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