Pharm 35 Objectives Flashcards
What is the building block for de novo steroid hormone synthesis?
Cholesterol
What are the four major safety concerns with statin medications?
- Pregnancy
- Liver Damage
- Muscle Damage
- Development of DM
Pt is a taking a statin and c/o muscle pain, you do a complete lab workup and there is no increase in creatine kinase what do you do?
- Lower current statin dose or go to QD
- Go to lower risk statins (Fluvastatin, pravastatin)
- Add Co-enzyme Q10 and/or Vit D
- D/c statin or use a non statin lipid lower agent
Bone mineral density loss + fracture risk is increased by what drugs?
- Long term Glucocorticoids- prednisone
- Antiestrogens (cancer tx), antiandrogens, and MPA (depo)
- Carbamazepine, phenobarbital, phenytoin
- Excessive thyroid supplement
- Drug induced hyperprolactinemia (antipsychotic)
- DM drugs: thiazolidinediones, SGLT-2
Fracture risk only is increased by what drugs?
- PPI
- Antiparkinsonian drugs
- Insulin (hypoglycemic episodes)
What is the appropriate clinical use for quinine sulfate in the U.S?
Malaria
What are the risks associated with quinine sulfate when inappropriately used for leg cramps?
- Hematological adverse events (thrombocytopenia, hemolytic uremic syndrome, thrombotic thrombocytopenia purpura)
- Chronic renal impairment
- Hypersensitivity rxn
- QT prolongation
- Cardiac arrhythmias
- Torsade’s de pointes
- Death
What are some possible tx for nocturnal leg cramps?
- Potassium, magnesium, calcium
- Stretching
- Walking and jiggling by leg elevation
- Hot shower w/ steam
- Ice massage
- Homeopathic quinine OTC
- Tonic water
What drugs can contribute to nocturnal leg cramps?
- Inhaled long acting beta agonist (LABA)
- Potassium-sparing diuretics
- Thiazide-like diuretics
- Loop diuretics and statins (small increased risk)
What does DMARD stand for?
Disease-modifying antirheumatic drugs
What are the non-biologic, “small molecule” DMARDS (oral)?
- Methotrexate
- Leflunomide
- Hydroxychloroquine
- Sulfasalazine
- Tofacitinib (Xeljanz)
What are the biological DMARDs (injection)/anti-TNF antibodies?
- Adalimumab
- Etanercept
- Infliximab
[A, E, I]
What are the anti-inflammatory/analgesics: COX inhibitor and or glucocorticoids
- Rofecoxib and Celecoxib
- Methylprednisolone or Prednisolone.
What is the 1st line DMARD for RA, psoriasis, and JIA?
Methotrexate (once wkly)
- inhibit T-cells
What are the toxicities associated with Methotrexate?
- Anemia/pancytopenia-check CBCs
- Liver
- GI
- Kidney
- Pulmonary
- Alopecia
- CNS
What supplement should a pt take when taking Methotrexate?
Folic acid (helps reduce hepatoxicity)
What is the rescue medication for Methotrexate tox?
Leucovorin
What is the MOA of Leflunomide?
Inhibits pyrimidine synthesis
What are the CI of Leflunomide?
Pregnancy: teratogenicity and embryolethality
Leflunomide is tx for RA and what else?
Relapsing-remitting MS
Hydroxychloroquine is tx for RA and what else?
SLE
What is required when a pt is on Hydroxychloroquine?
Regular eye exams are required
- risk for retinopathy
What is the tx regiment for a SLE flair?
Prednisone (short term) + hydroxychloroquine (long term)
What is the first line tx for SLE?
Avoiding exacerbating drugs and tobacco cessation
What is 2nd line tx for SLE if inadequate response to topical steroid or topical calcineurin inhibitors for discoid and subacute cutaneous lupus erythematosus?
Hydroxychloroquine (200-400 mg daily)
Sulfasalazine is tx for RA and what else?
Juvenile rheumatoid arthritis
What warning is given with Sulfasalazine?
Sulfa drug- warning in pt with sulfa allergies
- metabolized to 5-ASA
What pregnancy category is Sulfasalazine?
- Cat. B
- Should increase folic acid intake to 2 mg per day
Tofacitinib is a DMARD and also considered an oral what?
Oral TNF-a-inhibitor
What are the BBWs of Tofacitinib?
Serious infection and malignancy
Adalimumab is the recombinant form of what?
Human anti-TNF-a-mAb
Etanercept is the recombinant form of what?
p75 TNF-receptor/IgG1 FC construct
linker
Infliximab is the recombinant form of what?
Chimeric anti-TNF-a mAb
mouse
What are the BBWs for Adalimumab, Etanercept and Infliximab?
Serious infection and malignancy
Adalimumab binds to what and prevents what?
- Binds: TNF-a
- Prevents: TNF-a/TNF-r activation
How often is Adalimumab injected?
Every other week
What is the MOA of Etanercept?
Acts as a receptor for TNF, binds to TNFa and LTa
How often is Etanercept injected?
Once weekly BUT sometimes given twice weekly
What is the MOA of Infliximab?
Inactives TNFa, binds soluble and membrane TNF
Infliximab is used for RA and what else?
Crohns
Infliximab has been found to be more effective when combined with what?
Methotrexate
How often is Infliximab administered?
Administered IV every 4-12 wks
Why does cancer chemotherapy lead to a gout attack?
As cell dies they break down DNA and releases uric acid
What should be administered before chemotherapy to prevent gout attacks?
Allopurinol should be administered before chemotherapy starts
What is the tx for active gout (reduce inflammation)?
- NSAIDS- indomethacin (1st line)
- Prednisone
- Colchicine
What are the ASEs of colchicine?
- GI distress (n/v, diarrhea-MC)
- Rhabdomyolysis
- Bone marrow suppression
- Peripheral neuropathy
- Kidney or liver problems
What is the preventative tx for gout (prevent the buildup of uric acid)?
- Allopurinol: XOI
- Probenecid: a uricosuric agent
- Pegloticase: recombinant form of uric acid oxidase
What is the MOA of Allopurinol?
- Inhibits xanthine oxidase
- Best for uric acid overproducers
- Reduced blood uric acid levels
- Prevents new tophus formation
- Decreases risk of nephropathy from deposition of urate crystals in kidney
What is the ASEs of Allopurinol?
- Cataracts (if used >3 yrs)
- Fatal hypersensitivity syndrome- if rash or fever develops —–> d/c immediately
What is the MOA of Probenecid?
Inhibits uric acid reabsorption in renal tubules which increases excretion.
What drugs are delayed in excretion when pt take Probenecid?
PCNs
Cephalosporins
Indomethacin
What are the ASEs of Probenecid?
- May increase deposition of urate in the kidney resulting in kidney damage.
- Increase 2.5-3 L of fluid daily during the first few days of tx
What is the MOA of Pegloticase?
- Inhibits the conversion of plasma uric acid to urate crystals deposited in joints
Pegloticase is CI in a pt with what?
G6PD
What are the ASEs of Pegloticase
- Hypersensitivity rxn – anaphylaxis 6.5%
- Tx with antihistamine and glucocorticoid required
- Infusion rxn in 26-41%
What is the general role of NSAIDs and anti-inflammatory steroids for RA and gout?
- Pain and inflammation management
- NSAIDs can be given with allopurinol and Probenecid to prevent gouty attacks
What IV drugs are used for severe hypocalcemia (and potential use in hyperkalemia and cardiotox)?
- Calcium chloride
- Calcium gluconate
What is the ASE of Calcium chloride?
Tissue necrosis and sloughing
Which is preferred Calcium chloride or
Calcium gluconate?
- Calcium gluconate- d/t lower risk of tissue necrosis if extravasation.
What are the CIs of IV calcium?
- incompatible w/ phosphate (caution in “total parental nutrition (TPN)) and carbonate
- Ventral fibrillation
- Infusion rate faster than 10-20 minutes can lead to cardiac arrest
- Pts w/ hypokalemia
- Pts on digoxin
What are the fastest-acting therapies for hypercalcemia, and the class and route of the most commonly employed and most effective antiresorptive therapy?
- IV fluids w/ isotonic saline
- IV bisphosphonates
- IM Calcitonin (less effective than others but onset is a bit faster (6-12hrs) - alternative to bisphosphonates
What are the indications for Bisphosphonates?
- Osteoporosis: prevention or tx (weekly)- primary use.
- Paget’s disease: high dose, often daily for 3 mos
- Bony complications of cancer: require high dose
What should be supplemented when taking Bisphosphonate for tx of osteoporosis?
Calcium and vitamin D
What would you tell your pt to do when taking an oral bisphosphonate?
- Take 1 hr before food with water only
- Sit upright a min of 30 minutes after taking
How often is IV and oral bisphosphonates administered?
IV: q3 mos
PO: daily or wkly
What is the severe ASE of IV bisphosphonates?
Osteonecrosis of the jaw
What are a few warnings for all bisphosphonates?
- Fracture of femur
- Heartburn, nausea, GI irritant
What are the effects of hyperparathyroidism on bone mineral homeostasis?
Pts with continuous elevation of PTH results in major bone resorption (osteoclast activity) and hypercalcemia
What are the effects of once-daily teriparatide injections on bone mineral homeostasis?
- Pulse dose of teriparatide promotes bone formation (stimulation of osteoblastic activity)
- Promotes renal retention of Ca and phosphate excretion.
What are the physiological effects of vitamin-D on calcium metabolism?
- Stimulated intestinal absorption of Ca2+ and PO4-
- Promotes bone formation and resorption
- Enhances renal retention of Ca2+
What are the skeletal effects of vitamin-D deficiency?
- Reduced calcium and phosphate availability
- Reduced osteoblast fxn
- Results in rickets or osteomalacia
What is typically used for vitamin-D deficiency in patients with healthy kidneys?
Ergocalciferol (Rx) and cholecalciferol (OTC)
What is typically used for vitamin-D deficiency in patients with kidney failure?
Paricalcitol (Rx) and Doxercalciferol (Rx)
What is the Rx dose of Vitamin D?
- 50,000 IU taken once weekly.
- D2 form-Ergocalciferol
What is the OTC dose of Vitamin D?
- Dose ranges from 400-800 IU taken once daily.
- Usually D3 form- Cholecalciferol
A woman experiencing intolerable menopausal symptoms – which drug(s)?
- Oral estradiol and oral progestin
- Oral conjugated equine estrogens + medroxyprogesterone acetate
A woman at risk for osteoporosis who also wishes to prevent breast cancer, also – which drug(s)?
Raloxifene or Tamoxifen
When is Denosumab an appropriate therapy for osteoporosis and hypercalcemia?
Pts w/ high risk of osteoporotic fracture who cannot take other drugs but $$$$$
What is required when taking Denosumab?
Concurrent calcium and vitamin D supplementation
What are the ASEs of Denosumab?
- MSK pain, hypercholesterolemia, and some immunologic activities
- CI w/ live vaccines
- Increase risk for cystitis, cellulitis, other infections
- Eczema, dermatitis, rashes
- May increase risk for malignant cell growth
