Diabetes medications

Background

1. Hypoglycemics
   1. Sulfonylureas
   2. Benzoic acid derivatives
2. Antihyperglycemics
   1. Biguanides
   2. Alpha glucosidase inhibitors
   3. Thiazolidinediones

Insulin

Sulfonylureas

1. increase insulin secretion and enhance activity
2. second and third gen sulfonyls are lipid soluble so penetrate cell mem better and have selective binding
3. stimulate insulin release from panc beta cells by inhibiting atp dependent potassium channel.
4. Decrease hepatic insulin clearance= increase insulin conc
5. Elevated insulin level feeds back to liver and causes decrease hepatic gluc prod
6. Secondary treatment failure from noncompliance, wt gain, desensitized beta cells, and escalating insulin resistance and increased insulin deficiency
7. Sulfon has hepatic metab, renal exretion and prolonged activity
8. Toxicity related to hypoglycemia
9. Risk factors for hypoG- elderly, poor diet, alcohol, renal/ hepatic dz, polypharmacy
10. Time to peak effect and duration of effect important in OD
11. Chlorpropamide, glyburide and glypizide most likely to cause hypoG
12. Do not use glyburide in pt with CRI since renally excreted
13. If pt well and young, will not get hypoG during fast due to counterregulatory hormones for glucose homeostasis
14. Chlorpropamide can cause hyponatremia regardless of dose- induces ADH secretion- risk increases with elderly and if on thiazide diuretics
15. Chlorpropamide can also give cholestatic jaundice, resolves with discontinuation
16. Glypizide- enterohepatic recirculation- prolonged action if liver dz. Long duration of action since metabolite still active. All metabolites renally cleared

Biguanides

1. E.g. Metformin, buformin
2. Metformin does not cause wt gain like sulfonyls
3. Effect is to decrease hep glucose prod, inhibit intestinal glucose absorption
   1. Also decreases fatty acid oxidation
4. Increases insulin sensitivity and decreases insulin resistance
5. Decrease sugar of DM pt not same as nl person so is antihyperglycemic agent not hypoglycemic agent
6. 100% renal excretion
7. Most serious side effect is lactic acidosis due to increased lactate production
8. Signs of lactic acidosis
   1. Nausea/vomiting, abd pain, sleepy, tachypnia, lethargy
   2. Seen mostly if renal/ liver dz, alcohol, heart dz, infection
9. Metformin exclusion criteria
   1. CRI, cardiac/ pulm insuff, h/o lactosis, profound infectionc, liver dz, alcohol, iv contrast agents
10. fatality from metformn lactosis not related to lactate levels or metformin level but rather to concomitant condition (hypoxia) resulting in elevated lactate
11. OD- hypoglycemia rare, can get lactosis- obs for 6-8 hr and tx c bicarb and consider hemodialysis

Alpha Glucosidase Inhibitors

1. acarbose, miglitol, voglibose
2. competitively and reversibly inhibit alpha glucosidase brush border hydrolase enzyme- makes postprandial decrease in carbohydrate absorption since complex polysaccharides not broken down into absorbable monosaccharides
3. does not affect lactose absorption
4. if hypoG- sucrose/ table sugar will not work- use glucose- po or iv
5. take these meds with each meal with first bite
6. since limited aborption, stays in gut and side effects mostly GI- bloating, gas, diarrhea
7. contraindications- cirrhosis, IBD, malabsorption synd
8. alpha glucs do not cause hypoG when used as monotx
9. acarbose- can cause transaminitis/ liver inj
10. since min absorption- systemic tox from OD unlikely

Thiazolidinediones

1. rosiglitazone and poiglitazone
2. enhance insulin effect on muscle, fat, liver without increasing panc insulin secretion
3. protein bound and hep metab- not good if liver dz
4. side effects- induce ovulation, increase plasma vol bad if CHF, decrease effectiveness of OCP's

Benzoic Acid Derivatives

1. repaglinide- mono or combo tx c metformin
2. binds to atp dependent potassium channel like sulfonyls but at different site.
3. Unlike sulfonyls, it decreases insulin lvls
4. Dose 30 min before meal to decrease post prandial hyperglycemia

Source

6/06 MISTRY