Diabetes Flashcards
classification of DM
-type I Diabetes (IDDM) (10-15% of DM)
-Onset < 30 y.o.
-autoimmune
-destruction of pancreatic B cells
-severe insulin deficiency predisposing pt to ketoacidosis and ketonemia
-insulin required for survival
-Type II Diabetes (NIDDM) (85-90% 0f DM)
-Onset > 30 y.o.
-associated with obesity
-hyperglycemia due to the following factors:
- genetics
-insulin resistance
-hepatic glucose production
-B cell deficiency (defect in normal insulin secretion):
i. Phase 1 insulin secretion (bolus of insulin secreted minutes after meal)
ii. Phase 2 insulin secretion (steady insulin secretion as long as there is
glucose stimulation)- this tends to get worse in diabetics as they progress
-Treatment
-Diet, exercise and weight loss
-Oral medications
-Insulin (as disease progresses and B cell insulin secretion worsens)
insulin
-normally produced in B cells in Islets of Langerhans in pancreas (glucagon in A cells)
-Normal functions:
-transport of glucose from blood to cell
-conversion of glucose to glycogen (glycogenesis)
-conversion of glucose to fatty acids (lipogenesis)
-stimulates protein synthesis
early manifestation
-acute metabolic abnormalities from lack of insulin result of:
-decreased glucose uptake by muscle and adipose
-increased hepatic output of glucose
-increased catabolism of proteins in muscle tissue
-increased lipolysis and release of fatty acids from adipose tissue
-reduction in glucose utilization w/ increase in hepatic glucose production results in
hyperglycemia which causes:
-glycosuria
-osmotic diuresis
-polyuria
-polydipsia
-polyphagia
-dehydration, weight loss
-increased lipolysis -> increased ketones in liver -> body cant metabolize ketones ->
keto acids secreted in urine -> ketoacidosis
-increased catabolism of proteins and loss of nitrogen in the urine urea and uric acid
long term complications
-Microvascular
-Nephropathy
-Retinopathy
-Macrovascular
-Cerebrovascular disease
-Hypertension
-Dyslipidemia
-Coronary artery disease*
-Peripheral vascular disease
-Neuropathic complications
-Related to protein synthesis and glucose related demyelination
strategies for controlling blood glucose
-increase circulating insulin levels
-improve insulin sensitivity- exercise
-regulate glucose production in liver
-decrease postprandial glucose
-diet and exercise are always essential components
treatment guidelines
-ACE- young pts
-ADA- older pts
injectable insulin preparations
-Sources:
-animal derived - pork derived, don’t use bovine anymore b/c mad cow disease
-human:
-Humulin (genetically engineered E.coli)
-Novolin (insertion of human AAs)
-Administration & Storage: dead scar (soft), doesnt hurt, small needles
-SQ, IV
-fridge
-Dosing: Various dosing regimens available. Need to individualize and adjust according to
patient response, diet (carb exchanges), glucose levels, HBA1C and ADRs
-low and slow
-ADRs
-Hypoglycemia
-Local allergy
-Systemic allergy (more common w/ animal insulin)
-Immunological resistance (similar to tolerance) – increase dose
-Local fat atrophy/hypertrophy decreased absorption of insulin
-Advantages – no maximum dose, improves cholesterol profile, low cost. -Available in a variety of dosage forms.
-Considered 2nd line for Treatment of Type 2 DM per ADA (or initial treatment if FPG > 250
mg/dL or HbA1c > 10% or ketonuria or symptoms of hyperglycemia
Somogyi effect and Dawn Phenomenon***
-Somogyi effect:
-nocturnal hypoglycemic effect
-falsely elevated in morning
-compensatory
-elevated glucose in the morning with nightmares *
-decrease insulin
-Dawn Phenomenon: MC
-decrease tissue sensitivity between 5-8AM to insulin
-GH
-increase insulin
-you can have both at the same time
types of insulin
-regular and NPH are less used
-long acting are used more -less injections
-TEST- know the general onset and peak duration of each
Biguanides
-Metformin (Glucophage) - only drug in the class
-Considered 1st line treatment in patients with Type 2 DM (if no
contraindications) – according to ADA
-MOA – inhibits gluconeogenesis by liver, increase glucose uptake into muscle, increases insulin receptor sensitivity
-!!Contraindications: Cr > 1.5 mg/dL in males and > 1.4 mg/dL in females. Drug can accumulate and cause lactic acidosis. Hold drug for 48 hours if receiving iodinated radiocontrast
-Precautions: Use with caution in CHF, hepatic disease, pulmonary disease, MI and with ethanol abuse.
-Advantages – NO weight gain!
-ADRs – lactic acidosis!, diarrhea!, nausea, bloating, metallic taste, anorexia, decreased folate and b12 absorption.
-DDIs – sulfonylureas (incr hypoglycemia), alcohol (incr lactic acidosis* risk), cimetidine, nifedipine, ranitidine, digoxin and vancomycin (all can increase metformin
levels)
-Comments:
-Rarely causes hypoglycemia when used alone b/c doesn’t stimulate insulin release
-Gradually titrate due to GI distress, can give w/ meals to minimize
-Also used for Gestational Diabetes and PCOS
type 2 can become
type 1
sulfonylureas
-First oral agents introduced to market for Type 2 DM – not useful in Type I DM
-1st generation – Rarely used now, replaced by second generation. Includes chlorpropamide (Diabinese), tolazamide (Tolinase) and tolbutamide (Orinase)
-2nd generation – includes glipizide (Glucotrol), glyburide (Micronase, Diabeta) and glimeripide (Amaryl).
-Most given once a day, can be given BID, glipizide preferred in elderly b/c shorter half life.
-Considered 2nd line treatment of Type 2 DM per ADA.
-MOA – stimulate insulin release from B cells and bind to specific sulfonlyurea receptor, also decrease hepatic clearance of insulin. Both effects will therefore increase circulating insulin levels.
-Precautions - sulfur containing drugs, avoid in pts allergic to sulfa. May need to adjust doses in renal dysfunction
-ADRs – Hypoglycemia!, weight gain!, CNS effects, skin reactions, GI effects,
hematologic SEs, !Chlorpropramide – SIADH and disulfiram-like rxn with alcohol! (metronidazole too)
-DDIs
-hypoglycemia – coumadin, fluconazole, H2 blockers, Mg salts, sulfonamides, tricyclic
antidepressants
-hyperglycemia – beta blockers, calcium channel blockers, steroids, phenytoin, thiazide
diuretics
-Comments:
-Take 30 minutes before meals.
-Lose effectiveness after 1-2 years
-When used in combo with insulin and other oral antidiabetic agents – increase risk of hypoglycemia
meglitinides
-includes repaglinide (Prandin) and nateglinide (Starlix)
-MOA – stimulates insulin release from B cells, by closing K+ channels and opening
Ca2+ channels on B cells- Not useful in Type 1 DM.
-Precautions: hepatic dysfunction
-ADRs – hypoglycemia, nausea, vomiting, diarrhea, sweating, tremor, URI, arthralgias
-DDIs – increased effects with azoles and macrolides (due to P450 enzyme
inhibition); caution w/ highly protein bound drugs like NSAIDS, aspirin, sulfonamides and coumadin; decreased effectiveness with P450 enzyme inducers (like barbiturates, carbamazepine and rifampin)
-Comments
-Dose 30 min prior to meals (like sulfonlyurea)
-Can use with metformin or thiazolidinediones, NOT w/ insulin or sulfonlyureas
-Poor compliance
thiazolidinediones
-includes pioglitazone (Actos) and rosiglitazone (Avandia)
-Considered 2nd line for Type 2 DM per ADA.
-MOA – Unique, reduces insulin resistance at target tissue by increasing insulin sensitivity in muscle and adipose. Binds to specific receptors, requires presence of insulin to work. Also decreases hepatic glucose production.
-Indications - can be used in Type 1 DM (with insulin) and Type 2 DM
-Precautions: Liver dysfunction. Monitor LFTs every 2 months for first year and periodically thereafter (Rezulin was removed from market in 2000 due to liver toxicity leading to liver transplants and death)
-Black box warning - Caution in CHF (Avoid in Class 3 and 4 Heart Failure due to increased edema)
-Rosiglitazone –has an additional black box warning for MI. Drug will no longer be available from retail pharmacies after Nov 18, 2011. Will have to get from specialty pharmacy if pt meets certain criteria (previous use, intolerant to other DM meds incl pioglitazone)
-Advantages: Good reduction in HbA1c, beneficial effect on lipid profile
-ADRs – weight gain, edema, fluid retention, increased risk of fractures, mild anemia, hypoglycemia (esp. when combined w/ other agents); NEW data – risk of bladder
cancer w/ pioglitazone
-DDIs – decreased effectiveness of oral contraceptives, increased effect of pioglitazone with P450 enzyme inhibitors
-Comments
-Can be taken w/o regard to meals b/c of unique MOA
-Dose adjustments only after 12 weeks based on BG and HbA1C b/c of unique MOA*
-increases MI risk*
alpha-glucosidase inhibitors
-includes acarbose (Precose) and miglitol (Glyset)
-MOA – Reversible inhibitor of alpha glucosidase in the small intestine, therefore interfering with the hydrolysis of complex carbs and dietary disaccharides
-Reduces intestinal absorption of starches and disaccharides and slows the absorption of carbohydrates -> lower postprandial glucose
-Contraindications: IBD, colonic ulceration or intestinal obstruction (bc it slows down tract)
-ADRs – flatulence, diarrhea and abdominal pain
-DDIs – not significant b/c works locally in gut and not absorbed systemically
-Beano or pancreatic enzymes may decrease drug effectiveness
-Comments
-Must be given with first bite of each meal
-Titrate dose slowly to minimize GI effects
-lowers post-prandial glucose by 50-60 mg/dL, effect on FBG minimal and less effect on HbA1C than other classes.
