Drugs Affecting Endocrine and Metabolic Function

MENNONITE COLLEGE OF NURSING

AT

ILLINOIS STATE UNIVERSITY

Pharmacotherapeutics for Advanced Practice Nursing 433

Drugs Affecting Endocrine and Metabolic Function

Thyroid Hormones

A little A & P review…

·  Hypothalamus à TRH (thyrotropin releasing hormone)à Pituitary à TSH (thyroid-stimulating hormone)à Thyroid à T4, which is converted to T3 in the tissues of the thyroid, liver, and brain

·  The thyroid cells put iodine and tyrosine together to form T4.

·  Thyroxine (T4) and triiodothyronine (T3) are the two hormones produced by the thyroid gland. T4 has 4 iodine atoms; conversion causes loss of 1 iodine atom and the resultant T3. 80% of thyroid hormone is T4; 20% is T3. T3 is 40X more potent than T4.

Hypothyroidism

·  Types of hypothyroidism

o  Primary hypothyroidism is caused by an abnormality in the thyroid gland itself.

o  Secondary hypothyroidism may result from a dysfunctional pituitary gland (lowered TSH level).

o  Tertiary hypothyroidism is due to hypothalamic rather than pituitary dysfunction (lowered TRH level)

§  Tertiary hypothyroidism similar to secondary in that the stimulus needed for secretion of thyroid hormone is absent.

o  All three types of hypothyroidism are amenable to thyroid hormone replacement.

·  Thyroid replacement

o  Given to replace what the thyroid gland cannot itself produce in order to achieve normal thyroid levels (euthyroid)

o  Natural and synthetic thyroid hormone

§  Natural preparations are derived from animal thyroid and include thyroid and thyroglobulin

§  Synthetic preparations include:

·  levothyroxine (Levoxine, Synthroid, Levoxyl) = synthetic T4

·  liothyronine (Cytomel) = synthetic T3

·  liotrix (Thyrolar, Euthroid) = synthetic T3/T4 combination

§  Levothyroxine is the preferred agent because its hormonal content is standardized and its effect is therefore predictable.

o  Dosing: Start low and go slow!

§  With levothyroxine (Synthroid, for example), starting dosages:

·  If young, OK à start on 0.1 mg po/day

·  If > 45 yr. old, no CV disease à start on 0.05 mg/day

·  If elderly, have CV disease, have longstanding hypothyroidism à started on 0.025 mg/day

§  Increase dosage by 0.025 mg every 4 weeks until TSH within normal limits

§  Elderly patients are much more sensitive to thyroid hormone replacement therapy à more liable to suffer more adverse reactions to thyroid hormones than patients in any other age group.

·  Because the symptoms of hypothyroidism may be confused with those of other diseases, nonspecific symptoms such as stumbling, falling, depression, incontinence, cold intolerance, and weight gain should be thoroughly evaluated and documented before a diagnosis of hypothyroidism is rendered.

o  Contraindicated in adrenal insufficiency, MI, hyperthyroidism

o  Common adverse effects

§  Usually result of overdose (s/sx of hyperthyroidism)

§  CNS: insomnia, tremors, headache

§  CV: tachycardia, palpitations, angina, dysrhythmias, HTN, cardiac arrest

§  GI: N, diarrhea, increased or decreased appetite, cramps

§  Other: menstrual irregularities, weight loss, sweating, heat intolerance, fever, thyroid storm

o  Interactions

§  For patients on Coumadin (warfarin), the addition of thyroid hormones leads to increased catabolism of clotting factors, resulting in an increased INR. A decrease in Coumadin may be needed, but should be based on careful monitoring of the Protime/INR.

§  ¯ oral absorption of cholestyramine (antilipemic agent)

§  Diabetics – may need to ­ dose of hypoglycemic agents

§  Thyroid + epinephrine in patients with coronary disease may à cardiac insufficiency

o  Patients on thyroid hormone replacement therapy should avoid adding iodine food containing iodized salt, soybeans, tofu, turnips, some types of seafood, and some breads.

o  Important to take the medication exactly as prescribed, at the same time everyday, and not to switch brands, unless approved by the health care provider

o  Therapeutic effects of thyroid agents may take several months to occur

Hyperthyroidism

·  Caused by excessive secretion of thyroid hormone from the thyroid gland

·  Due to different diseases or drugs

·  Diseases = Graves’ disease (includes hyperthyroidism with diffuse goiter or thyroid gland enlargement), and multinodular disease

·  Treated with surgery or antithyroid drugs

·  Antithyroid drugs

o  Called thioamide derivatives and consist of mainly methimazole (Tapazole) and propylthiouracil (PTU)

o  Drugs act by inhibiting the incorporation of iodine molecules into the amino acid tyrosine, a process required to make the precursors of T3 and T4

§  PTU also inhibits conversion of T4 to T3 in the peripheral circulation

o  By inhibiting the formation of the precursors of thyroid hormone, they prevent its formation.

o  Neither drug can inactivate already existing thyroid hormone

o  Common adverse effects of antithyroid medications (watch for bone marrow and liver toxicity)

§  CNS: drowsiness, headache, vertigo, fever, paresthesia

§  Skin: rash, pruritus, hyperpigmentation

§  GI: N & V, diarrhea, jaundice, hepatitis, loss of taste

§  MSK: myalgia, arthralgia, nocturnal muscle cramps

§  Hematologic: agranulocytosis, leukopenia, thrombocytopenia, hypothrombinemia, lymphadenopathy, bleeding

§  Other: enlarged thyroid, nephritis

o  Interactions

§  Additive agranulocytosis with other bone marrow depressants

§  Increased activity of oral anticoagulants

Adrenal Hormones

Adrenal gland characteristics

Adrenal cortex

·  Endocrine tissue

·  2 types of hormones

·  glucocorticoids (betamethasone, corticotropin [ACTH], cortisone, dexamethasone, hydrocortisone, methylprednisolone, paramethasone, prednisolone, triamcinolone)

·  Biologic functions

·  Anti-inflammatory actions

·  Maintenance of normal blood pressure

·  Carbohydrate and protein metabolism

·  Fat metabolism

·  Stress effects

·  mineralcorticoids (aldosterone, fludrocortisone, desoxycorticosterone)

·  Biologic functions

·  Sodium and water resorption

·  Blood pressure control

·  Potassium levels and pH of blood

Adrenal medulla

·  Neuroendocrine tissue

·  1 type of hormone

·  catecholamines (epinephrine, norepinephrine)

·  Diseases

·  Addison’s disease = failure of adrenocortical function (undersecretion)

·  Cushing’s disease = oversecretion

Synthetic corticosteroids available in several forms

·  Topical (for dermatitis)

·  Nasal spray (for allergic rhinitis)

·  Inhalers (for asthma)

·  Intra-articular

·  Systemic (oral, IM, IV)

·  Can be given short term (as with Medrol Dose Pak)

·  Can be given on a regular basis

Examples of corticosteroids

·  Hydrocortisone (Cortef, Hydrocortone, Solu-Cortef) = natural short-acting glucocorticoid

·  Prednisone (Deltasone) = synthetic intermediate-acting glucocorticoid

·  Dexamethasone (Decadron) = synthetic long-acting glucocorticoid

Adrenocortical hormones used to treat:

·  Adrenocortical deficiency

·  Bacterial meningitis

·  Cerebral edema

·  SLE

·  Dermatologic disease

·  Endocrine disorders

·  GI diseases (ulcerative colitis)

·  Hematologic

·  Ophthalmology

·  Transplants

·  SCI

·  Polymyalgia rheumatia (PMR)

·  Temporal arteritis (giant cell arteritis)

·  Rheumatoid arthritis

·  Tendonitis

·  Low back pain

·  Bell’s palsy

Corticosteroids: Common Adverse Effects

·  CNS: convulsions, HA, vertigo, mood swings, psychic impairment, insomnia

·  CV: CHF, cardiac edema, HTN (all due to electrolyte imbalances)

·  High-dose corticosteroid therapy (≥ 7.5 mg/day) increases the risk of developing atrial fibrillation

·  Endocrine: growth suppression, Cushing’s syndrome, menstrual irregularities, carbohydrate intolerance, hyperglycemia, HPA axis suppression

·  Cushingoid symptoms include moon face, weight gain, muscle wasting, and increased deposition of fat in the trunk area, leading to truncal obesity

·  GI: peptic ulcers with possible perforation, pancreatitis, ulcerative esophagitis, abdominal distention

·  Skin: fragile skin, petechiae, ecchymoses, facial erythema, poor wound healing, hirsutism, urticaria

·  MSK: osteoporosis, muscle weakness, loss of muscle mass, avascular necrosis

·  Ocular: increased IOP, glaucoma, exophthalmos, cataracts

·  Immunity: Increased risk of infection

Interactions

·  With non-potassium sparing diuretics (thiazides, loop) à severe hypocalcemia

·  With ASA, NSAIDs, ulcerogenic drugs à additive effects

·  With anticholinesterase drugs à weakness in myasthenia gravis patients

·  Patient teaching: once-a-day dosing corticosteroids should be administered between 6 and 8 a.m. to minimize adrenal suppression.

Sudden discontinuation of adrenal agents can precipitate an adrenal crisis caused by a sudden drop in the serum levels of cortisone.

·  The higher the dosage and the longer the duration of therapy, the more difficult the process of tapering.

·  The administration of glucocorticoids for a short time (< 14 days) is relatively safe.

·  Suppression of the HPA axis can occur with use of “superpotent” topical steroids such as betamethasone dipropionate (Diprosone) and clobetasol propionate (Temovate) ointments.

·  Application of high-potency corticosteroids should be limited, when possible, to twice-daily dosing and to no more than 3-4 weeks.

·  Adrenal suppression has even been reported to occur after prolonged use of a steroid nasal spray (1992 study)

Algorithm for corticosteroid withdrawal

Source: Kountz, DS & Clark, CL (February 1, 1997). Safely withdrawing patients from chronic glucocorticoid therapy. American Family Physician, 55(2), 521-525.

·  Need to adjust steroid dosage and plan rate of withdrawal to prevent relapse of the disease and allow the HPA axis to recover its physiologic function.

·  Before starting the steroid withdrawal program, the health care provider should review the signs and symptoms that suggest adrenal insufficiency with the patient and family

·  Medic-Alert bracelet indicating steroid dependency

·  Prepackaged syringe of dexamethasone (Decadron) 4 mg, for family members of the patient to administer in case of unexplained loss of consciousness.

·  Stage 1: Gradually decrease dosage until a dosage of 5 mg per day of prednisone or equivalent is reached

·  As the corticosteroid is tapered, the patient may experience some mild withdrawal symptoms, including fatigue, anorexia, nausea and orthostatic dizziness

·  During this taping period the patient is most vulnerable to acute stress.

·  If a minor illness occurs or a surgical procedure is to be performed during this period, the steroid taper should be suspended, and the steroid dosage temporarily increased to the equivalent of 25 mg of prednisone (hydrocortisone is a better choice in the preop setting because it can be given IM or IV, in a dosage of approx. 100 mg bid)

·  If the patient is under more intense stress, the dosage may have to be increased to the equivalent of 250-300 mg of hydrocortisone per day to mimic the normal adrenal response to stress.

·  After the stress is resolved, the steroid is again taped and stabilized at a dosage equivalent to 5 mg prednisone per day.

·  The patient should remain on this physiologic replacement dosage (5 mg) for 4 weeks after the resolution of the acute stress or surgery.

·  At this time, a direct challenge to the HPA axis can be performed through a cosyntropic (Cortosyn) challenge.

·  Performed any time of the day with need to fast

·  Cosyntropin is administered IM, 25 U (0.25 mg, same as 250 mcg)

·  The plasma cortisol level is measured just before and 30 minutes after the injection.

·  If the patient’s cortisol level is augmented by 6 mcg per dL and the peak cortisol level is > 20 mcg per dL, the HPA axis has recovered and exogenous steroid can safely be discontinued

·  If the increase in cortisol is < 6 mcg per dL and/or the peak cortisol value is < 20 mcg per dL, a slower steroid taper is recommended

·  Stage 2: If the patient “failed” the corticotropin challenge, the HPA axis is still suppressed.

·  Prednisone should be continued and tapered slowly to a dosage of 5 mg every other day, and the challenge should be retried.

·  Stage 3: In cases of ambiguity or in patients with persistently poor augmentation of plasma cortisol, other problems should be considered, such as coexistent pituitary or adrenal disease, or an associated endocrinopathy (hypothyroidism).

Diabetes Mellitus

·  Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both.

·  The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels.

·  Several pathogenic processes are involved in the development of DM. These range from autoimmune destruction of the beta-cells of the pancreas with consequent insulin-deficiency to abnormalities that result in resistance to insulin action.

·  The basis of the abnormalities in carbohydrate, fat, and protein metabolism in DM is deficient action of insulin on target tissues.

·  Deficient insulin action results from inadequate insulin secretion and/or diminished tissue responses to insulin at one or more points in the complex pathways of hormone action.

·  Impairment of insulin secretion and defects in insulin action frequently coexist in the same patient, and it is often unclear which abnormality, if either alone, is the primary cause of the hyperglycemia. Thus, the reason for frequent use of multiple medications in treatment of Type 2.

Type 1 (formerly insulin dependent, or IDDM):

·  No production of insulin due to destruction of pancreas’ beta cells, thought to be a result of genetically prone autoimmune response (immune mediated)

·  Associated with Grave’s, Hashimoto’s, Addison’s

·  Variable beta cell destruction (when down to 20% beta cells left, symptoms appear)

·  Insulin-dependent

·  Produces ketones with hyperglycemia

·  Without insulin, will die (ketosis)

Type 2 (formerly noninsulin-dependent, or NIDDM):

·  Minimal production of insulin due to hyperplastic beta cells (insulin deficiency)

·  Insulin-resistant Type 2 is exacerbated by poorly responding insulin receptors, thus requiring larger doses of insulin to respond.

·  Rarely produces ketones with hyperglycemia

·  7-8 million diagnosed/8 million undiagnosed

·  Usual onset 8 years before diagnosis

·  Usually > 40 years old, overweight

Diagnosis of Diabetes:

Symptomatic person (polyuria, polydipsia, or weight loss)

Random plasma glucose > or = 200 mg/dL (confirm with one of two other tests:

FPG or 2 hr PG

Asymptomatic person

FPG ≥ 126 mg/dL

2 hr PG ≥ 200 mg/dL

A1c ≥ 6.5%

NOTE: Pre-diabetes (increased risk of developing diabetes in the future) is indicated by A1c of 5.7% - 6.4%

·  In this range, the higher the percentage, the higher the risk for diabetes and cardiovascular disease. Those over 6.0% (very high risk) need intensive interventions and vigilant follow-up, emphasizes the American Diabetes Association (ADA).

Source: http://www.bing.com/images/search?q=image+of+a1c+ranges&qpvt=image+of+a1c+ranges&qpvt=image+of+a1c+ranges&FORM=IGRE#view=detail&id=28844D2D3CF0A13980D5AFFF8F9EB333899A700C&selectedIndex=21