ptp 546 endocrine pharmacology module 11 jayne hansche lobert, ms, rn, acns-bc, np 1lobert

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PTP 546Endocrine Pharmacology

Module 11

Jayne Hansche Lobert, MS, RN, ACNS-BC, NP

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Endocrine PharmacologyAdrenalcorticoids

• Naturally Occurring Adrenal Corticoids– Negative feedback loop

• Hypothalamus CRH Pituitary ACTH adrenal cortex cortisol

– Glucocorticoids • Cortisol, Corticosterone

– Glucose, protein and lipid metabolism– Anti-Inflammatory effects– Immunosuppressive effect

– Mineralcorticoids • Aldosterone

– Fluid and electrolyte control

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• Pharmacologic Glucocorticoids – Ex:Dexamethasone (Decadron)– Ex:Hydrocortisone (Cortef)– Ex:Methylpredisolone (Medrol)– Ex:Prednisone (Deltasone)– Ex:Triamcinolone (Azmacort)

• Routes of Administration– IV, inhaled, oral, intraarticular, topical, nasal,

ophthalmic, otic, etc.

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• Glucocorticoids– Action: inhibit the production of proinflammatory

substances suppression of inflammation; inhibit immune cell synthesis suppression of the immune response

– Therapeutic Use• Replacement associated with adrenal insufficiency• Reduce inflammation in many conditions• Suppression of the immune response

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Inflammatory Disorders• Allergic Reactions,

Anaphylaxis• Psoriasis, Dermatitis• Osteoarthritis, Gouty

Arthritis, Rheumatoid Arthritis

• Bursitis, Synovitis• Leukemia's, Lymphomas• Closed Head Injury, Spinal

Cord Injury, Brain Tumors

• Organ Transplantations• Crohn’s, Ulcerative Colitis• Bronchial Asthma, COPD• Pneumonias• Scarcidosis• Multiple Sclerosis,

Myasthenia Gravis• Systemic Lupus

Erythematosus (SLE)

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• Glucocorticoids– Side Effects:

• Dyspepsia, gi upset, gi bleed, peptic ulcers• Increased risk for infection• Mood changes, labile emotions• Sodium retention, hypertension• Bone loss, osteoporosis, fracture risk• Muscle atrophy, delayed wound healing• Hyperglycemia• Increased appetite, weight gain• Changes in appearance: “Moon face”, truncal obesity, acne, “buffalo hump”,

thin limbs, increased body hair

– Side Effects:• Reflect an excess of adrenal hormone; Cushing’s Syndrome/Disease; Adrenal

Hypersecretion

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• Precautions– Avoid abrupt withdrawal• Taper off prior to discontinuation of med • Rapid Adrenal Insufficiency Addison’s

Syndrome/Disease/ Adrenal Crisis– Life Threatening Effects: lethargy, confusion & coma

– Recognize value of glucocorticoids– Recognize significant side effects of

glucocorticoids

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• Mineralcorticoids– Ex: Fludrocortisone (Florinef)– Action: causes sodium reabsorption & water

retention, potassium loss in distal renal tubules– Therapeutic Effect: replacement of

mineralcorticoids with conditions of adrenal insufficiency such as Addison’s Disease; Post Adrenalectomy

– Side Effects: hypertension, sodium retention, water retention, edema, weight gain, hypokalemia

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Endocrine PharmacologySex Hormones

• Naturally Occurring Male Sex Hormones– Androgens• Testosterone

– Effect of Androgens• Development of male sexual characteristics

– Increased body hair, increased skeletal muscle mass, voice change, maturation of external genitalia

• Stimulation of spermatogenesis– Facilitate growth and maturation of developing sperm

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• Pharmacologic Androgens– Examples:• Fluxymesterone (Android)• Methylestesterone (Durabolin)• Oxandrolone (Oxandrin)• Testosterone Gel (Androderm)• Testosterone Transdermal (Androgel)

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• Pharmacologic Androgens– Action: mimic androgenic effects development of male

sexual characteristics and mimics anabolic effects development of muscles, increase in the lean muscle mass

– Therapeutic Use:• Replacement therapy• Catabolic states• Delayed puberty• Breast Cancer

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• Pharmacologic Androgens– Side Effects:• Women: hair growth, voice deepening, irregular

menstruation, acne• Male: bladder irritation, breast swelling, prolonged

erections, increased risk of prostate cancer• Children: accelerated sexual maturation, impairment of

bone growth• General: hypertension, elevation in lipid profile, liver

damage, liver cancer

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• Naturally Occurring Female Hormones– Estrogen• Estradiol

– Progestins• Progesterone

– Effects:• Development of female sexual characteristics• Development of female reproductive system• Facilitation and maintenance of pregnancy

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• Pharmacologic Female Hormones– Examples:• Conjugated estrogens (Premarin)• Estradiol(Estraderm, Depo-Estradiol)• Medroxyprogesterone (Provera)• Levonorgestrel (Norplant)

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• Pharmacologic Female Hormones– Action: mimics naturally occurring hormones

– Therapeutic Use:• Replacement therapy• Hypogonadism• Failure of ovarian development• Menstrual irregularities• Endometriosis• Carcinoma

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• Pharmacologic Female Hormones– Side Effects:• Myocardial Infarctions, thromboembolism, stroke• Abnormal clotting thrombophlebitis, pulmonary

embolism• Increase risk for ovarian, endometrial and breast

cancers• Transient nausea• Sodium and water retention

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• Selective Estrogen Receptor Modulators– Ex: Tamoxifen (Nolvadex)– Ex: Raloxifene (Evista)– Action: blocks estrogen receptors– Therapeutic Effect: used for treatment of hormone

specific cancers– Side Effects: hot flashes, joint pain, nausea and

vomiting

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• AntiProgestins– Ex: Mifepristone (RU486)– Action: stimulate uterine contractions embryo

expulsion– Therapeutic Effect: pregnancy termination– Side Effects: excessive contractions, incomplete

abortion, excessive bleeding

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• Hormonal Contraceptives– Ex: Estradiol & Norethidrone (Loestrin)– Ex: Estradiol & Etonogestrel (Nuva Ring)– Ex: Levonorgestrel (Norplant)– Ex: Medroxyprogesterone (Depo-Provera)

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• Hormonal Contraceptives– Action: inhibit ovulation, impairs uterine

endometrial implantation– Therapeutic Effect: prevention of pregnancy– Side Effects: cardiovascular effects such as

thromboembolism, stroke, MI, liver cancer with prolonged use, nausea, headache, weight gain

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Endocrine PharmacologyThyroid & Parathyroid Hormones & Drugs Affecting Bone Mineralization

• Naturally Occurring Thyroid Hormone– T4 (Thyroxine) and T3 (Triiodothyronine)• Maintain body temperature• Increase basal metabolic rate• Facilitates normal growth and development• Increase heart rate and myocardial contractility • Enhance glucose absorption• Enhance lipolysis

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• Drugs to Treat Hyperthyroidism– Antithyroid Agents• Ex: Methimazole (Tapazole)• Ex: Propylthiouracil (PTU)

– Iodide• Ex: SSKI

– Radioactive Iodine • Ex: RA 131

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• Drugs to Treat Hyperthyroidism– Antithyroid Agents• Ex: Methimazole (Tapazole)• Ex: Propylthiouracil (PTU)

– Action: inhibits conversion of T4T3; blocks thyroid peroxidase enzyme

– Therapeutic Effect: reduction of thyroid hormone synthesis

– Side Effects: agranulocytosis, itching, rash

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• Drugs to Treat Hyperthyroidism– Iodide• Action: inhibits all steps in thyroid hormone synthesis;

dramatically reduces thyroid hormone in limited situations • Side Effects: stains teeth

– Radioactive Iodine: RA 131• Action: destroys thyroid tissue• Side Effects: hypothyroidism

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• Drugs to Treat Hypothyroidism– Thyroid Hormone• Ex: Levothyroxine (Levothroid, Synthroid)• Ex: Liothyronine (Cytomel)

– Action: Supplement/replace T3 and/or T4 reduction of TSH; mimics function of the thyroid gland

– Therapeutic Effect: treatment of thyroid deficiency related to hypothyroidism, thryroidectomy, etc.

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Side Effects of too little thyroid hormone replacement

• Lethargy• Weight gain• Constipation• Bradycardia• Weakness• Facial edema• Concentration difficulties• Fatigue• Coarse skin

Side Effects of excess thyroid hormone replacement

• Fatigue• Weight loss• Diarrhea• Tachycardia• Muscle wasting• Increased appetite• Insomnia• Menstrual irregularities• Exopthalmos

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• Regulation of Bone Mineral Homeostasis– Parathyroid Hormone (PTH)

• Increases blood calcium levels & increases phosphate excretion; stimulates Vitamin D increased calcium absorption from intestines

• High levels of PTH bone breakdown• Normal levels of PTH bone synthesis

– Vitamin D• Helps increase calcium, phosphate enhances bone formation

– Calcitonin• Physiologic antagonist of PTH; lowers blood calcium by

stimulating bone formation; incorporates phosphate into bone

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• Phamacoloigics for Bone Mineral Homeostasis– Calcium Supplements– Vitamin D– Biphosphonates– Calcitonin– Estrogen

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• Calcium Supplements– Ex: Calcium Carbonate (Os-Cal); Calcium Citrate

(Citracal)– Action: mimics calcium effects in body– Therapeutic Effect: supports bone formation

assoc. with dietary insufficiency, hypoparathyroidism; rickets

– Side Effects: constipation, fatigue– Post Menopausal Intake: 1200-1500 mg/day

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• Vitamin D Supplements– Ex: Vitamin D (OsCal & D)– Action: mimics Vit D effects in body; necessary for

calcium absorption in the intestines– Therapeutic Effect: enhances bone mineralization– Side Effects: headache, thirst, metallic taste

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• Biphosphonates– Ex: Alendronate (Fosamax) – Action: directly reduces bone resorption– Therapeutic Effect: prevent bone loss assoc with

steroid use; treatment of osteoporosis to reduce risk of vertebral fractures; treatment of Pagets disease

– Side Effects: gi upset and esophagitis (remain upright for 30 minutes following administration to prevent)

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• Calcitonin– Ex: Calcitonin (Calcimar)– Action: mimics endogenous calcitonin decreased

blood calcium levels ensuring calcium availability for bone mineralization

– Therapeutic Effect: use in conditions that are characterized by increased bone resorption

– Side Effects: redness & swelling following injections, gi upset

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Endocrine PharmacologyTreatment of Diabetes Mellitus

• Type I Diabetes– Etiology: young age, viral trigger for autoimmune

response– Pathophysiology: destruction of pancreatic beta

cells total lack of insulin production– Clinical Signs & Symptoms: rapid onset of the

clinical manifestations of polyuria, polydipsia, polyphagia

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• Type II Diabetes– Etiology: aging individuals; genetic predisposition;

obesity, lack of exercise, poor dietary intake– Pathophysiology: reduced tissue sensitivity to

insulin (insulin resistance); reduction in insulin production; irregular release of insulin

– Clinical Signs & Symptoms: slow and gradual onset of the clinical manifestations of delayed wound healing, fatigue; blurred vision

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• Complications of Diabetes– Microvascular• Retinopathies blindness• Nephropathies renal failure• Neuropathies

– Sensory– Autonomic

– Macrovascular• Hypertension, myocardial infarction, cerebral vascular

accidents, peripheral arterial disease, amputations

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• Prevention of Complications– Diabetes Control and Complications Trial (DCCT) &

United Kingdom Prospective Diabetes Study (UKPDS)• Prolonged elevations in blood glucose structural and

functional changes in vascular cells

– Tight Glycemic Control Prevents Complications• Maintain blood glucose 70-100mg/dl• Side Effect: risk for hypoglycemia

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• Management of Diabetes Mellitus– Diet– Exercise– Medications• Oral hypoglycemic agents• Insulin

– Blood Glucose Monitoring

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• Insulin– Types (Onset/Peak/Duration)• Immediate Acting (<0.5 hr/1.5 hr/3-6hr)

– Lispro (Humalog); Aspart (Novolog)

• Rapid Acting (.5 hr/2-4hr/5-7 hr)– Regular (Humulin R, Novolin R)

• Intermediate Acting (1-3 hr/6-12hr/18-24 hr)– Isophane (Humulin N, Novolin N)– Insulin Zinc (Humulin L, Novolin L)

• Long Acting ( 2hr/ no peak/24 hrs)– Glargine (Lantus)

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• Insulin– Routes: IV, subcutaneous injections, insulin pump

subcutaneous– Action: mimics endogenous insulin; facilitates

glucose transport into cells– Therapeutic Effect: reduction of blood glucose– Side Effects: Hypoglycemia

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• Antidiabetic Agents– Sulfonylureas

• Ex: Glipizide (Glucotrol)

– Biguanides• Ex: Metformin (Glucophage)

– Alpha-Glucosidase Inhibitors• Ex: Acarbose (Precose)

– Thiazolinediones• Ex: Rosiglitazone (Avandia)

– Meglitinides• Ex: Repaglinide (Prandin)

– Glucagon Like Peptide/ Incretin Mimic• Ex: Exenatide (Byetta)

– Dipeptidyl Peptidase-4 Inhibitor (DDP-4)

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• Oral Antidiabetic Agents– Sulfonylureas– Ex: Glipizide (Glucotrol); Glyburide (DiaBeta)– Action: increase insulin secretion from pancreatic

beta cells– Therapeutic Effect: reduces blood glucose; reduces

hepatic glucose production– Side Effects: weight gain, hypoglycemia, gi upset

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• Oral Antidiabetic Agents– Biguanides• Ex: Metformin (Glucophage)

– Action: decreases hepatic glucose production; increases muscle tissue sensitivity to insulin

– Therapeutic Effect: reduction of blood glucose– Side Effects: diarrhea, gi disturbances; rarely lactic

acidosis occurs, to avoid hold IV contrast media for 48 hrs

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• Oral Antidiabetic Agents– Alpha-Glucosidase Inhibitors• Ex: Acarbose (Precose)

– Action: inhibits breakdown of glucose and delays absorption of glucose in the intestine

– Therapeutic Effect: reduction of blood glucose– Side Effects: gi disturbances, bloating, gas,

diarrhea

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• Oral Antidiabetic Agents– Thiazolinediones• Ex: Rosiglitazone (Avandia)

– Action: increases glucose uptake in muscles, decreases glucose production

– Therapeutic Effect: reduces blood glucose– Side Effects: weight gain, edema

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• Oral Antidiabetic Agents– Meglitinides• Ex: Repaglinide (Prandin)

– Action: stimulates rapid release of insulin from the pancreas

– Therapeutic Effect: reduces blood glucose– Side Effects: weight gain, hypoglycemia

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• Oral Antidiabetic Agents– Dipeptidyl Peptidase-4 Inhibitor (DDP-4)• Ex: Sitagliptin (Januvia)

– Action: enhances incretin system, stimulates release of insulin from the pancreas, decreases hepatic glucose production

– Therapeutic Effect: reduces blood glucose– Side Effects: upper respiratory tract infections,

sore throat, diarrhea

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• Miscellaneous Injectable Antidiabetic Agents– Glucagon Like Peptide/Incretin Mimic• Ex: Exenatide (Byetta)

– Amylin Analog• Ex: Pramlintide (Symlin)

– Action: decrease gastric emptying, decrease glucagon production, increased satiety

– Therapeutic Effect: reduces blood glucose– Side Effects: hypoglycemia, nausea, vomiting

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• Hypoglycemic Side Effect– Signs & Symptoms

• Confusion, irritability, diaphoresis, tremors, hunger, weakness, visual disturbances coma, seizures, death

– Treatment• Oral Glucose

– 10-15 g of CHO= 6 oz. Orange juice, 8 oz. milk– Glucose tablets, glucose paste

• IV Glucose– 50% Dextrose Injection

• Intramuscular Glucagon

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• Hypoglycemia– Causes/Contributing Factors• Imbalance of exercise, meds and meals• Hypoglycemic unawareness

– Prevention• Education• Awareness• Preparedness

ptp 546 endocrine pharmacology module 11 jayne hansche lobert, ms, rn, acns-bc, np 1lobert

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