NURS 5334 ADVANCED PHARMACOLOGY EXAM 3 STUDY GUIDE

NURS 5334 Pharmacology Exam 3 Study Guide • What drugs are used to treat gestational diabetes? o Metformin and Insulin • What A1C value indicates diabetes mellitus? Pre-DM? o 6.5% or greater is considered diabetes o 5.7-6.4% pre-diabetes • What fasting and random values indicate DM? o Fasting plasma glucose—126 or greater is diabetes o Random (casual) plasma glucose—anything greater than 200 is diabetes • What are complications of insulin therapy? o Hypoglycemia o Can develop lipohypertrophy ▪ Accumulation of subcutaneous fat that occurs when it is injected too frequently at the same site o Allergic reactions ▪ Characterized by red and intensely itchy welts, breathing becomes difficult ▪ If severe allergy develops: • Desensitization procedure (small doses to larger doses) o Hypokalemia ▪ Promotes the uptake of potassium cells and insulin activates a membrane-bound enzyme with sodium potassium and ATPase that pumps potassium into the cells and sodium out • Drug interactions? o Hypoglycemic agents ▪ Can intensify the hypoglycemia included by insulin ▪ Examples: sulfonylureas, glinides, alcohol o Use with caution with hyperglycemic agents ▪ Examples: thiazide and glucocorticoids and sympathomimetics • What effect do beta blockers have on insulin? o delay awareness of and response to hypoglycemia by masking the signs that are associated with stimulation of sympathetic nervous system o Impair glycogenolysis o Prevent the bodies counter-regulatory response • What are other therapeutic uses besides DM? o Hyperkalemia o Aids in diagnosis of GH deficiency o Diabetic ketoacidosis • Insulin dosage must be coordinated with what? o Carbohydrate intake • What is B/P goal in diabetic? o To be controlled, within normal 120/80 • What medication can be given to decrease risk of diabetic nephropathy? o ACE inhibitor or ARB 2 • What role does exercise play in treatment of both type 1 and type 2 DM? o Exercise increases cellular responsiveness to insulin and increases glucose tolerance o 150 minute per week of moderate intensity exercise is recommended • What are the 4 steps in the 4-step approach? o Step 1—diagnosis ▪ Lifestyle changes plus metformin o Step 2 ▪ Lifestyle changes plus metformin and a second drug (sulfonylurea, TZD or a DPP4 inhibitor, a sodium glucose cotransporter or SGLT-2 inhibitor, a glucagon-like peptide 1, or a GLP-1 receptor agonist or basal insulin ▪ Second drug choice made considering efficacy, the hypoglycemia risk of the patient, the patient tolerability, and weight-related considerations (some help weight loss, some cause weight gain), cost o Step 3 ▪ Three drug combination • Metformin • Plus 2 other drugs from step 2 o Decided based on a drug and patient specific considerations o Step 4 ▪ If 3 drug combination that includes basal insulin fails after 3-6 months, more complex insulin regimen ▪ Usually in combination with one or more non-insulin medications • When a patient is on insulin therapy what are the blood glucose goals before meals? At bedtime? o Before meals—70-130 o Bedtime—100-140 • What is the A1C goal? When is goal below 7 not appropriate? o 7% or below o Those with severe hypoglycemia risk, limited life expectancy, advanced microvascular or macrovascular complications—not below 7 • What are the short acting insulins? Intermediate? Long acting? o Short duration: Rapid acting ▪ Insulin lispro [Humalog] ▪ Insulin aspart [NovoLog] ▪ Insulin glulisine [Apidra] o Short duration: Slower acting ▪ Regular insulin [Humulin R, Novolin R] o Intermediate duration ▪ Neutral protamine Hagedorn (NPH) insulin ▪ Insulin detemir [Levemir] o Long duration ▪ Insulin glargine • When are short duration insulins used? 3 o Administered in association with meals to control the post-prandial rise in blood glucose between meals and at night • When are intermediate insulins needed? o Administer 2-3 times daily to provide glycemic control between meals and during the night • How long is duration of glargine? Levemir? Degludec? o Glargine—up to 24 hours o Levemir ▪ Low dose (0.2 units/kg)—12 hours ▪ High doses (0.4 units/kg)—20-24 hours o Degludec—up to 42 hours • What are routes of administration? Which can be inhaled? o SQ injection o IV infusion o Inhalation—Afrezza, mealtime insulin • What is typical dosing for type 1? Type 2? o Total doses may range from 0.1 unit/kg body weight to more than 2.5 units/kg o Type 1 ▪ Initial doses typically range from 0.5-0.6 units/kg per day o Type 2 ▪ Initial doses range from 0.2-0.6 units/kg per day ▪ Dosage increased or decreased according to carb intake, activity • What are the 3 dosing schedules? o Twice daily dosing o Intensive basal/bolus strategy o Continued subcutaneous insulin • How does metformin work? o Inhibits glucose production in the liver o Reduces glucose absorption in the gut o Sensitizes insulin receptors in target tissues (fat and skeletal muscle) thus increase glucose uptake and response to whatever insulin is available • What are side effects? BB warning? o GI effects—diarrhea o Lactic acidosis • How does alcohol effect? o Inhibits the breakdown of lactic acid • What are the therapeutic uses other than DM? o Gestational diabetes o PCOS • Sulfonylureas o First generation ▪ Chlorpropamide [Diabinese] ▪ Tolazamide [Tolinase] 4 ▪ Tolbutamine [Orinase] o Second Generation: ▪ Glyburide [Diabeta, Glynase, Micronase] with metformin [Glucovance] ▪ Glypizide (Glucotrol, Glucotrol XL); with metformin [metaglip]) ▪ Glimepiride (Amaryl; with metformin [Amaryl M], with pioglitazone [Duetact] with rosiglitazone [Avandaryl] o MOA? ▪ Promote insulin release o Main side effect? ▪ Hypoglycemia ▪ Weight gain o How does cimetidine effect? Beta blocker? ▪ Cimetidine—intensifies the response ▪ Beta blockers—diminish the benefits by suppressing the insulin release • Meglitinides (Repaglinide and Nateglinide) o MOA—stimulate pancreatic insulin release o Drug/Drug interaction—gemfibrozil • Thiazolidinediones (glitazones) o Reduce glucose levels primarily by decreasing insulin resistance o Only indication is type 2 diabetes, mainly as an add-on to metformin o Rosiglitazone [Avandia]: Restricted use o Pioglitazone [Actos] o Can they be used in patient with CHF? ▪ No • Alpha-glucosidase inhibitors (Acarbose or Precose; Miglitol (glyset)) o What races are these more effective in? ▪ Latinos and African Americans • DPP-4 inhibitors (gliptins) o MOA—promote glycemic control by enhancing the actions of the incretin hormones and they stimulate glucose dependent release of insulin ▪ Suppress your post-prandial release of glucagon o What is the % of A1C reduction? ▪ 0.5% • Sodium-glucose cotransporter 2 (SGLT-2) inhibitors (Canagliflozin, Dapagliflozin) • How does colesevelam work in treatment of DM? Bromocriptine? o Colesevelam—bile acid sequestrant used to lower cholesterol and helps lower blood glucose ▪ Many with diabetes also have high cholesterol so 2 birds-1 stone o Bromocriptine—adjunct to diet and exercise (0.5% reduction) • Injectables o Amylin memetics? ▪ Pramlintide ▪ Side effects—hypoglycemia when used with insulin ▪ Drug/Drug—insulin 5 o GLP-1 receptor agonists (or incretin mimetics) ▪ Can cause medullary thyroid cancer • What is treatment of diabetic ketoacidosis (DKA)? Hypoglycemia? o Insulin replacement, reverse acidosis with bicarbonate, replace water, sodium, potassium, normalize glucose levels o Hypoglycemia—IV glucose, glucagon is glucose not available • What is hyperosmolar hyperglycemia state (HHS)? o Large amount of glucose excreted in the urine and results in dehydration and loss of blood volume o Increases blood concentration of electrolytes and nonelectrolytes, particularly glucose and hematocrit o When does this occur? ▪ Most frequently with type 2 diabetics with acute infection or illness or other stressors o Treatment? ▪ Correcting hyperglycemia and dehydration with IV insulin, fluids, and electrolytes • What effect does iodine have on thyroid? o When iodine availability is low production of thyroid hormones decrease • Why is normal thyroid function important in first trimester of pregnancy? How much does requirement unusually increase in pregnant women taking thyroid supplements? o Fetus is unable to produce its own hormones, without can result in permanent neuropsychologic deficits o Usually increases as much as 50% • When is fetal thyroid gland full functional? o 16 weeks • If not treated, what does hypothyroidism cause in an infant? o Large protruding tongue, potbelly, and dwarfish stature o The development of the nervous system, bones, and teeth is impaired • When should treatment be stopped? How long? o At 3 years of age for 4 weeks, then TSH is checked o If rise—deficiency is permanent, thyroid replacement needed o If normalize—transient deficiency, no further replacement required • How is Graves’ Disease treated? o Surgical removal, destruction of the thyroid tissue, suppression of the thyroid hormone synthesis and/or beta blockers o Non-radioactive iodine can be used to distract the thyroid tissue • Thyroid Storm? o Hyperthermia, severe tachycardia, restlessness, agitation, tremor o Unconscious, hypotensive, heart failure o Cannot be identified by lab testing, not triggered by a rise in thyroid hormones o Treatment—methimazole, beta blocker, sedation, cooling, glucocorticoids, IV fluids • Levothyroxine 6 o T4 o Long half life o How should this be taken? ▪ In the morning, at least 30 to 60 minutes before breakfast o Side effects—tachycardia, angina tremors o Drug/Drug ▪ Warfarin—intensify effects ▪ Drugs that reduce absorption • H2 receptor blockers, PPIs, cholestyramine, colestipol, Maalox, Mylanta, calcium supplements, iron, magnesium, orlistat ▪ Accelerate metabolism • Phenytoin, carbamazepine, rifampin, sertraline, phenobarbital ▪ Catecholamines—increase cardiac responses ▪ Increase requirements of insulin and digoxin o How is this dosed? How does dosage differ for someone over 50? 65 and older? Someone with heart disease? Overweight? Underweight? ▪ 1.6-1.8 mcg/kg/day ▪ Obese—go by ideal body weight ▪ Underweight—actual weight ▪ Older patients with CAD—start with 12.5-25 mcg ▪ Elderly—start low and go slow ▪ Younger than 3 months—10 to 15 mcg/kg/day ▪ Children (3-5 months)—8 to 10 mcg/kg/day ▪ Children (6-11 months)—6 to 8 mcg/kg/day ▪ Children 1-5 years—5 to 6 mcg/kg/day ▪ Children 6-12—4 to 5 mcg/kg/day • Liotrix—a mixture of synthetic T4 plus synthetic T3 in a 4:1 fixed ratio o Because levothyroxine alone produces the same ratio of T4 to T3, Liotrix offers no advantage over levothyroxine for most indications • Armour—consists of desiccated animal thyroid glands. o Standardization is based on content of iodine, levothyroxine, and liothyronine. o The ratio of levothyroxine to lipthyronine is not less than 5:1 o Thyroid is available in tablets (15-300 mg) • Methimazole—used in hyperthyroidism o Cell form of therapy for Graves’ disease o Adjunct to radiation therapy until the effects of radiation become manifested o Suppresses the thyroid hormone synthesis in preparation for thyroid gland surgery o Thyrotoxic crisis • Propylthiouracil o Inhibits thyroid hormone synthesis o Second line for graves o Short half-life o Full benefits—6 to 12 months 7 o Uses—graves’, adjunct therapy to radiation, preparation for thyroid gland surgery, thyrotoxic crisis o Adverse effects—agranulocytosis, severe liver damage o Pregnancy? Crosses the placenta less and concentrations in breastmilk are lower than methimazole • Radioactive Iodine 131 (lugol solution) o Effect on the thyroid is destruction of thyroid tissue by emission of beta particles o Advantages—low cost; spared the risk, discomfort, and experience of thyroid surgery; death is extremely rare; no tissue other than thyroid is injured o Disadvantages—treatment is delated, taking several months to become maximal; treatment is associated with significant incidents of delayed hypothyroidism from destruction of thyroid tissue (need levothyroxine) o Diagnostic uses? ▪ Hyperthyroidism, hypothyroidism, and goiter o Pregnancy—contraindicated o What are indications for Lugol solution? ▪ Adults with hyperthyroidism ▪ Patients who have not responded adequately to anti-thyroid drugs or subtotal thyroidectomy ▪ Thyroid cancer o Side effects? ▪ Brassy taste, burning sensation in the mouth and throat, soreness of the teeth and gums, frontal headache, coryza, salvation and skin eruptions • What are stages of menstrual cycle? o Follicular phase o Luteal phase o Full cycle about 28 days • What are estrogen effects on primary and secondary sex characteristics? o Influence the physiologic processes related to reproduction o Affects the ductal growth in the breasts, the thickening and cornification of the vaginal epithelium, the proliferation of the uterine epithelium, and the copious secretion of thickened mucus form the endocervical glands • Metabolic effects of Estrogen? o Positive effect on bone mass—block bone resorption o Favorable effects on cholesterol levels ▪ Decrease LDL, raise HDL o Effect on blood coagulation ▪ Increasing the levels of the coagulation factors o Affect glucose homeostasis ▪ Increase insulin sensitivity and promote glucose uptake • Adverse effects of estrogen? o Endometrial hyperplasia and carcinoma 8 o Increase cardiovascular events, N/V, gallbladder disease, jaundice, headache and chloasma • Therapeutic uses of Estrogen? o Menopausal hormone o Female hypogonadism o Acne • SERMS—Selective estrogen receptor modulators o drugs that activate estrogen receptors in some tissues and block them in others o Why were these developed? ▪ Provide the benefits of estrogen ▪ protection against vaginal atrophy ▪ Reduction of LDL cholesterol, but avoiding the drawbacks o What is Duavee? ▪ Conjugated estrogens with bazedoxifene • Combine estrogen with an estrogen agonist or antagonist ▪ Used for treatment of vasomotor symptoms and osteoporosis in postmenopausal women ▪ Bazedoxifene—reduces the risk of excessive growth of the uterine lining that is posed by the estrogen component • What are noncontraceptive uses for progesterone? o Postmenopausal hormone therapy o Dysfunctional uterine bleeding o Amenorrhea o Infertility o Prematurity prevention o Endometrial carcinoma and hyperplasia • When is estrogen therapy (ET) alone indicated? Estrogen/Progesterone (EPT)? o Estrogen alone—women who have had a hysterectomy o EPT—all other women • What are benefits? Risks? o Benefits ▪ Relief of vasomotor symptoms ▪ Management of urogenital atrophy ▪ Prevention of osteoporosis and related fractures ▪ Cardioprotection ▪ Prevention of colorectal cancer ▪ Positive effect on wound healing ▪ Tooth retention ▪ Glycemic control ▪ Physiologic doses of estrogen (with or without progestin) ▪ Taken to manage symptoms caused by loss of estrogen in menopause • Hot flashes, sleep disturbances, urogenital atrophy, bone loss, altered lipid metabolism • Use of hormone replacement therapy (HRT) has declined sharply 9 o Risks ▪ Cardiovascular events: Myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis ▪ Endometrial cancer ▪ Breast cancer ▪ Ovarian cancer ▪ Gallbladder disease ▪ Dementia ▪ Urinary incontinence • What are 3 approved indications? o Treatment of moderate to severe vasomotor symptoms associated with menopause o Treatment of moderate to severe symptoms of vulvar and vaginal atrophy associated with menopause o Prevention of postmenopausal osteoporosis • Birth Control o What are pharmacologic and nonpharmacologic methods of birth control? ▪ Pharmacologic methods of contraception • Oral contraceptives • Etonogestrel implants • Injectable medroxyprogesterone acetate • Intrauterine devices • Vaginal rings • Transdermal patches ▪ Nonpharmacologic methods of contraception • Surgical sterilization (tubal ligation, vasectomy) • Mechanical devices (condom, diaphragm, cervical cap) • Avoiding intercourse during periods of fertility (calendar method, temperature method, cervical mucus method) o How should you select a method? ▪ Consider effectiveness, safety, personal preference • Oral contraceptives o MOA—inhibit ovulation o What are categories? Subgroups? ▪ Classification (two main categories) • Combination oral contraceptives (OCs) • Estrogen and progestin • Progestin-only OCs (“mini-pills”) ▪ Three major subgroups of combination OCs • Monophasic • Biphasic • Triphasic o What are 3 estrogens in OCPs? Progesterone? 1st gen? 2nd gen? 3rd gen? 4th gen? ▪ Estrogens—ethinyl, estradiol, estriol and estradiol valerate ▪ Progesterone—4 generations 10 • Combination Ocs • 1st generation—ethynodiol diacetate and norethindrone • 2nd gen—levonorgestrel and norgestrel • 3rd gen—desogestrel and norgestimate • 4th gen—dienogest and drospirenone o Adverse effects? ▪ Thyrombolytic disorders • Increase risk—heavy smoking, a history of thrombo embolism, thrombophilias ▪ Hypertension ▪ Cancer ▪ Stroke in patients with migraine ▪ Teratogenic effects ▪ Abnormal uterine bleeding ▪ Use in pregnancy and lactation ▪ Benign hepatic adenoma ▪ Glucose intolerance o Noncontraceptive uses? ▪ Decrease risks of ovarian cancer, endometrial cancer, ovarian cysts, pelvic inflammatory disease, benign breast disease, iron deficiency anemia, and acne ▪ Favorable effect on menstrual cycles • Diminished cramps; lighter, shorter, more predictable flow o What drugs reduce the effects? ▪ Rifampin ▪ Ritonavir ▪ Antiepileptic drugs ▪ St. John’s wort o What drugs effects are decreased by OCs? ▪ Warfarin ▪ Insulin ▪ Oral hypoglycemics o What are drugs whose effects are increased by Ocs? ▪ Several agents, including theophylline, tricyclic antidepressants, diazepam, and chlordiazepoxide o What are unique properties of Beyaz and Safyral? Natazia? ▪ Beyaz and Safyral • Contain levomefolate (metabolite of folic acid) o Reduce risk for fetal neural tube defects and spinal bifida, if pregnancy should occur despite contraceptive use ▪ Natazia • Estradiol valerate—prodrug that undergoes rapid conversion to estradiol, does not cause potassium retention • Dienogest—fourth gen progestin • What are missed dosing schedules for 28-day cycle Ocs? Extended and continuous cycle? 11 o 28-day-cycle schedules ▪ One or more pills missed first week: Take one pill as soon as possible (ASAP) and continue with the pack; use an additional form of contraception for 7 days ▪ One or two pills missed second or third week: Take one pill ASAP and continue with active pills in the pack; skip placebo pills and go straight to a new pack once all the active pills have been taken ▪ Three or more pills missed second or third week: Follow instructions given for missing one or two pills; also, use an additional form of contraception for 7 days o Extended cycle and continuous schedules ▪ Up to 7 days can be missed with little or no increased risk of pregnancy, provided the pills had been taken continuously for the prior 3 weeks • Progestin only: what are drawbacks? Why do most women stop? o Less effective and irregular bleeding • How is NuvaRing used? o Inserted into vagina once a month o Left for 3 weeks then removed and a new ring is inserted 1 week later • Long-acting contraceptives o Implants—irregular bleeding, can stop period all together o Depot medroxyprogesterone acetate ▪ Side effects? • Menstrual irregularities • Bone loss ▪ How often are injections given? • Every 3 months o IUDs ▪ What are the different types and how long can they remain in place? • Copper T 380A [ParaGard] – 10 years • Levonorgestrel-releasing intrauterine system [Mirena] – 5 years o Spermicides—Chemical surfactants that kill sperm by destroying their cell membrane • What are drugs used for medical abortion? o Mifepristone (RU 486) with misoprostol • What is Plan B? o Single high dose tablet, 1.5 mg of levonorgestrel o Must be taken within 72 hours of unprotected intercourse • What are the indications of prostaglandins? o Induction of abortion for cervical ripening before induction of labor o Control of postpartum hemorrhage • What are the therapeutic uses of testosterone? o Male hypogonadism o Replacement therapy o Delayed puberty o Replacement therapy in menopausal women o Wasting in patients with acquired immunodeficiency syndrome (AIDS) 12 o Anemias • What are adverse effects of Testosterone? o Virilization in women, girls, and boys o Premature epiphyseal closure o Hepatotoxicity o Effects on cholesterol levels o Use in pregnancy o Prostate cancer o Edema o Abuse potential (athletic performance) • What are the preparations? Instructions on use? o Preparations ▪ Oral androgens: Fluoxymesterone and methyltestosterone ▪ Intramuscular testosterone esters ▪ Transdermal testosterone patches ▪ Transdermal testosterone gels ▪ Transdermal testosterone under arms ▪ Implantable subcutaneous testosterone pellets ▪ Testosterone buccal tablets o Topical Applications ▪ Pick the location for application ▪ Avoid skin-to-skin contact transfer ▪ Wash hands with soap and water after every application ▪ Cover application site with clothing once gel is dry ▪ Women and children: Avoid contact ▪ Swimming and showering—5 to 6 hours after application • What are side effects of anabolic steroids? o Hypertension, suppression of release of LH and FSH, testicular shrinkage, sterility, gynecomastia, acne, reduction in HDL, increase in LDL o Hepatotoxicity with 17-alpha-alkylated compounds o Renal damage o Psychologic effects ▪ Mentally healthy: Minimal impact ▪ Psychologically unbalanced: Could intensify aggression • Phosphodiesterase type 5 (PDE-5) inhibitors (-afils) o Rare side effects? ▪ Nonarthritic ischemic optic neuropathy o Drug interactions? ▪ Nitrates (could cause life-threatening hypotension) ▪ Alpha blockers (can cause symptomatic postural hypotension) ▪ Inhibitors of cytochrome P450 (CYP3A4) (can suppress metabolism) o MOA? ▪ Only enhances normal erectile response in the presence of stimuli ▪ Relaxes arterial and trabecular smooth muscle in the penis 13 o What are the injectables? ▪ Papaverine ▪ Alprostadil • Benign Prostatic Hyperplasia o 5-Alpha-reductase inhibitors (mechanical obstruction) ▪ Finasteride ▪ Dutasteride o Alpha1-adrenergic antagonists (dynamic obstruction) ▪ Terazosin [Hytrin] ▪ Doxazosin [Cardura] ▪ Tamsulosin [Flomax] ▪ Alfuzosin [Uroxatral] ▪ Silodosin [Rapaflo] ▪ MOA • Blockade of alpha1 receptors relaxes smooth muscle in the bladder neck (trigone and sphincter) ▪ Side effects • Tamsulosin [Flomax] and alfuzosin [Uroxatral] o Less likely to cause the effects of terazosin and doxazosin o Tamsulosin can cause abnormal ejaculation • Terazosin [Hytrin] and doxazosin [Cardura] o Hypotension, fainting, dizziness, somnolence, and nasal congestion • These drugs do not decrease PSA levels ▪ Drug Interactions? • Exercise caution with other medications that lower blood pressure o Organic nitrates, antihypertensive drugs, PDE-5 inhibitors used for ED o Inhibitors of CYP3A4 • Cataract surgery: “Floppy-iris syndrome” • Overactive bladder o Tolteridine o Oxybutynin o Solifenacin o Tolterodine o Trospium o Botulinum toxin • What does activation of H1 receptors cause? o Dilation of small blood vessels • What are the actions of H2 receptors? o Regulate the secretion of gastric acid • H1 antagonists o First generation (sedating)—Benadryl ▪ MOA 14 • Block the actions of histamine at H1 receptors • Do not block H2 receptors • Some bind to muscarinic receptors ▪ Therapeutic uses? • Mild allergy • Severe allergy—used in adjunct with other treatments • Motion sickness (promethazine and dimenhydrinate) • Insomnia (Diphenhydramine) ▪ Adverse effects • Sedation • GI effects • Dizziness • Fatigue • Coordination problems • Confusion • Anticholinergic effects—dry mouth, constipation, etc. • Severe respiratory depression • Severe local tissue injury ▪ Drug/Drug • Alcohol • CNS depressants o Second Generation (non-sedating) ▪ Examples: Cetirizine, fexofenadine, loratadine ▪ Fexofenadine [Allegra, Allegra Allergy, Allegra ODT] • Uses: Oral therapy of seasonal allergic rhinitis and for chronic idiopathic urticaria • Of second-generation antihistamines, offers best combination of efficacy and safety • Use with caution in patients with renal impairment • Do not take with fruit juice ▪ Cetirizine [Zyrtec] • Uses: Allergic rhinitis and chronic idiopathic urticaria • Food delays absorption • More sedating than other second-generation antihistamines but less sedating than first-generation drugs ▪ Levocetirizine [Xyzal] • Uses: Allergic rhinitis and chronic idiopathic urticaria • More sedating than other second-generation antihistamines but less sedating than first-generation agents • Most common side effects: Drowsiness, fatigue, muscle weakness, dry mouth • Avoid alcohol and other CNS depressants ▪ Loratadine [Claritin] • Use: Seasonal allergic rhinitis 15 • Generally, well tolerated • Food delays absorption • Use with caution in patients with significant hepatic and renal impairment ▪ Desloratadine [Clarinex] • Uses: Seasonal allergic rhinitis, perennial allergic rhinitis, and chronic idiopathic urticaria • Allergic Rhinitis o Inflammatory disorder of the upper airway, lower airway, and eyes o Seasonal and perennial o Triggered by airborne allergens o Allergens bind to immunoglobulin E (IgE) on mast cells o Triggers release of inflammatory mediators ▪ Histamine, leukotrienes, prostaglandins o Drug Classes used to treat ▪ Intranasal glucocorticoids • First choice • Side effects o Drying of nasal mucosa or sore throat o Epistaxis (nosebleed) o Headache o Rarely, systemic effects (adrenal suppression and slowing of linear pediatric growth) ▪ Intranasal and oral antihistamines—Azelastine and Olopatadine • Best used prophylactically • For children over 12 and adults • 1-2 weeks to take affects • Side effects o Systemic absorption can be sufficient to cause somnolence o Nosebleeds o Anticholinergic effects o Unpleasant taste ▪ Intranasal and oral sympathomimetics • Reduce nasal congestion (do not reduce rhinorrhea, sneezing or itching) • Activate alpha1-adrenergic receptors on nasal blood vessels • Adverse effects o Rebound congestion o CNS stimulation o Cardiovascular effects and stroke o Abuse • Factors in topical administration o Should not be used longer than 5 consecutive days o Drops or sprays 16 • Comparison: Oral versus Nasal o Topical agents act more quickly than oral agents and are usually more effective o Oral agents act longer than topical preparations o Systemic effects occur primarily with oral agents; topical agents usually elicit these responses only when dosage is higher than recommended o Rebound congestion is common with prolonged use of topical agents but rare with oral agents o Montelukast ▪ Benefits derive from blocking binding of leukotrienes to their receptors o Omalizumab ▪ Is a monoclonal antibody directed against IgE, an immunoglobulin (antibody) that plays a central role in the allergic release of inflammatory mediators from mast cells and basophils? ▪ Used for asthma and allergic rhinitis • Cough o What are the nonopioid antitussives? ▪ Dextromethorphan ▪ Diphenhydramine ▪ Benzonatate (Tessalon) o Opioid antitussives ▪ Codeine and hydrocodone o How does Benzonatate work? ▪ Structural analog of two local anesthetics, tetracaine and procaine, and I suppress cough by decreasing the sensitivity of the respiratory tract stretch receptors. o What are the expectorants? ▪ Guaifenesin (Mucinex) o What are the inhaled mucolytics? ▪ Hypertonic saline and acetylcysteine • Cold o Do cold remedies work? ▪ No, can make it worse by thickening the secretions ▪ Convenient ▪ May contain ingredients that a patient does not even really need o What are AAP recommendations? ▪ Restricting the use of these medications to children older than six • Asthma/COPD o What is the pathophysiology of asthma and COPD? ▪ Asthma—result from a combination of inflammation and bronchoconstriction, so treatment must address both components ▪ Symptoms of COPD result largely from two pathologic processes: Chronic bronchitis and emphysema 17 o How do they differ? ▪ Asthma—immune mediated airway inflammation is the cause ▪ COPD—cause is cigarette smoking o What are the 3 delivery systems for inhaled treatments? ▪ Metered dosed inhalers ▪ Respimat—soft mist inhalers ▪ Dry powder inhalers (DPIs) ▪ Nebulizers o What are the anti-inflammatory agents used? ▪ Glucocorticoids (budesonide and fluticasone) ▪ MOA—suppress inflammation • Considered the most effective antiasthma drugs available • Decrease synthesis and release of inflammatory mediators • Reduce infiltration and activity of inflammatory cells • Decrease edema of the airway mucosa ▪ Adverse effects? • Adrenal suppression • Oropharyngeal candidiasis • Dysphonia ▪ Adverse effects of oral forms? • Short-term therapy—none • Long-term therapy o Adrenal suppression o Osteoporosis o Hyperglycemia o Peptic ulcer disease o In young patients: Growth suppression • Leukotriene Modifiers o In patients with asthma, leukotriene modifiers can reduce bronchoconstriction and inflammatory responses such as edema and mucus secretion o Used 2nd line if cannot tolerate inhaled glucocorticoids o Can cause psychiatric adverse effects • Cromolyn o Indications ▪ Chronic asthma ▪ Exercise-induced bronchospasm (EIB) ▪ Allergic rhinitis o Adverse effects ▪ Safest of all antiasthma medications ▪ Cough ▪ Bronchospasm • Monoclonal Antibody: Omalizumab o Indications 18 ▪ Patients age 12 years or older with moderate to severe asthma that (1) is allergy related and (2) cannot be controlled with an inhaled glucocorticoid o Adverse effects ▪ Injection-site reactions ▪ Viral infection ▪ Upper respiratory infection ▪ Sinusitis ▪ Headache ▪ Pharyngitis ▪ Cardiovascular events ▪ Malignancy ▪ Life-threatening anaphylaxis • Bronchodilators o SABA—short acting beta agonist ▪ PRN to abort an ongoing attack, exercise-induced bronchospasm (take prior to exercise to prevent attack), hospitalized patients undergoing severe acute attack o LABA—long acting beta agonist ▪ Long-term control in patients who experience frequent attacks ▪ Preferred over SABAs for patients with stable COPD ▪ Must always be used with inhaled corticosteroid—if treating asthma o Methylxanthines ▪ Theophylline ▪ Very narrow therapeutic index (levels of 10-20 mcg/ml) ▪ Used in asthma and COPD ▪ Maintenance therapy for chronic stable asthma ▪ No longer recommended for treatment of COPD o Anticholinergic drugs ▪ Ipratropium • Short acting • Relieves bronchospasms • Therapeutic effects begin within 30 secs, reach 50% of maximum in 3 mins and persist about 6 hours ▪ Long acting • Tiotropium o Maintenance therapy of bronchospasm associated with COPD o Not approved for asthma • Aclidinium o Management of bronchospasm associated with COPD • Umeclidinium o Management of bronchospasm associated with COPD • Management of Asthma o Classes of asthma severity ▪ Intermittent ▪ Mild persistent 19 ▪ Moderate persistent ▪ Severe persistent o Goal of treatment? ▪ Reduce impairment and reduce risk ▪ Prevent chronic and troublesome symptoms ▪ Reduce use of SABAs for symptoms relief to two days a week or less ▪ Maintain normal pulmonary function ▪ Maintain normal activities ▪ Meeting patient and family expectations regarding asthmas care ▪ Prevent recurrent exacerbations ▪ Minimize need for ER visits or hospitalizations ▪ Prevent progressive loss of lung functions ▪ Provide maximal benefits with minimal adverse effects o Step wise therapy? ▪ Step chosen for initial therapy is based on pretreatment classification of asthma severity ▪ Moving up or down a step is based on ongoing assessment of asthma control ▪ 6 steps • No daily medication needed, SABAs PRN • Low dose inhaled corticosteroid plus SABA • Low doses inhaled corticosteroid plus LABA or medium dose inhaled glucocorticoid (and SABA as well) • Medium dose inhaled glucocorticoid plus LABA plus SABA • High dose inhaled glucocorticoid steroids plus LABA plus SABA • High-dose inhaled glucocorticoids plus LABA plus oral glucocorticoids plus SABA o Exacerbation management ▪ Important to reduce exposure to allergens and triggers ▪ Sources of allergens: House dust mites, pets, cockroaches, mold ▪ Factors that can exacerbate asthma: Tobacco smoke, wood smoke, household sprays • Management of COPD o What is the FEV1/FVC that indicates COPD? ▪ Less than 0.7 o What are the stages of severity of COPD? Treatment of each? ▪ Stage I: Mild: • FEV1/FVC 0.70 • FEV1 ≥ 80% predicated ▪ Stage II: Moderate • FEV1/FVC 0.70 • 50% ≤ FEV1 80% ▪ Stage III: Severe • FEV1/FVC 0.70 • 30% ≤ FEV1 50% 20 ▪ Stage IV: Very Severe • FEV1/FVC 0.70 • FEV1 30% or • FEV1 50% plus chronic respiratory failure ▪ Treatment • Bronchodilators • Glucocorticoids • Phosphodiesterase-4 inhibitors o Classifications: ▪ SABA for symptom control all groups • Group A: Few symptoms; low risk o First choice: Consider LAMA or LABA o Persistent symptoms: combination LAMA/LABA • Group B: Increased symptoms; low risk o First Choice: LAMA OR LABA o Persistent symptoms: combination LAMA/LABA • Group C: Few symptoms; high risk o First LAMA o Management of persistent symptoms: LABA/LAMA (preferred) or LABA/IGC • Group D: Increased symptoms; high risk o First Choice: LAMA; OR LAMA/LABA; OR IGC/LABA o Management of persistent symptoms: LAMA/LABA/IGC ▪ If exacerbations persist add Roflumilast, Azithromycin o Exacerbation management ▪ SABAs (specifically inhaled, either alone or in combination with inhaled anticholinergics) are preferred for bronchodilation during COPD exacerbations ▪ Systemic glucocorticoids ▪ Antibiotics ▪ Supplemental oxygen to maintain an oxygen saturation of 88% to 92% • Glaucoma o How do drugs lower intraocular pressure (IOP)? ▪ Facilitate the aqueous humor outflow and can also reduce aqueous humor production o First line ▪ Beta-adrenergic blocking agents • Timolol ▪ Alpha2-adrenergic agonists • Brimonidine (Alphagan) ▪ Prostaglandin analogs • Latanoprost (Xalatan) o Second line ▪ Cholinergic agonists o Beta-Adrenergic Blocking agents 21 ▪ Approved for use in glaucoma: Betaxolol, carteolol, levobunolol, metipranolol, and timolol ▪ Lower IOP by reducing production of aqueous humor ▪ Used primarily for open-angle glaucoma ▪ Initial therapy and maintenance therapy ▪ Which are recommended for patients with asthma? • Betaxolol and levobetaxolol o How do prostaglandin analogs work? (prosts) ▪ Lowers intraocular pressure by facilitating aqueous humor outflow o How do alpha2-adrenergic agonists work? ▪ Lowers intraocular pressure by reducing aqueous humor production and possibly by increasing outflow ▪ Two approved: Apraclonidine and brimonidine o How does pilocarpine work? ▪ Direct-acting cholinergic agonist that causes miosis and contraction of the ciliary muscle o How do cholinesterase inhibitors work? ▪ Inhibits the breakdown of acetylcholine and promotes accumulation of acetylcholine at the muscarinic receptors o How do Carbonic anhydrase inhibitors (CAIs) work? ▪ Reduces intraocular pressure by decreasing production of aqueous humor • Cycloplegics and Mydriatics o Cycloplegics: paralyze ciliary muscles o Mydriatics: dilate the pupil o Used to measure refraction o Intraocular examination o Treatment of anterior uveitis • Allergic conjunctivitis o Mast-cell stabilizers o NSAIDS (ketorolac) ▪ Side effects with long term use? • Cataract, eye infection and elevation of interocular pressure o Ocular decongestants (naphazoline, phenylephrine) ▪ Activating alpha one adrenergic receptor on the blood vessels, causing vasoconstriction • Age Related Macular Degeneration o Dry ▪ Drusen—yellow deposits under the retina ▪ Treatment—high doses of antioxidants and zinc o Wet ▪ Growth of new subretinal blood vessels which are often very fragile and leak ▪ Treatment—laser therapy, photodynamic therapy, or angiogenesis inhibitors (pegaptanib, ranibizumab, aflibercept, and bevacizumab)