Pharm Unit 3 Blueprint - spring 2009

Remember - concentrate on important administration concepts, maximum doses on relevant drugs when given, storage directions, patient teaching concepts for dosing or application of drugs, prevention and management of adverse effects, and labs to monitor for various therapies. I hope this helps you focus your studies.

70, 71, 73 (coxes 1st & 2nd gen, glucocorticoids, Calcium) - 18 questions

Cox 1 vs Cox 2 (sometimes referred to as prostaglandin) Cox 1 Enzyme Only

• helps prevent gastric ulcers(protects stomach)• causes platelet aggregation (bad for heart disease)

Cox 1 & 2 • Both maintain renal Function, dilation and perfusion

Cox 2 enzyme only• Causes inflammation (bad for RA • Causes fever• Causes pain • Causes fever

COX InhibitorsAnti-inflammatory properties NSAIDs – Non steroid anti-inflammatory drug 1 generation drugs (Asprin)

• inhibits both cox 1 and cox 2 enzyme 2nd generation (celebrex)

• Is selective to only inhibiting the effects of COX 2 enzymeNon- anti-inflammatory properties

o Acetaminophen (Tylenol) is a cox inhibitor, but does not have anti-inflammatory properties

Tylenol (2nd generation properties but Anti-inflamtory• MOA - Inhibits prostaglandin synthesis in CNS• Uses – pain, fever – not anti-inflammatory• Benefits – Ø GI (maintain protection in stomach( no ulcer

development) ,on bleeding(doesn’t effect platelets), renal impairment

• Adverse effects– Hepatotoxicity Tylenol has its main affect in the liver…(4g/d)– ETOH connection (¯g/d) lower Tylenol intake

• Acute Toxicity – Sxms 24-72 h post OD– N,V, D, sweating, abd. pain, liver failure, coma– Mucomyst the antidote for Tylenol overdose if given within 24h

Aspirin acetylsalicylic acid (ASA NSAIDs – Non steroid anti-inflammatory drug 1 generation drugs Non-selective(COX Inhibitor of both COX 1&2)

MOA / TE / Uses– Analgesic, antipyretic, anti-inflammatory– Suppression of platelet aggregation(irreversible for * days, life

of platelet• Treat / prevent Ischemic stroke (makes blood flow smoothly)

not hemorrhagic stroke, TIA, MIs (acute & old), anginas, addition to angioplasty & revascularization

• Dysmenorrhea (cramps) • Cancer prevention• Prevention of Alzheimer’s disease, not in treatment• An initial DOC for RA and juvenile arthritis• Dose related to use!

• ADME– Rapidly absorbed orally, slower rectally– Half-life (2 h to 20 h)– Distributes to all body tissues – pregnant? Contraindicated in

pregnancy– Excretion pH dependent (increase pH increase excretion 4x)

• Side effects– Gastric distress, heartburn, nausea

• Adverse effects– Gastrointestinal – (occult (hidden) and overt)– Bleeding– Renal impairment – Signs?

• acute/reversible – Na+/H2O• Pre-existing condition dependent• Cox1 is a broud specrum and 1st generation Imparest the

benefit of the cox 2 side, whch means can damage the kidneys– Salicylism (over dose of aspirin)– acid/base – tinnitis (symptom

of ringing in the ears) often irreversible– Reye’s syndrome( liver failure) in children, so contraindicated in

use of children.– Hypersensitivity – asthma –ranges from rhinorrhe to shock

• Contraindications– PUD & Bleeding disorders– Hypersensitivity– Extreme caution in pregnancy

• DDD– Anticoagulants & other NSAIDs– Glucocorticoids supress the effects of prostoglandin.. (gastric

ulcertion)– Ibuprofen – impairs cardioprotective properties

• Acute Poisoning– LD (lethal dose) adult = 20-25 g - LD children = 4 your body

becomes acidic– Sxms

• Resp excitation ® depression ® • Hyperthermia, stupor, coma, death

– Treatment• Supportive, charcoal, alkalinization of urine to help

ecrcretion , and dialysis

Glucocorticosteroids (immunosuppressant) in Non-endocrine Diseases Physiology

• Artificial nearly identical to natural, if you use you lose• Metabolic effects

– Breakdown of fats, proteins, carbs - glucose– Robs proteins for glucose production– Fats redistributed long-term to “moon” face

• Cardiovascular– Low levels – cause permeable vessels, dilated vessels, with hypotension– Increase RBCs and PMN (polymorhonucular) Leukocytes– Decrease Lymphs, Eosins, basophils, and monocyts– Effects during stress - define Glucocorticosteroids are produce

increasing amount during stress– Large qty glucocorts / epi secreted– If inadequate sreroids – circulatory failure® – Effects on water and electrolytes– Aldosterone effect – increased Na+,? H2O, decreases K+; hypokalemia – High doses – impair intestinal calcium absorption (hypocalcemia)– Respiratory system in neonates – RSD– Inhibits prostaglandins, leucotriens, and histamines – hinder phagocytes and lymphocytes in the inflammatory response

• TE / Uses– Anti-inflammatory and immunosuppressant effects (high doses)– Rheumatoid arthritis (Autoimmune disorders)– Systemic lupus erythematosus – Inflammatory bowel disease– Miscellaneous inflammatory disorders– Allergic conditions– Asthma– Dermatologic disorders– Neoplasms – toxic to malignant lymphocytes– Stimulates appetite– Suppression of allograft rejection– Prevention of respiratory distress syndrome

• Adverse effects– Adrenal insufficiency– Osteoporosis (resorption, rebuilding & calcium)– monitor for bone loss, use calcium and Vit D supplement– common can cause hyperglycemia– Infection – esp. Pneumocystis Carinii Pneumonia (PCP)– Glucose intolerance, can cause Diabetic– Myopathy – Fluid and electrolyte disturbance, monitor for fluid excess(crackes,

weight gain edema – Growth retardation– Psychologic disturbances– Cataracts and glaucoma– Peptic ulcer disease, Do take wth asprin, choose tylenol– Iatrogenic Cushing’s syndrome– Use in pregnancy and lactation

• DDD– Interactions related to potassium loss, whatever Na increases, K

decreases– Non-steroidal anti-inflammatory drugs

– Insulin and oral hypoglycemic – Vaccines. Won’t get the inflammation response, or the immune response you

looking for• Adrenal suppression

– Atrophy– Stress & “flat” response (Alt. day Tx)

• Glucocorticoid withdrawal– Don’t stop taking immunosupreants abruptly– Taper over 7 days– Switch from multiple doses to single doses– Taper the dosage to 50% of physiologic values– Monitor for signs of insufficiency, remember if you use the drud the

adrenal gland normal exretion of this is limited.. natural soiu• HypoTN, hyoglycemia, myalgia, arthralgia & fatigue

Drugs Affecting Calcium Levels and Bone Mineralization

Calcium Physiology • Critical to skeletal, nervous, muscular, and cardiovascular systems• Body stores – review, bones store 99% of calium• Absorption – occurs in the gut

– with PTH & vitD – Glucocorticoids – effect? Impair absorbtion in the gut

• Excretion in kidneys– Calcitonin augment (Boost) calcium eliminationVitamin D, calcitonin, and parathyroid hormone are essential in the metabolism of calcium.

Hypercalcemia: Drug Therapy • Usually asymptomatic (don’t know)• Causes: PTH, Vit D toxicity, thiazides (diuretic)• Drug Therapy

– Promote urinary excretion – furosemide & IV saline – Decrease mobilization from bone

• calcitonin, bisphosphonates, inorganic phosphates, gallium nitrate– Decrease intestinal absorption

• glucocorticoids Hypocalcemia: Drug Therapy

• Increases neuromuscular excitability• Causes: ¯PTH, ¯Vit D & Ca++

• Clinical presentation– Tetany, convulsions, and spasm of the pharynx Treatment

• Treatment– IV Calcium (calcium gluconate)– Vitamin D

Drugs for Ca++ Disorders: (IV bisphosphanates)

o Prototype: Alendronate (Fosamax)• MOA – TE – Uses

– Structural analogs of pyrophosphate of bone incorporated into bone and inhibit resorption by decreasing osteoclast activity and

– used to treat osteoporosis, glucocorticoid induced osteopororis, Paget’s, and hypercalcemia of malignancy.

• ADME - CRITICAL! • Bioavailability drops if taken with food (0.7%) or drinks other

than water (60%)! • Remains for decades once incorporated• Never to betaken with cofee or tea, food • only with water

• Adverse effects– Esophagitis – implications usually with IV admin– Ocular inflammation– Osteonecrosis of the jaw (ONJ) – mostly IV

Drugs for Ca++ Disorders:continued (Calcium supplementation) Calcium Salts

o Prototype: Calcium Citrate (Citracal)• MOA / TE / Uses –

• Keeps levels up, prevents resorption to treat mild hypocalcemia most often in children, adolescents, elderly, post-menopause, & pregnants

• Adverse effects – hypercalcemia • Signs- tachycardia, elevated BP, muscle weakness, constipation, lethargy

• DDD, DDF– Glucocorticoids (calcium may not be high enough so you may need to take

even higher doses of citracal.– Don’t eat;Spinach, beets, bran, cereals – impair absorption

• Adverse effects of IV administration– ONLY IV!, can cause necrosis if given another route– IM or extravasation can cause necrosis

May cause severe brady if on digoxinDrugs for Ca++ Disorders:continued (Vitamin D supplementation) Vitamin D

o Prototype: cholecalciferol (Vitamin D3)• MOA – TE – Uses –

• increases serum Ca++ and phosphorus levels to prevent osteomalacia / osteoporosis

• ADME– Daily exposure to sun (D2)/vs oral supplement– Dosage – 800-1000 IntUnits/d or more– Children – 200 or more IN FOODS only

• Adverse effects:• hypercalcemia

107, 79, 80, 104 (vitamins, herbs, enteral, parenteral,skin disorders ) - 17 questions

Saw PalmettoGarlicNiacinVitamin KFolic AcidEnteral - Parenteral feedingsAccutaneRetin-ATopical glucocorticoidsSunscreens

40, 56 (Diuretics, insulin) - 14 questionsfurosemide (Lasix)Hydrochlorothiazide (Hydrodiuril)Insulins - glargine, aspart, regular, NPHGlucagon