DCNP - Pharmacology Flashcards
corticosteroid osteonecrosis
joint pain (hip, knee, shoulder) and decreased ROM
pseudotumor cerebri
headache, visual change, nausea/vomiting
dapsone hypersensitivity syndrome
fever, fatigue, sore throat, morbilliform rash
drug combinations that have overlapping target organs of potential toxicity or alter the same metabolic pathway or metabolized by cytochrome P-450
MTX + acitretin = hepatotoxicity
MTX + Bactrim = pancytopenia (both effect folate metabolism)
azathioprine + allopurinol = hematologic complications
rifampin + OCP = decreased OCP efficacy
ketoconazole/erythromycin + cyclosporine = cyclosporine toxicity
if significant transaminase elevation occurs
check bilirubin, alkaline phosphatase & GGT for hepatobiliary obstruction
azathioprine (imuran)
immunobullous disease, vasculitis & CTD (SLE, dermatomyositis),
50 mg/day increased to maximum 2.5 mg/kg/day
Immunosuppression, leukocytopenia, thrombocytopenia, N/V
Increased toxicity: allopurinol, captopril
Decreased efficacy: warfarin, IUD
Baseline: thiopurine methyltransferase (TPMT), CBC, CMP, UA, (HCG)
CBC-diff, platelets q 2 wk x 3 mo
ALT/AST monthly x 3 mo then q 2 mo
May increase risk of developing cancer, esp skin cancer and lymphoma
can cause severe decrease in the number of white blood cells and platelets thereby increases your risk of infection and unusual bleeding or bruising
cyclosporine (neoral)
Papulosquamous dermatoses (L.P.), bullous dermatoses, autoimmuneconnective tissue diseases, neutrophilic dermatoses, neoplastic(Sezary), atopic dermatitis, alopecia, granulomatous dermatoses,disorders of keratinization (PRP), photosensitivity dermatoses, other(morphea, prurigo nodularis), urticaria
max 4 mg/kg/day then wean by 1 mg/kg/day q 2 weeks to minimumeffective dose* Use for 6-12 mo maximum for flare then initiate acitretin or Mtx,reducing cyclosporin by 1 mg/kg/day monthly
AEs: HTN, renal dysfunction, headache, hyperlipidemia, infections, nausea, diarrhea, paresthesia, tremor, hypertrichosis,gingival hyperplasia, hyperkalemia, hypomagnesemia, hyperuricemia,hyperlipidemia
Baseline: BP x 2, q 2 wks x 2 mo, then monthly* Baseline: CBC, CMP, lipid panel, magnesium, uric acid* CBC, CMP, lipid panel q 2 wks x 2 mo then monthly* creatinine clearance after 6 mo of therapy
methotrexate
Antimetabolite: immunosuppression; inhibits folic acid synthesis;
antiproliferative of keratinocytes and lymphocytes; and, anti-inflammatory.
FDA approved * Psoriasis, cutaneous T cell lymphoma, rheumatoid arthritis
Off-label * Autoimmune bullous disorders; proliferative disorders (i.e. PRP,PLEVA, etc); connective tissue diseases (DM); vasculitic andneutrophilic disorders
Sometimes used in combination with anti-TNF agents to reduceantibody formation
Dose 2.5 to 25 mg usually once weekly
Common side effects* Minimal side effects occur with low doses. N/V, anorexia, stomatitis,headache, dizziness, phototoxicitySerious adverseeventsMethotrexatepneumonitis* Teratogenic. Liver toxicity. Renal toxicity. Lymphoma.* Pancytopenia is the most common cause of death from MTX.Methotrexate-induced cirrhosis, rash, excessive fatigue, mentalconfusion, fever, chills, shortness of breath, dry cough, rapidheartbeat or palpitations, unusual bleeding or bruising, black stools,persistent stomach disturbances, changes in urinary frequency.Pulmonary toxicity is idiosyncratic on low doses* Dry cough, shortness of breath, fever; most often seen in the first 6months of MTX treatmentDiffuse interstitial pattern on x-ray; Bronchoalveolar lavage may beneeded to rule out infectionAcute mortality = 17%; 50%-60% recur with retreatment, whichcarries the same mortalityRisk factors: older age, RA lung, prior use of DMARD, low albumin,diabetes
Avoid alcohol, sulfa medications and NSAIDS
Causes sun sensitivity; practice sun protective measures* Do not take with milk-rich foods
Females planning contraception should be off drug for 3 months before conceiving andmen off for one ovulatory cycle for the female
Baseline: CBC w/diff, renal and liver function, Hepatitis B and C; TB,HIV, pregnancy test. Liver biopsy (see below)* Ongoing:* CBC w/diff: every 1-2 wks for first month; every 1-2 wks after doseincrease; then every 3-4 months when established on maintenancedose.* Renal panel: 1-2 times a year.* Liver function studies monthly x 6 months, then q 3mos. More oftenif change in dose or abnormal
AAD guidelines advocate:* The first liver biopsy after 3.5–4.0 g of the cumulative MTX dose has been given forpatients without risk factors for hepatotoxicity.* Baseline liver biopsy or within 2-6 months of starting treatment and repeated liverbiopsies after 1 - 1.5g of MTX for pts with risk factors for hepatotoxicity
prednisone
FDA Approval * Bullous: pemphigus vulgaris, bullous pemphigoid, SJS-TEN,Erythema Multiforme. Autoimmune connective tissue disease:Lupus erythematosus, dermatomyositis. Other: urticariaOff Label * Bullous: cicatricial pemphigoid, herpes gestationis, epidermolysisbullosa acquisita, linear IGA bullous dermatosis. Vasculitis:cutaneous, systemic. Neutrophilic dermatoses: pyodermagangrenosum, Behcet’s disease, Sweet’s syndrome.Papulosquamous dermatoses: contact dermatitis, exfoliativeerythroderma, lichen planus. Other: sarcoidosis, sunburn, androgenexcess, postherpetic neuralgia prevention
Pregnancy: avoid during 1st trimester (hard palate)* Risk of premature rupture of membrane, placental insufficiency,low birth weight, fetal growth restriction* Lactation: delay nursing for 4 hrs after high doses
Significant AdverseEffects* hypothalamic-pituitary-adrenal axis dysfunction (Cushingoidchanges, adrenal crisis). glucocorticoid (hyperglycemia) &mineralocorticoids (osteoporosis, osteonecrosis, hypocalcemia)dysfunction. HTN, CHF, hyperlipidemia, hypokalemia, excessiveweight gain. GI reflux, bowel perforation, peptic ulcer, cataracts,glaucoma, psychosisAdverse Effects * opportunistic infection, myopathy. cutaneous: impaired woundhealing, ulcers, striae, atrophy, telangiectasias. steroid acne,purpura, petechiae
Take prednisone in the morning, before 9 AM to more closely mimic your body’s naturalsecretion of cortisol
All corticosteroids, including prednisone, can cause salt and fluid retention, which maylead to blood pressure elevation and increased potassium excretion. Calcium excretionis also increased; supplements are advised* Limit or avoid alcohol use while taking prednisone to help reduce the risk of indigestionand the development of stomach ulcers.* If you are taking higher dosages of prednisone, you should not receive any live or live-attenuated vaccines. Your response to killed or inactivated vaccines may also bediminished.* Avoid contact with anybody known to have, or recently exposed to, viral illnesses suchas chickenpox or measles. If you inadvertently come into contact with somebody,contact your doctor immediately as immune globulin or antiviral treatment may berequired.* Prolonged prednisone use may affect growth and development in children.* Cataracts, glaucoma, eye infections, an increase in new episodes of optic neuritis andcorneal perforation associated with herpes simplex of the eye, have all been reported
May interact with a number of other drugs including some anti-infectives, antidiabeticagents, bupropion, NSAIDs, and drugs metabolized by CYP 3A4 liver enzymes
dapsone
antiproliferative
FDA proved Dermatitis herpetiformis; leprosyOff-label Autoimmune bullous disorders, neutrophilic dermatoses, vasculitis,granulomatous conditions (i.e. granuloma annulare, nodulocystic acne,granulomatous rosacea, etc.)MOA Bacteriostatic agent; inhibits folic acid pathwayDosage Usually starting at 25mg-100mg daily; gradual increase (25mg and100mg tablets) to 100-200mg/day; adjust to risk and response.
G6PD deficiency (below)Relative: allergy to sulfapyridine or sulfonamides (rare)
Common side effects Hemolytic anemia to some degree-dose related and usually within first6 weeks.Nausea, loss of appetite, HA, dizziness, insomniaSerious adverseeventsMethemoglobinemia (dose related)- blue lips, HA, lethargyHypersensitivity- fever, fatigue, rash, ST, lymphadenopathyUrticaria- hives lasting less than 24 hrsAgranulocytosis- persistent, fever, usually within first 8 wks of txHemolytic anemia- weakness, SOB, severe fatigueHepatitis- jaundiceInteractions Methotrexate; sulfonamide antibiotics, trimethoprim, didanosine,rifampin, probenecid, drugs/foods/herbals
LaboratorymonitoringBaseline: Glucose-6-phosphate dehydrogenase level (G6PD deficiency can cause severe hemolysis especially in pts with African, MiddleEastern, Asian ancestry)CBC-diff q wk x 1 mo; q 2 wks x 2 mo; then q 3-4 months
CBC-diff, Renal function, liver function, UA q 3-4 moReticulocyte count (if hemolysis needs monitoring)Methemoglobin level (if indicated)*More frequent follow up if high risk, dosage increases or abnormallabs or symptoms
hydroxychloroquine
antimalarial
FDA Approval subacute/cutaneous lupus erythematosus (SCLE/SLE); RA;malariaOff Label * polymorphous light eruption, sarcoidosis (PMLE), granulomaannulare, GVHD, panniculitis, lichen planus, dermatomyositisDosage * 200 – 400 mg/ day (max) or 5 mg/kg/d
safe in pregnancy
Adverse Effects * blue-gray to black discoloration (shins, face, palate, nailbeds), bleaching of hair roots, exanthem, N/V* eczematous skin eruptions esp. if on other meds that can alsocause skin eruptions. Risk for SJSSignificant Adverse Effects * (rare) retinopathy, vision changes: baseline + q 6-12 mo.ophthalmology exam* (rare) pancytopenia, hemolysis (G6PD deficient)
Baseline: EKG, CBC, CMP, G6PD (for patients high risk forhemolytic anemis) liver enzymes
slow onset; 3-4 mo to see effect
isotretinoin
off label: disorders of keratinization (Darier’s RPR),neoplastic processes (nevoid BCC, SOTR), misc (L.E., G.A., sarcoidosis)
0.5-2 mg/kg/day
Adverse Effects * xerosis, palmoplantar-digital desquamation, photosensitivity, cheilitis,sore mouth and tongue, PG, S aureus infections, telogen effluvium,paronychia, onycholysis, blepharoconjunctivitis, photophobia, reduced night vision, persistent dry eyes, nasal mucosa dryness,epistaxis, arthralgias, muscle weakness, tendinitis, diffuse skeletalhyperosteosis, osteophyte formation, epiphyseal closure headache,N/V, diarrhea, abdominal pain
Long-term therapy: ophthalmologic exam: cataracts, retinopathy.wrist, ankle, spine x-rays
acitretin
Off Label * Acneiform, keratinization (ichthyosis, Darier’s), chemoprophylaxis(Gorlin’s, NMSC in SOTR), neoplastic (BCC, SCC), sarcoidosis, LP, SLE
25-50 mg/day
contraindicated w/ methotrexate and tetracyclines
DA advises contraception for at least 3 years aftertreatment
Trifarotene (Aklief®) 0.005% cream
Only topical retinoid with selective retinoic acid receptor gamma (RAR gamma) agonist and minimal RAR beta-mediated effects increasing efficacy and decreasing irritation. Used daily for facial andtruncal acne in pts > 9 yrs old
spironolactone
anti-androgen
Off Label * acne, hidradenitis suppurativa, hirsutism, androgenetic alopeciaDosage * 50-200 mg/day
Adverse Effects * hyperkalemia (muscle cramps, weakness), gynecomastia, minor GIsymptoms, menstrual dysfunction, headache, dizzinessInteractions * increase toxicity: ace inhibitors, potassium supplements, digoxin* decrease efficacy: salicylates; OCPs with drospirenone may inc. K+
