pharmacology of diabetes

Question 1

insulin formulations

Answer 1

regular insulin- original formulation from the 20s clear solutions, human sequence, the only insulin available for intravenous use, short acting

NPH insulin- colloidal suspension, Colloidal suspension (cloudy), huma sequence- intermediate acting

Pre mixed insulins- mix of NPH and short acting

Short acting insulin analogs- lispro (sharter than regular,), aspart, glulisine

Longacting- insluline glargine, insulin detemir, insulin degludec

Question 2

insulin regimens

Answer 2

goal- keep glucoses as close to normal as possible while avoiding significant hypoglycemia

tools- a combination of longer and shorter acting insulins are given to mimic natural insulin secretion profiles

Long acting would be for basal and short for peaks

Question 3

Insulin therapy

Answer 3

All type 1 DMS need insulin to live
Some type 2 s require insulin to adequately control their blood sugars, often at high doses bc of insulin resistance

Insulin therapy can be given in a moderate range of intensity
Insulin regimens are adjusted based upon symptoms (usually hypoglycemia, fingerstick glucose results and the hemoglobin a1c

Question 4

goals for glycemic control

Answer 4

fasting and pre-prandial glucoses 70-130 mg
Post-prandial glucoses 2 hrs after a meal less than 180
Hb a1c less than 7% (associated with decreased risk of longterm complications)
Not all patients achieve these

Question 5

Hb A1c

Answer 5

covalent modification of hemoglobin by glucose
The percentage of Hb modified by glucose is proportional to the average glucose level over the life span of a red blood cell
a 3 month test
Used to both diagnose t2dm and to follow the adequacy of glycemic control

only insulin short acting is used in insulin pump

Question 6

insulin side effects

Answer 6

Hypoglycemia, insulin allergy, lipoatrophy, lipohypertrophy, insulin edema, weight gain, artherosclerosis and cancer risk

insulin is anabolic

Uncontrolled weight loss muscle and fat

Question 7

Non insulin drugs for diabetes (T2DM)

Answer 7

Sulfonylureas (oral), Meglinitides, metformin, th

Question 8

Non insulin drugs for diabetes Caveats

Answer 8

lifestyle modifications remain the foundation of therapy for type 2 DM, and help these meds work better, unlike insulin, there is a cap on their strength in lowering glucoses in type 2 diabeters

Question 9

Solfonylurease

Answer 9

stimulate insulin secretion by the pancreas (closing the K channel sin B cells

Glipizide, glyburide, glimepiride

SE: hyponatremia, disulfiram-like reaction, Rashes/GI side effects/ drug interactions, hypoglycemia (this is the main SE)

Question 10

Meglitinides

Answer 10

MOA: non sulfonylurea secretagogues, they close the potassium ATC channels in pancreatic beta cells (much like sulfonylureas)

Act faster and deactivate faster than sulfonylureas

2 medications in this : REPAGLINIDE and nateglinide
SE: hypoglycemia

Question 11

Insulin sensitizing drugs

Answer 11

thes meds reduce insulin resistance, thus a given amount of insulin is more effective at reducing blood glucose in the presence of these meds
Met formin , thiazolieniodenes

Question 12

Metformin (a biguanidine)

Answer 12

Increase the activity of AMP activated protein kinases
Major effect is to make the liver more sensitive to insulin, the principle result is decreased hepatic gluconeogenesis, there are extra hepatic effects as well

The major side effects are gastrointestinal (abdominal discomfort) most serious is lactic acidosis, this potentially fatal side effect is avoided by not prescribing metforrmin to patients with renal insufficiency, can also deplete b 12

Tiny effect on everything- so then everyone is good

Question 13

Metformin contraindications

Answer 13

> 30 eGFR, CHF, Hypoxic states, acute illnesses, liver dysfunction

Question 14

Thiazolidnediones

Answer 14

make peripheral tissues such as fat and muscle more sensitive to insulin (PPAR gamma agonists)

Wt gain and fluit retention in advanced heart failure,
Pioglitaxone (bladder cancer)

Question 15

alpha-glucosidase inhibitors

Answer 15

MOA: inhibits enteric alpha glucosidases that break down complex carbohydrates, resulting in partial malabsortion of carbohydrates
Reduces post prandial hyperglycemia

SE: bloating, abdominal discomfort, diarrhea, flatulence

Precose, a carbose, glysetmiglitol

Question 16

GLP-1 analog and DPP-4 inhibitors

Answer 16

GLP1 analog- exenatide, liraglutide
GLP 1 (short acting GI peptide secreted by the intestines into the portal circulation in response to eating, augments insulin secretion, increases beta cell mass, inhibits glucagon secretion, promotes a bit of weight loss, thru decreased appetite, delays gastric emptying
.), analogs are long acting SQ injection

DPP inhibitor- Sitaliptin- DPP4 rapidly degrades GLP1, so giving a DPP4 inhhibitor increases the half life of GLP1 well tolerated with a risk of pancreatitis

Question 17

GLP 1 Receptor agonists SEs

Answer 17

SE of nausea, emesis, diarrhea, headaches, gastroparesis, and possibly pancreatitis

Contraindicated in medullary thyroid cancer (MEN 2 Syndrome)

Can cause wt loss in addition to lowering glucose levels HgbA1c, liraglutide has a FDA indication to reduce risk for second CV events

Question 18

SGLT 2 inhibitors

Answer 18

Glucose is efficiently is efficiently reabsorbed in the kidney tubule by a specific transporter called sodium-glucose transport protein 2

Inhibitors of this transporter lowers glucose thru renal glucose loss (glycosuria), thereby decreasing serum glucose

SE: genital yeast infection and UTI (increased glucose in bladder), contraindicated in UTIs, necfasc in perineum, dehydration, diabetic ketoacidosis

Agliflozins-
Emp- lowers CV events
Contraindicated in renal patients