
Describe NSAIDs
NSAIDs are the treatment of choice
Indomethacin is the classic NSAID of choice, although all NSAIDs (e.g. naproxen, sulindac except aspirin) are effective in acute gouty attack
NSAIDs act by inhibition of COX and hence prostaglandin synthesis to reduce:
-Pain e.g. analgesic action
-Inflammatory reactions and phagocytosis of urate crystals
Why shouldn’t aspirin be used to treat acute gout caused by hyperuricemia?
Aspirin competes with the uric acid inside the renal tubules, it is not suitable for treatment of acute gouty attacks because at low doses (less than 2.6 g/day), it causes renal retention of uric acid
Describe corticosteroids
Corticosteroids e.g. methylprednisolone:
Markedly suppress inflammatory processes and reduce the synthesis of inflammatory mediators in the gouty joint.
They are indicated in:
-Severe symptomatic gout
-When NSAIDs and colchicine are not effective or contraindicated
They can be administered intra-articularly when only one or two joints are affected or systemically e.g. oral or parent real therapy, for widespread joint involvement. In case of systemic therapy, gradual withdrawal is necessary to minimise the risk of rebound flare of the symptoms
Describe colchicine
Colchicine has a specific anti-inflammatory effect in the gouty joint only, while it is ineffective in other forms of arthritis and it is devoid of direct analgesic activity
Colchicine is indicated in acute gouty arthritis in patients intolerant to NSAIDs because of its adverse effects. It is most beneficial when it is started within the first 12-36 hours of an attack and usually alleviates the pain within 12 hours
Why does colchicine cause drug toxicity?
Because it has a low therapeutic index so should not be used by pregnant women
What are the symptoms of drug toxicity caused by colchicine?
-Abdominal pain, nausea, vomiting and diarrhoea caused by the inhibition of mucosal cell division and renewal. These are the earliest signs of colchicine toxicity. The drug should be discontinued if these symptoms occur
-Bone marrow suppression with long term use
-Liver and kidney damage
Why should dose adjustment be used for colchicine?
It is metabolised by the liver so it might encounter CYP3A4 (clarithromycin and fluconazole) and P-glycoprotein inhibitors (verapamil) which inhibit its metabolism so it precipitates in the liver and enters the blood stream causing drug toxicity
Describe interleukin-1 inhibitors
These are drugs targeting interleukin-1 pathway (anakinra). It is suggested for treatment of acute gouty attacks in patients with contraindication to or found refractory to traditional therapies like NSAIDs, corticosteroids or colchicine
What are the indications for drugs for prevention of recurrent attacks?
-They should be started 1-2 weeks after the end of the acute attack of gouty arthritis
-Low dose colchicine, NSAIDs or corticosteroids should be initiated with urate-lowering therapy and continued for at least 6 months to prevent the development of an acute gout attack
-Should be administered to patients who have had/have:
2 or more acute attacks in a year
Chronic kidney disease/ renal stones or tophi (tissue deposit of urate crystals)
Who need to reduce the serum uric acid concentration to less than 6 mg/dL
Describe allopurinol
It inhibits uric acid synthesis (uricostatic)
Xanthine oxidase inhibitors
It also increases the reutilisation of hypoxyanthine and Xanthine for nucleotide and nucleic acid synthesis. This leads to feedback inhibition of de novo purine synthesis
Drugs which depend on Xanthine oxidase for elimination as azathioprine (immunomodulator) their dosage must be reduced when they are given concomitantly with allopurinol
