Methotrexate

-
Methotrexate is a folic acid antagonist derived from aminopterin. It inhibits dihydrofolate reductase, the enzyme required in the pathway supplying methyl donor groups for DNA, RNA and protein synthesis. Methotrexate has been used for the treatment of diseases characterised by inflammation or cellular proliferation. In 1985 the first randomised, placebo-controlled trials were published that demonstrated the short-term efficacy of low-dose weekly methotrexate in rheumatoid arthritis (RA). Methotrexate is now the most widely used disease-modifying antirheumatoid drug (DMARD) in the developed world. It was first used in the treatment of psoriatic arthritis (PsA) in 1951, and has been shown to be of clinical benefit in this condition.
However, methotrexate toxicity remains an important issue when considering its use, and is one of the main reasons for discontinuation. The most common adverse effects are gastrointestinal, such as anorexia, nausea, stomatitis and diarrhoea. CNS toxicity including headache, dizziness, fatigue and mood disturbance may occur. Haematological toxicity is not common, and although all types of cytopenia have been documented, an identifiable risk factor can usually be found, such as untreated folate deficiency, renal insufficiency or superimposed infection.

Comments

Post a Comment

Popular posts from this blog

Treatment Guidelines for Malaria Contd...

-
Treatment regimens for uncomplicated malaria in adults _ Oral quinine sulphate 600 mg/8 h for 5e7 days plus doxycycline 200 mg daily (or clindamycin 450 mg/8 h for pregnant women) for 7 days _ Atovaquoneeproguanil (Malarone_): 4 ‘standard’ tablets daily for 3 days or _ Co-artem ((artemetherelumefantrine_): if weight > 35 kg, 4 tablets  then 4 tablets at 8, 24, 36, 48 and 60 h   Child Initial dose 10 mg/kg/base then 5 mg/kg  base 6e8 h later and on days 2 and 3   However, both of these newer regimens need to be taken for only 3 days. In contrast, quinine needs to be taken for 5e7 days and is often associated with ‘‘cinchonism’’ (nausea, deafness and ringing in the ears), which often results in poor adherence. Although international recommendations suggest that quinine should be  taken for 7 days in endemic areas, 2  UK experience suggests  that 5 days treatment is adequate for the vast majority of cases. Quinine should be combined with a second drug (doxycycline for adults or clindam
Read more

Acute migraine treatments

-
Acetaminophen and NSAIDS First of treatment for mild migraines Time to onset: 1-2 hours Duration of effect: 2-3 hours, decreases with increasing frequency of use Side effects: can lead to GI bleeding, liver and renal dysfunction. Ergotamine Derivatives Ergotamine are fungal derivatives that are potent vasoconstrictors. Used for severe migraines. Time to onset: 15 min to 2 hours depending on route. Duration of effect: 2-4 hours. Side effects: increased BP, MI, stroke. Triptans Triptans are 5HT1B, 5HT1D agonists. Sumatriptan was the first to be introduced in 1991. Sumatriptan is used for severe migraine with 10 min time to onset and 60-70% efficacy with a duration of 2 hours. 2ndgeneration triptans have since been developed with increased efficacy and duration of action. Side effects are referred to as triptan sensations and include tingling, numbing, anxiety, heaviness or tightness in the chest and throat, and sensations of warmth, burning, cold, or pressure. Prophylaxis Treatment Beta
Read more

EFFECT OF ACETAMINOPHEN ON BLOOD PRESSURE

-
Acetaminophen produces its analgesic effect by inhibiting the same cyclooxygenase, prostaglandin H2 synthase, that is the target of NSAID and aspirin. However, acetaminophen blocks this enzyme at its peroxidase catalytic rather than at the cyclooxygenase catalytic site. Therefore, the acetaminophen-mediated inhibition is sensitive to changes in the tissue peroxide levels; higher concentrations of peroxide in activated leukocytes and platelets block the effect of acetaminophen on inflammation and platelet thrombosis. However, acetaminophen is able to inhibit prostaglandins in the central nervous system, thus providing relief of pain and fever. Therefore, acetaminophen is not an NSAID or anti-thrombotic agent.   Subscribe to Drugs Information Center by Email
Read more