4. 1. Fasting Blood Glucose (FBG) ≥126 mg/dl (fasting ≥ 8 hours)
   2. Casual blood sugar ≥200 mg/dl with symptoms of diabetes (not for routine use)
   3. Two hour post glucose challenge of ≥ 200 mg/dl (oral glucose tolerance test - OGTT)

1. Post Prandial glucose <140 mg/dl (PPG taken 2 hours after meal is begun)

2. Maintain glycated hemoglobin (HbA1c <7% - ADA; AACE goal in <6.5

3. Blood pressure < 130/80

4. Total cholesterol <200mg/ml

5. Lose weight if overweight

1. Type I

2. Type II with: 1. Symptoms uncontrolled by diet and exercise. 2. Symptoms not controlled by oral hypoglycemics. 3 Major stress or surgery.

3. Gestational Diabetes with sub-optimal control with diet or oral agents

4. Hyperalimentation (before you increase the dose of insulin- check the serum potassium)

5. Emergency situations: Ketoacidosis and hyperosmolar hyperglycemic states (HHS)

6. Used in ICU's to maintain BG control. Doing so has been shown to decrease mortality. Down side is inadvertantly causing hypoglycemia.

Insulin Preparations

Lispro (humalog) and Aspart

1. have the fastest onset of action and should be given within 5-10 minutes of a meal.

Insulin Preparaitons

Regular Insulin

Insulin Preparations

Glargine (lantus)

1. provides a very slow and even release of insulin from a subcutaneous injection site for a 24 hour period – administered at bedtime. Lantus may be used once daily in patients previously needing twice-daily injections of NPH. If switching to Lantus from NPH, reduce the total daily insulin dose by 20%.

Insulin Preparations

Detemir (Levemir)

4. long acting insulin can be given once or twice daily. If given once, dose should be in the evening. If given twice, one dose in morning and second dose approximately 12 hours later.

Insulin Preparations

Where can you administer them? And where has the fastest absorption?

-Speed of absorption: Abdomen > Arm > Thigh > Buttocks (does not apply to glargine or detemir)

- Massage and local heat will increase speed of absorption

What is the standard concentration for insulin?

What is given to patients with marked insulin resistance?

1. U-100 hass 100 units of insulin per ml. This concentraton is used most frequently.

2. U-500 (500 units per ml) is still mainly used in patients wih marked insulin resistance.

Always use a syringe compatible with the concentration.

REGULAR and RAPID-ACTING INSULINS

(all insulins can be given subcutaneous)

 concentration on vial (U-100 or U-500) as well as type Regular, NPH, etc

7. Always roll the vial of cloudy insulin preparation between palms of hand prior to use to ensure adequate mixing of the suspension. Do not shake vigorously. Doing so will cause bubbles to form in the liquid and decreasing the accuracy of the dose.

7. a. Do not freeze; clumping of the suspension may result.

8. b. Stable at room temperature for 30 days.
   c. Always observe expiration date on vial.
   d. A good rule of thumb is to keep in refrigerator

When switching from animal insulin to human insulin, the patient should be warned that their insulin requirement may be reduced and the nature of their hypoglycemic warning symptoms may change. For these reasons, increase monitoring is necessary after the transition to human insulin.

2. Lipohypertropy can be caused if one injection site is used too often. Injecting into this area can cause less pain but will also slow absorption of insulin.

2. hypoglycemia during early morning hours causes a rebound hyperglycemia that is observed as a high morning glucose

2. occurs in everyone, cortisol is highest in morning antagonizing insulin effect and causing an increase in serum glucose.

SULFONYLUREAS

Glyburide(Diabeta)

Glipizide (Glucotrol)

Glimepiride (Amaryl)

PHARMACOLOGY

SULFONYLUREAS

Glyburide(Diabeta)

Glipizide (Glucotrol)

Glimepiride (Amaryl)

Are they used for Type I or II DM?

SULFONYLUREAS

Glyburide(Diabeta)

Glipizide (Glucotrol)

Glimepiride (Amaryl)

What are some toxicities?

SULFONYLUREAS

Glyburide(Diabeta)

Glipizide (Glucotrol)

Glimepiride (Amaryl)

 What are patient related varialble?

1. Renal Dysfunction

2. Drug interactions: Oral anticoagulants, sulfonamides and chloramphenicol may enhance sulfonylurea effects while alcohol and rifampin may decrease the effect.

3. Chronic Liver Disease.

MEGLINITIDES

Repaglinide (Prandin)

Nateglinide (Starlix)

PHARMACOLOGY

MEGLINITIDES

Repaglinide (Prandin)

Nateglinide (Starlix)

CLINICAL USE

2. a. Not effective in Type 1 diabetes
   b. Use in the treatment of Type II diabetics with diet
   c. Particularly useful in a patient who eats at erratic times because of its fast onset d. Can be used alone or in combination with metformin

MEGLINITIDES

Repaglinide (Prandin)

Nateglinide (Starlix)

ADMINISTRATION

ALPHA-GLUCOSIDASE INHIBITORS (AGI)

Acarbose (Precose)

Militol (Glyset)

PHARMACOLOGY

ALPHA-GLUCOSIDASE INHIBITORS (AGI)

Acarbose (Precose)

Militol (Glyset)

CLINICAL USES

ALPHA-GLUCOSIDASE INHIBITORS (AGI)

Acarbose (Precose)

Militol (Glyset)

ADMINISTRATION

1. Acarbose - Take 25 mg at the start of meals (with first bite). Increase by 25mg/dose at interval of 4-8 weeks (max daily dose 150mg if <60kg and 300mg if >60kg).

2.Miglitol – Take 25 mg with each meal, may increase to 50mg with each meal after 4-8 weeks. Max dose is 100mg tid.

3. Hypoglycemia – While AGIs will not directly cause hypoglycemia, hypoglycemia might still occur because of other therapy (i.e., sulfonylurea). Teach the patient to use a glucose or fructose based product to treat hypoglycemia. NOTE - If a patient become hypoglycemic, and the only thing around is sucrose – Try it anyway.

ALPHA-GLUCOSIDASE INHIBITORS (AGI)

Acarbose (Precose)

Militol (Glyset)

What is the most common GI toxicity?

BIGUANIDE

Metformin (Glucophage)

Pharmacology

BIGUANIDE

Metformin (Glucophage)

Clinical Uses

BIGUANIDE

Metformin (Glucophage)

Administration

BIGUANIDE

Metformin (Glucophage)

DRUG INTERACTIONS

2. a. Cimetidine will increase the blood level of metformin by 50%.
   b. Iodinated contrast dyes – discontinue metformin on day of study and restart 48 hours following study (do not restart with metformin if renal function is not normal)

BIGUANIDE

Metformin (Glucophage)

PATIENT RELATED VARIABLES

BIGUANIDE

Metformin (Glucophage)

TOXICITY

THIAXOLIDINEDIOES

Pioglitazone (Actos)

Rosiglitazone (Avandia)

PHARMACOLOGY

THIAXOLIDINEDIOES

Pioglitazone (Actos)

Rosiglitazone (Avandia)

CLINICAL USES

1. a. Use in the treatment of Type 2 diabetes. Not effective in Type 1 diabetes
   b. Can be used as monotherapy or in combination with metformin or a sulfonylurea or insulin. c. Requires 4-12 weeks for maximum clinical effect.

THIAXOLIDINEDIOES

Pioglitazone (Actos)

Rosiglitazone (Avandia)

PATIENT RELATED VARIABLEs

1. Heart Failure – Can increase plasma volume and should be avoided in patients with heart failure (especially for NYHA class 3 or 4).(INCREASE PERIPHERAL EDEMA)

THIAXOLIDINEDIOES

Pioglitazone (Actos)

Rosiglitazone (Avandia)

TOXICITIES

1. Liver damage - monitor liver enzymes at baseline then every 2 months for first year then periodically thereafter.
   Pioglitazone – has least problem with increasing lipid levels.
   Avandia – FDA alert stemming from contradictory information suggesting an association with an increased risk of myocardial infarction.

Amylinomimetics

(amylin like Drug)

PHARMACOLOGY

Amylinomimetics

(amylin like Drug)

PRAMLINTIDE (Symlin)

Has actibivity of amylin

Incretin Analogs

Pharmacology

Incretin Analogs

Exentide (Byetta)

Has incretin like activity

1. Comes as either a 5mcg or 10mcg injection “pen” each containing 60 doses (one month’s supply)

2. Administered BID before morning and evening meals.
3. Refrigerate injection pens between injections
4. Do not use in patient’s with Type 1 diabetes
5. Side effects: most common are N/V diarrhea

Dipeptidyl Peptidase IV (DPP-IV) inhibitor

Sitagliptin (Januvia)

PHARMACOLOGY

1. GLP-1 facilitates glucose-dependent insulin secretion

2. DPP-IV is the major enzyme that degrades GLP-1

Dipeptidyl Peptidase IV (DPP-IV) inhibitor

Sitagliptin (Januvia)

1. Orally active: dose is 100mg daily
2. Toxicity: N/V/D
3. Only used in Type 2 diabetes

ACE inhibitors and angiotensin II blockers

also CCB

-Thiazide diuretics can cause insulin resistance but still can be used.

- Should be on beta-blockers if have CAD unless contrainsicated.

CHOLESTEROL MANAGEMENT

terms

Cholesterol

CHOLESTEROL MANAGEMENT

terms

TRIGLYCERIDE

1. A lipid made from fatty acids and glycerol;
   

2. provides fatty acids for energy storage and production.

CHOLESTEROL MANAGEMENT

terms

LIPIDS

CHOLESTEROL MANAGEMENT

terms

Lipoprotein

1. Carrier protein - combination of cholesterol, triglycerides and apolipoproteins which allows for transportation of cholesterol and triglycerides in the blood. Apolipoproteins are on the surface of lipoproteins and help bind the lipoprotein to cell surfaces and is a cofactor for breakdown of TGs.

CHOLESTEROL MANAGMENT

Terms

Chylomicron

1. Form in which cholesterol & triglycerides are transported from the intestine to the liver or general circulation.

CHOLESTEROL MANAGMENT

Terms

LDL

1. (low density lipoprotein) - main carrier of blood cholesterol from the liver to peripheral tissues. Results from loss of TG in VLDL particles. These particles are small and can deposit in arterial walls.

CHOLESTEROL MANAGEMENT

Terms

VLDL

1. (very low density lipoprotein) - main carrier of blood triglycerides (TG) from liver to peripheral tissues.

CHOLESTEROL MANAGEMENT

Terms

HDL

1. (high density lipoprotein), helps to remove cholesterol from peripheral tissues (extrahepatic tissue) and returns it to the liver. High levels are protective.

CHOLESTEROL MANAGEMENT

Total Cholesterol =

CHOLESTEROL MANAGEMENT

HMG-CoA Reductase

1. he rate limiting enzyme in cholesterol synthesis in the liver.

Which medications will decrease LDL? which medication may not?

*******

1. Bile Acid Sequestrants

2. Ezetimibe

3. Fibric Acids (may reduce by 30% or increase by 45%, may increase LDL if TG is high)

4. HMG-CoA Reductase

5. Nicotinic Acid

What cholesterol medication increases HDL?

*****

1. Bile Acid Sequestrants

2. Ezetimibe

3. Fibric Acids

4. HMG-CoA Reductase

5. Nicotinic Acid

What cholesterol medication decreases Triglycerides and which medication decreases Triglycerides?

*****

Bile Acid Sequestrants increase TG

Ezetimibe, Fibric acids, HMG-CoA Reductase Inhibitor and nicotinic acid all decreases TG

HMG-CoA Reductase Inhibitors

STATINS

What are the long acting statins?

STATINs

Atorvastatin and Rosuvastatin

What can they cause

they have the longest half life and they can cause evevated liver enzyme blood levels (AST an ALT)

STATINS

What are the two most liophylic?

Simvastatin and Lovastatin

 (most likely to cause elevated CK)

Except for Pravastatin and Rosuvastatin, the metabolism of all statins is decreasd by CYP3A4 inhibitors which increase risk of myopathy. CYP3A4 is inhibited by:

***

1. Erythromyocin which inhibits the metabolism of statins and increases the blood level.

2. and Grapefruit Juice which also increased the blood level of statin.

Other drugs that increase risk of myopathy when coadministered with statins are?

****

Gemifibrozil and Nicotinic Acid (potential muscle breakdown)

HMG-CoA Reductase Inhibitors

Pharmacology

is the rate limiting enzyme in the synthesis of cholesterol. Its inhibition reduces formation of cholesterol in the liver which in turn stimulates activity of LDL receptors in the liver. Increased activity of LDL receptors increases removal of LDL from circulating blood.

HMG-CoA Reductase

Administration

What is the most effective time to administer?

**

when given in the evening * except the long acting ones

-to allow maximum effect make adjustment only ever 4-6 weeks

STATINS

Patient Related Variables

What pregancy category is it?

STATINS

Toxicity

***

Bile Acid Sequestrants

Cholestyramine (Questran)

Colestipol (Colestid)

Colesevelam (WelChol)

DRUG INTERACTIONS

*****

Binds with many drugs; take other medications 1 hour before or 4 hours after bile acid sequestrants

1. Selectively inhibits absorption of cholesterol from small intestines

2. Can be used a lone or in combination with a statin

3. Dose: 10mg qd

4. Adverse effects- well tolerated.

FIBRATES

Gemfibrozil (Lopid)

Fenofibrate (Tricor)

Clofibrate (Atromid-S)

What cholesterol do these primarily decrease?

FIBRATES

Gemfibrozil (Lopid)

Fenofibrate (Tricor)

Clofibrate (Atromid-S)

What do they have a drug interaction with?

FIBRATES

Gemfibrozil (Lopid)

Fenofibrate (Tricor)

Clofibrate (Atromid-S)

ADVERSE EFFECTS

*****

LIVER AND MUSCLE (same as statins)

a. increase in CK and LFTs

b. Cholethiasis, cholecystitis

c. contraindicated in GB disease, liver dysfunction, severe kidney dysfunction.

NIACIN

(Nicotinic Acid, Vitamin, Vitamin B3)

PHARMACOLOGY

NIACIN

(Nicotinic Acid, Vitamin, Vitamin B3)

ADMINISTRATION TECHNIQUES

What do you want to try and minimize?

****

NIACIN

(Nicotinic Acid, Vitamin, Vitamin B3)

What are patient related variables?

*****

1. Diabetes: May worsen glucose control (increased insulin resistance)

2. Gout: may elevate uric acid(compete for clearance at renal tubule)

3. Ischemic Heart Disease: vasodilation can cause reflex tachycardia which can worsen ischemia.

4. Peptic Ulcer Disease: Niacin increases acid formation and may aggravate PUD

5. Drug interaction: Coadministration with HMG-CoA Reductase inhibitors may increase incidence of myositis.

NIACIN

Adverse effects

1. Elevated LFTs. may be more common with slow release preparations. Monitor AST and ALT

2. Dose related flushing of the face and neck, with or without puritis, is a dose limiting toxicity.

3. GI: heartburn, nausea, diarrhea, abdominal discomfort.

Omega-3- fatty acids

What do they decrease?

What adverse effects do they have

1. they decrease TG by effects on apoproteins

2. May cause diarrhea, excess bleeding and fishy taste.

What are positive symptoms of schizophrenia?

****

Caused by dopamine over activity in the mesoblimbic area of the brain (functional arousal, memory, stimulus processing and motivational behavior)-typical and atypical antipyschotics are effective because block dopamine in this are of the brain.

Paranoia

Aggression

Sleep disturbances

Disorganized thinking/speech

Hallucinations (generally voices)

Distorted perceptions

Delusions (generally paranoid of external forces)

decreased appetite

What are the negative symptoms of schizoprenia?

***8

caused by dopamine inactivity in mesocorital area of the brain (functional cognition, communication, social function and response to stress). Typical antipsychotics are non specific dopamine blockers and also block in this part of the brain causing further dopamine inactivity and worsening of negative symptoms. Atypicals (because they are selective for mesolimbic are) don't make negative symptoms worse and may have modest effect to improve

Disorientation

Poor memory

lack of insight

confusion

poor judgemet

anhedonia.

Antipsychotics

PHARMACOLOGY

***

1. Blocks dopamine receptors
2. Blocks acetylcholine receptors (except for Risperidone and Ziprasidone)

3. Blocks histamine-1 receptors (Risperidone and Ziprasidone very low)

4. Blocks alpha-1 adrenergic receptors.

Antipsychotic agents

What is the goal of therapy?

****

1. To reduce the symptoms of psychosis and improve the manageability and social functioning of the patient.

Response to Therapy:

FIrst week: Decreased agitaion (ACTION IS SLOW)

2-4 weeks: Improved socialization

4-6 weeks: Involvement in thought disorder, decreased hallucinations/delusions, conversation becomes more appropriate

Maintenance therapy may be necessary to prevent relapse.

4. Comparative studies have demonstrated equivalent efficacy of antipsychotic drugs when used in comparable doses. Exception: the atypical antipsychotics are more effective for negative symptoms.

Clozapine is generally effective for schizoprenia unresponsive to other therapies.

Antipsychotics

What can you assume with relationship between Extraparemetal effects and Anticholinergic?

If there is a lot of EPS side effects then there is less anticholinergic. And if there are more anticholinergic side effects there is les EPS side effects.

Antipsychotics

Extrapyramidal Symtoms (EPS)

EPS are thought to be the result of reduced dopamine activity in the basal ganglia, resulting in a relative cholinergic hyperactivity. Classification of EPS and treatment strategies for EPS are noted below.

Antipsychotics

Dystonia

1. sudden, often dramatic contractions of skeletal muscle groups; often involves head, neck, back or laryngeal muscles; generally occurs within 24 - 96 hours of therapy initiation or dosage increase.

Treatment: Treat as a medical emergency with anticholinergic agents such as diphenhydramine (IV or IM) or benztropine (Cogentin) (IM).

Pseudo-Parkinsonism

1. Stiffness, shuffling gait, pill rolling, mask-like facies, cog-wheeling at elbow.

2. Treatment: often responds to a decrease in antipsychotic dose or use of oral anticholinergics.

Antpsychotic Side effects

Akathisia

-Inability to sit still, urge to move about; easily mistaken for increased anxiety and agitation

-Treatment: Less responsive to anticholinergics; may respond to decrease in antipsychotic dose or switching to a low potency antipsychotic, or administration of beta blocker (propranolol is the drug of choice because of its lipid solubility allowing it to cross the blood brain barrier very well) or a benzodiazepine such as diazepam.

antipsychotic Side effects

Sedation

2. related to antihistaminic properties; more prominent with low potency antipsychotics. Tolerance develops.

antipsychotic side effects

orthostatic hypotension

2. related to alpha-1 adrenergic blockade; more common with low potency antipsychotics. Tolerance develops.

antipsychotics side effects

Anticholinergic

antipsychotics side effects

Skin reactions

5. photosensitivity with the low potency phenothiazines. Patients should protect themselves from the sun.

antipsychotic side efects

TARDIVE DYSKINESIA

CAN BE PERMANENT

antipsychotics side effects

Agranulocytosis

5. Can occur with any antipsychotic but is most common with clozapine. Occurs in about 1% of patients during the first 18 months of therapy. Greatest risk is during the first 6 months. Monitoring WBC count is mandatory – prior to initiation, every week for first 6 months then every other week for months 6-12, then every 4 weeks. Clozapine is discontinued if WBC count drops below 2000/mm3 or ANC drops below 1000/mm3.

antipsychotic side effects

Neuroleptic Malignant Syndrome

****

What is used to treat?

5. Can occur with any antipsychotic agent. (1-2% usually early in therapy or after the dose has been increased). Clinical S & Sx evolve over 24-72 hrs and include body temperature >38°C; autonomic dysfunction (↑HR, ↑↓BP, sweating, ↑RR), rigidity, and altered level of consciousness. Dantrolene (36 vials) and bromocriptine are used for supportive therapy.

What are side effects of all antipsychotics?

5. (except for clozapine and quetiapine – loose dopamine blockade) can increase prolactin because they block dopamine. Hyperprolactinemia develops in 1-5% (galactorrhea, menstrual cycle changes).

antipyschotics side effects

Erectile dysfunction

5. Erectile dysfunction in males and loss of libido in males and females occurs in 25-50% (treat with decrease in dose – if possible)

antipsychotic side effects

Cardiac

QTc prolongation – especially with mellaril, droperidol and ziprasidone. Most significant with droperidol which has a BLACK BOX WARNING regarding this effect

antipsychotics

Administration issues

***

*slow onset of action

*when combined with TCA, antiarrythmic, floroquinolones or erythromyocin it can cause QT prolongation. SEVERAL DRUGS be aware.

-SSRI esp Prozac and Paxil – increase blood levels of phenothiazines, haldol and risperidone
Fluvoxamine - increase metabolism of clozapine and quetiapine.
Smoking increases metabolism of clozapine and quetiapine (stop smoking can increase levels of clozapine and quetiapine and cause seizures)

antipsycotics

MONITORING PARAMETERS

-5 or more od the following symptoms during the same 2 week period and not attributable to drugs or a general medical condition. S.I.G.E.C.A.P.S. (Suicidal ideation, interest, guilt, energy, concentrating, appetitie, psychomotor agitation, sleep disturbances)

4-6 weeks. geriatrics patients can take up to 12 weeks.

Non-tricyclic antidepressants

Have what?

(5-HT, DA, & NE reuptake inhibitors) 75-375 mg ( large range)

SSRI's (antidepressants)

Have what?

- Lower doses and is what is used initial in all patients

1. Blocks cholinergic

2. Blocks alpha-1 adrenergic receptors

3. Blocks histamine 1-receptors

May increase agitation (FDA warning, primarily with children, slight increase in the # of suicides)

4-9 months: acute phase

1 or more years: Maintenance phase ( necessary in some patients to avoid relapse)

May consider discontinuation of therapy following a single episode of depression where the patient is fully remitted for at least 6 months (on therapy) and has no family history. If patient relapses within 5 years, therapy should be continued indefinitely. Patients with 3 or more episodes of depression should be on life long therapy (relapse off of therapy is >90%).

Can plasma level monitoring be used for some patients?

***

YES

-TCA have a curvilinear relationship between plasma levels and antidepressant effect (poor response is seen with plasma levels that are either too low or too high). SWEET SPOT

-Dose response for SSRIs are relatively flat (max dose is not much higher then minimum dose.)

-Dose response for Venlafaxine is steep, maximum dose is considerably higher than minimum dose.

Tricyclic Antidepressants

Adverse Effects

***

* Patients with suicidal tendancies are being treated with a potentially lethal drugs that take up to 3-6 weeks to work (may want to give them a small amount and follow up on progress frequently)

SSRI's

Adverse Effects

(Only need to know class effect, not each individual drug)

Bupropion (wellbutrin)

Adverse effects

low incidence of weight gain, low incidence of sedation, no clinically relevant anticholinergic or antihistaminic effects. Most common side effects are insomnia and agitation. May increase risk of seizures in patients at risk of seizure activity.

Venlafaxine

adverse effects

Amoxapine

***

What symptoms can it cause?

adverse effects

1. Extrapyramidal symptoms secondary to DA receptor blockade, seizures, sedation, anticholinergic effects.

14 days after D/C'd

HYPERTENSIVE CRISIS can occur with concomitant sympathomimetic use or foods high in tyramine. Hypertension can be treated with phentolamine.

When you discontinue an antidepressant you should...?

***

*-taper the drug over 1-2 weeks to avoid withdrawal symptoms.

7. a. Low dose lithium (0.4 – 0.6 mEq/L)
   b. Levothyroxine in a patient with borderline hypothyroidism
   c. Atypical antipsychotics
   d. Stimulants (Ritalin / Dexadrine) in patients who are apathetic, amotivational or lack energy

St. John's Wart

Antidepressant

-may be effective for mild to moderate depression

-It is a food supplement so there is no regulation/no control

What is the acute treatment for Manic or mixed episodes of Bipolar?

****

1. Lithium + antipsychotic (olanzapine or risperidone) OR

2. Valproate (preferred over lithium for mixed episode) + antipsychotic (olanzapine or risperidone) PREFERRED OVER LITHIUM FOR MIXED EPISODES.

What is the preffered treatment for Depressive Episodes?

***

1. Antidepressant monotherpay is NOT recommended ( can throw the patient into a manic episode) manic phase will be unmasked.

FIRST Line : lithium or lamotrogine

ADD on therapy if necessary: second line buprion

third line venlafaxine or MAO inhibitor

treatment for refractory and depression with psychosis or catatonia.

What is the best maintenance therapy for bipolar?

***

Lithium

Place in therapy

***

-First line in all patients diagnoses with bipolar disorder except for mixed episodes

-Clinical response onset is a week to 10 days

How should lithium be dosed?

***

When should lithium blood levels be measured?

***

Blood concentration levels of lithium should be measured no sooner than 12 hours after last dose. 

How is lithium secreted out of the bosy and what will affect elimination?

***

-Lithium is elminated by the kidneys; Renal dysfunction will decrease elimination and increase risk for toxicity.

-Dramatic changes in Na and fluid intake can change lithium levels

-Maintain good fluid intake.

-Hyponatremia and/or hypovolemia will decrease elimnation of lithium: thiazide diuretics, NSAIDS (including COX-2 inhibitors), ACeI, salt restricted diets

Adverse toxicities of lithium include?

***

- Polyuria, polydipsia, weight gain, cognitive problems (dulling, mental slowness, poor concentration, confusion), fine hand tremor, sedation, impaired coordination.

-

Adverse effects

Lithium

Hypothyroidism

-minimize by titrating the dose slowly and by using divided doses or sustained release formulations

-treat by using a single daily dose (sustained release) at bedtime

-Use beta blockers if necessary

What can happen with an overdose level of lithium?

***

N/V/D

Course tremor, ataxia, dysarthria

marked confusion

seizure, coma

Lamotrogine

Bipolar

What does have a black box warning for?

increased risk with rash with combination therapy.

Osteoporosis

Who does it affect?

What are the causes of primary and secondary?

-Most common skeletal disorder.

-Affects over 10 million Americans (80% women)

-Primary cause unknown

-Secondary cause (drugs and other diseases)

- Primary mostly in postmenopausal women.

-Secondary mostly in me and premenoponopausal women.

-Low bone density

-Current cigarette smoking

-Low body weight

-Advanced Age

-ETOH consumption >2 drinks per day

-Glucocorticoid Steroid therapy

-Female

-Osteoporotic fractures in first degree relative

-Caucasian ethnicity

-low physical activity

What are drugs associated with causing Osteoporosis?

What is the main one?

******

-Anticonvulsants (Dilantin, Phenobarbital)

-Aromatose inhibitors

-Methotrexate

-Glucocorticoids (>5 mg prednisone per day for 3 months) decrease GI calcium absorption and increase calcium excretion. Systemic steroids, NOT inhaled

-Immunosuppresents

-Lithium

bone remodeling

OSTEOCLASTS

bone remodeling

OSTEOBLASTS

FORM NEW BONE IN CAVITIES CREATED BY OSTEOCLASTS (puts down new bone)

decrease in estrogen level leading to increased bone remodeling (15% of bone loss in first 5 years and 1 % per year afterwards) Increased risk for fractures due to bone loss.

-Women over 65 y/o

-Men over 70 y/o

-Individuals > 50 y/o with history of fracture, or secondary cause of OP

-FRAX- evaluates 10 year risk for hip or major osteoporosis fracture.

What are the goals of therapy in osteoporosis?

-Preventing fractures

-Maintaining or increasing Bone Mineral Density (BMD)

-Preventing Bone Loss from secondary causes.

-Decreasing morbitdity and mortality

-Nutrition: dietary Ca and Vitamin D

-Exercise: weight bearing exercise

-Preventing of falls: avoiding medicaitons that affect change in mental status if possible (an tipsychotics, benzo, TCAs, sedative/hypnotics, anticholinergic and DIURETICS)

What calcium supplement has the most calcium in it?

What is the lowest?

-Calcium Carbonate (40%) Os-Cal, Caltrate, Tums

Body can only absorb 500 mg at a time so never dose more that that. Need 1500 mg per day so dose TID.

-Calcium gluconate (9%)

What is the only calcium preparation that should not be taken with food?

*****

Calcium Citrate: preferred salt for patient on agent that reduce stomach acid. Prefferred with a patient that is on a PPI (acid is reduced)

What are drug interactions with calcium replacement?

****

PPI, H2 blockers, iron, tetracycline, fluoroquinolones

JUST SEPERATE FROM CALCIUM, DON'T COADMINISTER

BISPHOSPHONATES

Alendronate, ibandronate

What line of therapy are they and how do they work?

BISPHOSPHONATES

Alendronate, ibandronate

What are the adverse effects of Biophosphonates?

*****

-N/V/D (why injection is given once a week to reduce toxicity effects) esophageal irritation, dyspepsia, esophogeal reflux

-Influenza like symptoms with IV formulation

-Osteonecrosis of the Jaw: RARE Risk factors include chemo, corticosteroids, infection, pre-excisting dental disease

BISPHOSPHONATES

Alendronate, ibandronate

What lab values do you want to get a baseline of as well as continue to monitor?

-Serum Cr

-alk phos

-phosphate

-Mg

-Ca, prior to IV administration

BISPHOSPHONATES

Alendronate, ibandronate

What is a big administration factor you want to be sure you teach your patient before you administer this medication?

-Food and calcium supplements decrease PO absorption take 30-60 mins before first meal of the day with 6-8 oz of water. (very poorly absorbed)

-Sit upright for 30-60 min after PO administration (Large pills stuck in the esophagus can burn through wall).

-Swallow tablets whole

- Renally eliminated

Selective Estrogen Receptor Modulators

(SERMs)

Raloxifene

How do they work?

-decrease bone resorption and turnover

-increase BMD and decreases fractures

Selective Estrogen Receptor Modulators

(SERMs)

Raloxifene

What are the major adverse reactions?

*****

hot flashes, leg cramps, increase risk of VTE (Venous Thrombus Embolism)

Hx of VTE is contraindicated to use

Is hormone therapy recommended for Osteoporosis?

*****

NO, not recommended for OP treatment alone

-HERS study found increase in VTE and Breast CA even though it does decrease fractures in postmenopausal women.

osteoporosis

Calcitonin

how does it work?

Who may it help?

-Hormone that regulates calcium levels (Salmon is more potent and longer acting than mammalian)

-Binds to osteoclast receptors and inhibits bone resporption

-Decreases vertebral fractures

-May be helpful for patients with pain for vertebral fractures.

osteoporosis

Calcitonin

How can it be administered?

What other benifit does it have other than helping with OP?

****

-Intranasal or SQ/IM: Intranasal preferred because of less toxicity

-Benefits from parenteral administration decrease over time (antibodies decrease form a decrease effectiveness overtime)

osteoporosis

Teriprartide

How does it work?

how do you administer?

-recombinant human parathyroid hormone

-stimulates osteoblast activity.

- Increase BMD and decreases fractures

-Administer SQ daily

osteoporosis

Teriparatide

What are the adverse effects?

*****

What is seen in aninimals but not yet in humans?

Nausea, headache, leg cramps, dizziness, injection site pain, hypercalcemia, orthostatic hypotension

-Osteosarcoma reported in animal studies, Report not seen in humans *Maxiumum durations recomended 2 years because No studies over that time period

osteoporosis

What is the first line treatment for men?

Alendoronate and teriparatide approved for treatment of OP in men

the permanent cesation of menses; no menses dor at least 12 months to make a diagnosis; occurs between ages 40 and 58 naturally; perimenopause occurs 2-8 years before menopause; irregular mentrual cycles, longer cycle intervals, decreased length of menses, vasomotor symtoms.

-With age, ovarian follicles decrease.

-High levels of FSH, needed for follicles to mature and ovulation to occur

-During perimenopause, FSH concentrations can be higher during some cycles and low during others, leading to irregular menses.

-During menopause, estradiol, decreases 90% leading to an increase in FSH and LH secretion

-Symptoms associated with decreased estradiol concentrations. (hot flashes, night sweats, vaginal dryness, atrophy, mood swings, and insomnia)

-Goal of therapy is to decrease symptoms, improve quality of life, and minimize adverse effects.

- Most effective treatment for vasomotor symptoms and vulvovaginal atrophy is hormone therapy (estrogen therapy).

Quit smoking

Limit alcohol and caffein intake

Limit hot beverage/spicy foods

Keep cool, dress in layers

Reduce stress

Increase exercise.

Urinary incontinence: kegel exercises

Estrogen

how does it work in the treatment of menopause?

-Treats vasomotor symptoms and vulvovaginal atrophy

-use appropriate route, lowest dose, shortest duration

-can be used alone in patients with hysterectomy

Estrogen

What are the different way to administer?

-topical route for vaginal symptoms

-Oral or tansdermal for vasomotr symptoms.

-Transdermal: lowerrisk of VTE, increasing TG, or liver functional abnormalities.

What should be given with estrogen in women with an intact uterus to decrease the risk of endometrial hyperlasia/cancer?

*******

Progesterones

At lease 12-14 days of the month

Nausea, headache, bloating, breast tenderness, bleeding,

Serious: CHD, stroke, VTE, breast cancer, gallbladder disease

-Nausea, weight gain, headache, bleeding, irritability, depression

-Serious: VTE, decreased bone mineral denisity

What are the contraindications for Estrogen and Progesterone Therapy?

*****

-CHD, or significant CHD risk farctors, Breast cancer, History or active VTE, pregnancy, liver disease, undiagnosed vaginal bleeding.

Hormone Replacement Therapy

What was discovered in the HERS trial 1998?

-Study in women with established CHD

-Increased risk of CHD in 1st year of estrogen therapy

-Increased gallbladder disease

-Increased risk for VTE

Hormone Replacement Therapy

Women's Health Initiative

(WHI) Study

What was discovered in this study?

-In women without CHD; ages 50-79 y/o with intact uterus; HRT vs. placebo for 8.5 years

-Stopped after 5.2 years (increased risk for breast cancer in HRT group)

-Nonsignificant increase in rish in CHD, stroke, VTE

-Decreased in fractures. (helps osteo)

(use short term 5 years or less)

How should Hormone Replacement therapy be discontinued?

****

-Should be taperd to prevent recurrence of hot flashes

-May take 3-6 months to taper.

-Dose taper or day taper methods

-Should try to taper after 1 year.

-May need to reintiate if symptoms continue.

Nonhormonal/ Alternative Therapy

What does SSRI's/venlafaxine help treat in menopause?

-Depression, anxiety, hot flashes.

Nonhormonal/ Alternative Therapy

Phytoestrogens

Should these be used as first line treatment for menopause?

POOR DATA

-Similar to human estrogens

-Source is soy protein

- Measured by amount of isoflavone

-Should not be used in women with estrogen-dependent cancers.

Nonhormonal/Alternative Therapy

Black Cohosh

Is there good data for treatment of menopause?

Just from reported improvement/no data

-Unknown mechanism

-Mild-moderate hot flashes

-Lack of good data, not recommended for use

Nonhormonal/ Alternative Therapy

Gabapentin

How is this used for menopause?

-decrease severtiy and frequency of hot flashes

Nonhormonal/Alternative Therapy

Clonidine

Is this a good treatment for menopause?

Decreased hot flashes

Good evidence, careful with hypotension

-Symptoms/QOL

-Hormonal therapy (Bleeding/spotting)

-Adverse effects

-Blood Pressure

-Breast Exams/mammograms

-BMD every 5 years

-TSH

-regulates energy metabolism and functions in the development of fetal growth.

-T3 and T4 are produced by binding of iodine to tyrosine molecules on thyroglobulin (organification)

-Monoiodotyrosine (MIT) and diiodotyrosine (DIT) bind to form T3 and T4 (T3 has the activity)

thyroid hormone production

What is the acting hormone?

-80% of thyroid hormone is T4

-majority of physiologic activity is from T3

-T4 is converted to T3 in peripheral tissues

-Hypothalamic-pituitary-thyroid-axis controls production and release of thyroid hormone

the thyroid

TSH levels

Free T3 and T4 (thyroid hormone are highly protein bound)

Different antibodies can be measured in patients with autoimmune thyroid disorders.

-Autoimmune thyroiditid (Hashimoto's disease)

-Drugs (amiodarone, iodides, sulfonlureas,lithium)

-Lithium inhibits release of thyroid hormones from the gland, may cause thyrotoxicosis if withdrawn in patients with hyperthyroidism

-Sulfonylureas inhibit thyroid organification

-Iodine deficiency

-Pituitary Disease

-Hypothalmic Disease

-fatigue, depression, cold intolerance, dry skin, weight gain, bradycardia, nonpitting edema, hyporeflexia, constipation LOW ENERGY

What is the treatment goal for hypothyroidism?

What is the hormone of choice?

****

-Goal: achieve euthroid state and alleviate symptoms.

-Synthetic-L-thyroxine (T4) is the drug of choise

-Preparations come in: T4 (L-thyroxine), T3 (liothyronine), T3/T4 combination (liotrix, Armor Thyroid)

What is the half life of T4?

(thyroid replacement)

****

How should thyroid medication be dosed?

If a dose is missed again can they take the missed dose the next day?

 When should you check TSH levels after initiation of thyroid therapy?

*****

6-8 weeks

Thyroid Replacement therapy

When you swich administration methods, do you need to adjust the dose? (from Oral to parental)

****

decrease the dose by 50% or hold in short term discontinuation. Injection needs to prepared just before administration

*****

hyperthyrodism

exacerbation of ischemic heart disease

transient hair loss

GI hypotility

Arrythmias

-Phenytoi and phenobarbital may increase clearance of T4

-Clearance of T4 decreases with age

-Cardiac disease and hyptertension.

-If identified as hypo, full replacement doses of thyroid hormone should be prescribed (dose replacement is based on age)

-Free T4 levels should be monitored and used for dose titration in INFANTS

-Life threatening condition (60-70% mortality)

-severe, longstanding hypothyroidism

-300-500 mcg IV levothyroxine

-convert to full replacement dose of oral T4

Hyperthyroidism

What are the causes?

Graves Disease (most common)

-Thyroid nodules or multinodular goiter [more common in elderly]

-thyroid cancer

-iodine excess

-excess thyroid hormone intake

-Drug induced (amiodarone, iodine, interfieron)

Heat intolerance, weight loss, increased sweating, palpitaitons, tachycardia, diarrhea, warm moist skin, expothalamous, hyper-reflexia

Goal: acieve and maintain clinical euthyroid state, control symptoms.

Therapy: Decrease hormone production (Pr opylythiouracil (PTU), methimazole, iodides

-Block hormone activity (beta adrenergic blockers)

-Chemical Destruction of gland: I (radiaoactive iodine)

PTU and Methimazole

(Tx. of hyperthyroidism)

Which is first line treatment unless the patient is pregnant?

PTU: pregnant

Methimazole: everyone else

PTU and Methimazole

(Tx. of hyperthyroidism)

What are some administration considerations that need to be made?

-Onset of action is slow since the gland may contain large amounts of stored hormone. Time to achieve a euthyroid state is 3-12 weeks.

-Initial doses are higher than maintenance doses.

-Initial doses have to be decreased after 4-6 weeks.

-Monitor T4 Serum Concentrations.

-May be tapered and stopped after 12-24 months

PTU and Methimazole

(tx. in hyperthyroidism)

 What are adverse effects?

******

-Rarely agranulocytosis: may be present initially as a sore throat and a fever (reversible)

-hypothyroidism

-hypersensitivity: usually self limiting

PTU and Methimazole

(tx. in hyperthyroidism)

What are patient related variables?

Pregnancy

******

-Pregnancy: although both drugs cross the placenta, PTU is preferred because it crosses to a lesser extent than MMI.

tx. of hyperthyroidism

Iodides

How do they work?

-A daily thyroidal iodine uptake of 100 mcg is required for normal thyroid function.

-High amounts of iodine (>30 mg/day):

     -reduce iodine trapping by the gland

     -inhibit iodine organification

     -inhibit release of T3 and T4 from the gland

-Effects of high doses of iodine are short term

-Long term therapy leads to "escape" of these effects and hormone levels increase to higher than baseline.

tx. of hyperthyroidism

What are some administration consideraitons?

What is important to be aware of?

*****

-Short term for sever hyperthyroidism.

-Preoperative preperation for Grave's patient.

-Onset of action is faster than PTU or MMI

-IMPORTANT NOTE: difference in concentrations. Lugol's solution. 6.3 mg/drop. SSKI's mg iodine/drop

tx. for hyperthyroidism

How should iodine solution be administerd?

****

-Through a straw into the back of the mouth to avoid staining teeth

-Give flavored because it tastes terrible

-Discontinue 2-3 weeks prior to radioactive iodide. Decrease uptake of radioactive iodine into the thyroid gland.

tx. of hyperthyroidism

Iodine

What are the adverse effects?

-Bitter taste, dental staining, and gastritis

-Fever, rash

-Iodine induced hyperthyroidism, severe headache

-Concentration in the thyroid gland and leads to destruction of the gland

-Administration: Do not use in pregnancy;Do not administer other iodide 2-3 weeks prior.

-Adverse Effect: Hypothyroidism

-Propranolol" inhibits concersion of T4 to T3.

-Blocks the adrenergic manifestations of hyperthyroidism.

E.g tremors, palpitations, excessive sweating.

- Mainly control symptoms and do not alter the disease.

euthyroid

Subtotal thyroidectomy for patients with goiters or thyroid cancers and those who do not respond to other therapy.

Pregnancy may worsen hyperthyroidism

-B-hCg is a TSH agonist.

Neonates and perdiatric hyperthyroidism: neonates of mothers with Graves Disease may be hyperthyroid at birth.

PTU, methimazole, SSKI may be used to treat