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PHARMACOLOGY FOR THE ENDOCRINE AND HEMATOLOGICAL SYSTEMSN402

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THE ENDOCRINE SYSTEM (KP1)

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ENDOCRINE SYSTEM OF THE BRAIN (KP2,3)

Influences all cells and physiologic processes

Individual cells secrete specific hormones

Pituitary(“King”)

RH and IH turn Pituitary “on” and “off”

Determined by negative feedback systems

Hypo-thalmus (“Power behind

throne”)

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MAJOR HORMONES SECRETED BY BRAIN (KP1)

Hormone Target Effect

Anterior Pituitary

GH Liver, adipose tissue

Promotes growth, metab

TSH Thyroid Secrete thyroid hormones

ACTH Adrenal gland Secretion glucocorticoids

Prolactin Mammary glands Milk production

LH Ovary Reproduction

FSH Ovary Reproduction

Posterior Pituitary

ADH Kidney Conserve body water

Oxytocin Ovary Milk; uterine contraction

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DIABETES INSIPIDUS

In humans, most common type is Central DI Caused by deficiency of ADH Excessive thirst Excretion of large amounts of highly dilute urine Urine does not contain glucose (unlike DM) High risk of dehydration and loss of

potassium

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TREATMENT OF DI

Desmopressin (DDAVP) Vasopressin analog May be required after pituitary surgery (pituitary

tumors) Given IV over 1 minute Precise I&O required as frequently as q 15 minutes Potential water intoxication and cerebral edema:

Headache, memory loss, stupor, irregular breathing Difficulty speaking, walking Neck pain or stiffness, visual changes Nausea or vomiting Dizziness, loss of consciousness, seizures

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HYPOTHYROIDISM VS HYPERTHYROIDISM (KP4)

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PHARMACOTHERAPY FOR HYPOTHYROIDISM (KP4)

Levothyroxine (Levothroid, Synthroid) Dosing is highly individualized Monitored closely until desired levels reached TSH levels most effective measurement Usual range approximately 0.4–4.2 milliunits

pre liter (mU/L) Side effects include symptoms of

hyperthyroidism: Palpitations, dysrhythmias Hypertension

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THERAPY FOR HYPERTHYROIDISM (KP5)

Pharmacotherapy includes propylthiouracil (PTU)

Interferes with synthesis of T3 and T4

Short half-life; given several times a day Overtreatment results in symptoms of

hypothyroidism Other therapies for hyperthyroidism:

Beta blockers Thyroidectomy Radioactive iodine

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STEROIDS SECRETED BY THE ADRENAL CORTEX (KP6, 7)

Glucocorticoids

• Increase BG• Suppress

immune response

• Suppress inflammatory response

• Promote bronchodilation

• E.g., cortisol

Mineralo-corticoids

• Primarily aldosterone

• Regulate plasma volume

• Renin → angiotensin II → aldosterone

Gonadocorticoids

• Androgens • Small amounts of

estrogens• Primary source of

estrogens in postmenopausal women

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CORTISOL AWAKENING RESPONSE (CAR)

Rises occur in response to anticipated stress Highest secretion in second half of night Peak production in early morning Levels decline throughout day Affected by

Waking up early increases the response Shift work—greater responses in nurses working

day shifts and waking between 0400 and 0530 Not affected by naps Caffeine can increase cortisol levels in

stressed individuals!

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NONENDOCRINE INDICATIONS FOR GLUCOCORTICOID THERAPY (KP8)

In addition to acute adrenocortical insufficiency… Allergic response Asthma Cancer Edema from hepatic, neurologic and renal

causes Inflammatory bowel disease Rheumatic disorders Shock Skin disorders Transplant rejection prophylaxis

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DISCONTINUING GLUCOCORTICOIDS (KP9)

Can cause opposing symptoms, especially if discontinued abruptly: Weakness and fatigue Hypotension and fainting Hypoglycemia

Best practice, if possible is short term use with tapering withdrawal Example: Medrol dose pack

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ADVERSE EFFECTS OF LONG-TERM CORTICOSTEROID THERAPY (KP10)

Behavioral disorders

Cataracts, open-angle glaucoma

Infections

F&E disturbance

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Muscle wasting

Osteoporosis

PUD

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EFFECT OF INSULIN (KP11)

Glucose rises after

meal

Pancreas releases insulin

Liver produces glucogen

Glucose enters cells from blood

Blood glucose level falls

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EFFECT OF GLUCAGON (KP11)

Low glucose level

Pancreas releases glucagon

Liver breaks down glucogen

Blood glucose level rises

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EFFECTS OF SPECIFIC DRUGS ON BLOOD GLUCOSE LEVELS

Can raise BG

Phenytoin

NSAIDs

Diuretics

Can lower BG

ETOH

Lithium

ACE-inhibitors

β-blockers

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WHAT IS TYPE 1 DIABETES? (KP12)

Destruction of pancreatic beta cells Therefore, no insulin secretion Hyperglycemia (FBG > 126mg/dl) Polyuria Polyphagia Polydipsia Glucosuria Weight loss Fatigue

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LONG-TERM EFFECTS OF UNTREATED DIABETES

Arterial damage Heart disease Stroke Kidney disease Blindness

Decreased peripheral circulation Potential gangrene

Neuropathy and loss of sensation Lipids used as alternate energy source by cells

Waste products of lipids are ketoacids Accumulation causes ketoacidosis

Polyuria, polydipsia Stupor, coma, death

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INSULIN THERAPY (KP13)

Insulin usage highly individualized based on the patient’s needs

Needs to correlate with Glucose in the blood (food intake) Body’s demand for glucose by the cells (activity)

Complicated by Skipping or adding meals Inconsistent activity

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RAPID ACTING INSULIN EXAMPLES (KP13)

Insulin aspart (NovoLog)

Insulin lispro (Humalog)

Onset 15 minutes 5-15 minutes

Peak 1-3 hours 0.5-1 hour

Duration

3-5 hours 3-4 hours

Notes Give each subcutaneouslyCan give with NPH. Draw

5-10 minutes before a mealrapid acting up first.

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SHORT ACTING INSULIN EXAMPLE (KP13)

Insulin regular (Humalin R, Novalin R)

Onset 1-2 hours

Peak 4-12 hours

Duration 18-24 hours

Notes Subcutaneously 30-60 minutes before a mealCan mix with NPH, sterile water, or normal salineOnly form of insulin that may be given IV

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INTERMEDIATE ACTING INSULIN EXAMPLE (KP13)

Insulin isophane (NPH, Humulin N, Novolin N)

Onset 1-2 hours

Peak 4-12 hours

Duration 18-24 hours

Notes Give subcutaneously 30 minutes before 1st meal and possibly 30 minutes before supper.Can mix with aspart, lispro, or regular. Do not mix with glargine

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LONG ACTING INSULIN EXAMPLE (KP13)

Insulin glargine (Lantus)

Onset 1.1 hour

Peak 3-4 hours

Duration

10-24 hours

Notes Can last as long as intermediate, but peaks earlier causing longer total acting time.Given daily.Do not mix with other insulins.

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PREMIXED INSULIN COMBINATIONS (KP13)

Provides a basal blood level + shorter acting before a meal

*Protamines slow down onset and increase duration of insulin

Combination Longer acting(basal)

Shorter acting(meal coverage)

Humulin 70/30Novolin 70/30

70% NPH(intermediate)

30% regular(short)

Humulin 50/50 50% NPH(intermediate)

50% regular(short)

Novolog mix 70/30

70% aspart protamine*

30% aspart

Humulog mix 75/25

75% lispro protamine*

25% lispro

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CHARACTERISTICS OF TYPE 2 DIABETES (KP15, 17)

Pancreas produces enough insulin Target cells become unresponsive to insulin

(defect in receptor function) Blood glucose levels rise Pancreas produces more insulin Leads to beta cell exhaustion and beta cell

death Therefore, treatment aimed toward:

Increase insulin receptor activity through exercise Lower circulating insulin through diet

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LIFESTYLE CHANGES RECOMMENDED FOR TYPE 2 DIABETES (KP14)

Monitor portion sizes Every meal well balanced Coordinate meals and medications Avoid sugar-sweetened beverages Exercise: 30 minutes per day, most days of the week Stay hydrated Report problems to PCP

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MAJOR TYPES OF DRUGS FOR TYPE 2 DIABETES: ALPHA-GLUCOSIDASE INHIBITORS (KP16)

Block enzymes in small intestine Carbohydrates do not break down into

monosaccharides and cannot be absorbed Digestion of glucose is delayed Minima adverse effects—cramping, diarrhea,

flatulence Do not produce hypoglycemia alone; may in combination with insulin or sulfoylurea Example: Acarbose (Precose)

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STRATEGIES FOR TYPE 2 DIABETES TREATMENT (KP 17)

Step 1: diabetes education, monitor blood glucose, make lifestyle modifications

Step 2: add a medicine (e.g., Metformin) Step 3: add a second medicine, insulin or

another non-insulin medicine Step 4: add a 3rd medicine Step 5: Insulin (intensified therapy) with or

without other medicines

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MAJOR TYPES OF DRUGS FOR TYPE 2 DIABETES: BIGUANIDES (KP16)

Decreases hepatic production of glucose Reduces insulin resistance Effect is not based on stimulating insulin

secretion; can therefore be effective in patients who no longer secrete insulin

Preferred oral antidiabetic for type 2 diabetes Does not cause hypoglycemia Lowers triglycerides and LDL Adverse effects are GI related Example: Metformin (Glucophage)

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MAJOR TYPES OF DRUGS FOR TYPE 2 DIABETES: INCRETIN ENHANCERS (KP16)

Incretins secreted by small intestine mucosa Signal pancreas to increase insulin secretion Signal liver to stop producing glucagon “Enhancing” incretin secretion will promote

these signals and thereby lower blood glucose levels

Incretin enhancers slow gastric emptying, delaying glucose absorption

Must be given subcutaneously; do not cause hypoglycemia

Example: Exenatide (Byetta)

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MAJOR TYPES OF DRUGS FOR TYPE 2 DIABETES: MEGLITINIDES (KP16)

Stimulate release of insulin from pancratic islet cells

Short duration (2-4 hours) Can cause hypoglycemia Examples: Repaglinide (Prandin) and

Nateglinde (Starlix)

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MAJOR TYPES OF DRUGS FOR TYPE 2 DIABETES: SULFONYLUREAS (KP16)

First class of oral hypoglycemics available Stimulate release of insulin from pancreatic

islet cells Increase sensitivity of insulin receptors Hypoglycemia common ETOH can cause flushing, palpitations Example: Tolbutamine (Orinase)

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MAJOR TYPES OF DRUGS FOR TYPE 2 DIABETES: GLITAZONES (AKA THIAZOLIDINEDIONES) (KP16)

Decrease insulin resistance Inhibit hepatic gluconeogenesis May take 3 to 4 months for optimal effect Hypoglycemia does not occur

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WHAT IS “HEMOSTASIS?” (KP1)

The opposite of hemorrhage…it is the process of keeping blood within a damaged blood vessel Normally, endothelial cells of intact vessels prevent clotting with a heparin-like molecule When injury occurs, secretion of coagu- lation inhibitors stops and von Willebrand factor is secreted to initiate hemostasis Steps of hemostasis:

Vasoconstriction Platelet plug formation Blood coagulation

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STEPS OF HEMOSTASIS (KP1)

Vascular spasm

• Vessel constricts

• Reduces flow

• Limits blood loss

Platelet plug formation

• Adhere to collagen fibers of the wound

• Become “sticky” when activated by vWF

Blood coagulation

• Fibrinogen converts to fibrin

• Fibrin mesh forms• Prothrombin

allows formation of a thrombus

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ROLE OF THE LIVER (KP1)

Many factors involved in clotting are made in the liver

Circulate in inactive form Vitamin K required for clotting factor

formation Vitamin K is the antidote for Coumadin

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FIBRINOLYSIS (KP2)

Prevents clots from remaining in place longer than necessary

Plasminogen produced in the liver During clot formation, plasminogen is locked

inside the clot with an activator Once healing starts, activator is released Plasminogen is converted to plasmin Plasmin breaks clot into smaller pieces Pieces are circulated and expelled

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COMMON THROMBOEMBOLIC DISORDERS (KP3)

DVT

• Often in legs• Atrial fib• May become embolus

Thrombo-cytopenia

• Platelets < 150,000

• Hemostasis fails to occur

Hemophilia

• Genetic disorder

• Deficient in specific clotting factos

von Willebrand’s

disease• Inherited• Deficient vWF

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COMMON LABORATORY TESTS FOR COAGULATION DISORDERS (KP4)

Test Purpose Significance

Activated clotting time (ACT)

Monitor heparin therapy; 70-180 sec

High values = risk for bleeding

Activated partial thromboplastin time (aPTT)

Monitor heparin therapy; 1.5-2 times initial values

High values = risk for bleeding

Bleeding time Diagnosis of bleeding disorders; 2-9 min from forearm

Long bleeding time = low platelet count

Platelet count 150,000 to 350,000 Required for clotting; < 20,000 = thrombocytopenia

Prothrombin time (PT)

INR 2-3.5 High values = risk for bleeding

Thrombin time Fibrinogen deficiency; 13-15 sec

Effectiveness of heparin therapy

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INR—INTERNATIONAL NORMALIZED RATIO (KP4)

Ratio of patient’s prothrombin time to a control sample

ISI value is a factor assigned by manufacturer comparing batch to international reference

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DRUG MECHANISMS FOR MODIFYING HEMOSTASIS (KP5)

Anticoagulants—prolong bleeding time

Antiplatelets—interfere with platelet aggregation

Thrombolytics—promote fibrinolysis

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ANTICOAGULANTS (KP5)

Prevent clot formation in veins Prolong bleeding time Prevent thrombus formation Inhibit specific clotting factors Include:

Warfarin (Coumadin) Enoxaparin (Lovenox) Dabigatran (Pradaxa)*

Risk of hemorrhage Risk of heart failure, sepsis, internal

hemorrhage greater with direct thrombin inhibitors*

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ANTIPLATELETS (KP5)

Used to prevent clot formation in arteries Can increase bleeding time significantly Note aspirin specifically!

Available OTC Some patients see it as “benign” May not report use, “not important”

Includes Aspirin (ASA, etc.) ADP receptor blocker clopidogrel (Plavix)

Not for use in patients with active bleeding

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NURSING CARE OF PATIENTS RECEIVING ANTICOAGULANTS AND ANTIPLATELETS

Monitor for signs of bleeding Encourage activity, early ambulation Educate regarding thrombus prevention Lifestyle changes, especially smoking

cessation Minimize potential bleeding opportunities

Soft toothbrush, electric razor Avoid harmful physical activities

Dietary changes Avoid high or low vitamin K foods Eliminate alcohol Protein supplements often contain vitamin K

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THROMBOLYTICS (KP5, 7)

Digest and remove existing clots; anticoagulants and antiplatelets do not do this! Goal: restore blood flow to tissue quickly Should be given within 4 hours of clot formation Narrow margin of safety!

Monitor VS continuously Monitor for signs of bleeding

Discontinuation results in immediate termination of thrmbolysis

Usually converted to anticoagulant after thrombolytic therapy

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A NOTE ON HEMOSTATICS…. (KP8)

Opposite of anticoagulants Shorten bleeding time by slowing blood flow Treat excessive bleeding from surgical sites

(Unrelated picture, topic of conversation!)

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HEMATOPOIESIS (KP9)

Blood cell formation Occurs primarily in red bone marrow Requires additional components:

B vitamins Vitamin C Copper Iron

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ANEMIA—DEFINITION

Lack of hemoglobin Tissue is unable to obtain adequate

oxygenation Generally considered as follows:

Adult males < 14 gm/dL Elderly males < 12.4 gm/dL Adult females < 12 gm/dL Elderly females < 11.7 gm/dL

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CELLULAR CLASSIFICATIONS OF ANEMIA (KP 11)

Type Description Examples

Macrocytic-normochromic

Large, irregular erythrocytes; normal Hbg concentration

Pernicious anemiaFolate-deficiency anemia

Microcytic-hypochromic

Small, irregular erythrocytes; decreased Hgb concentration

Iron deficiency anemiaThallasemia

Normocytic-normochromic

Destruction, depletion of erythroblasts or erythrocytes

Aplastic anemiaHemorrhagic anemiaSickle cell anemiaHemolytic anemia

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CAUSES OF ANEMIA (KP 10)

Blood loss GI conditions (PUD, hemorrhoids, cancers,

NSAIDs) Menstruation Trauma

Faulty red blood cell production Sickle cell Iron deficiency Vitamin deficiency Bone marrow, stem cell disturbances

Destruction of red blood cells (hemolytic) Infections Toxins of disease, drugs venoms, food

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TREATMENT OF ANEMIA PRINCIPLES

Treatment is based on cause of anemia Regardless of cause if Hgb falls < 7 g/dL and

there is no cardiopulmonary contraindication, RBC transfusion should be considered

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USE OF ERYTHROPOIESIS-STIMULATING DRUGS

Stimulates stem cells to increase erythrocyte production

Also stimulates hemoglobin production Useful in treating anemia caused by chronic

kidney disease Cannot be used in place of RBC transfusion Therapeutic results after 2-6 weeks Generally give subcutaneiously Example: Epoetin (Epogin, Procrit)

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TREATMENT OF ANEMIA WITH VITAMIN B12 (KP 13)

Treatment of B12 deficient anemia only! Purified form is cyanocobalamin IM or subcutaneously either weekly or

monthly Oral treatment requires sufficient intrinsic

factor Potential sodium retention!

Use cautiously in heart disease Contraindicated in severe pulmonary disease

Useful in pernicious and megaloblastic anemias

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TREATMENT OF ANEMIA WITH FOLIC ACID (KP12)

Required for normal DNA and RNA synthesis B12 deficiency will cause a lack of folic acid Most common cause is insufficient dietary

intake Common in alcoholics Can occur with fad diets Dietary sources include:

Green vegetables Dried beans Wheat products

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TREATMENT OF ANEMIA WITH IRON (KP12)

Most common cause of anemia Decreased iron reserves causes a reduction in

erythropoiesis Most iron-deficient patients have some form of

GI bleeding Mild forms treated nutritionally

Fish Red meat Fortified cereals and whole grain breads

Supplements required for more severe forms Iron oxidizes vitamin C; C included in many

supplements to prevent deficiency May require parenteral administration if patient

is unable to take orally

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PATIENT TEACHING FOR PHARMACOTHERAPY FOR ANEMIA (KP14)

Nutritional guidelines Encourage rest when fatigued Monitor lab results regularly Review administration guidelines

Encourage vitamin C with iron preparations Take iron on empty stomach

Assess for adverse effects Skin rash Hypokalemia (B12 helps build new cells which will

take up potassium so extracellular potassium is diminished)

Constipation Black stools from iron