Musculoskeletal Pharm
Terms
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- Some examples of Opioid analgesics are: (7)
- Morphine, fentanyl, codeine, heroin, methadone, meperidine, dextromethorphan
- Mechanism of Opioid analgesics:
- Act as agonists at opioid receptors to modulate synaptic transmission (mu = morphine, delta = enkephalin, kappa = dynorphin)
- Clinical use of Opioid Analgesics:
- Pain, cough suppression (dextromethorphan), diarrhea (loperamide and diphenoxylate), acute pulmonary edema, maintenance for addicts (methadone)
- Toxicities of Opioid analgesics:
- Addiction, *respiratory depression, constipation, miosis (pinpoint pupils), additive CNS depression with other drugs
- How do you Tx Opioid toxicity?
- Naltrexone, naloxone (opioid receptor antagonists) - oxygen is contraindicated if morphine overdose, might worsen respiratory failure
- Some examples of NSAIDs are: (4)
- Ibuprofen, naproxen, indomethacin, ketorolac
- Mechanism of NSAIDs:
- Reversible inhibition of COX1 & COX2. Block PG synthesis.
- Clinical use of NSAIDs:
- Antipyretic, analgesic, anti-inflammatory. Indomethacin used to close PDA (recall: prostaglandins needed to maintain a PDA).
- Toxicities of NSAIDs:
- Renal damage (acute interstitial nephritis), aplastic anemia, GI distress, ulcers
- COX2 inhibitors, celecoxib and valdecoxib, are clinically used for:
- Rheumatoid arthritis, osteoarthritis
- Mechanism of acetaminophen:
- Reversibly inhibits COX, mostly in CNS. Inactivated peripherally.
- Clinical use of acetaminophen:
- Antipyretic, analgesic.
- Toxicity of acetaminophen; antidote:
- Overdose --> hepatic necrosis, depletes glutathione and forms toxins in liver; N-acetylcysteine --> regenerates glutathione
- Colchicine:
- Acute gout. Depolymerizes microtubules, impairing WBC chemotaxis and degranulation. GI side effects. (Note: indomethacin less toxic, more commonly use.)
- Probenecid:
- Chronic gout. Inhibits reabsorption of uric acid (also inhibits secretion of penicillin).
- Allopurinol:
- Chronic gout. Inhibits xanthine oxidase, dec. conversion of xanthine to uric acid. Also used in lymphoma and leukemia to prevent tumor lysis-associated urate nephropathy.
- Etanercept mechanism:
- Recombinant human TNF receptor that binds TNF-a
- Etanercept clinical use:
- RA, psoriasis, ankylosing spondylitis
- Infliximab mechanism:
- TNF-a antibody
- Infliximab clinical use:
- Crohn's, ulcerative colitis, RA, ankylosing spondylitis
- Cyclosporine mechanism:
- Bind to cyclophilins. Complex blocks differentiation and activation of T-cells by inhibiting calcineurin, preventing production of IL-2 and its receptor
- Cyclosporine clinical use:
- Supress organ rejection after transplant; select autoimmune disorders
- Cyclosporine toxicity:
- Predispose to viral infections and lymphoma; nephrotoxic (preventable with mannitol diuresis)
- Tacolimus (FK506) mechanism:
- Binds to FK-binding protein, inhibiting IL-2 secretion and other cytokines.
- Tacrolimus clinical use:
- Potent immunosuppressive used in organ transplant recipients
- Tacrolimus toxicity:
- Nephrotoxicity, peripheral neuropathy, HTN, pleural effusion, hyperglycemia
- Azathioprine mechanism:
- Antimetabolite derivative of 6-MP that interferes with metabolism and synthesis of nucleic acids. Toxic to proliferating lymphocytes.
- Azathioprine clinical use:
- Kidney transplant, autoimmune disorders (glomerulonephritis and hemolytic anemia)
- Azathioprine toxicity:
- Marrow suppression. Active metabolite mercaptopurine is metabolized by xanthine oxidase; this, toxic effect may be inc. by allopurinol.
- Aldesleukin =
- IL-2 (usef for renal cell CA and metastatic melanoma)
- Erythropoietin =
- for anemias, esp. in renal failure
- Filgrastim =
- G-CSF (recovery of bone marrow)
- Sargramostim =
- GM-CSF (recovery of bone marrow)
- a-IFN =
- Hepatitis B & C, Kaposi's sarcoma, malignant melanoma, leukemia
- b-IFN =
- multiple sclerosis
- gamma-IFN =
- chronic granulomatous disease
- Oprelvekin =
- IL-11 (thrombocytopenia)
- Thrombopoietin =
- for thrombocytopenia
- Rh3 (D) immune globulin is an immunosuppressive that acts:
- at the antigen recognition stage (B and T-cells)
- Antilymphocytic globulin and monoclonal anti-T-cell antibodies are immunosuppressives acting at:
- antigen recognition, lymphocyte proliferation, and differentiation & synthesis stages
- Dactinomycin =
-
[see First Aid p309]
- intercalates in DNA
- for Wilm's, Ewing's, rhabdomyosarcoma
- myelosuppression toxicity