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Insulin THerapy COnsiderations
: Insulin therapy is required for the treatment of DM1. Insulin must be given SQ or IV. All insulin is now synthetic. Consistency and rotation of injection sites is recommended. Site selection is based on different rates of absorption.
Insulin Lispro
(short duration rapid action): used for immediate treatment of blood glucose levels. Approximately 15 minutes for onset
Regular Insulin
(short duration, slower acting): for use before meals. 30-60 minutes for onset. Take 30 min before meals
NPH Insulin
(intermediate duration): onset in 3 hours. Give BID
Insulin glargine
(long duration): given once daily. 1-3 hours onset. Often used as basal insulin in DM2 with inadequate control to transition to insulin- lasts up to 24 hours.
Biguanides (Metformin):
used as a first line for DM2 when diet and exercise modifications have changed. It can also be used to treat prediabetes. Does not cause hypoglycemia.
Biguanides MOA
enhances receptor sensitivity to insulin n muscle and fat. Inhibits liver production of glucose and liver breakdown of glycogen into glucose. It also slightly reduces glucose absorption in the gut.
Biguanides Adverse Effects
GI side effects are the most common (gas, bloating). These usually subside after two weeks of treatment.
Biguanides Precautions
this drug should be stopped the day prior to procedures where dye will be injected. Following the test, a creatinine test will be drawn and if that test is WNL, the medication may be stopped in 48 hours. This drug may cause megaloblastic anemia
Biguanides Contraindications
contraindicated in patients with renal disease, liver disease, severe infection or those who consume excess alcohol due to an increased chance of fatal lactic acidosis. Also contraindicated in patients at increased risk for hypoxic events such as COPD or CHF.
Biguanides Patient Education
will not cause hypoglycemia. Patients should take this medication with an evening meal.
Sulfonylureas (Glyburide)
considered tier one due to low cost and efficacy.
Sulfonylureas MOA
stimulate the beta cells of the pancreas to secrete insulin. They also increase tissue sensitivity to insulin. Sulfonylureas are NOT contraindicated in patients with sulfa allergies- this is a common misnomer.
Sulfonylureas Adverse Effects
first generations were notorious for causing hypoglycemia… these have been mostly replaced with 2nd generation agents.
Sulfonylureas Precautions
hypoglycemia. Multiple drug-drug interactions (NSAIDS) these drugs are highly protein bound so competitive binding causes more of the drug to be available in the circulation, leading to increased hypoglycemia. Beta-blockers can mask the signs of hypoglycemia and diminish the effectiveness of sulfonylureas. Antivirals can cause an additive effect resulting in liver toxicity. There is reduced efficacy of this drug over time.
Sulfonylureas COntraindications
no longer contraindicated in pregnancy bust should be used with caution in the 1st trimester and at the end of the 3rd trimester. There are safer drugs to use during pregnancy (this one is a Cat C)
Sulfonylureas patient education
signs and symptoms of hypoglycemia
Thiazolidinediones (Glitazones)- (Rosiglitazone) (TZD
not a first-line option, so first optimize Metformin and then select a second agent based on A1C lowering, side effects, and cost.
Thiazolidinediones MOA
enhances insulin sensitivity in muscle and fat by increasing glucose transporter expression. Tends to lower triglycerides and raise HDL.
Meglitinide (Repaglinide):
Recommended as an add-on therapy if A1C is 6.5-9%. Third line agent. Weight neutral.
Meglitinide MOA
stimulate insulin release from beta cells0 different from other sulfonylureas. Has a rapid onset and short half-life, so there is less hypoglycemia than with other agents. Often given with metformin. Can be given to patients with sulfa allergies.
Meglitinide Adverse Effects
bloating, abdominal cramping, diarrhea, and flatulence
Meglitinide Precautions
multiple drug-drug interactions- especially gemfibrozil. Also NSAIDS and anti-hypertensives.
Meglitinide Patient Education
drug-drug interactions
Alpha-Glucosidase Inhibitors (Acarbose) MOA
these drugs work in the gut to prevent glucose absorption. They inhibit the enzyme that cleaves sucrose into glucose and fructose. There is little risk of hypoglycemia because these agents work in the gut.
Alpha-Glucosidase Inhibitors (Acarbose) Adverse Effects
diarrhea, flatulence, stomachache and bloating. These effects can be decreased if the patient decreases sugar intake
Alpha-Glucosidase Inhibitors (Acarbose) Patient Education
these drugs only affect postprandial glucose levels, so they are to be taken with the first bite of every main meal (TID).
Incretin Mimetics (Exenatide, Victoza, Symlin)):
mimic hormones that help regulate blood glucose.
Incretin Mimetics MOA
: incretins are secreted in the stomach after meals. They stimulate insulin secretion and slow stomach emptying thereby reducing hunger. It is generally used in DM2 with poor glycemic control prior to starting insulin. This therapy is expensive.
Incretin Mimetics Adverse Effects
causes nausea in 43% of patients
Incretin Mimetics Precautions
this is a tier 2 therapy after lifestyle modifications/metformin/sulfonylureas and insulin, but may be tier one in certain patients where the risk of hypoglycemia must be reduced, such as truck drivers.
Incretin Mimetics Patient Education
patients should take other meds at least 1 hour prior to injecting due to decreased gastric absorption following administration.
Incretin Enhancers (Sitagliptin):
considered third line therapy and in patients with an A1C >9%. Weight neutral.
Incretin Enhancers (Sitagliptin): MOA
: inhibits degradation of endogenous incretins, which increases insulin secretion and decreases glucagon secretion
Pre-existing Diabetes in Pregnancy
a. Fewer risks associated with pregnancies in diabetic women if blood glucose is well-controlled prior to conception.
c. For women with preexisting DM, medications may need to be adjusted due to the tendency toward hypoglycemia in pregnancy
GDM
b. Treatment for GDM includes diet, exercise, and meds when necessary
d. With GDM, the pancreas is unable to make enough insulin to maintain euglycemia, which leads to hyperglycemia. Many women following a diabetic diet and maintaining regular exercise can avoid the need for medications- this is idea. When medications are indicated in pregnancy, insulin is the gold standard, however oral drugs are gaining popularity
Insulins in Pregnancy
NPH and regular insulin are safe (cat B in pregnancy) as are the newer insulin analogs. Check the safety profile of the med before prescribing; certain insulins are avoided during pregnancy due to limited information about their safety. During labor, IV insulin infusions are often used.
Oral Hypoglycemics in Pregnancy
i. Glyburide/ 2nd generation sulfonylureas- do not cross the placenta in significant amounts. This is a Category C drug, but is generally considered safe during pregnancy and maternal and fetal outcomes are similar to those with insulin use.
ii. Metformin: Category B during pregnancy. Metformin crosses the placenta. Should be reserved for special cases. Research indicates that Metformin is ideal for use in obese or overweight women.
Lactation and Insulin
euglycemia is important. Normal insulin levels are needed for successful lactation. NPH and regular insulin are considered safe during lactation. Studies are lacking about newer insulins in lactation.
h. Lactation and Oral Diabetic Meds
Metformin is probably safe during lactation- use caution in infants with renal impairment and prematurity. With all oral hypoglycemic agents, monitor the infant’s blood glucose levels. There is a lack of data regarding 2nd generation sulfonylureas in lactation, however drug levels in breast milk are minimal. There is no information on thiazolidinediones in lactation. There is little data on the alpha-glucosidase inhibitors in lactation. Studies show that the maternal GI system absorbs minimal amounts of these drugs so amounts found in breast milk would be negligent or non-existent.
current recommendations related to health promotion in diabetics
a. Lowering A1C to 7% in adults decreases microvascular and neuropathic complications of DM. A1C should be performed at least 2x/year in patients meeting their treatment goals.
b. Modest weight loss has been shown to reduce insulin resistance. Structured programs emphasizing lifestyle changes including moderate weight loss, regular physical activity (150 min/week) with dietary strategies can reduce the risk for developing DM. Alcohol intake should be limited to a moderate amount. Bariatric surgery may be suggested for clients with a BMI >35.
c. Diabetes self-management educations should be provided upon diagnosis and PRN after that.
d. Glucose is the preferred treatment for hypoglycemia. Glucagon should be prescribed for all individuals at high risk for hypoglycemia and family members should be instructed in its administration.
e. Annual flu vaccines are recommended, as are pneumococcal vaccines.
f. Blood pressure should be maintained at less than 130/80. ACEIs or ARBs are preferred for HTN in DM. Thiazide diuretics are preferred with GFR >30, and loop diuretics for GFR <30.
g. Lipid profiles annually. Consider statins for DM patients with CVD risk factors along with lifestyle modifications.
h. Consider aspirin therapy for primary or secondary prevention in patients with DM and increased CV risk.
i. Annual test for urine albumin in DM1 to assess for renal damage.
j. To reduce retinopathy, optimize glucose control. Annual eye exams are suggested.
k. Annual comprehensive foot exam. Check for foot pulses and loss of protective sensation.
Levothyroxine MOA
synthetic thyroid hormone
Levothyroxine Adverse Effects
hyperthyroidism with inappropriate dosage
Levothyroxine Precautions
Stay with one brand of levothyroxine. Evaluation should not be done for 6-8 weeks after initiating therapy. A TSH target of 0.5-2 is appropriate for most patients. Monitor TSH and T3 levels.
Levothyroxine Patient Education
Take at same time every day 30 minutes before eating or 2 hours after eating. Numerous drug-drug interactions:
1. Calcium products reduce absorption of levothyroxine
2. Cholestyramine products reduce absorption of levothyroxine
3. Iron preparations reduce absorption of levothyroxine
4. Anticoagulant effects are increased
5. Estrogen reduces availability of levothyroxine
6. Levothyroxine increases metabolism of OCPs
7. Levothyroxine may decrease effects of oral hypoglycemics
8. Some SSRIs and anticonvulsants increase metabolism of levothyroxine
Levothyroxine in Pregnancy and Lactation
thyroid hormone replacement needs increase 30-50% during pregnancy. Increase dosage by 30% as soon as pregnancy is confirmed.
Methimazole and Propylthiouracil (PTU)
used to treat Graves’ disease, in preparation for thyroid surgery, and to patients experiencing thyrotoxicosis
Methimazole and Propylthiouracil (PTU) MOA
block thyroid hormone synthesis. Does not destroy existing stores of thyroid. Once therapy has begun, it may take 3-12 weeks to produce a euthyroid state.
Methimazole and Propylthiouracil (PTU) Adverse Effects
rare- agranulocytosis- usually develops in the 1st two months of therapy. Manifests as sore throat and fever- patients must know to report this if it happens. Stop PTU if agranulocytosis occurs. Too much can cause hypothyroidism. The most common undesired effect is rash.
Methimazole and Propylthiouracil (PTU) Precautions
propranolol can be prescribed to treat anxiety and tachycardia that goes along with hyperthyroidism
Methimazole and Propylthiouracil (PTU) Pregnancy and Lactation
Both meds are cat D in pregnancy, but endocrinologists sometimes prescribe them due to the risks of untreated hyperthyroidism during pregnancy. PTU is preferred in pregnancy because methimazole crosses the placenta more readily. It is also preferred during breastfeeding.
Osteoporosis Goal of Therapy
to prevent fractures. THis is acheived using anti-resorptive agents, and in some cases bone-forming agents
Conjugated equine estrogens (Premarin) MOA
acts indirectly to suppress osteoclast proliferation, and thereby maintains a brake on bone resorption.
Conjugated equine estrogens (Premarin) Adverse Effects
HRT increases the risk for breast CA, cholecystitis, MI, and stroke.
Conjugated equine estrogens (Premarin) Precautions
women who are currently using HRT for bone resorption blockage should be encouraged to switch
Raloxifene (Selective estrogen receptor modulator) MOA
chemical agents that bind to receptor sites and create an agonist or antagonist effect at that site. SERMS reduce osteoclast activity while reducing the estrogen effect on the breasts and endometrial tissue, thereby preventing breast cancer.
Raloxifene (Selective estrogen receptor modulator) Adverse Effects
Venous thromboembolism. Hot flushes. Category X in pregnancy.
Raloxifene (Selective estrogen receptor modulator) Precautions
for maximum effectiveness, should be given with calcium and vitamin D.
Raloxifene (Selective estrogen receptor modulator) COntraindications
pregnancy
Alendronate (bisphosphonate)
can be used for osteoporosis in men, postmenopausal osteoporosis, Paget’s disease of bone
Alendronate (bisphosphonate) MOA
These drugs undergo incorporation into the bone. benefits derive from inhibiting bone resorption by osteoclasts.
Alendronate (bisphosphonate) Adverse Effects
Esophagitis, ocular inflammation, osteonecrosis of the jaw, and a-fib.
Alendronate (bisphosphonate) Precautions
must be accompanied by adequate calcium and vitamin D intake.
Alendronate (bisphosphonate) Patient Education
should be taken with a full glass of water as it can cause esophagitis if passage is not complete. The patient should be instructed to maintain an upright position after administration. Should be taken in the morning before breakfast. No juice, coffee, or food for 30 minutes after administration.
Calcitonin-salmon Nasal Spray
used for osteoporosis and Paget’s disease of bone. . It is used to treat established osteoporosis, but not prevent it
Calcitonin-salmon Nasal Spray- MOA
inhibiting osteoclastic activity, and increasing calcium excretion. It is used to treat established osteoporosis, but not prevent it.
Calcitonin-salmon Nasal Spray Adverse Effects
has been used for over 20 years with no long-term adverse effects
Calcitonin-salmon Nasal Spray Patient Education
intranasal spray
Bone Forming Agent: Teriparatide (Forteo)
a form of parathyroid hormone (PTH) produced by recombinant DNA technology. Reserved for extreme cases and those people with high risks of fractures.
Teriparatide (Forteo) Mechanism of Action
increases bone resorption by osteoclasts and increase bone deposition by osteoblasts. The net effect- resorption or deposition- depends on how the drug is administered. When given by IV infusion it produces a steady decrease in BMD. When given SQ it causes an increase in BMD.
Teriparatide (Forteo) Adverse Effects
generally well-tolerated. Has caused a rare form of bone cancer in rats, but not in monkeys. May see dizziness and orthostatic hypotension with first doses. Other reported adverse effects include nausea, HA, back pain, and leg cramps.
Teriparatide (Forteo) precautions
expensive treatment
Corticosteroids Uses
They are most commonly used to suppress immune function in conditions such as asthma, COPD, allergic reactions, severe pain, RA, IBD unresponsive to 1st line treatment, relapsing MS, and other autoimmune conditions
Corticosteroids MOA
Have an effect on virtually every cell of the body. They affect glucose metabolism and utilization, lipid metabolism, fluid and electrolyte balance, immunological, bone, GI, neuropsychological, and developmental processes
COrticosteroids Adverse Effects
i. Altered metabolism- may lead to hyperglycemia with short-term use, and protein wasting and increased lipid deposition with long-term use.
ii. Altered immune response: this may be desirable but the drug also masks signs of infection
iii. Bone maintenance- will cause calcium to leech out of bones and could increase the risk for osteoporosis with long-term use.
iv. Skin- may thin skin if used in large quantities topically. Chronic use may exacerbate acne.
v. Neuro- cranial nerve palsy, neuropsychiatric balance- may cause tremor, hunger, agitation
vi. Cardiac- may increase HTN due to fluid retention associated with its impact on excretion of potassium and retention of sodium and water
vii. Ocular- angle-closure glaucoma and cataracts with long-term use, cataracts, exophthalmus, papilledema
Corticosteroids Precautions
avoid abrupt discontinuation. needs to be tapered.
Corticosteroids in Pregnancy and Lactations
: betamethasone in preterm labor- accelerates fetal organ maturity in women between 24-34 weeks gestation. Topical preparations can be used in pregnancy, but start low and go slow for the shortest amount of time. Often used to treat PUPPS that is resistance to other comfort measures. Prednisone is compatible with breastfeeding. High potency steroids should not be applied on or near the nipple in a breastfeeding woman. Systemic corticosteroids are contraindicated in pregnancy. Inhaled corticosteroids are acceptable.
two types of weight loss medications
Central acting appetite suppresants (diethylpropion- Tenuate, phentermine- Adipex-P) these are schedule IV drugs
off label weight loss medications
i. Bupropion (Wellbutrin, Zyban)
ii. Exenatide (Byetta)
iii. Topiramate (Topamax)
iv. Zonisamide (Zonegran)
v. HCG
vi. Thyroid hormone
Central Acting Appetite Suppressants- MOA
sympathomimetic-amines, which mimic amphetamines. They do result in short-term weight loss, but studies reveal that once the drug is discontinued, the weight returns. They are meant for short-term use only.
Central Acting Appetite Suppressants- Adverse Effects
addictive potential. Pulmonary HTN, valvular heart disease, psychosis, tachycardia, elevated BP, tremors, euphoria, dysphoria, HA, and GI complaints.
Central acting appetite suppressants- Contraindications
pregnancy
Peripherally acting appetite suppressants ( Orlistat) OTC: MOA
induction of lipid maldigestion
Peripherally acting appetite suppressants ( Orlistat): adverse effects
gas, oily spotting, fecal incontinence, cholelithiasis, abdominal or rectal pain, nausea, pancreatitis, hepatitis
Peripherally acting appetite suppressants ( Orlistat): precautions
patients should take a multivitamin containing ADEK and beta-carotene 2 hours before or after orlistat or at bedtime.
Peripherally acting appetite suppressants ( Orlistat): contraindication
patients with malabsorption syndrome or cholestasis
Peripherally acting appetite suppressants ( Orlistat): patient Education
dosing with metamucil can decrease the GI effects greatly
considerations in medication prescribing after bariatric surgery
a. Because pregnancy rates after bariatric surgery in adolescents are twice that in the general adolescent population, contraceptive counseling is especially important in these patients.
b. Administration of hormonal contraception by non-oral routes should be considered in patients with a significant malabsorption component after bariatric surgery because these patients have an increased risk for oral contraception failure.
c. Testing drug levels may be necessary for medications in which a therapeutic drug level is critical to ensure a therapeutic effect.