Post on 21-Dec-2015
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PHARM II EXAM 9 – Diabetes Mellitus HINTS
Relative insulin deficiency and insulin resistance Type II DM Sulfonylureas (protein bound)
Drug of choice for newly diagnosed type II diabetic pts
Biguanides:Metformin
MOA: Binds to sulfonylurea receptors on B-cells & stimulates pancreatic secretion of insulin
Avoid in Renal Insufficiency (if SCr > 1.5 in males & 1.4 in females)
Metformin(can be used for PCOS)
1st Gen: Chlorpropamide
Causes more hypoglycemia
Thiazolidinediones:Glitazones AE’s:
Med: Pioglitazone (Actos)
Edema / weight gainOsteopenia / cholesterol 2nd Gen:
Glipizide
In general: more potent, fewer AE’s & DI’s.
Extensive Protein binding / CYP 450
(30 min b4 meals, shorter ½ life, less likely to cause hypoglycemia)
SE’s: GI: Flatulence, diarrhea, abd cramps
Acarbose (precose):Alpha-Glucosidase Inh.
AE’s: Hypoglycemia / weight gain.
Caution: hepatic / renal impairment. Start slow.
Postprandial Glu lowering agents
Acarbose (precose):Alpha-Glucosidase Inh. Meglitinides (postprandial glucose regulators)
Nateglinide (Starlix):Meglitinides
MOA: same as sulfonylureas but produces more insulin release and lowers BG postprandially.
Pramlintide (Symlin®):Amylin Analog
CYP 450, rapid onset Administered b4 meal, if meal skipped so should med.
MoA: Incretin mimetic; Glucagon-like peptide (GLP) - for DM Type II
Exenatide (Byetta®)suppresses glucagon, slows gastric emptying
Meds:Nateglinide (Starlix)
AE’s: same as Sulfonylureas, but less severe.
Incretin enhancer DDP-4 Inhibitors(end in “Gliptins”) Cautions:
1. CYP 450 inhibitors:2. CYP 450 inducers:
Hepatic impairment1. ↑ risk of hypoglycemia2. ↓ effectiveness of meglitinides
Incretin Actions
1. Slows gastric emptying2. Suppresses glucagon3. Increases the amount of insulin that is released in response to PO glucose
Slows Gastric Emptying
Pramlintide (Symlin®):Amylin AnalogExenatide (Byetta®)Incretin Mimetics
If renal dysfunction, no adjustment is needed for which “Gliptin”?
LinagliptinDM II Treatment ConsiderationsMay be used in pts that are risk for hypoglycemia
Alpha-glucosidase inhibitors
____ may be used in pts intolerant or with a contraindication to metformin
GlitazonesHyperglycemia when __of Beta cells are destroyed 80-90%Glucose & BP control are most important for prevention of
Nephropathy(ACEI 1st TX)
Near-normal weight may be treated with
SecretagoguesNateglinide (Starlix):Meglitinides
1st line therapy for HTN in DM patients ACEI Obese pts should be
startedMetformin (if no contraindications)
Results in an absolute deficiency of insulin
DM Type IPolydipisia, polyuria, weight loss, polyphagia
Failure of initial therapy should result in
addition of a 2nd drug
Prevelance of DM-1 5-10% of Diabetics Meds that cause DMGlucocorticoidsThiazide Diuretics
Impaired glucose (IGT) tolerance is DX’d with
Oral Glucose Tolerance Testing (OGTT)2 Hour BG > 200 mg/dL
IGT is when fasting BG 110-126mg / dL
Induces K uptake into cells (and out of the bloodstream)
Insulin Longer-acting insulins tend to be less readily absorbed & therefore have a longer onset & duration
May be used in hyperkalemic emergencies
Insulin secretion is most often due to blood glucose levels1. Products of glucose metabolism results in generation of ATP2. Rising ATP causes blocking of K+ channels3. Blocking K+ channels leads to membrane depolarization & influx of Ca4. Influx of Ca causes pulsatile insulin exocytosis
Administration:Sites of Insulin injection
SubcutaneousAreas of “loose skin” abdomen, thighs, upper arms, upper buttocks
AE’s of Insulin
HYPOGLYCEMIAWeight gainLipodystrophyAllergic reactionsLocal irritation
Lispro (Humalog)Aspart (Novolog)
Ultra Short Acting Human Insulin(15 before or 20 min after)
Long-acting basal insulin analog, w/ up to 24 h duration of action
Detemir (Levemir)
Onset: ≤ 30 min Peak: 30 – 2 hrs Duration: 3-4 hrWhen mixing NPH and regular
Draw up regular insulin first then the NPH
Regular Insulin(Humulin R, Novolin R)
Short ActingHuman Insulin
Onset: 30-60min Peak: 2-3 hrs Duration: 3-6 hr Pre-Mixed InsulinsNPH (“N”)Lente (“L”)
Intermediate ActingHuman Insulin
70 / 301. Novolog2. Novolin3. Humulin
70: Aspart protamine30: Aspart
Onset: 2-4 hrs Peak: 6-12 hrs Duration: 10-18 hrs 70: NPH / 30: RegularUltralente (“U”)Glargine (Lantus)
Long Acting (Basal)Human Insulin
70: NPH30: Regular
“U” Onset: 6-10 hrs Peak: 10-16 hrs Duration: 18-20 hrsLantus Onset: 4 hrs Peakless Duration: 24 hrs
75 / 25: Humalog 75: NPL 25: Lispro
Standard TX Intensive TX (insulin) 50 / 50: Humulin NPH / Regular
1. 2 injections daily2. less control over BG3. More risk of complications w/ DM4. Less risk of HYPOglycemia and AE’s of insulin
1. Normalize BG2. More frequent BG checks / injections3. Insulin pump4. less risk of complications w/ DM5. More risk of AE’s from insulin -hypoglycemia
Regular Sliding Scale Insulin (RSSI)(slide 48)
Based on BG andAC Insulin DoseProlonged use as sole form of insulin coverage is discouraged.
Palpitations / Tremor Diaphoresis / ConfusionSyncope / presyncope
S/S: Hypoglycemia(most common SE of insulin)
TX: HYPOglycemia(if alert: 15-30g Carbs = 25-50mg ↑ in BG)
Glucose 10-15 g PODextrose IV 25 g IVGlucagon Ig IM