Disease-Modifying Antirheumatic Drugs part 2

Methotrexate Methotrexate is now considered the DMARD of first choice to treat rheumatoid arthritis and is used in 50–70% of patients. It is active in this condition at much lower doses than those needed in cancer chemotherapy. Mechanism of Action Methotrexate's principal mechanism of action at the low doses used in the rheumatic diseases probably relates to inhibition of aminoimidazolecarboxamide ribonucleotide (AICAR) transformylase and thymidylate synthetase, with secondary effects on polymorphonuclear chemotaxis. There is some effect on dihydrofolate reductase and this affects lymphocyte and macrophage function, but this is not its principal mechanism of action. Methotrexate has direct inhibitory effects on proliferation and stimulates apoptosis in immune-inflammatory cells....

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Posted in: Anti inflamatory drugs

Disease-Modifying Antirheumatic Drugs

DMARDs Careful clinical and epidemiologic studies have shown that rheumatoid arthritis is an immunologic disease that causes significant systemic effects which shorten life in addition to the joint disease that reduces mobility and quality of life. NSAIDs offer mainly symptomatic relief; they reduce inflammation and the pain it causes and often preserve function, but they have little effect on the progression of bone and cartilage destruction. Interest has therefore centered on finding treatments that might arrest—or at least slow—this progression by modifying the disease itself. The effects of disease-modifying therapies may take 6 weeks to 6 months to become evident although some biologics are effective within 2 weeks; generally, they are slow-acting compared with NSAIDs.These...

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Posted in: Anti inflamatory drugs

Sedative-Hypnotics Pharmacokinetics

Pharmacokinetics: Absorption and Distribution The rates of oral absorption of sedative-hypnotics differ depending on a number of factors, including lipophilicity. For example, the absorption of triazolam is extremely rapid, and that of diazepam and the active metabolite of clorazepate is more rapid than other commonly used benzodiazepines. Clorazepate, a prodrug, is converted to its active form, desmethyldiazepam (nordiazepam), by acid hydrolysis in the stomach. Most of the barbiturates and other older sedative-hypnotics, as well as the newer hypnotics (eszopiclone, zaleplon, zolpidem), are absorbed rapidly into the blood following oral administration.Lipid solubility plays a major role in determining the rate at which a particular...

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Posted in: CNS acting drugs,sedative-hypnotics

Opioid Analgesics Pharmacokinetics

Some properties of clinically important opioids are summarized in following table: Common Opioid Analgesics. Generic Name Receptor Effects1   Approximately Equivalent Dose (mg) Oral:Parenteral Potency Ratio Duration of Analgesia (hours) Maximum Efficacy delta mu kappa Morphine2   +++ + 10 Low 4–5 High Hydromorphone +++ 1.5 Low 4–5 High Oxymorphone +++ 1.5 Low 3–4 High Methadone +++ 10 High 4–6 High Meperidine +++ 60–100 Medium 2–4 High Fentanyl +++ 0.1 Low 1–1.5 High Sufentanil +++ + + 0.02 Parenteral only 1–1.5 High Alfentanil +++ Titrated Parenteral only 0.25–0.75 High Remifentanil +++ Titrated3   Parenteral only 0.054   High ...

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Posted in: CNS acting drugs,opoid analgesics