Endocrine Flashcards
What are 5 drugs that impact the endocrine system?
Bisphosphonates
Hypothalamic and pituitary hormones
Exocrine pancreatic enzymes
Antidiabetic agents
Thyroid and antithyroid agents
Pancreatic Enzyme Uses
Cystic fibrosis and pancreatitis
Some bariatric procedures require supplements
Pancreatic Enzyme Pharmacodynamics
Inactivated by ph values less than 4; do not crush or chew. Sprinkle on food if powdered form. Take immediately before or with meal.
Pancreatic Enzyme Pharmacokinetics
Absorption: none, acts locally in GI tract.
Excretion: feces
Pancrelipase made from pork; pancreatin made from pork, beef, or vegatable sources.
Precautions: antacids decrease effectiveness, decreases absorption of oral iron.
Pancreatic Enzymes: ADR and Drug Selection
Skin irritation, rashes, stomatitis, nausea
High doses: hyperuricosuria, hyperuricemia
Watch products because they are NOT bioequivalent. Most old formulas are no longer FDA approved.
Pancreatic Enzyme Monitoring
Pancreatitis: contraindicated during acute exacerbations of chronic illness.
Hypersensitivities: may need products from vegetable sources.
Growth, charts, albumin, cholesterol, glucose, CBC, iron levels, serum uric acid.
Steatorrhea: rates and intensity help monitoring dosing.
Pancreatic Enzyme Facts
Each drug is specified in lipase, protease, and amylase units. Drugs are prescribed in units of lipase.
Many older formulations are not available in FDA approved source, so finding the right dosing is more complex; this is improving over time.
Pancreatic Enzymes Education
Do not chew, crush or drink with water.
Avoid leaving in mouth.
Enteric-coated formulations should not be mixed with alkaline foods prior to ingestion.
If powder spills, wash off skin immediately.
With infants/toddlers; water for aspiration, inhalation.
Lifestyle management: follow dietary guidelines.
Insulin Pharmacodynamics
Binds at insulin receptor sites on cell membrane allowing glucose to enter cells.
Acts on liver to increase storage of glucose as glycogen.
Promotes protein synthesis on muscle cells.
Reduces circulation of free fatty acids and promotes storage of triglycerides in adipose tissue.
Types of Insulin (4)
Rapid acting
Short acting
Intermediate acting
Long acting
Rapid-acting
Lispro (humalog), aspart (novolog) or glulisine (apidra), onset about 5 minutes, peaks in 1 hour, duration about 4-5 hours.
Short-acting
Regular (humulin) insulin sometimes used around mealtime. Taken about 30-45 minutes before eating.
Peaks in 3-4 hours
Duration 4-10 hours.
Intermediate acting
Normal pressure hydrocephalus mixed with protamine, delaying absorption; insulin looks cloudy and must be mixed before it is injected.
Onset one-half to 1 hour
Peak 4 to 10 hours
Duration 12 to 24 hours
Long-acting
Glargine (lantus), detemir (levemir), degludec (tresiba) insulins.
Onset 2-4 hours
Duration 24 hours with little or no peak
Insulin Pharmacokinetics
Absorption determined by type of insulin, injection site and volume injected.
Abdominal site absorbs 50% more than other sites
Metabolism: induces CYP1A2
Excretion: urine
Watch for standardized U 100/ml, needs U100 needles.
Insulin ADR
Hypoglycemia, diabetic ketoacidosis
Watch alcohol use; increases hypoglycemia
Beta blockers mask hypoglycemia symptoms
Pregnant women can use rapid- or short-acting insulin; does not cross placenta.
-Insulin aspart, insulin glargine, and insulin glulisine
Hypothyroidism: delays insulin breakdown; therefore may require less insulin units.
Hyperthyroidism: increases renal clearance, requiring more insulin than baseline
Insulin Monitoring
Glycohemoglobin, renal function, CBC
A1C test twice a year in patients who are meeting treatment goals and have stable glycemic controls
A1C test quarterly in patients whose treatement has changed/not meeting goals
Point-of-care testing A1C allows for timely decisions on treatments changes
Insulin Patient Education
Goal A1C less than 7% for most nonpregnant adults
Individualized goals for older adults with long-time diagnoses
Administration, understanding types of insulin
Glucose monitoring frequency and recording
Emergency plan for glucose readings and “flu”
Lifestyle management, diet, exercise
Injection site selection
Oral Diabetic Agents Mechanism
Type 2 DM more than just insulin resistance
- Insufficient production of endogenous insulin. Sulfonylureas: cause an increase in insulin production.
- Tissue insensitivity to insulin. Thiazolidinediones: improve insulin sensitivity. Biguanides: do the same.
- Impaired response of beta cells. Meglitinides: increase secretion of insulin.
- Excessive production of glucose by the liver. Metformin: improves hepatic response to elevated BG, decreases glucose production and decreases GI absoprtion. Alpha-flucosidase inhibitors: inhibit absorption of carbohydrate in GI tract
- Impaired glucagon-like peptide-1 (GLP-1) activity: rapid intestinal glucose dumping. Use of dipeptidyl peptidase 4 (DPP-4) medications to slow inactivation.
- Continuous weight gain. DPP-4 may stop it or be weight neutral.
Sulfonylureas
Glipizide (glucotrol)
Glyburide (diabeta)
Glimepiride (amaryl)
All stimulate insulin release from beta cells.
All potentiate effects of ADH.
Hypoglycemia is a major side effect.
Sulfonylureas Precautions, C.I., ADR and Drug Interactions
Cross-sensitivity with sulfonamides or thiazide diuretics
Avoid in pregnant women
Older adults more sensitive to hypoglycemia events
Pediatric: use in children 10-18, but it is unlabeled.
ADRs: hypoglycemia, GI, dermatological rashes, SIADH, hemolytic anemia, leukopenia, thrombocytopenia, weight gain.
D.I.: may increase or decrease hypoglycemic effect
Sulfonylureas: Clinical Dosing for DM and DI
Clinical use and dosing for DM
- Use second-generation agents most of the time
- Individualized dose progression is based on response
- Start with lowest dose and ncrease every 4-7 days.
Neurogenic diabetes insipidus
-Chlorpropamide is used off-label.
Sulfonylureas: Rational drug selection/dosing
Age: chlorpropamide and glyburide used in older adults (use short-acting glipizide)
Cost: many generics available
Concurrent renal disease: glipizide or tolbutamide, or glyburide
Concurrent insulin: only glimepiride FDA labeled for co-administration, but most second-generation agents used
Sulfonylureas
Monitoring: Hga1c: baseline, then every 3 months while adjusting, then every 6 months.
CBC at onset, then annual unless more if symptoms
Patient education
- Administration
- ADRs
- Lifestyle management
Biguanides
Metformin (glucophage, glucophage XR)
-Decreases glucose production in liver, decreases GI glucose absorption, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
-Dose not stimuate insulin release for beta cells
-Inhibits platelet aggregation and reduces blood viscosity
Patients may lose weight: not labeled use, mostly weight neutral
Biguanides: Pharmacokinetics
Absorption: 50-60% after oral dosing; food decreases and delays absorption
Metabolism: no hepatic metabolism
Excreted by kidneys
Alcohol potentiates drug’s effect on lactate metabolism
Biguanides: Precautions, C.I., ADRs
Renal or hepatic disease is contraindicated.
Withhold drug 48 hours before and after procedures involving iodine-based contrast mediums.
Watch patients with Vitamin b12 anemia/deficiency.
Not recommended for children younger than 10 years of age.
ADRs: Metabolic acidosis risk! (lactic acid)
Rare, except in dehydration episodes.
Renal disease; watch patients at risk for metabolic acidosis.
Liver disease: risk for lactic acidosis is increased.
GI ADRs usually resolve in 2 weeks after starting dose.
Biguanides: Rational drug selection/dosing and Monitoring
Immediate release vs. extended release
Type 2 DM: start with 500mg twice/day and titrate up.
If patients do not respond to 4 weeks of high dosing, consider adding oral sulfonylurea or other medication .
Monitoring: assess renal function, ketones, hba1c before starting dosing; check every 6 months.
Biguanides: Patient Education
Administration
ADRs: report diarrhea lasting more than 2 days, dehydration
Lifestyle management
Usually not the source of any hypoglycemia
Alert imaging staff about drug presence
Alpha-glucosidase Inhibitors
Acarbose (precose)
Miglitol (glyset)
Inhibit the absorption of carbohydrate from GI tract, lowering the BG levels after meals
These are not monotherapy drugs.
Hypoglycemia treated with milk, lactose not sucrose.
Alpha-glucosidase Inhibitors: Pharmacokinetics
Absorption: less than 2% of acarbose absorbed as active drug
Metabolized by intestinal bacteria and digestive enzymes (lots of gas production!)
Excreted by the kidneys
Alpha-glucosidase Inhibitors: Precations, C.I., ADRs
Should not be used in patients with IBD or those at risk for bowel obstruction or renal impairment.
Should not be used during pregnancy.
Not to be used in pediatric population
ADRs: GI symptoms: flatulence, diarrhea, abdominal pain. Do not cause hypoglycemia.
Alpha-glucosidase Inhibitors: Drug interactions and Clinical Dosing
Acarbose; digoxin.
Miglitol: propanolol, ranitidine
Clinical use and dosing
- Initial dose is 25mg 3 times per day
- Increase dose in 4-8 week intervals.
Alpha-glucosidase Inhibitors: Patient Education
Administration: should be taken with first bite of meal
Lifestyle: Type 2 DM care
Thiazolidinediones
Pioglitazone (actos)
Rosiglitazone (avandia)
Pharmacodynamics:
- Improve target cell response to insulin by activating receptor cell proteins that improve insulin action.
- Increase utilization of insulin by liver and muscle cells and reduce liver glucose production.
Thiazolidinediones: Pharmacokinetics
Absorption: rapid after oral dosing.
Metabolism: liver via CYP2C8 and 3A4 to both active and inactive metabolites; substrate inhibits CYP2C8, CYP2D6 induces weakly CYP3A4
Greater than 99% protein bound
Excretion: in urine (15% to 30%) and feces as metabolites
Thiazolidinediones: Precautions, CI, ADR
Chronic Liver Disease- heavy liver processing
Fluid retention: exacerbates HF
FDA loosening restrictions, but still dangerous drug.
Not approved for children younger than 18.
ADRs: CV- edema, URI, headache, fatigue
Watch for signs of CHF, use with caution with patients with elevated liver enzymes.
Increased r/o bladder CA with pioglitazone use.
Drug interactions: birth control requiring higher dosing of oral contraceptives.
Watch for drugs metabolized by CYP3A4: coricidin, corticosteroids, ketoconazole
Monitoring: liver enzymes at start of therapy, hga1c
Thiazolidines: Rational drug selection and Patient education
Careful selection of patient population
Monotherapy or combination with sulfonylureas, insulin
Initial dosing: 15-30mg/day; maximum dosing: 45mg/day
Strong recommendation for endocrine co-management
Patient education: once-daily dosing
-Administration, ADRs, lifestyle management
Meglitinides
Nateglinide (starlix)
Repaglinide (prandin)
Pharmacodynamics
- Meglitinides increase insulin release from beta cells by closing potassium channels, which leads to the opening of calcium channels, and it is the influx of calcium that release the insulin.
- Time in plasma is short, less than 2 hours, so these agents only lower postprandial blood glucose levels.
Meglitinides: Precautions, CI, ADRs, Drug interactions
Liver impairment
Not approved in pediatric population
Hypoglycemia in vulnerable populations
CYP3A4 and CYP2C9 inducers increase meglitinide metabolism.
Antifungals (ketoconazole) and antimicrobials (erythromycin) inhibit metabolism, increasing risk for hypoglycemia.
Meglitinides
Rational drug selection: repaglinide (prandin)
For patients with postprandial hyperglycemia
Patients with hba1c less than 8: start with 0.5 mg before each meal.
Patients with hba1c greater than 8: start with 1 mg before each meal.
Increase slowly: may double every 2 weeks for maximum 16mg/24 hours
Meglitinides
Monitoring: get baseline hba1c and recehck in 3 months
Patient education
- Administration: no more than 30 minutes before a meal; hold if not eating
- ADRs
- Lifestyle Management
DPP-4 Inhibitors
-Pharmacodynamics
Gliptins
Sitagliptin (Januvia) and saxagliptin (onglyza)
-Inhibits DPP-4
-breaks down GLP-1 and gastric inhibitory polypeptide, which are released in response to a meal
-Leads to increase in the secretion of insulin and suppresses the release of glucagon by the pancreas
-Promotes pre- and postprandial glucose levels
-Promotes mild weight loss in obese patients with diabetes
DPP-4 Inhibitors: Precautions, C.I., ADRs, Drug interactions, Clinical use and dosing
Renal dysfucntion
Pregnancy (check with obstetrician for necessity)
Not approved in children
ADRs: GI, headache
Drug interactions: ACE-Inhibitors: increased r/o angioedema
Clinical use and dosing: Monotherapy or in combination with other anti-diabetic drugs
DPP-4 Inhibitors: Rational drug selection and Monitoring, Patient Education
Age: well-tolerated by older adults
Weight/obesity: patients may lose weight
Cost: more expensive than older drug families
Monitoring: Renal function at baseline and annually
Hba1c every 3 months
Patient education
- Administration: taken once daily in the morning
- ADRs: well-tolerated
- Lifestyle: changes still needed
Monitor for potential thyroid medullary cancer conerns, especially in those with previous nodules
GLP-1 Agonists
Exenatide (byetta) and others
Pharmacodynamics
- Injectable drugs
- Promote insulin release from pancreatic betal cells in the presence of elevated glucose
- Mimic natural incretins: slow glucose absorption from gut, promote satiety, slow postprandial spikes.
GLP-1 Agonists Precautions, C.I., Drug Interactions
Precautions & C.I.- Acute pancreatitis noted in post-marketing surveillance
Severe GI disease (colitis, crohn’s)
Pregnancy (cehck with specialists)
D.I.- Increased INR if administered with warfarin
Digoxin
GLP-1 Agonists Clinical use, Monitoring, Patient Education
Clinical use only for type 2 DM
Add on therapy is typical
Combine with metformin, sulfonylurea, others
Monitoring
-Glycemic control and GI distress
-Potential site reactions
ADRs- GI upset/nausea (major cause of noncompliance)
Patient Education
Administration of subcutaneous injection for rapid release
-60 minutes before meals
-Dosed 6 hours apart
-If dose is missed, wait for next scheduled time
-Lifestyle
Extended-release forms; weekly injections. works as well or better than rapid release on hba1c and weight.
GI issues more transient- rapid and extended release have different impacts on postprandial vs fasting glucose levels.
SGLT-2 Inhibitors
The “flozin” meds- canaglilozin, dapagliflozin
Reduces blood glucose by blocking absorption of glucose in kidneys
Also reduces BP and can lead to mild weight loss
First choice to add if hga1c is not at goal with metformin d/t significant reducation of CV risk and progression of renal functional loss.
Can cause genital yest infections which can trigger the rare fournier’s gangrene
Sometimes linked with increased K+, bladder cancer and increased lipid levels
Glucagon
Considered an insulin antidote; used in patients with diabetes who experience hypoglycemia or insulin overdose.
Stimulates hepatic gluconeogenesis and glycogenolysis, raising BG levels.
BG concentration rises within 10 minutes of injection, and maximal concentrations are attained at approximately a half hour after injection.
Hepatic stores of glycogen are necessary for glucagon to produce an anti-hypoglycemic effect.
Well absorbed after parenteral administration.
Extensively metabolized by the liver and kidneys.
Glucagon Pharmacokinetics, Precautions, C.I.s. ADRs, D.I.
Well absorbed after parenteral administration
Extensively metabolized by the liver and kidneys
Precautions/C.I.s: May be used with pregnant women and children. Administered cautiously to patients suspected of having pheochromocytoma or insulinoma
ADRs: Nausea, vomiting, allergic reactions
Drug interactions: increased anticoagulant effects of oral anticoagulants
Glucagon Clinical Use and Dosing. Monitoring, Patient Education
Reversal of hypoglycemia; prevention of low sugars for colonoscopy after 3-day preparations
In primary care setting: IM dosing
- Less than 20kg weight: 0.5 mg or 20-30mcg/kg/dose, repeat every 20 minutes
- Less than 20 kg weight: adult dosing 1mg/IM, may repeat in 20 minutes
Monitoring BG levels immediately prior to and after injection
Patient Education: Educate family on how to test BG and how to administer IM glucagon.
Glucagon depletes glycogen stores; patient should be given supplemental carbohydrates as soon as he or she awakens and is able to swallow, especially children or adolescents.
ADRs
Lifestyle
Thyroid Hormone Synthesis
Synthesis is dependent on the hypothalamic-pituitary-thyroid axis.
Thyrotropin-releasing hormone is released by the hypothalamus.
Thyroxine (t4) stimulates synthesis of TSH.
T4 and T3 are synthesized from iodine and tyrosine molecules.
Thyroid Function Tests
TSH- used to screen for hypothyroidism and hyperthyroidism
Free T4 and free T3 can confirm diagnosis.
Thyroid scan can be used to evaluate for goiter.
Routine screening is not recommeneded.
Screen women before pregnancy and in first trimester.
Hyperthyroidism
Excessive levels of thyroid hormone
- May be life-threatening
- Caused by Grave’s disease, anterior pituitary disorders, plummer’s disease, amiodarone therapy
Clinical effects from hypermetabolic state
-Heat intolerance, tachycardia
Treatment: antithyroid drugs
-PTU and methimazole
Antithyroid Agents
PTU, methimazole (Tapazole)
Pharmacodynamics
-Block snythesis of thyroxine and triiodothyronine
-Neither drug treats the underlying pathology in hyperthryoidism
-High relapse rates; studies how less if treated for 18-24 months
Goal of treatment: correcting hypermetabolic state
Hyperthyroidism: Rational Drug Selection
Antithyroid drugs
Radioactive Iodine
Surgery
Iodides
Hyperthyroidsm: Drug Therapy
Antithyroid drugs used for remission are:
- Beta blockers may be used to reduce symptoms while waiting for antithyroid drugs to work.
- Iodidies (potassium iodide of lugol’s solution) may be used as adjuvant treatement.
Antithyroid drugs are used for at least a year in treating Grave’s disease.
Older patients may respond best to radioactive iodine.
Pregnant patients treated with ptu because it is safer.
Antithyroid Agents Precautions and Contraindications
Pregnancy risk factor D readily crosses placenta
-Recommendation NOT to get pregnant while on these drugs.
PTU not recommended in children
ADRs: agranulocystosis, drowsiness, headache, alopecia, skin rashes, renal/hepatic failure
Drug interaction: lithium, warfarin
Preoperative Drugs to Avoid Thyroid Storm While Awaiting Thyroid Surgery
Antithyroid drugs
Beta Blockers
Potasium iodide
Hyperthyroidism: Drug Therapy Monitoring, Outcome Evaluation, Patient Education
Monitoring
- Clinical Status
- Thyroid function tests (TSH and free T4)
- Assessment of visual acuity
Outcome Evaluation
- Based on TSH and free T4 levels
- Referral to endocrinology necessary
Patient Education
- Overall treatment plan
- Length of treatment (1 year for Grave’s disease)
- Medication administration
- Precautions if treated with iodine-131
Hypothyroidism
Primary hypothyroidism
- Congenital hypothyroidism
- Hashimoto’s thyroiditis: an immune-mediated disorder where TSH receptors are damaged
- Subacute thyroiditis: is inflammation of thyroid
Secondary hypothyroidism
- Pituitary or hypothalamic failure
- Cushing’s syndrome
- Overtreatment with antithyroid drugs
Goals of Treatment for Hypothyroidism
Correction of hypometabolic state and return to euthyroid state
Rational drug selection: synthetic thyroid hormone. Generic vs. brand name controversy.
Thyroid Hormones
T4, T3 and liotrix (a 4:1 mixture of T4 and T3)
Pharmacodynamics
- These hormones produce the same effects in the body as do endogenous thyroid hormones.
-They also produce a negative feedback loop to reduce further secretion of tsh and thyroid hormones.
-T4 is the drug of choice for thyroid replacement and suppression therapy because of its longer half-life.
Hypothyroidism: Pregnancy and Children
Pregnancy
- Untreated increases maternal health risks, still births, low birth weight and possible abnormal fetal brain development.
- T4 is pregnancy category a.
Infants and children with hypothryoidism need treatement for normal cognitive and physical development.
Hypothyroidism and Concomitant Diseases
Recent acute MI
CAD
Osteoporosis: women require careful monitoring
Infertility and menstrual irregularity: may improve with thyroid hormone replacement
Depression: hypothyroid evaluation should be part of depression workup
Hypothyroidism Monitoring
TSH and free T4 levels should be evaluated every 4-8 weeks until euthyroid state reached.
Druing pregnancy at 8 weeks and 6 months gestation.
Clinical symptoms frequently do not parallel actual value.
Evaluate for anemia.
Monitor BP and lipids.
Hypothyroidism Outcome Evaluation
Reduction of clinical symptoms and normal TSH/free T4
Endocrine consult considered for:
-Pediatric
-Pregnant
-Cardiac
-Complex patients or those not reponsding to therapy
Hypothyroidism Patient Education
Overall treatment plan and disease process
Role of iodine intake
Pregnancy
Need for regular follow-up and lab tests, especially dual energy x-ray absorptiometry
Drug administration
-Taken in the AM on empty stomach
-Many drug interactions
Hormone Regulation
- Bone Formation
- Growth Formation
- Metabolic Rate Control
- BP and Fluid Balance Control
Bone Formation:
-PTH: calcium, phosphorous
Growth Formation:
- Estrogens, androgens, testosterone
- GHRH->GH (somatropin)
Metabolic rate control
-TSH, TH
BP and fluid balance control
-Cortisol, aldosterone, ADH
Human Growth Hormone
Somatropin (genotropin)
- Recombinant DNA technology is true human factor.
- Stimulates the growth and metabolism of nearly every cell in the body
- Uses: short stature with or without normal GH levels
Contraindicted: patients with closed epiphyses
Dosing is highly individualized on the basis of child’s growth rate and anticipated trajectory of genetic height
Human Growth Hormone Pharmacodynamics
Initially there is an insulin-life effect
Stimulates growth of linear bones, skeletal muscles and organs.
Stimulates erythropoietin
Human Growth Hormone Pharmacokinetics and ADRs
IM and SC drugs well absorbed
Metabolism: hepatic, renal 90%
Excretion: renal
ADRs
- Antibody development
- Hyperglycemia, edema
- Hypothryoidism
- Arthralgia, headache, dizziness, flu-like symptoms
Human Growth Hormone Patient Education. Monitoring and Rational Drug Selection
Pediatric administration: total weekly dose (0.16 to 0.24mg/kg) divided into 6-7 doses.
ADRs
Lifestyle Management and need to rpevent abuse
Monitoring
- Hepatic/renal function before and during treatment
- TSH, glucose, glycohemoglobin, based on symptoms and prior illnesses
Rational drug selection: Not initiated by NP in primary care practice; work with endocrinologist.
Thyroid Hormone Pharmacokinetics
Absorption: oral- erratic 40-80%; decreased by age, food, health of GI tract, greater than 99% is protein bound.
Metabolism: liver T4 is converted to T3 in the body; T4 produces both hormones.
Excreted: bile/feces
Thryoid Hormone Precautions, C.I., and ADRs
Contraindicated after acute MI or thyrotoxicosis
Pregnancy risk factor A, and safe with children.
- Replacement is advised for all pregnant women.
- Increased metabolic rate during pregnancy may require higher dosing from baseline.
- Thyroid hormones are minimally excreted in breast milk.
- Children with hypothyroidism need treatment
ADRs
-Symptoms of hyperthyroidism
CV: angina, BP increase, flushing, palpitations
CNS: anxiety, HA, insomnia
-Long term thyroid replacement associated with decreased bone density in hip/spine in postmenopausal women
Thyroid Hormones: Drug Interactions
Bile-acid sequestrants, iron salts, antacids decrease absorption: estrogen may decrease response.
Drugs may decrease action of warfarin, digoxin and beta blockers
Treatment of Hypothyroidism
Indicated in patients with TSH levels greater than 10uiu/ml or in patients with TSH levels between 5-10 in conjunction with goiter or positive antithyroid peroxidase antibodies (or both).
Replacement is typically lifelong.
Consult with pediatric endocrinologist before treating a pediatric patient.
T4 Dosing
For patients with no known CV disease
- Initial dose can be started at 50mcg/day for 2-4 weeks and may be increased in inrements of 25mcg/day.
- Average full replacement 100-125mcg/day.
For patients 50+ years with CV disease or with long-standing hypothyroidism
-Initial dosage of T4 is 12.5 to 25 mg/day.
-An increase of 12.5 to 25 mcg increments at approximately 1- month intervals avoids rapid increases in cardiac workload and symptoms of ischemic heart disease.
If exacerbation’s of angina pectoris occurs, the previous dosage regimen should be administered and titrated up in smaller increments.
T4 Rational Drug Selection
Drug of choice for thyroid replacement and suppression therapy.
In older adults with no cardiac disease, consider consulting with endocringologist regarding useing t3 or t4 or liotrix.
Monitoring T4
TSH level should be mesausred in 6-8 weeks, and the T4 dose should be adjusted, as necessary.
The target tsh level should be between 0.3 and 3.0uiu/ml.
Once stable, annual exam is appropriate.
Monitor for osteoporosis in high-risk populations.
Many drugs affect tsh levels.
T4 Patient Education
Take medication each day in the morning, before breakfast because absorption is increased.
Learn how to measure HR
Lifestyle management
Propylthiouracil and Methimazole (Antithyroid agents)
PTU, tapazole
Both block synthesis of T4 and T3
Neither drug treats the underlying pathology in hyperthyroidism.
High relapse rates exist but are less likely if treated for 18-24 months
Antithyroid Agent Pharmacokinetics
Absorption: rapidly absorbed after oral dosing; peaking within 1 hour 85-95% bioavailability.
PTU is 75-80% protein bound, methimazole is NOT protein bound.
Both metabolized in the liver; both have short half-life; excreted in urine. 35% of PTU, 80% of methimazole
Antithyroid Agent Precautions, C.I., ADRs
Pregnancy major concern; readily crosses the placenta. Recommend that patient not get pregnant while on these drugs.
High concentration in breast milk.
Not recommended in children.
ADRs; agranulocytosis, drowsiness, HA, alopecia, skin rashes, renal/hepatic failure
Drug reaction: Lithium, warfarin
Antithyroid Agent Rational Drug Selction/Monitoring
Thyroid studies, CBC, liver/renal panels before starting drug
Recheck in 1-2 months after starting drug
Antithyroid Agent Patient Education
Administration: very important to NOT miss doses; if missed, do NOT make it up.
Teach about hypothyroid symptoms; prolonged sub clinical hyperthyroidism is associated with bone loss, a-fib, and impaired left ventricular diastolic filling.
Dietary sources of iodine should be reduced because they interfere with action of drugs.
Watch use of OTC cold medications.
Posthyperthyroid Treatement
Patients need to expect that they will become hypothyroid.
This may not occur for several months.
Patients must take thyroid supplements for life.
Diabetes Mellitus
Chronic, progressive metabolic disorder resulting from abnormalities in glucose, protein, and fat metabolism
Categorized into four clinical classes
Type 1 diabetes, which results from beta-cell destruction, leading to absolute insulin deficiency
Type 2 diabetes, which results from a progressive insulin secretory defect or insulin resistance
Diabetes resulting from other causes (e.G., Genetic defects in beta-cell function or insulin action; diseases of the exocrine pancreas, such as cystic fibrosis; and drug- or chemical-induced)
Gestational diabetes mellitus (GDM), which is diagnosed during pregnancy
Type 1 Diabetes Mellitus
Pathophysiology
Autoimmune destruction of the pancreatic beta cells
Genetically linked susceptibility
Long preclinical period
Absolute deficiency of insulin production by beta cells
Treatment
Insulin
Type 2 Diabetes Mellitus
90% of cases are type 2 DM
Pathophysiology
Genetics
Insulin resistance
Obesity
Insulin may be low, normal, or high.
Patients develop hyperlipidemia and hypertension.
We now understand the role of glucose absorption from the gut associated with alteration of dipeptidyl peptidase 4 (dpp-4) and glucagon-like peptides (glps).
Complications of Diabetes Mellitus
Macro and Microvascular diseases of: Eyes Kidneys Heart Peripheral Vascular System Periodontal disease Lipid metabolism Platelet function Neuropathy -Autonomic -Peripheral
Screening for Type 2 DM
Patients 45 years of age or more with body mass index (BMI) greater than or equal to 25 kg/m2 should be tested. Those with values within normal limits should be tested every 3 years.
Patients younger than 45 years of age with bmi greater than or equal to 25 kg/m2 who have additional risk factors should have more frequent testing.
Additional risk factors are physical inactivity; having a first-degree relative with diabetes; member of high-risk ethnic group (african american, hispanic, native american, asian american, pacific islander).
Delivery of a baby weighing more than 9 lb or previous diagnosis of GDM
hypertension (blood pressure - BP - greater than 140/90 mm hg)
high-density lipoprotein (HDL) cholesterol less than or equal to 35 mg/dl and/or triglyceride level greater than or equal to 250 mg/dl
polycystic ovary syndrome (PCOS)
impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) on previous testing
other clinical conditions associated with insulin resistance (PCOS or acanthosis nigricans)
history of cardiovascular disease.
Insulin
Pharmacodynamics
Promotes protein synthesis by increasing amino acid transport into cells
Stimulates glucose entry into cells as energy source
Increases storage of glucose as glycogen (glycogenesis) in muscle and liver cells
Inhibits glucose production in liver and muscle cells (glycogenolysis)
Enhances fat storage (lipogenosis) and prevents mobilization of fat for energy (lipolysis and ketogenesis)
Inhibits glucose formation from noncarbohydrate sources, such as amino acids (gluconeogenesis)
Tight Insulin Dosing Plan
Dosing: 50% bolus, 50% basal needs
Depends on blood gas (BG) levels, diet, exercise, weight
Based on type of DM, type of insulin, calories, exercise
Average insulin doses: 0.3 to 0.8 units/kg/24 hours
Example: 60 kg adult type 1 DM (using 0.5 units/ kg/24 hours)
Requires 30 units
Insulin glargine (lantus): 15 units at bedtime
Insulin lispro: 15 units total divided over meals
Before breakfast: 5 units
Before lunch: 5 units
Before dinner: 5 units
Selecting Oral Antidiabetic Agents
Insufficient production of endogenous insulin
Sulfonylureas cause an increase in insulin production.
Meglitinides, insulin secretagogues, increase secretion of insulin from beta cell.
Dpp-4 inhibitors act on the incretin hormone system to indirectly increase insulin production.
Tissue insensitivity to insulin
Thiazolidinediones (tzds) improve insulin sensitivity.
Impaired response of beta cells
Meglitinides increase secretion of insulin.
Selecting Non-Insulin Injectables
The goals for treatment remain the same.
Same micro-gauge needles; similar availability of pens.
Not for insulin pumps; not insulin substitutes!
Also come in extended release weekly modes which increase adherence.
Goal of DM Treatment
Near normalization of blood glucose
Individualized goals for children, pregnant women, and older adults
Prevention of acute complications
Prevention of chronic complications
Appropriate individualized self-management
DM Treatment Targets
Glycemic control
Hba1c less than 7% (unless > 65 years)
Pre-prandial plasma glucose 70 to 130 mg/dl
2-hour postprandial plasma glucose less than 180 mg/dl
BP less than 130/80 (if tolerated, and not frail older adult)
Lipids
Low-density lipoprotein (LDL) less than 100 mg/dl
Triglycerides less than 150 mg/dl
HDL greater than 50 mg/dl
Random urine albumin/creatinine (cr) less than 30 mcg/mg creatinine
DM Rational Drug Selection
Treatment protocol is chosen on the basis of:
Type of diabetes
Desired glycemic target
Severity of hyperglycemia
Patient variables
Review most recent american diabetes association guidelines.
Setting Glycemic Targets
HBA1C is primary target for glycemic control.
Should be less than 7%
Goals should be individualized, especially for older adults.
Special populations require special considerations: children, pregnant women, older adults.
Less intense glycemic goals may be indicated in persons with severe or frequent hypoglycemia.
With change of control to below 6.5% in previously high HBA1C, patients should be evaluated for frequent hypoglycemic episodes and NOT assumed to have actual control.
Lifestyle Modifications
All patients should be referred to a certified diabetes educator for self-management education.
Individualized plan for all patients
Medical nutrition therapy goals are:
Attain and maintain recommended targets.
Modify nutritional intake as appropriate.
Improve health through healthy food choices and physical activity
For children: ensure adequate growth.
For pregnant women: maintain adequate energy.
Self-Management Education
Seven target behaviors Monitoring Medications Meal planning Activity/exercise Healthy coping Problem solving Preventing complications
Type 1 DM Drug Therapy
Insulin Multidose injections required Basal: long- or intermediate-acting Bolus: rapid- or short-acting Common insulin dosing regimens (refer to text) Possible need for glucagon kit
Basic Knowledge Before Dosing Insulin
Each 15 gm CHO serving raises BG approximately 50 mg/dl.
1-unit bolus of insulin lowers glucose approximately 20 to 60 mg/dl.
Determine cho-to-insulin ratio.
Split basal insulin needs and bolus insulin needs evenly (50% each).
Generally, 50% to 75% of daily insulin is given as an intermediate- or long-acting form of insulin.
Initial dose of insulin is 0.3 to 0.5 units/kg/day in divided doses.
Patient needs to have emergency plan for hypoglycemia.
Patient needs to have “sick day” plan when oral intake is compromised.
Diabetic Drug Therapy Impacts
Metformin: weight loss, low risk of hypoglycemia.
Sulfonylurea: weight gain and hypoglycemia
Tzds: weight gain, edema, heart failure (HF)
DPP-4: weight neutral, nausea
GLP receptor agonists: weight loss, low risk of hypoglycemia
Sodium–glucose transport protein-2 (SGLT-2) inhibitors: genital yeast infections, potential weight loss
Insulin: weight gain, hypoglycemia
DM Drug Therapy in Children
Children
Managed by specialty team
Modify glycemic targets for planned activity and growth.
Insulin for type 1 dm
Type 2 DM treatment
Metformin and/or insulin and/or liraglutide if >10 years
Lifestyle changes
Drug Therapy in Older Adults
Older adults
10% higher glycemic targets
Avoid first-generation sulfonylureas, tzds.
DM Patient Variables
Obesity
Metformin, DPP-4, SGLT-2 and GLP-1 RA help with weight loss.
Coronary artery disease/hf
Intensive therapy with insulin reduces microvascular damage.
Angiotensin-converting enzyme inhibitor (acei), aspirin, and statin
SGLT-2 and GLP-1 meds have CV risk and heart failure reduction
Hyperlipidemia: statins
Hypertension: ace or angiotensin II receptor blockers until chronic kidney disease (CKD) stage 3
Nephropathy: ace preferred; SGLT-2 and GLP-1 retard progression.
Neuropathy: tricyclic antidepressants, gabapentin/pregabalin (lyrica)
DM Frequency of Preventative Care
Annually Lipids Comprehensive foot examination Dilated retinal examination Microalbumin Dental examination Every 3-6 months Bp Hba1c Foot examination if risk Depression screening Smoking cessation Weight management
