Disorder of carbohydrate metabolism- most commonly occuring carbohydrate metabolism disorder Deficiency of insulin- type 1- juvenile diabetes, complete insulin diabetes. Beta cells dont make insulin Resistance to action of insulin- older age diabetes. Initially is a resistance to beta cells(insulin_) and then a deficency for the body to procduce insulin.
What are the sx of sustained hyperglycemia?
Sustained hyperglycemia, polyuria(sugar is noticed in the urine at 180ml), polydipsia, ketonuria(gives the fruity smell), and weight loss(can't convert the glucose so then start to waste)
type 1 diabetes
Type 1 diabetes- abrupt onset days to weeks) 5% to 10% of all cases Also called insulin-dependent diabetes mellitus (IDDM) Or called juvenile-onset diabetes mellitus Primary defect is destruction of pancreatic beta cells- no longer producing insulin
type 2 Diabetes
Type 2 diabetes Most prevalent form of diabetes Approximately 19 million Americans have it Also called non–insulin-dependent diabetes mellitus (NIDDM) Or called adult-onset diabetes mellitus Obesity is almost always present Insulin resistance and impaired insulin secretion
Short Term Complications of Diabetes.
Short-term Hyperglycemia(can lead to diabetic ketoacidosis- occur from high blood glucose levels- occur in type one) and) hypoglycemia(hypoglycemia coma
Long Term complications of Diabetes- macrovascular.
Long-term Macrovascular(large blood vessels) damage Heart disease(risk equivalant- risk is as high as if you already had an MI) Hypertension- stenotic vessels, Stroke-puts patient at risk for having a stroke. (carotid arteries) Hyperglycemia Altered lipid metabolism- triglycerides are high
Long term complications of diabetes- microvascular.
Microvascular damage Retinopathy(type 1 and type 2- eye opthamoloist) Nephropathy(attacks vessels in kidneys, uncontrolled HTN and uncontrolled diabetes are the reason ppl are put on dialysis) Neuropathy(vessels in the periphery, are attacked by the high level of glucose- can't feel) Gastroparesis(paralysed gastric emptying. Nausea, vomiting, dyspepsia, nutritional malabsorption) Amputations secondary to infections Erectile dysfunction(part of micro and macro vascular complication. Sensation is gone.)
Diabetes and Factors in Pregnancy
Factors during pregnancy Placenta produces hormones that antagonize insulin’s actions(babies are larger birth weights when born to a diabetic mother- baby is born hypoglycemic- screening is done 24 to 28 weeks gestation. If one number is wrong its impaired glucose tolerance. If two numbers are wrong then it is gestational diabetees.) Production of cortisol increases threefold Glucose can pass freely from the maternal to the fetal circulation – fetal hyperinsulinemia
Diagnosis of Diabetes.
Excessive plasma glucose is diagnostic of diabetes Patient must be tested on two separate days, and both tests must be positive Three tests Fasting plasma glucose < than 100 mg/dl(FPG) 100-126(impaired fasting glucose) Casual plasma glucose- drawn two hours post meal. <140, then indicative of diabetes. Oral glucose tolerance test (OGTT) Hemoglobin A1c, oral glucose tolerance test. Should be less than 6%.
Impaired fasting plasma glucose between 100 and 125 mg/dL Impaired glucose tolerance test Increased risk for developing type 2 diabetes May reduce risk with diet and exercise and possibly certain oral antidiabetic drugs ACE protects kidneys from diabetes Beta Blockers can lower blood glucose Thiazides will cause an increase in glucose.
Tx of Type 1
Requires comprehensive plan Integrated program of diet, self-monitoring of blood glucose, exercise, and insulin replacement Dietary measures Total carbohydrates – not the type of carbohydrates – are most important Glycemic index
Tx of Type 2
requires comprehensive plan Should be screened and treated for: Hypertension, nephropathy, retinopathy, neuropathy, dyslipidemias Glycemic control with: Diet and exercise Drug therapy May or may not require insulin. May require at iniation of therapy. Period of high stress may require insulin for the type 2 diabetic. Depending on how elevated the blood glucose is it may take 2-3 months before effects occur.
Short duration- Rapid Acting Insulins
Short duration: rapid acting* Insulin lispro (Humalog)- with meals Insulin aspart (NovoLog) Insulin glulisine (Apidra)
Short Duration- Slower Acting Insulins
Short duration: slower acting Regular insulin (Humulin R, Novolin R)- ONLY INSULIN AVAILABLE FOR IV
Mixing insulins NPH with short-acting insulins Short-acting insulin drawn first Clear, cloudy, cloudy clear
Subcutaneous injection Syringe and needle Pen injectors(alow patient to dial in the dose, requires no drawing up) Jet injectors(high pressurized canister can push insulin through) Rotate Sites because lipodistrophy can occur.
Exubera – withdrawn 2007, because it was hard to control the actual amount of insulin that was introduced into the body.
Administration- subcut infusion pump
Subcutaneous infusion Portable insulin pumps Implantable insulin pumps(needle should idealy be changed every 24 hours, but can be 24-72 hours.
Administration- IV infusion
Administered with only Regular Insulin.
Storage of Insulin
Unopened vials should be stored under refrigeration until needed Should not be frozen Can be used until expiration date if kept in refrigerator After opening, can be kept up to 1 month without significant loss of activity Keep out of direct sunlight and extreme heat
Storage of Insulin
Mixtures of insulin in vials are stable for 1 month at room temperature and 3 months under refrigeration Mixtures in prefilled syringes should be stored in refrigerator for up to 1 week and should be stored vertically – needle pointing up
Theraputic Use of Insulin
Indications Principal – diabetes mellitus Required by all type 1 and some type 2 patients IV insulin for DKA(short-term complication of type 1 diabetes) Hyperkalemia – can promote uptake of potassium
Complication of Insulin Therapies
Hypoglycemia*** (most commonly occurring) Lipodystrophies- wasting or scarring of fat tissue Allergic reactions Hypokalemia- insulin can cause. Insulin lowers potassium levels. Drug interactions Hypoglycemic agents Hyperglycemic agents Beta adrenergic blocking agents
Oral Hypoglycemic Drugs- Biguanides
Also called metformin. Most commonly prescribed oral hypoglycemic. Inhibits glucose production in liver. Reduces glucose absorption slightly in gut. Sensitizes insulin receptors in target tissues. Rarely causes hypoglycemia when used alone. Safe in the use of pregnancy. Great for people who skip meals. Also used to tx poly-cystic ovarian disease.
Oral Hypoglycemic Drugs- Biguanides- Side effects
Side effects Decreased appetite, nausea, diarrhea**(most commong side effect) Decreases absorption of B12 and folic acid Patients lose average of 7-8 pounds Toxicity – lactic acidosis**- toxic sx of metforim use, fatal in half the patietns that develop it. Rare. Alcohol, cimetidine (Tagamet), and iodinated radiocontrast media may intensify acidosis(hold metformin if patient is going to receiving the dye)
Oral Hypoglycemics- Sulfonylureas
First oral hypoglycemics-Promote insulin release-Major side effect is hypoglycemia** First-generation controversy- no longer used Cause profound hypoglycemia Cardiovascular toxicity Second-generation agents-Much more potent than first-generation drugs-Significant drug-drug interactions less common
Oral Hypoglycemics- Sulfonylureas- Drug Interactions
Drug interactions Alcohol- increases risk of hypoglycemia Beta-adrenergic blocking agents- can increase the risk of hypoglycemia and mask the sx of hypoglycemia.
Oral Hypoglycemics- Glinides
Repaglinide(pramindin) and nateglinide-Same mechanism as that of sulfonylureas-3x a day, administered with a meal. Adverse effect: hypoglycemia Drug interaction: gemfibrozil (Lopid)
Rosiglitazone (Avandia) and pioglitazone (Actos)-Reduce glucose levels by decreasing insulin resistance. Not related chemically or functionally to sulfonylureas, biguanides, or alpha-glucosidase inhibitors Rarely cause hypoglycemia. Do not cause higher levels of insulin to be produced Undergoing post-marketing survellience…possibly causes HF and liver failure
Oral Hypoglycemics- Rosiglitazone
Only minor side effects (hmmm….)-Renal retention of fluid- edema associated with HF and Raises levels of plasma lipids Drug interactions- Insulin also promotes fluid retention, hence the combination poses increased risk for heart failure Gemfibrozil (Lopid) can raise plasma levels of rosiglitazone
Oral Hypoglycemics- Pioglitazone (Actos)
Newest glitazone No hepatoxicity Adverse effects – generally mild, URI, headache, sinusitis, myalgia,Promotes water gain Drug interaction- Gemfibrozil (Lopid)
Oral Hypoglycemics- Alpha-Glucosidase Inhibitors
Acarbose and miglitol- Only lower blood glucose if it needs to be ordered. Work within the gut, decrease the absorption of sugar. Act in intestine to delay absorption of carbohydrates Do not depend on the presence of insulin. Monotherapy or combination. Adverse effects Flatulence, cramps, distention, borborygmus, and diarrhea (fermentation of carbohydrates) Long-term high dose may cause liver dysfunction Monitor every 3 months Should avoid concurrent use with metformin due to GI effects**
Oral Hypoglycemics- Sitagliptin (Januvia), tradgenta, and onglyza.
Enhances the actions of incretin hormones Very closesly meets the ideal drug standards. Enhance the action of the hormones that stimulate the release of insulin when blood glucose rise. Doesn't cause hypoglycemia. Safe in pregnancy. Can be used alone or in combination. Stimulates glucose dependent release of insulin Suppresses postprandial release of glucagon Monotherapy or combination Generally well tolerated- URI, headache, inflammation throat/nasal
Oral Hypoglycemics- Colesevelam (Welchol)
Bile-acid sequestrant – used to lower plasma cholesterol Can also help lower blood glucose FDA-approved for type 2 treatment in 2008 Many diabetic patients have high cholesterol Constipation is the number one side effect.
Injectable Diabetic Insulins-Pramlintide (Symlin)
Pramlintide (Symlin) Supplement to mealtime insulin (type 1 or type 2) Adverse effect: hypoglycemia Work like gliptons
Injectable Diabetic Insulins- Exenatide (Byetta)
Exenatide (Byetta) Adjunctive therapy to improve glycemic control in patients with type 2 diabetes Adverse effects-Hypoglycemia, Gastrointestinal effects **Nausea and vomiting are the number one side effects**. Profound weight loss. - stop over eating. Small frequent meals.
Diabetic ketoacidosis (DKA)- acute adverse reaction of type 1. linked with high blood glucoses. and hyperglycemic hyperosmotic nonketotic syndrome
(HHNS)- acute adverse reaction of type 2. – both conditions are hyperglycemic crises. Hyperglycemia is more severe in HHNS No ketoacidosis in HHNS
SX of DKA
Severe manifestation of insulin deficiency Symptoms evolve quickly – period of hours or days Most common complication in pediatric patients and leading cause of death Characteristics Hyperglycemia Ketoacids Hemoconcentration Acidosis Coma
SX of DKA
Altered glucose metabolism- Hyperglycemia Water loss- dilute urine Hemoconcentration- dehydrated, risk of clots Altered fat metabolism Production of ketoacids
TX of DKA
Insulin replacement- regular IV Bicarbonate for acidosis Water and sodium replacement- correct dehydration Potassium replacement Normalization of glucose levels
HHNS- what happens?
Large amount of glucose excreted in urine, 2000mg + Dehydration and loss of blood volume- not as acidotic Increases the blood concentrations of electrolytes and nonelectrolytes (particularly glucose); also increases hematocrit Blood “thickens” and becomes sluggish
SX of HHNS
Different from DKA Little or no change in ketoacid levels Little or no change in blood pH No sweet or acetone-like smell to urine or breath **HHNS occurs most frequently with type 2 DM with acute infection, acute illness, or some other stress***
HHNS development and TX
Can evolve slowly Metabolic changes begin a month or two before signs and symptoms become apparent If untreated, HHNS can lead to coma, seizures, and death Management Correct hyperglycemia and dehydration with IV insulin, fluids, and electrolytes
TX of Insulin OD
Preferred treatment is IV glucose Immediately raises blood glucose level Also dosed IM or Sub cut 0.5 mg to 1 mg may repeat in 20-25 minutes Glucagon can be used if IV glucose is not available Delayed elevation of blood glucose
Actions of the thyroid hormone
Stimulation of energy use Stimulation of the heart Promotion of growth and development
What hormones does the thyroid produce?
Triiodothyronine (T3) Synthetic T3 is liothyronine- cytomel(drug name) Thyroxine (T4, tetraiodothyronine) Synthetic T4 is levothyroxine(synthroid)*/(leboxil) High TSH indicates hypothyroid. TSH measures the stimulating hormone. TSH low, hyperthyroid
How to test thyroid function.
Serum TSH* most common screening test Screening and diagnosis of hypothyroidism Elevated TSH is indication of hypothyroidism Serum T4 test Can measure either total T4 or free T4 Serum T3 test Can measure either total T3 or free T3
Clinical presentation (adults) Pale, puffy, and expressionless face Cold and dry skin Brittle hair or loss of hair Heart rate and temperature are lowered Lethargy and fatigue Intolerance to cold Impaired mentality Buffalo hump, fatty deposits seen in myxedema coma.
Usually due to malfunction of the thyroid Hashimoto’s disease**(most common causes) – chronic autoimmune thyroiditis Insufficient iodine in the diet Surgical removal of thyroid and destruction of thyroid with radioactive iodine(because of goiter or caner of thyroid) Adults – insufficient secretion of TSH and TRH
Levothyroxine (Synthroid) Synthetic preparation of thyroxine (T4) and drug of choice for hypothyroidism Conversion to T3, Half-life – 7 days, Used for all forms of hypothyroidism. Should be taken on empty stomach in the morning at least 30 minutes before breakfast(allows with most absorption) Adverse effects Tachycardia Angina Tremors Can intensify effects warfarin
Thyroid Preparations- Cytomel (Synthetic T3)
Cytomel (Synthetic T3) Not as commonly used Equally effective Different lab testing- harder to monitor
Hyperthyroidism- Graves’ disease
Graves’ disease Most common form Affects women 20-40 years of age Causes exophthalmos(blurred vision, dry eyes)
Hyperthyroidism- Toxic Nodular Goiter
Toxic nodular goiter (Plummer’s disease)- thyroid gland is not normally palpated in the female.
TX of hyperthyroidism
Treatment Surgical removal of thyroid tissue(could push out a bolus of thyroid hormone, or accidentaly removal of parathyroid gland) Destruction of thyroid tissue Suppression of thyroid hormone synthesis(
Thyroid Storm- cause
Cause Patients with thyrotoxicosis who undergo significant stress (surgery, illness, etc.) Not triggered by a rise in thyroid hormones Can’t always be identified with lab tests
Thyroid storm- signs
Hyperthermia (105° F or higher), severe tachycardia, restlessness, agitation, tremor, unconsciousness, coma, hypotension, heart failure
Thyroid Storm TX
Potassium iodide, PTU(blocks the synthesis), and beta-blocker Sedation, cooling, glucocorticoids, IV fluids
Hyperthyroid Drug- Propylthiouracil (PTU)
Inhibits thyroid hormone synthesis Drug of choice to supress hyperthyroidism Short half-life (about 75 minutes) Full benefits may take 6-12 months Therapeutic uses: Graves’ disease, Adjunct to radiation therapy, Preparation for thyroid gland surgery, Thyrotoxic crisis
Adverse effects Agranulocytosis (most serious)* Hypothyroidism Pregnancy and lactation(may be used)
Radioactive isotope of stable iodine Emits gamma and beta rays Half-life – 8 days 2-3 months for full effect Used in Graves’ disease Effect on the thyroid Advantages and disadvantages of 131I therapy
Radioactive Iodine-131- whose it for and what's it do
Candidates Patients over the age of 30 Contraindicated in pregnancy and lactation Action Produces clinical remission with destruction of thyroid gland
What do drugs of the adrenal cortex do?
Affect multiple processes Maintenance of glucose availability Regulation of water and electrolyte balance Development of sex characteristics Life-preserving responses to stress
Adrenal Hormones and they cause
Three classes of steroid hormones from the adrenal cortex Glucocorticoids Mineralocorticoids Androgens Two most familiar forms of adrenocortical dysfunction Adrenal hormone excess Cushing’s syndrome Adrenal hormone deficiency Addison’s disease
Effects of Glucocortoids
Physiologic effects (occur at low levels) Carbohydrate metabolism Protein metabolism Fat metabolism Cardiovascular system Skeletal muscle Central nervous system Stress Respiratory system in neonates
Effects of mineralcortocoids
Influence renal processing of sodium, potassium, and hydrogen Aldosterone Promotes sodium and potassium hemostasis Maintains intravascular volume Harmful cardiovascular effects with high levels Regulated by renin-angiotensin-aldosterone system (RAAS)
Disease caused by adrenal hormone excess.
Cushing’s syndrome Causes Hypersecretion of adrenocorticotropic hormone (ACTH) Hypersecretion of glucocorticoids Administering glucocorticoids in large doses Clinical presentation Obesity Hyperglycemia Glycosuria Hypertension Fluid and electrolyte disturbances
TX of Cushing's
Cushing’s syndrome (cont’d) Treatment Carcinoma/adenoma – surgical removal of adrenal gland Replacement therapy with steroids
Excessive secretion of aldosterone Causes Hypokalemia, metabolic alkalosis, hypertension Treatment Based on underlying cause Surgery or aldosterone antagonist (spironolactone)
Adrenal Hormone Insufficiency
General therapeutic considerations Replacement therapy with glucocorticoids Should mimic normal patterns of corticosteroid secretion Give entire dose at bedtime (rise during sleep and peak at waking hours) 2/3 in the morning and 1/3 in the afternoon Doses for endocrine disorders are much smaller than for nonendocrine disorders Increase dosage in times of stress
Adrenal Hormone Insufficiency
Addison’s disease (primary adrenocortical insufficiency) Clinical presentation and causes Weakness and hypotension Emaciation Hypoglycemia, hyperkalemia, hyponatremia Increased pigmentation of skin and mucous membranes
TX of ADDISON
Treatment Replacement therapy with adrenocorticoids Hydrocortisone is the drug of choice
Acute adrenal insufficiency (Adrenal crisis)
Acute adrenal insufficiency (Adrenal crisis) Can lead to death Clinical presentation Hypotension Dehydration Weakness Lethargy GI symptoms (vomiting and diarrhea) Causes Adrenal failure Pituitary failure Inadequate doses of corticosteroids or abrupt withdrawal
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