Pharm Exam 4

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
Hyperglycemia(can lead to diabetic ketoacidosis- occur from high blood glucose levels- occur in type one) and) hypoglycemia(hypoglycemia coma

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

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.)

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

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.

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

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*
Insulin lispro (Humalog)- with meals
Insulin aspart (NovoLog)
Insulin glulisine (Apidra)

Short duration: slower acting
Regular insulin (Humulin R, Novolin R)- ONLY INSULIN AVAILABLE FOR IV

Intermediate duration
Neutral protamine Hagedorn (NPH) insulin
Insulin detemir (Levemir)

Lantus

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.

Subcutaneous infusion
Portable insulin pumps
Implantable insulin pumps(needle should idealy be changed every 24 hours, but can be 24-72 hours.

Administered with only Regular 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

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

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

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

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.

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)

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

Drug interactions
Alcohol- increases risk of hypoglycemia
Beta-adrenergic blocking agents- can increase the risk of hypoglycemia and mask the sx of hypoglycemia.

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

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

Newest glitazone
No hepatoxicity
Adverse effects – generally mild, URI, headache, sinusitis, myalgia,Promotes water gain
Drug interaction- Gemfibrozil (Lopid)

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**

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

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.

Pramlintide (Symlin)
Supplement to mealtime insulin (type 1 or type 2)
Adverse effect: hypoglycemia
Work like gliptons

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

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

Altered glucose metabolism- Hyperglycemia
Water loss- dilute urine
Hemoconcentration- dehydrated, risk of clots
Altered fat metabolism
Production of ketoacids

Insulin replacement- regular IV
Bicarbonate for acidosis
Water and sodium replacement- correct dehydration
Potassium replacement
Normalization of glucose levels

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

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***

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

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

Stimulation of energy use
Stimulation of the heart
Promotion of growth and development

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

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

Therapeutic strategy
Lifelong replacement therapy
Levothyroxine (T4)
Liothyronine (T3)

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

Cytomel  (Synthetic T3)
Not as commonly used
Equally effective
Different lab testing- harder to monitor

Graves’ disease
Most common form
Affects women 20-40 years of age
Causes exophthalmos(blurred vision, dry eyes)

Toxic nodular goiter (Plummer’s disease)- thyroid gland is not normally palpated in the female.

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(

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

Hyperthermia (105° F or higher), severe tachycardia, restlessness, agitation, tremor, unconsciousness, coma, hypotension, heart failure

Potassium iodide, PTU(blocks the synthesis), and beta-blocker
Sedation, cooling, glucocorticoids, IV fluids

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

Candidates
Patients over the age of 30
Contraindicated in pregnancy and lactation
Action
Produces clinical remission with destruction of thyroid gland

Affect multiple processes
Maintenance of glucose availability
Regulation of water and electrolyte balance
Development of sex characteristics
Life-preserving responses to stress

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

Physiologic effects (occur at low levels)
Carbohydrate metabolism
Protein metabolism
Fat metabolism
Cardiovascular system
Skeletal muscle
Central nervous system
Stress
Respiratory system in neonates

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)

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

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)

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

Addison’s disease (primary adrenocortical insufficiency)
Clinical presentation and causes
Weakness and hypotension
Emaciation
Hypoglycemia, hyperkalemia, hyponatremia
Increased pigmentation of skin and mucous membranes

Treatment
Replacement therapy with adrenocorticoids
Hydrocortisone is the drug of choice

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