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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
s
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