DM-Table 1 Flashcards
Type 1 DM
requires insulin, autoimmune destruction of pancreatic beta cells
Type 2 DM
Progressive, chronically over wt/obese pts, lifestyle modifications, insulin resistance and eventual shut down of beta cells eventually
What are some complications of DM?
Emergent hypoglycemia, hyperosmolar hyperglycemic syndrome(HHS-2) or DKA(children-1), microvascular and macrovascular damage, neuropathic damage
how does DM present?
polyuria, polydipsia, polyphagia,
How do you dx?
If with symptoms-random blood glucose >200mg/dL asymptomatic: fasting bg>=126mg/dLx2, oral glucose tolerance >=200, A1C>=6.5%
What is A1C?
Measure of glycosylated hgb- it gives a good idea of glucose control over past 3months
What are the 3 levels of A1C and how they differ in therapy?
=9%=Triple therapy(metformin+two other meds)
When is metformin contraindicated?
Renal failure, liver or lung disease d/t acidemia(lactic acidosis)
Cornerstone of DM2 therapy?
Metformin
What are other antihyperglycemic drugs?
Sulfonylureas (hypoglycemia/wt gain), thiazolidinediones (pioglitazone, rosiglitazone-EDEMA-wt neutral), GLP-1 agonist(CI-men2, medullary syndrome- exenatide, liraglutide-secretagogs- wt loss), DPP-4 inhibitors(sitagliptin, linagliptin-protein that increases endogenous GLP-1 preservation=secretagogues- wt neutral)
When should secretegogues be discontinued?
S/sx of pancreatitis (nawing back pain-burrowing)
What are some ADRs of metformin?
Lacitic acidosis, GI upset
What PO anti-hyperglycemic drug causes wt gain?
Sulfonylureas- glipizide, gliburide, chlorpropamide
What PO anti-hyperglycemic drug causes water retention?
thiazolidinediones (pioglitazone, rosiglitazone)- don’t use in HF pts
What are wt neurtral PO anti-hyperglycemic drugs?
Thiazolidinediones, DPP-4, metformin
What subQ anit-hyperglycemic drug causes wt loss?
GLP-1 agonist (exenatide, liraglutide), CI: MEN2 and hx of medullary thyroid cancer
Muscle can take up glucose without insulin(T/F)?
True, this is why you should probably not inject insulin before working out…
DKA presentations?
Only occurs in type 1 dm, often no previous dx of DM1, s/sx: polyuria,polydipsia, N/V, malaise, fatigue, tachypnea, palpitations, abdominal pain, ALOC(altered conciousness)
HHS-hyperosmolar hyperglycemic state
more type 2 dm, older/infirmed or non-compliant patients
What is DKA?
Severe insulin deficiency- lipolysis occurs=ketone bodies, acidemia(anion gap will be high),
How do you dx DKA?
Clinical and labs: fingerstick glucose>250, UA+dipstick(glucose and ketones), CMP(hyperkalemia(glucose travels with potassium..), hyponatremia, low bicarb, high anion gap), CBC(left shift=infections), ABG(metabolic acidosis), EKG, serum hydroxybutyrate(high=monitor progress)
What often times percipitates DKA?
inflammatory process/drug use-cocaine/non-compliance
What is PE for DKA?
dry skin, dry mucous membranes, reduced skin turgor, hypotensive, tachycardic, confusion, ill-looking patient
What is DKA tx?
ADMIT: Based on ABCs: circulation(depleted fluids)=NS bolus(up to 5L given), administer normal insulin IV(monitor KqH), Hypokalemia(if
What are some electrical changes seen on EKG d/t hypokalemia?
Flat T waves, prominant U waves
What is the underlying problem with HHS?
Profound dehydration, high glucosuria
What is clinical presentation of HHS?
ALOC, focal/global neurologic deficits, thirst polyuria
How do you dx HHS?
clinical: fingerstick glucose(>600mg/dl), cmp, ua+ dipstick(high glucose), CBC, CSP, CXR(look for infection), EKG, CT, AZOTEMIA-d/t elevated BUN(less perfusion to kidneys)
What is the tx for HHS?
ABC: Replenish fluid volume very first 1-2L of NS in first hr- get serial CMPs qH, once azotemia resolved, can start insulin, monitor K,
Hypoglycemia is recognized as?
Sympathetic activation(sweating, tremor, tachycardia, palpitations, anxiety, nausea, vomiting), blurred vision, behavioral changes, fatigue, ALOC
What are the normal levels for fasting blood glucose?
70-120mg/dL
What is the dawn phenomenon?
increased insulin required in early morning dt GH
What is the somogyi effect?
rebound hyperglycemia from night time hypoglycemia.
What is the usual insulin to carb ratio?
1:15
What is the usual correction factor?
1:50
What are rapid acting insulin?
lispro, aspart, apidra
what should you do to insulin when adding Pramlintide?
reduce pre-prandial insulin by 50%
When should you screen children for DM2?
when BMI over 85th precentil, or wt over 120% of ideal,
What is metabolic syndrome?
3 of 5 criteria met (PHAT)
What are the ranges for metabolic syndrome?
BP>130/85, HDL cholesterol 102men/>88women, TG>= 150, Fbg >=110
What are the characteristics of metabolic syndrome?
impaired lipids, impaired
What happens when there is low blood glucose?
Glucagon is released by alpha cells of the pancreas
Liver releases glucose into the blood
What happens when there is high blood glucose?
Insulin released by beta cells of the pancreas
Fat cells take in glucose from the blood
what are the types of DM?
Type I, II, gestational, other
What is the cause of Type I?
Due to B cell destruction, usually leading to absolute insulin def
What is Type II caused by?
d/t progressive insulin secretory defect on the background of insulin resistance
What are the other types of DM?
Monogenic diabetes- neotnatal, MODY
Dz of endocrine pancreas and drug/chemical induced
What is MODY?
Dysregulation of glucose sensing or insulin secretion
AD mutation
Occurs beore 25
Insulin resistance and hypertriacyclglycerolemia absent
What causes gestational DM?
Rise in HPL and other hormones that contribute to insulin resistance
What is diabetes mellitus?
Metabolic disorder in which carbohydrate metabolism is reduced while that of proteins and lipids in increased
How is Diabetes diagnosed?
•Fasting plasma glucose (FPG) ≥ 126mg/dl
OR
•Symptoms of diabetes + casual plasma glucose ≥ 200 mg/dl
OR
•Oral glucose tolerance test (OGTT): 2-h postload glucose ≥ 200 mg/dl
What needs to be taken into consideration with A1C?
Need to take into account age, race, anemia or hemoglobin issues
What are contraindications to A1C testing?
Use of plasma glucose
When should you test for DM?
1) Adults overweight or obese and who have 1 or more additional risk factors for diabetes
2) all pts testing at age 45
3) repeat at a minimum of 3 yr interval if results are normal
What are the additional risks for overweight/obese diabetics?
–Physical inactivity –First degree relative with diabetes –High risk race/ethnicity (AA, Latino, Native American, Asian American, Pacific Islander) –Women who delivered a baby weight > 9 pounds or were diagnosed with GDM –HTN (> 140/90 or on therapy) –HDL cholesterol 250mg/dL –Women with Polycysic ovarian syndrome –A1C > 5.7% on previous testing –Severe obesity or acanthosis nigricans –History of CVD
When should you test for gestational diabetes?
- Test for undiagnosed diabetes type 2 in pts with risk factors at first prenatal visit
- test at 24-28 wks gestation in women with no hx of dm
- screen women with GDM for persistent DM at 6-12 wk post partum and lifelong screening at least q 3 yrs
What is GDM associated with ?
Fetal macrosomia
Higher rate of pre-eclampsia
Mother is at risk for developing type 2
What puts women at very high risk for GDM?
Severe obestity, prior hx of GDM or delivery of LGA infants, presence of glycosuria, diagnosis of PCOS, or strong family hx
When should women be screened for GDM?
Women at high risk as soon as pregnancy is confirmed
All other at 24-28wks of gestation
How is GDM diagnosed?
- Fasting ≥ 95 mg/dL
- 1h ≥ 180 mg/dL
- 2h ≥155 mg/dL
- 3 h ≥ 140 mg/dL
- Women with GDM should be screened for type 2 diabetes 6-12 weeks postpartum
What are common comorbid conditions with diabetes?
Depression, OSA, fatty liver dz, CA, fractures, cognitive impairment, low testosterone in men, periodontal dz, and hearing impairment
When should you monitor glucose on intensive insulin regimens?
Prior to meals and snacks, occasionally post-prandial, at bedtime, prior to exercise, when they suspect low blood glucose, after treating low blood glucose, and prior to critical tasks
When should A1C be monitored?
At least 2x yr in pts that are meeting treatment goals
Quarterly in pts not meeting goals
What is the cause of type I diabetes?
Absolute insulin def
Autoimmune destruction of the B cells of the pancreas
What markers are present in type I diabetes?
Islet cell antibodies
Autoantibodies to insulin
Autoantibodies to glutamic acid decarboxylase( GAD65)
Autoantibodies to tyrosine phosphates IA-2 and IA-2B
What are risk factors for type I DM?
Strong genetic component, environmental factors
White
Other autoimmune disorders
What are the 4 main features of the progression of diabetes type I?
1) pre-clinical period with the presence of immune markers
2) hyperglycemia after 80-90% of B cells are destroyed
3) honeymoon phase
4) established disease
What is the clinical presentation of hyperglycemia??
Polyuria, polydipsia, polyphagia, wt los, fatigue, infection, blurred vision, poor healing, growth failure in children, N/V
What is the tx for type I DM?
Provide exogenous insulin to replace endogenous loss
- insulin
- pramlintide
What are the types of insulin?
- rapid acting
- short acting-regular insulin
- intermediate acting- NPH
- long acting-basal insulin
What are the rapid acting insulins?
Humalog, novolog, apidra
What are the short acting regular insulins?
Novolin, humulin R
What are the intermediate acting NPH?
Novolin and humilin N, Neutral protamine Hagedorn (NPH)
What are the long acting basal insulins?
Levemir (detemir) and lantus (glargine)
What are the high insulin state effects?
- liver: glucose uptake, glycogen synthesis, lipogensis
- muscle: glucose uptake, glucose oxidation, glycogen synthesis, and protein synthesis
- adipose tissue: glucose uptake lipid synthesis and TG uptake
What are the low insulin state effects?
- liver: glucose production, glycogenolysis, ketogenesis
- muscle: fatty acid, ketone oxidation, glycogenolysis, proteolysis and amino acid release, NO glucose uptake
- adipose tissue: lipolysis and fatty acid release. NO glucose or TG uptake
What is the onset of insulin detemir(levemir)?
Onset 2 hrs
What is the peak and duration of insulin detemir?
6 to 9 hrs (blunted)
and 24 hr duration
What is the onset, peak, and duration of insulin glargine (lantus)?
Onset 4-5hrs
Peak none or blunted
Duration 22+ hrs
What should you do before using NPH?
Roll or invert 10 times
What Is the onset, peak, duration of NPH?
Onset of 1-4hrs
Peaks at 6-10hrs
Duration of 12-18 hrs
Can NPH also be used as a basal insulin?
Yes if dosed multiple times a day
When should short acting regular insulin be injected?
30 min before eating
Onset, peak, and duration of short acting regular insulin?
Onset ½- 1 hr
Peak of 2-5 hrs
Duration of 4-6 hrs
What insulin most closely mimics the bodys response to glucose absorption?
Rapid-acting insulin
When should rapid-acting insulin be injected?
Immediately before eating
What is the onset, peak and duration of rapid acting insulin?
Onset: 5-15min
Peak: ½ to 1.5 hrs
Duration: 3.5 -5hrs
What is the pre-mixed insulin basal/bolus?
-NPH+regular
70/30
-NPH-like insulin +rapid acting
-aspart protamine/aspart(novolog mix 70/30)
-neutral protamine lispro/lispro (humalog mix 75/25, or 50/50)
What is the adverse effect of insulin?
Hypoglycemia- blood glucose
What is hypoglycemia a result of?
Decrease of insulin, decreased or delay in meals, increase in exercise
What are the S/S of hypoglycemia?
Tremors, palpitation, sweating, excessive hunger, HA, mood changes, irritability, unconsciousness, and seizures
How is hypoglycemia tx?
15g of glucose, wait 15min if still
What are sources of carbs?
½ cup of juice, 3 graham crackers….liquids are much faster acting
What is hypoglycemia unawareness?
Secretion of glucagon and epi are blunted, reducing symptoms of hypoglycemia
How does admin affect absorption?
Rate of absorption varied by route and location
IV>IM>SC
Ab>arm>thigh>butt
What can pts do to help enhance absorption?
Rub injection site- blood flow enhances
How is most insulin stored?
Room temp for up to 28 days
What are the exceptions for insulin storage?
–Humalog Mix Pen: 10 days at room temperature
–NPH-Regular Mix Pens : 10 days
–NPH Pens: 14 days
–Novolog Mix Pen: 14 days
What does the insulin pump do?
Deliver microliter amounts of insulin continuously as a basal insulin
When should the insulin pump be activated?
Before a meal to deliver a bolus
What is pramlintide?
Synthetic analog of human amylin, which is co-secreted with insulin from the pancreas in response to a meal
What are the 3 primary mechanisms of amylin?
- suppress postprandial glucagon secretion
- regulates the rate of gastric emptying
- reduce food intake
Amylin is deficient in which form of diabetes?
Both I and 2
What is the primary use of pramlintide?
FDA approved for I/II in pts on optimal insulin therapy who are sill not at goal
What is type I dosing for pramlintide?
15mcg SC before meals
meals must be >30g of carbs or >250kcals
What do you HAVE to do when starting a pt on pramlitide?
Reduce pre-prandial insulin by 50%
What are CI/ precautions with pramlintide?
Gastroparesis, hypoglycemic unawareness, recurrent episodes of hypoglycemia in the last 6 mo, A1C >9%, poor adherence to insulin or self monitoring
What is the black box warning for pramlintide?
Hypoglycemia
Usually within 3 hrs of injection
This is why you have to reduce preprandial insulin by 50% at initiation
What are other adverse effects of pramlintide?
Nausea, drug interactions, and delayed gastric emptying
What are the ADA guidelines for glycemic control of TypeI/II?
•A1C
What are steps for recommended therapy in diabetes type I?
- Use of multiple dose insulin injections
–3-4 injections/day of basal and prandial insulin - Matching prandial insulin to:
–Carbohydrate intake
–Premeal BG
–And anticipated activity - Use of insulin analogs as prandial insulin
What is the standard of care in type I diabetes?
- miminum of 4 injections
- basal admin once/day typically at bedtime
- rapid acting bolus given just before meals
What is initial insulin dosing based off of?
Weight
What is the max insulin units that can be absorbed or injected at one site?
50 units
What are the 2 parts to prandial insulin dosing?
- insulin to carb ration (I:C)
2. correction factor
What is the typical starting I:C?
1:15
1 unit of insulin covers 15 g of carbs
What is correction factor?
Number of mg/dL the blood glucose will drop after injecting 1 unit of rapid-acting or regular insulin
What is a typical starting CF dose?
1:50
1 unit of insulin for every 50 mg/dL above 100
What is the 1500 rule using TDD to calculate the CF?
1500/TDD mg/dL the blood glucose will drop after 1 unit of insulin
What are causes of fasting hyperglycemia?
Dawn phenomenon: increased insulin requirement late in the sleep cycle- nocturnal hyperglycemia
Somogyi phenomenon: nocturnal hypoglycemia followed by rebound hyperglycemia
When does the somogyi effect more often happen?
When intermediate insulins are used with dinner
How does the somogyi effect happen?
Happens when hypoglycemia causes the release of counterregularoty hormones hich stimulate hepatic glucose production which leads to rebound hypergycemia
When should you measure blood glucose levels of suspecting somogyi effect?
Btwn 2 and 4 am then again at 7am
–If they are 180-200 mg/dL rebound hyperglycemia may have occurred
What is the dawn phenomenon?
An increased insulin requirement in the early morning
About 1-3am d/t a surge of growth hormone relsease
What is the cause of postprandial hyperglycemia (>180)? When does it occur? How is it treated?
Not enough insulin given with the meal
Happens 1-2 hrs after eating
Increase the pre-meal insulin dose
How should the I:C be adjusted if the post prandial glucose is consistently >180?
Adjust by 2-5 grams of carbs
How should the I:C be adjusted if it is at 1:15 and the 2hr post prandial blood glucose levels are 210?
Increase to 1:12
What are strategies to avoid hypoglycemia?
- planned exercise: decrease pre-prandial insulin dose before the exercise
- unplanned exercise: consume an additional 15-30g of carbs for each 30 min of exercise
- might need to decrease pre-prandial insulin dose for the meal after exercising
What should you always check during illness if your blood glucose is consistently over 240?
Urine ketones!
persistent is early sign of DKA
What are complications of DM I?
Hypoglycemia
Ketoacidosis
What are s/s of ketoacidosis?
–Develop rapidly –Fruity or acetone breath –N+V –Dehydration- typically 6L or more –Polyuria –Polydipsia –Deep, rapid breathing Lethargy, HA, weakness
What is the diagnostic criteria for ketoacidosis?
–Hyperglycemia (> 250mg/dL)
–Ketosis (anion gap > 10)
–Acidosis (arterial pH
How is DKA tx?
Reverse underlying metabolic abnormality
Rehydrate with NS at 1L/hr
Normalize serum glucose with regular insulin at 0.1-0.2 unit/kg/hr by CI
What is the pathophys of DM II?
Insulin resistance and relative insulin def
What are the other physiologic issues that happen in Type II DM?
Reduced circulating levels of GLP-1
Loss of first phase insulin response post meal
Loss of amylin
What are risk factors for type II?
- Physically inactive
- 1st degree relative with diabetes
- Minority ethnic groups
- Gestational diabetes or delivering baby >9 lbs
- Hypertension
- HLD 250 mg/dL
- Polycystic ovary syndrome
- Previous impaired glucose tolerance (IGT) or impaired fasting glucose (IFG)
- History of vascular disease
- Psychiatric illness
When should you consider screening for DM?
Pts of any age if their BMI >/= 25kg.mg and they have additional risk factors for DM
If NO risk factors begin at age 45
How often should screening be repeated?
Q 3 yrs
What indicate screening for type 2 DM in kiddos?
Overweight: BMI >85th percentile for age and sex, wt for height >85th percentile, or weight >120% of ideal for height
PLUS 2 of the following
Fhx in 1st or 2nd degree relative, ot white, signs of insulin resistance, GDM
When should testing in kiddos be done?
Start at 10 or onset of puberty
Test FPG q 2yrs
What is the definition of pre-DM?
IFG= 100-125 IGT= 2hr post load glucose 140-199
IFG and IGT indicate risk factor for what?
Diabetes and CV disease
What is diagnostic for DM II?
FPG >/= 126mg/dL OR Symptoms of diabetes + casual plasma glucose >/= 200 mg/dL OR Oral glucose tolerance test (OGTT): 2hr-postload glucose >/= 200 mg/dL A1C>/= 6.5
What is the preferred test for diagnosing DM?
FPG./= 126mg/dL
What are the 3 major metabolic abnormalities that contribute to hyperglycemia?
- Defective glucose-induced insulin secretion
- Increased hepatic glucose output
- Inability of insulin to stimulate glucose uptake in peripheral target tissues.
What are some other causes of insulin resistance?
Cushings- excessive corticosteroids
Acromegaly- excessive GH
PCOS
What are the microvascular complications of DM?
Retinopathy, nephropathy, neuropathy
What are the macrovascular complications of DM?
Atherosclerotic CV diagnosis, dyslipidemia
What is the A1C goal for adults in general? Why?
What are some ways to prevent DM in pts with IGT or IFG?
Wt loss of 7% body weight and increase PE to 150 min/week
Add 14g of dietary fiber/ 1000 kcal
Meds
What drugs have been studied for prevention of DM?
Metformin, rosiglitazone, acarbose, troglitazone, orlistat
How can DM be clinically managed?
Diet/ exercise are cornerstones of DM management regardless of severity and symptoms
Meds highly individualized
What is the goal in clinical management of DM?
To improve symptoms of hyperglycemia, reduce onset & progression of microvascular and macrovascular complications, reduce mortality & improve QOL.
What are some ways to improve sugars and manage CV risk factors?
Smoking cessation, lipid management, BP control, and antiplatelet therapy
How often should glucose be self monitored?
If insulin injection: at least 3x/day
If oral: use to achieve glycemic goals
How often should A1C be monitored?
At least 2x yearly in pts at goal
Q 3 mo in pts who aren’t meeting goals or who have had a change in meds
What are the oral therapy options for DM II?
Biguanides- Metformin
Secretagogues- sulfonylureas
Short acting secretagogues- meglitinides
Insulin sensitizers- TZD, thiazolidinediones
Alpha-glucosidase inhibs
Dipeptidyl peptidase-4( DPP-4)inhib
Bile acid sequestrants
Colesevelam (welchol)
D2 agonists- bromocriptine
Sodium glucose transporter 2 inhib( SGLT2 inhib)- canaglifozin, dapagliflozin, empagliflozin
What is the MOA of metformin?
Decreases: production of hepatic glucose production, intestinal glucose absorption
Increases: peripheral glucose uptake and insulin sensitivity
What are the clinical used of metformin?
Works best in pts with significant hyperglycemia
First line in type 2 DM pharm tx
Shown to decrease CVD in DM
What are the ADRs of metformin?
GI- diarrhea, ab bloating, nausea
Vit B12 def
Lactic acidosis
How can GI affects be minimized?
Take with food, titrate dose at weekly intervals to minimize
What is an ADR of metformin that is actually beneficial?
Hypoglycemia
What needs to be monitored and when if your pt is taking metformin?
SCr at baseline
FPG at 2 weeks
A1C at 3 mo
What is the pathophys behind metformin associated lactic acidosis?
Increased production of lactate n the intestine leads to increased portal lactate concentrations which decreases liver pH, decreasing lactate metabolism and leads to accumulation in the blood
What are CI with metformin?
Renal impairments, acute or chronic metabolic acidosis
What are the precautions of metformin?
Radiocontrast studies, age>80 unless normal GFR, hypoxic states, alcoholism, heart failure requiring pharm tx
What are some benefits of metformin?
- no weight gain
- no hypoglycemia as a monotherapy
- inexpensive
- approved an monotherapy and a combo therapy
What is the MOA of sulfonylureas?
Direct stimulation of insulin release from viable pancreatic beta-cells thus reducing blood glucose levels
Blocks ATP-sensitive K+ channels, resulting in depolarization and Ca++ influxrelease of insulin
Which generation of sulfonylureas are no longer used?
Generation 1 because of the higher risk of hypoglycemia
What are the 2nd generation sulfonylureas?
Glyburide, Glipizide, Glimepiride, Gliclazide
What are the clinical used of 2nd generation sulfonylureas?
Mild to moderate Type 2 diabetes
What are the ADRs of 2nd gen sulfonlyureas?
Hypoglycemia, weight gain, muscular weakness, dizziness, confusion, skin rash, photosensitivity, blood dyscrasias, cholestatic jaundice
What are the specific directions or risks with glyburide?
Admin with breakfast or first main meal
Greater risk of hypoglycemia d/t longer half life
Don’t use if CrCl
What are directions and risks with Glipizide?
- Administer 30 min before first main meal
- Not recommended if CrCl
What are specifics for Glimepiride?
- Administer with first main meal
- Not recommended if CrCl
What affects the absorption of sulfon?
Reduced GI absorption if blood glucose is >250mg/dL
What needs to monitored if your pt is on sulfonylureas?
FGP- 2 weeks
A1C- in 3 mo
What are CI/ cautions for sulfonylureas?
Cross sensitivity to sulfa, higher risk with hypoglycemia in pts with renal or hepatic dz, avoid with ETOH, CI in pregnancy since it can cross the placenta
What are the drug interactions with sulfonylureas? what are they doing?
May potentiate hypoglycemia via reduced hepatic metabolism, decreased urinary excretion or displacement from plasma proteins
- Sulfonamide antibacterials
- Propranolol
- Salicylates
- Phenylbutazone
- ETOH
What is the MOA of the short acting secretagogues (meglitinides)?
Stimulate insulin release from pancreatic beta cells- increases insulin secretion
When should meglitinides be taken?
With meals to target postprandial glucose levels
What are the meglitinides?
Repaglinide and nateglinide
What is repaglinide approved for?
Monotherapy or with metformin
When should repagalinide be given?
Taken before meals 3x daily
What is nateglinide approved for?
Monotherapy or combo with metformin
What is the difference with nat and rep?
Nate has a faster onset of action and shorter duration of action than rep, less A1C reduction than rep
Also take 3x daily before meals
What are the ADRs of meglitinides?
Hypoglycemia and weight gain
What do you need to be monitoring if your pt is on meglitinides?
FGP at 2 weeks
Postprandial glucose at initiation
A1C at 3 months
What are the TZDs?
Rosiglitazone and pioglitazone
What is the MOA of TZDs?
regulate glucose metabolism resulting in increased insulin sensitivity in adipose, liver and skeletal muscle
they REQUIRE INSULIN for action
Whats shouldn’t you give with rosiglitazone?
Exogenous insulin! Will lead to edema
About how long does it take for the biological effect of TDZs to be seens?
4 weeks
What are the CV effects of pioglitazone?
HDL; triglycerides = decreased CVD
What are the CV effects of rosiglitazone?
: LDL(not so great) and HLD
What are the ADRs of the TZDs?
Fluid retention and peripheral edema, weight gain, new onset heart failure, bone fractures, increased risk of MI
What are the CI of TDZs?
Alcohol abuse, elevated liver enzymes, hepatotoxicity, hepatic dz, and HF in class III or IV
What are the black box warnings for the TDZs?
Both: CHF
Ros: MI risk
What are the alpha- glucosidase inhibitors?
Acarbose and miglitol
What do the alpha-glucosidase inhibitors do?
Delay intestinal carb absorption
Prevents glucose absorption and decreases post-prandial glucose levels
Is there a risk for hypoglycemia with Alpha Glucosidase inhibitors?
Nope
What are the ADR of the alpha glucosidase inhibs?
Not well tolerated
GI- loose stool, flatulence, abdominal cramping
Bonus: NO WT GAIN
How can you minimize GI effects of the alpha-gs?
Starting low and increase slowly
Curtailment of carb consumption
What are the CI for alpha-gs?
Chronic intestinal dz and cirrhosis
What needs to be monitored if your pt is on alpha gs?
Post prandial glucose at initiation and A1C in 3 months
What are the DPP-4 inhibitors?
Sitagliptin, saxagliptin, algoliptin, linagliptin, and vildagliptin
What is the MOA of the DPP-4 inhibitors?
Prevent the egredation of endogenous glucagon like peptide 1 and insulinotropic polypeptide
Results in increased insulin release and decreased glucagon levels in circulation in glucose dependent manner
When does the dosage of DPP-4 inhibs need to be adjusted?
CrCl
What are the ADRs of DPP-4 inhibs?
HA and UTI
Generally well tolerated
Investigated for pancreatic toxicity and increase in heart failure
What should you be monitoring if your pt is on DPP-4 inhibs?
Renal fxn
A1C in 3 mo
What is the bile acid sequestrant?
Colesevelam (welchol)
What is the moa of colvesevelam?
bind bile acid in intestinal tract, increasing hepatic bile acid production- possibly decrease hepatic glucose production and increase incretin levels
Is colvesevelam used as a monotherapy?
No
What are the ADRs of colvesevelam?
Constipation/nausea/indigestion
triglycerides
May decrease absorption of other medications
What are the CI of colvesevelam?
Bowel obstruction
History of hypertriglyceridemia-induced pancreatitis
Triglycerides >500 mg/dL
What is the D2 agonist?
Bromocriptine
What is the MOA of bromocriptine?
activate dopamine receptors, modulate hypothalmic regulation of metabolism, increase insulin sensitivity
What are the benefits of bromocriptine?
No hypoglycemia and decreased CVD
What are the ADRs of bromocriptine?
Dizzy/syncope, V, fatigue, rhinitis
What are the SGLT2 inhibitors?
Canagliflozin, dapagliflozin, empagliflozin
What is the MOA of SGLT 2 inhibs?
Inhibits SGLT2 in proximal nephron; Reduces reabsorption of filtered glucose thereby increasing urinary excretion of glucose
What are the benefits of SGLT2 inhibs?
No hypoglycemia, decreased weight, decreased BP
What stage of DM are SGLT2 inhibs effective at?
All the stages
Mono or adjunct therapy
What are the ADRs of SGLT2 inhibs?
Increased potassium, renal insufficiency (with baseline GFR
What do you need to make sure is corrected prior to initiating SGLT2 inhib tx?
Correct any volume depletion!
Not for pts with GFR
What are the non oral therapies for DM II?
GLP-1 agonists, pramlintide or symlin, and insulin
What are the GLP-1 agonists?
Exenatide, Liraglutide, Albiglutide, Lixisenatide, Dulaglutide
What is the MOA of GLP-1 agonists?
Increase insulin secretion(glucose dependant), decrease glucagon secretion, slows gastric emptying, increase satiety
What are GLP-1 agonists resistant to?
Degredation by DPP-4
What is the FDA approved use for GLP-1 agonists?
Type 2 DM in pts on metformin, sulfonylurea, TZD, or a combo who are not at goal
What are GLP-1 agonists NOT approved for?
Use with basal insulin
What are the ADRs of GLP-1 agonists?
- N/V/D (30-45%)
- Increase Heart Rate
- Acute Pancreatitis-possibly
- SQ injection
- Anti-exenatide antibodies
What are the precautions of GLP-1s?
-ClCr
What are the benefits of GLP-1?
- No hypoglycemia
- Modest weight loss
- Decrease of some cardiovascular risk factors
What should you monitor in a pt who is on GLP-1 tx?
Renal fxn and A1C in 3 mo
What is pramlintide approved for?
Type I/II DM in pts on optimal insulin therapy who are still not at goal
Can be with or without metformin and or sulfon tx
When should pramlintide be administered?
In conjunction with mealtime insulin
What are the the 2 pens and their dosages for pramlintide?
- SymlinPen 60: for doses of 15, 30, 45 or 60 mcg
- SymlinPen 120: for doses of 60 or 120 mcg
If your pt has type II DM and HTN, how should you control their HTN?
ACEI or ARB, potential combo with a thiazide
Diet and lifestyle
When should you screen your DM pts for dyslipidemia?
At DM initial evaluation and or at age 40 and q 1-2 yrs after
What is the first choice for lowering LDL in your DM pts?
Statin
When should a stain and lifestyle be added regardless of the lipid levels of your DM pt?
- Overt CVD
- Without CVD who are over the age of 40 and have one or more other CVD risk factors
- In pts whose LDL goal can’t be achieved, a 30-40% reduction is acceptable
If you pt has DM and CHD, how should they be tx?
Daily ASA unless CI
What is hyperosmolar hyperglycemia state?
HHS- life threatening condition similar to DKA
Extreme hyperglycemia and fluid deficits that arises from inadequate insulin but occurs primarily in older type II DM pts
What does HHS lack?
Lipolysis, ketonemia, and acidosis
What pts are at greatest risk for developing HHS?
Hyperglycemia and dehydration lasting days to weeks
What is the diagnostic criteria for HHS?
- Plasma glucose > 600mg/dL
- Serum osmolality of > 320 mOsm/kg
How is HHS tx?
- Rehydration
- Correction of electrolyte imbalances
- Continuous insulin infusion
What are the 3 hormones secreted by the thyroid gland?
T3-triiodothyronine
T4- thyroxine
Calcitonin
What is required for hormones synthesis?
Iodine
Which hormone is more potent?
T3
How is t3 produced?
Majority is produced from the peripheral conversion of T3-T4
What inhibits the conversion to T3?
BBlockers, corticosteroids, and amiodarone
What stimulates the pituitary to syntesize and release TSH? thyrotropin-releasing hormones?
thyrotropin-releasing hormone TRH, from the hypothalamus
What can block the transport of iodide into thyroid?
Bromide, fluoride and lithium
What can impair the coupling of thyroid hormones?
Sulfonylureas and thionamides
Thyroid hormones are released following what?
Proteolytic cleavage from the thyroglobulin
What can block this release?
High levels of iodine or lithium
What is free T4 level used to evaluate?
Free levels in euthyroid sick pts
What does sensitive TSH valuate? When it is increased? Decreased?
Evaluates the pituitary negative feedback system
Increased: primary hypo
Decreased: primary hyper
What is the definition of sub clinical hypothyroidism?
Serum TSH concentration above statistically defined upper limit of reference range
What is it measured by?
Serum free thyroxine within reference range
What are effects of hypothyroidism?
Increased risk of CHD —Systolic Dysfunction —Reduced stress tolerance during exercise —Cardiac autonomic dysfunction —Reduced oxygen uptake during exercise —Diastolic hypertension —Increased arterial stiffness —Pro-atherosclerotic profile Insulin resistance Pro-coagulative pattern Decreased activity ◦Von Willebrand factor ◦Factor VIII
increase risk for placental abruption and preterm delivery
What are the s/s of hypothyroidism?
◦Tiredness ◦Lethargy, Muscle pains ◦Weight gain ◦Intolerance to cold ◦Dry skin, Coarse skin ◦Bradycardia ◦Mental impairment ◦Dry thinning hair
What effect does hypothyroidism have on certain drugs?
- digitalis: decreases volume of distribution
- insulin: impaired degradation
- warfarin: delayed catabolism of clotting factors
What are causes of primary hypothyroidism?
◦Hashimoto’s Disease
◦Iatrogenic hypothyroidism-radioactive iodine ingestion, post thyroidectomy
Iodine deficiency
What are common causes of secondary hypothyroidism?
Pituitary dz and hypothalamic dz
What type of pts are at increased risk for hypothyroidism?
◦Postpartum women
◦Family history of autoimmune thyroid disorders
◦Patients with previous head and neck of thyroid irradiation or surgery
Other autoimmune endocrine
Non-autoimmune: celiac disease, vitiligo, MS, pernicious anemia, Down’s syndrome
What are the s/s of hypothyroidism in elderly pts?
◦Hoarseness ◦Deafness ◦Confusion ◦Dementia ◦Ataxia ◦Depression ◦Dry skin ◦Hair loss
What is the most common cause of hypothyroidism?
Hashimotos thyroiditis
What is Hashimotos thyroiditis ?
An autoimmune disease resulting in fibrosis of the thyroid gland, antibodies to TSH receptor
What does congenital hypothyroidism result in?
dwarfism and mental retardation (cretinism)
What is myxedema?
When pts appear to have edema under the skin-most severe form of hypothyroidism
What are the clinical features of myxedema?
◦Hypothermia
◦Advanced hypothyroid symptoms
Altered sensorium
What can myxedema lead to?
Myxedema coma- high mortality rates
What is the drug of choice for hypothyroidism management?
levothyroxine
What is the MOA of levothyroxine?
Isomer of T4 is converted to T3
What are the ADRs of levothyroxine?
◦Arrhythmias ◦Tachycardia ◦Anginal pain ◦Cramps ◦HA ◦Restlessness ◦Sweating ◦Weight loss ◦Osteoporosis
What is the CI for levothyroxine?
Thyrotoxicosis
What how often do you need to be monitoring your pt if taking levthyroxine?
◦Every 6-8 weeks until TSH normalized, then every 6-12 months
◦If doses changed, recheck TSH in 2-3 months
Levothyroxine has many drug interactions. What does it alter absorption of?
◦Cholestyramine
◦Ferrous sulfate
◦Sucralfate
Aluminum hydroxide
Levothyroxine has many drug interactions. What does it incease the metabolism of?
◦Rifampin
◦Phenytoin
◦Carbamazepine
What is the effect of oral contraceptives or estrogen with levo?
◦Increase thyroid binding globulin, resulting in lower free thyroid hormone
What is the effect of lithium with levo?
◦Inhibits synthesis and release of thyroid hormone
What is the effect of amiodarone with levo?
Block conversion T4 to T3
What is the effect of warfarin with levo?
Increases metabolism of clotting factors
What are the other 2 drug choices for hypothyroidism management?
Liothyronine sodium and liotrix
Why is liothyronine generally not used for maintenance?
therapy because of its short half-life and duration of action.
What are the indications for liothyronine?
–Initial therapy of myxedema (skin disorder) and myxedema coma
–Short-term suppression of TSH in patients undergoing surgery for thyroid cancer.
–Patients w/5’-deiodinase deficiency who cannot convert T4 to T3.
Is liotrix any more effective than levo?
No
What is the specific tx regime for myxedema coma?
◦IV bolus levothyroxine 300-500mcg
◦Maintenance 75-100 mcg IV until able to switch to PO
◦IV hydrocortisone 100mg q 8h until coexisting adrenal suppression is ruled out
◦Supportive therapy- ventillation, euglycemia, blood pressure, body temp maintained
What is the specific tx for congenital hypothyroidism?
◦Initial therapy within 45 days of birth at 10-15mcg/kg/d, associated with improved IQ’s in treated infants
◦Dose progressively decreased to typical adult dose beginning 11-20 years
- aggressive tx important for normal development!
How is hypothyroidism tx in pregnancy?
Treatment: levothyroxine
◦20% requires dose increase during pregnancy/ decrease after
◦Typically require 36 mcg/day increase in dosage
What causes hyperthyroidism?
◦Overproduction of endogenous hormone
◦Exposure to excess endogenous hormone
◦Elevated free and total T3, T4 or both serum concentrations
What are the subclinical and clinical serum levels of TSH for diagnosis?
Subclinical
◦TSH 13.2 mcg/dL
What are S/S of hyperthyroidism?
◦Nervousness ◦Anxiety ◦Palpitations ◦Increased basal metabolic rate (BMR) ◦Weight loss ◦Increased appetite ◦Increased body temp (heat intolerance) ◦Sweating ◦Fine Tremor ◦Tachycardia ◦Classical ophthalmic signs
What is the most common cause of hyperthyroidism?
Graves dz
What is graves dz?
Autoimmune syndrome that includes hyperthyroidism, diffuse thyroid enlargement, myxedema, thyroid acropachy
What forms against the thyroid cell?
IgG antibodies bind and activate the receptor
Why is TSH undetectable in graves?
From the negative feedback from elevated thyroid hormone- disproportionate increase in T3 compared to T4
What is the most common cause of hyperthyroidism in preggo?
Graves
Inappropriate production of hCG can cause subclinical or overt hyperthyroidism
What are common complications if hyperthyroidism is left untreated in the preggos?
◦Spontaneous abortion
◦Premature delivery
◦Low birth weight
◦Eclampsia
What is the drug of choice for tx graves in preggo?
PTU at the lowest effective dose
What is a thyroid storm?
Life threatening medical emergency characterized by ◦Severe thyrotoxicosis, high fever (often > 103 F), tachycardia, tachypnea, dehydration, delirium-coma, N/V, and diarrhea
What are the precipitating factors to a thyroid storm?
◦Infection, trauma, surgery radioactive iodine treatment, withdrawl from antithyroid drugs
How can you tx a thyroid storm?
◦Suppression of thyroid hormone formation and secretion
◦Anti-adrenergic therapy
◦Administration corticosteroids
◦Treatment of complications
What are the pharmacologic options for hyperthyroidism?
Thioamides, Iodines and iodine containing agents. Radioiodine, Lithium carbonate, Beta adrenergic antagonists, corticosteroids
What are the thioamides?
PTU- propylthiouracil
MMI- methimazole
What is the MOA of the thioamides?
Block thyroid hormone synthesis
PTU also inhibits DI which deiodinates peripheral T4 to T3
What are the indications for the thioamides?
◦Management of hyperthyroidism
◦Thyrotoxic crisis
◦In the preparation of patients for surgical subtotal thyroidectomy
Why might MMI be preferred?
Generally has fewer side effect and is 10x more potent than PTU, meaning it requires lower dosages
What are the most frequent ADRs of thioamides?
–Rash –Arthralgia –Myalgia –Cholestatic jaundice –Lymphadenopathy –Drug fever –Psychosis –Alopecia
What are the most serious ADRs of the thioamides? When do they typically happen?
Within first 3 mo of therapy
–Arganulocytosis-must obtain baseline white blood cell count (stop if develop fever or sore throat)
–Hepatotoxicity-baseline white blood cell count (stop if pt. develops fever or sore throat)
–Vasculitis-drug induced lupus or anti-neutrophil
What can thioamides cause in excessive amounts over long periods of time?
Hypothyroidism and enlargement of the thyroid gland
What are indications for the iodines and iodine containing agents?
◦Preoperatively for thyroidectomy (7-14 days)
◦Used after RAI (3-7 days), to allow RAI to concentrate in thyroid
What are the CI for iodines?
Should not be given to breastfeeding women- can cause goiter in infants
How are the iodines administered?
Iodine and iodide are given 10-14 days prior to partial thyroidectomy w/PTU or methimazole
Should you give iodines long term?
No- they loose effectiveness
What are the ADRs of the iodines?
◦Hypersensitivity rxn ◦HA ◦Lacrimation ◦Conjunctivitis ◦Laryngitis ◦Thyrotoxicosis in patients w/nontoxic goiter ◦Drug fever ◦Acneform rash ◦Metallic taste in mouth
When is radioiodine used?
For thyroid ablation in the management of hyperthyroidism
When is radioiodine the agent of choice?
Graves, toxic autonomous nodules, toxic multinodular goiters
What is the goal of radioiodine? MOA?
To destroy overactive thyroid cells
◦Taken up by other organs- organification only in thyroid
◦The ablative effect is exerted primarily through beta-particle emissions, which destroy thyroid tissue.
What is the major disadvantage to using radioiodine?
◦Hypothyroidism in most patients
◦Can not be used in pregnancy
◦Hypothyroid often occurs months-years after RAI
◦African Americans are most likely to be resistant to RAI (require multiple doses)
What is the MOA of lithium carbonate?
◦Lithium inhibits thyroidal incorporation of I- into thyroid gland which inhibits the secretion of thyroid hormones from follicular cells
What are the indications for lithium carbonate?
Offers no advantage over thioamide
Can be used for temporary control of thyrotoxicosis in pts allergic to thioamides and iodine
When are beta-adrenergic antagonists used in hyperthyroidism?
to ameliorate thyrotoxic symptoms: palpitations, anxiety, tremor, heat intolerance
Is it a primary or adjunct therapy?
Adjunct! No effect on peripheral thyrotixicosis and therapeutic effect
Which corticosteroids can be used in hyperthyroidism?
—Dexamethasone
—Prednisone
—Methylprednisolone
Hyrocortisone
What are the effects of the corticosteroids?
◦Decreases thyroid action
◦Decreases immune response in Grave’s disease
reduce T3
When are corticosteroids useful?
Thyroiditis and thyroid storm
When is a thyroidectomy indicated?
large glands, severe ophthalmopathy, lack of remission on treatment
What pts should not have a thyroidectomy?
On pts with low RAI uptake
What medications should the pt be on before during and after the surgery?
—Propylthiouracil (PTU) or methimazole (MMI) until pt is euthyroid (6-8 weeks) followed by iodide 500 mg/day x 10-14 days
—Beta blocker (propranolol/ nadolol) pre- and post-surgery to maintain HR
What are complications of a thyroidectomy?
◦Hyperthyroidism
◦Hypothyroidism
◦Hypoparathyroidism
◦Vocal cord abnormalities
What are drugs your pt may be taking that if you added a thyroid or antithyroid agent would have interactions?
◦Warfarin
◦Lithium
◦Diabetes medication requirements may change
◦Potassium iodide used as expectorants
◦Cardiac glycosides such as digoxin may require dosage adjustments
◦Amiodarone
CNS depressants
Amiodarone and iodinated contrast media can inhibit conversion of T4 to T3 in peripheral circulation and the pituitary gland. What are the levels and when do these happen?
–Iodinated Contrast
Reduction in levels in week 1
Return to normal by week 2
–Amiodarone
Transient elevation in TSH during first 3 months
Persistent FT4 elevations and reduced T3 in on-going therapy
What prescription drugs containing iodides can induce thyroid dz?
–Amiodarone
–Radiocontrast dye
–Povidone iodine
–Iodinated glycerol
What non-prescription drugs containing iodides can induce thyroid dz?
–Cough and cold
–Kelp
–Herbals
–Dietary supplements/ weight loss products
What is iodine induced hyperthyroidism called?
Jod-basedow dz
When does jod-b develop and how is it tx?
◦Develops within 3-8 weeks after exposure in up to 5% pts
◦Treatment with thioamides and beta blockers
What pts are at risk of developing iodine induced hypothyroidism?
Pts being tx with Amiodarone
How is iodine induced hypothyroidism tx?
levothyroxine replacement
What other drug can induce hypothyroidism? How is this tx?
Lithium- more like if tx >2ys
Tx: levo to reverse
◦Can spontaneously resolve without treatment
◦Stopping lithium does not always resolve symptoms or goiter
◦May require surgical intervention
When might interferon alpha induced thyroid dz present?
within 6-8 weeks of starting therapy or occur 6-23 months after start
How is IFNa induced dz tx?
Hypothyroidism resolves spontaneously within 2-3 months after stopping therapy in most patients- may take longer
What are the 3 hormones secreted by the thyroid gland?
T3-triiodothyronine
T4- thyroxine
Calcitonin
What is required for hormones synthesis?
Iodine
Which hormone is more potent?
T3
How is t3 produced?
Majority is produced from the peripheral conversion of T3-T4
What inhibits the conversion to T3?
BBlockers, corticosteroids, and amiodarone
What stimulates the pituitary to syntesize and release TSH? thyrotropin-releasing hormones?
thyrotropin-releasing hormone TRH, from the hypothalamus
What can block the transport of iodide into thyroid?
Bromide, fluoride and lithium
What can impair the coupling of thyroid hormones?
Sulfonylureas and thionamides
Thyroid hormones are released following what?
Proteolytic cleavage from the thyroglobulin
What can block this release?
High levels of iodine or lithium
What is free T4 level used to evaluate?
Free levels in euthyroid sick pts
What does sensitive TSH valuate? When it is increased? Decreased?
Evaluates the pituitary negative feedback system
Increased: primary hypo
Decreased: primary hyper
What is the definition of sub clinical hypothyroidism?
Serum TSH concentration above statistically defined upper limit of reference range
What is it measured by?
Serum free thyroxine within reference range
What are effects of hypothyroidism?
Increased risk of CHD —Systolic Dysfunction —Reduced stress tolerance during exercise —Cardiac autonomic dysfunction —Reduced oxygen uptake during exercise —Diastolic hypertension —Increased arterial stiffness —Pro-atherosclerotic profile Insulin resistance Pro-coagulative pattern Decreased activity ◦Von Willebrand factor ◦Factor VIII
increase risk for placental abruption and preterm delivery
What are the s/s of hypothyroidism?
◦Tiredness ◦Lethargy, Muscle pains ◦Weight gain ◦Intolerance to cold ◦Dry skin, Coarse skin ◦Bradycardia ◦Mental impairment ◦Dry thinning hair
What effect does hypothyroidism have on certain drugs?
- digitalis: decreases volume of distribution
- insulin: impaired degradation
- warfarin: delayed catabolism of clotting factors
What are causes of primary hypothyroidism?
◦Hashimoto’s Disease
◦Iatrogenic hypothyroidism-radioactive iodine ingestion, post thyroidectomy
Iodine deficiency
What are common causes of secondary hypothyroidism?
Pituitary dz and hypothalamic dz
What type of pts are at increased risk for hypothyroidism?
◦Postpartum women
◦Family history of autoimmune thyroid disorders
◦Patients with previous head and neck of thyroid irradiation or surgery
Other autoimmune endocrine
Non-autoimmune: celiac disease, vitiligo, MS, pernicious anemia, Down’s syndrome
What are the s/s of hypothyroidism in elderly pts?
◦Hoarseness ◦Deafness ◦Confusion ◦Dementia ◦Ataxia ◦Depression ◦Dry skin ◦Hair loss
What is the most common cause of hypothyroidism?
Hashimotos thyroiditis
What is Hashimotos thyroiditis ?
An autoimmune disease resulting in fibrosis of the thyroid gland, antibodies to TSH receptor
What does congenital hypothyroidism result in?
dwarfism and mental retardation (cretinism)
What is myxedema?
When pts appear to have edema under the skin-most severe form of hypothyroidism
What are the clinical features of myxedema?
◦Hypothermia
◦Advanced hypothyroid symptoms
Altered sensorium
What can myxedema lead to?
Myxedema coma- high mortality rates
What is the drug of choice for hypothyroidism management?
levothyroxine
What is the MOA of levothyroxine?
Isomer of T4 is converted to T3
What are the ADRs of levothyroxine?
◦Arrhythmias ◦Tachycardia ◦Anginal pain ◦Cramps ◦HA ◦Restlessness ◦Sweating ◦Weight loss ◦Osteoporosis
What is the CI for levothyroxine?
Thyrotoxicosis
What how often do you need to be monitoring your pt if taking levthyroxine?
◦Every 6-8 weeks until TSH normalized, then every 6-12 months
◦If doses changed, recheck TSH in 2-3 months
Levothyroxine has many drug interactions. What does it alter absorption of?
◦Cholestyramine
◦Ferrous sulfate
◦Sucralfate
Aluminum hydroxide
Levothyroxine has many drug interactions. What does it incease the metabolism of?
◦Rifampin
◦Phenytoin
◦Carbamazepine
What is the effect of oral contraceptives or estrogen with levo?
◦Increase thyroid binding globulin, resulting in lower free thyroid hormone
What is the effect of lithium with levo?
◦Inhibits synthesis and release of thyroid hormone
What is the effect of amiodarone with levo?
Block conversion T4 to T3
What is the effect of warfarin with levo?
Increases metabolism of clotting factors
What are the other 2 drug choices for hypothyroidism management?
Liothyronine sodium and liotrix
Why is liothyronine generally not used for maintenance?
therapy because of its short half-life and duration of action.
What are the indications for liothyronine?
–Initial therapy of myxedema (skin disorder) and myxedema coma
–Short-term suppression of TSH in patients undergoing surgery for thyroid cancer.
–Patients w/5’-deiodinase deficiency who cannot convert T4 to T3.
Is liotrix any more effective than levo?
No
What is the specific tx regime for myxedema coma?
◦IV bolus levothyroxine 300-500mcg
◦Maintenance 75-100 mcg IV until able to switch to PO
◦IV hydrocortisone 100mg q 8h until coexisting adrenal suppression is ruled out
◦Supportive therapy- ventillation, euglycemia, blood pressure, body temp maintained
What is the specific tx for congenital hypothyroidism?
◦Initial therapy within 45 days of birth at 10-15mcg/kg/d, associated with improved IQ’s in treated infants
◦Dose progressively decreased to typical adult dose beginning 11-20 years
- aggressive tx important for normal development!
How is hypothyroidism tx in pregnancy?
Treatment: levothyroxine
◦20% requires dose increase during pregnancy/ decrease after
◦Typically require 36 mcg/day increase in dosage
What causes hyperthyroidism?
◦Overproduction of endogenous hormone
◦Exposure to excess endogenous hormone
◦Elevated free and total T3, T4 or both serum concentrations
What are the subclinical and clinical serum levels of TSH for diagnosis?
Subclinical
◦TSH 13.2 mcg/dL
What are S/S of hyperthyroidism?
◦Nervousness ◦Anxiety ◦Palpitations ◦Increased basal metabolic rate (BMR) ◦Weight loss ◦Increased appetite ◦Increased body temp (heat intolerance) ◦Sweating ◦Fine Tremor ◦Tachycardia ◦Classical ophthalmic signs
What is the most common cause of hyperthyroidism?
Graves dz
What is graves dz?
Autoimmune syndrome that includes hyperthyroidism, diffuse thyroid enlargement, myxedema, thyroid acropachy
What forms against the thyroid cell?
IgG antibodies bind and activate the receptor
Why is TSH undetectable in graves?
From the negative feedback from elevated thyroid hormone- disproportionate increase in T3 compared to T4
What is the most common cause of hyperthyroidism in preggo?
Graves
Inappropriate production of hCG can cause subclinical or overt hyperthyroidism
What are common complications if hyperthyroidism is left untreated in the preggos?
◦Spontaneous abortion
◦Premature delivery
◦Low birth weight
◦Eclampsia
What is the drug of choice for tx graves in preggo?
PTU at the lowest effective dose
What is a thyroid storm?
Life threatening medical emergency characterized by ◦Severe thyrotoxicosis, high fever (often > 103 F), tachycardia, tachypnea, dehydration, delirium-coma, N/V, and diarrhea
What are the precipitating factors to a thyroid storm?
◦Infection, trauma, surgery radioactive iodine treatment, withdrawl from antithyroid drugs
How can you tx a thyroid storm?
◦Suppression of thyroid hormone formation and secretion
◦Anti-adrenergic therapy
◦Administration corticosteroids
◦Treatment of complications
What are the pharmacologic options for hyperthyroidism?
Thioamides, Iodines and iodine containing agents. Radioiodine, Lithium carbonate, Beta adrenergic antagonists, corticosteroids
What are the thioamides?
PTU- propylthiouracil
MMI- methimazole
What is the MOA of the thioamides?
Block thyroid hormone synthesis
PTU also inhibits DI which deiodinates peripheral T4 to T3
What are the indications for the thioamides?
◦Management of hyperthyroidism
◦Thyrotoxic crisis
◦In the preparation of patients for surgical subtotal thyroidectomy
Why might MMI be preferred?
Generally has fewer side effect and is 10x more potent than PTU, meaning it requires lower dosages
What are the most frequent ADRs of thioamides?
–Rash –Arthralgia –Myalgia –Cholestatic jaundice –Lymphadenopathy –Drug fever –Psychosis –Alopecia
What are the most serious ADRs of the thioamides? When do they typically happen?
Within first 3 mo of therapy
–Arganulocytosis-must obtain baseline white blood cell count (stop if develop fever or sore throat)
–Hepatotoxicity-baseline white blood cell count (stop if pt. develops fever or sore throat)
–Vasculitis-drug induced lupus or anti-neutrophil
What can thioamides cause in excessive amounts over long periods of time?
Hypothyroidism and enlargement of the thyroid gland
What are indications for the iodines and iodine containing agents?
◦Preoperatively for thyroidectomy (7-14 days)
◦Used after RAI (3-7 days), to allow RAI to concentrate in thyroid
What are the CI for iodines?
Should not be given to breastfeeding women- can cause goiter in infants
How are the iodines administered?
Iodine and iodide are given 10-14 days prior to partial thyroidectomy w/PTU or methimazole
Should you give iodines long term?
No- they loose effectiveness
What are the ADRs of the iodines?
◦Hypersensitivity rxn ◦HA ◦Lacrimation ◦Conjunctivitis ◦Laryngitis ◦Thyrotoxicosis in patients w/nontoxic goiter ◦Drug fever ◦Acneform rash ◦Metallic taste in mouth
When is radioiodine used?
For thyroid ablation in the management of hyperthyroidism
When is radioiodine the agent of choice?
Graves, toxic autonomous nodules, toxic multinodular goiters
What is the goal of radioiodine? MOA?
To destroy overactive thyroid cells
◦Taken up by other organs- organification only in thyroid
◦The ablative effect is exerted primarily through beta-particle emissions, which destroy thyroid tissue.
What is the major disadvantage to using radioiodine?
◦Hypothyroidism in most patients
◦Can not be used in pregnancy
◦Hypothyroid often occurs months-years after RAI
◦African Americans are most likely to be resistant to RAI (require multiple doses)
What is the MOA of lithium carbonate?
◦Lithium inhibits thyroidal incorporation of I- into thyroid gland which inhibits the secretion of thyroid hormones from follicular cells
What are the indications for lithium carbonate?
Offers no advantage over thioamide
Can be used for temporary control of thyrotoxicosis in pts allergic to thioamides and iodine
When are beta-adrenergic antagonists used in hyperthyroidism?
to ameliorate thyrotoxic symptoms: palpitations, anxiety, tremor, heat intolerance
Is it a primary or adjunct therapy?
Adjunct! No effect on peripheral thyrotixicosis and therapeutic effect
Which corticosteroids can be used in hyperthyroidism?
—Dexamethasone
—Prednisone
—Methylprednisolone
Hyrocortisone
What are the effects of the corticosteroids?
◦Decreases thyroid action
◦Decreases immune response in Grave’s disease
reduce T3
When are corticosteroids useful?
Thyroiditis and thyroid storm
When is a thyroidectomy indicated?
large glands, severe ophthalmopathy, lack of remission on treatment
What pts should not have a thyroidectomy?
On pts with low RAI uptake
What medications should the pt be on before during and after the surgery?
—Propylthiouracil (PTU) or methimazole (MMI) until pt is euthyroid (6-8 weeks) followed by iodide 500 mg/day x 10-14 days
—Beta blocker (propranolol/ nadolol) pre- and post-surgery to maintain HR
What are complications of a thyroidectomy?
◦Hyperthyroidism
◦Hypothyroidism
◦Hypoparathyroidism
◦Vocal cord abnormalities
What are drugs your pt may be taking that if you added a thyroid or antithyroid agent would have interactions?
◦Warfarin
◦Lithium
◦Diabetes medication requirements may change
◦Potassium iodide used as expectorants
◦Cardiac glycosides such as digoxin may require dosage adjustments
◦Amiodarone
CNS depressants
Amiodarone and iodinated contrast media can inhibit conversion of T4 to T3 in peripheral circulation and the pituitary gland. What are the levels and when do these happen?
–Iodinated Contrast
Reduction in levels in week 1
Return to normal by week 2
–Amiodarone
Transient elevation in TSH during first 3 months
Persistent FT4 elevations and reduced T3 in on-going therapy
What prescription drugs containing iodides can induce thyroid dz?
–Amiodarone
–Radiocontrast dye
–Povidone iodine
–Iodinated glycerol
What non-prescription drugs containing iodides can induce thyroid dz?
–Cough and cold
–Kelp
–Herbals
–Dietary supplements/ weight loss products
What is iodine induced hyperthyroidism called?
Jod-basedow dz
When does jod-b develop and how is it tx?
◦Develops within 3-8 weeks after exposure in up to 5% pts
◦Treatment with thioamides and beta blockers
What pts are at risk of developing iodine induced hypothyroidism?
Pts being tx with Amiodarone
How is iodine induced hypothyroidism tx?
levothyroxine replacement
What other drug can induce hypothyroidism? How is this tx?
Lithium- more like if tx >2ys
Tx: levo to reverse
◦Can spontaneously resolve without treatment
◦Stopping lithium does not always resolve symptoms or goiter
◦May require surgical intervention
When might interferon alpha induced thyroid dz present?
within 6-8 weeks of starting therapy or occur 6-23 months after start
How is IFNa induced dz tx?
Hypothyroidism resolves spontaneously within 2-3 months after stopping therapy in most patients- may take longer
What are the precipitating factors to a thyroid storm?
◦Infection, trauma, surgery radioactive iodine treatment, withdrawl from antithyroid drugs
How can you tx a thyroid storm?
◦Suppression of thyroid hormone formation and secretion
◦Anti-adrenergic therapy
◦Administration corticosteroids
◦Treatment of complications
What are the pharmacologic options for hyperthyroidism?
Thioamides, Iodines and iodine containing agents. Radioiodine, Lithium carbonate, Beta adrenergic antagonists, corticosteroids
What are the thioamides?
PTU- propylthiouracil
MMI- methimazole
What is the MOA of the thioamides?
Block thyroid hormone synthesis
PTU also inhibits DI which deiodinates peripheral T4 to T3
What are the indications for the thioamides?
◦Management of hyperthyroidism
◦Thyrotoxic crisis
◦In the preparation of patients for surgical subtotal thyroidectomy
Why might MMI be preferred?
Generally has fewer side effect and is 10x more potent than PTU, meaning it requires lower dosages
What are the most frequent ADRs of thioamides?
–Rash –Arthralgia –Myalgia –Cholestatic jaundice –Lymphadenopathy –Drug fever –Psychosis –Alopecia
What are the most serious ADRs of the thioamides? When do they typically happen?
Within first 3 mo of therapy
–Arganulocytosis-must obtain baseline white blood cell count (stop if develop fever or sore throat)
–Hepatotoxicity-baseline white blood cell count (stop if pt. develops fever or sore throat)
–Vasculitis-drug induced lupus or anti-neutrophil
What can thioamides cause in excessive amounts over long periods of time?
Hypothyroidism and enlargement of the thyroid gland
What are indications for the iodines and iodine containing agents?
◦Preoperatively for thyroidectomy (7-14 days)
◦Used after RAI (3-7 days), to allow RAI to concentrate in thyroid
What are the CI for iodines?
Should not be given to breastfeeding women- can cause goiter in infants
How are the iodines administered?
Iodine and iodide are given 10-14 days prior to partial thyroidectomy w/PTU or methimazole
Should you give iodines long term?
No- they loose effectiveness
What are the ADRs of the iodines?
◦Hypersensitivity rxn ◦HA ◦Lacrimation ◦Conjunctivitis ◦Laryngitis ◦Thyrotoxicosis in patients w/nontoxic goiter ◦Drug fever ◦Acneform rash ◦Metallic taste in mouth
When is radioiodine used?
For thyroid ablation in the management of hyperthyroidism
When is radioiodine the agent of choice?
Graves, toxic autonomous nodules, toxic multinodular goiters
What is the goal of radioiodine? MOA?
To destroy overactive thyroid cells
◦Taken up by other organs- organification only in thyroid
◦The ablative effect is exerted primarily through beta-particle emissions, which destroy thyroid tissue.
What is the major disadvantage to using radioiodine?
◦Hypothyroidism in most patients
◦Can not be used in pregnancy
◦Hypothyroid often occurs months-years after RAI
◦African Americans are most likely to be resistant to RAI (require multiple doses)
What is the MOA of lithium carbonate?
◦Lithium inhibits thyroidal incorporation of I- into thyroid gland which inhibits the secretion of thyroid hormones from follicular cells
What are the indications for lithium carbonate?
Offers no advantage over thioamide
Can be used for temporary control of thyrotoxicosis in pts allergic to thioamides and iodine
When are beta-adrenergic antagonists used in hyperthyroidism?
to ameliorate thyrotoxic symptoms: palpitations, anxiety, tremor, heat intolerance
Is it a primary or adjunct therapy?
Adjunct! No effect on peripheral thyrotixicosis and therapeutic effect
Which corticosteroids can be used in hyperthyroidism?
—Dexamethasone
—Prednisone
—Methylprednisolone
Hyrocortisone
What are the effects of the corticosteroids?
◦Decreases thyroid action
◦Decreases immune response in Grave’s disease
reduce T3
When are corticosteroids useful?
Thyroiditis and thyroid storm
When is a thyroidectomy indicated?
large glands, severe ophthalmopathy, lack of remission on treatment
What pts should not have a thyroidectomy?
On pts with low RAI uptake
What medications should the pt be on before during and after the surgery?
—Propylthiouracil (PTU) or methimazole (MMI) until pt is euthyroid (6-8 weeks) followed by iodide 500 mg/day x 10-14 days
—Beta blocker (propranolol/ nadolol) pre- and post-surgery to maintain HR
What are complications of a thyroidectomy?
◦Hyperthyroidism
◦Hypothyroidism
◦Hypoparathyroidism
◦Vocal cord abnormalities
What are drugs your pt may be taking that if you added a thyroid or antithyroid agent would have interactions?
◦Warfarin
◦Lithium
◦Diabetes medication requirements may change
◦Potassium iodide used as expectorants
◦Cardiac glycosides such as digoxin may require dosage adjustments
◦Amiodarone
CNS depressants
Amiodarone and iodinated contrast media can inhibit conversion of T4 to T3 in peripheral circulation and the pituitary gland. What are the levels and when do these happen?
–Iodinated Contrast
Reduction in levels in week 1
Return to normal by week 2
–Amiodarone
Transient elevation in TSH during first 3 months
Persistent FT4 elevations and reduced T3 in on-going therapy
What prescription drugs containing iodides can induce thyroid dz?
–Amiodarone
–Radiocontrast dye
–Povidone iodine
–Iodinated glycerol
What non-prescription drugs containing iodides can induce thyroid dz?
–Cough and cold
–Kelp
–Herbals
–Dietary supplements/ weight loss products
What is iodine induced hyperthyroidism called?
Jod-basedow dz
When does jod-b develop and how is it tx?
◦Develops within 3-8 weeks after exposure in up to 5% pts
◦Treatment with thioamides and beta blockers
What pts are at risk of developing iodine induced hypothyroidism?
Pts being tx with Amiodarone
How is iodine induced hypothyroidism tx?
levothyroxine replacement
What other drug can induce hypothyroidism? How is this tx?
Lithium- more like if tx >2ys
Tx: levo to reverse
◦Can spontaneously resolve without treatment
◦Stopping lithium does not always resolve symptoms or goiter
◦May require surgical intervention
When might interferon alpha induced thyroid dz present?
within 6-8 weeks of starting therapy or occur 6-23 months after start
How is IFNa induced dz tx?
Hypothyroidism resolves spontaneously within 2-3 months after stopping therapy in most patients- may take longer
What are indications for the iodines and iodine containing agents?
◦Preoperatively for thyroidectomy (7-14 days)
◦Used after RAI (3-7 days), to allow RAI to concentrate in thyroid
What are the CI for iodines?
Should not be given to breastfeeding women- can cause goiter in infants
How are the iodines administered?
Iodine and iodide are given 10-14 days prior to partial thyroidectomy w/PTU or methimazole
Should you give iodines long term?
No- they loose effectiveness
What are the ADRs of the iodines?
◦Hypersensitivity rxn ◦HA ◦Lacrimation ◦Conjunctivitis ◦Laryngitis ◦Thyrotoxicosis in patients w/nontoxic goiter ◦Drug fever ◦Acneform rash ◦Metallic taste in mouth
When is radioiodine used?
For thyroid ablation in the management of hyperthyroidism
When is radioiodine the agent of choice?
Graves, toxic autonomous nodules, toxic multinodular goiters
What is the goal of radioiodine? MOA?
To destroy overactive thyroid cells
◦Taken up by other organs- organification only in thyroid
◦The ablative effect is exerted primarily through beta-particle emissions, which destroy thyroid tissue.
What is the major disadvantage to using radioiodine?
◦Hypothyroidism in most patients
◦Can not be used in pregnancy
◦Hypothyroid often occurs months-years after RAI
◦African Americans are most likely to be resistant to RAI (require multiple doses)
What is the MOA of lithium carbonate?
◦Lithium inhibits thyroidal incorporation of I- into thyroid gland which inhibits the secretion of thyroid hormones from follicular cells
What are the indications for lithium carbonate?
Offers no advantage over thioamide
Can be used for temporary control of thyrotoxicosis in pts allergic to thioamides and iodine
When are beta-adrenergic antagonists used in hyperthyroidism?
to ameliorate thyrotoxic symptoms: palpitations, anxiety, tremor, heat intolerance
Is it a primary or adjunct therapy?
Adjunct! No effect on peripheral thyrotixicosis and therapeutic effect
Which corticosteroids can be used in hyperthyroidism?
—Dexamethasone
—Prednisone
—Methylprednisolone
Hyrocortisone
What are the effects of the corticosteroids?
◦Decreases thyroid action
◦Decreases immune response in Grave’s disease
reduce T3
When are corticosteroids useful?
Thyroiditis and thyroid storm
When is a thyroidectomy indicated?
large glands, severe ophthalmopathy, lack of remission on treatment
What pts should not have a thyroidectomy?
On pts with low RAI uptake
