Ch 57: Drugs for Diabetes Mellitus Flashcards
In addition to affecting carbohydrate metabolism, insulin deficiency disrupts metabolism of…
…proteins and lipids as well.
p. 667
What are the possible triggers for immune-mediated destruction of pancreatic beta cells?
Genetic, environmental, and infectious,
p. 668
What are the target tissues of insulin?
liver, muscle, and adipose tissue
p. 668
Insulin resistance appears to result from 3 causes:
reduced _______ of _______ to its receptors, reduced receptor _______, and reduced receptor ______________.
binding of insulin,
numbers,
responsiveness
(p. 668)
What is the cause of microvascular damage in diabetics?
Thickening of the basement membrane, causing blood flow in these narrow vessels to fall.
(p. 669)
Diabetic nephropathy is characterized by…
…proteinuria, reduced glomerular filtration, and increased BP.
(p. 669)
Diabetic gastroparesis affects __% to __% of patients with long-standing diabetes.
20% - 30%
p. 669
Meglitinides, aka glinides, have the same mechanism of action as _____________, which is…
sulfonylureas; stimulation of pancreatic insulin release.
p. 688
What 2 drugs are meglitinides (glinides)?
repaglinide and nateglinide
p. 688
What type of drug is metformin?
a biguanide
What is the mechanism of action of metformin?
To decrease glucose production by the liver and increase tissue response to insulin.
What are the major adverse effects of metformin?
GI symptoms: decreased appetite, nausea, diarrhea, and rarely lactic acidosis
(p. 685)
Metformin is a good drug for patients who…
…skip meals.
How is metformin metabolized?
It is not metabolized. It is excreted unchanged by the kidneys.
(p. 684)
Metformin is contraindicated in….
….patients with renal insufficiency, and patients with severe heart failure or alcoholism, both of whom are already predisposed to lactic acidosis.
(p. 686)
Sulfonylureas act primarily by…
…stimulating the release of insulin from pancreatic islets.
They bind with and block ATP-sensitive potassium channels in the cell membraine. As a result, the membrane depolarizes, thereby permitting influx of calcium, which in turn causes insulin release.
(p. 687)
Name the 3 second generation sulfonylureas.
glipizide
glyburide (long-acting)
glimepiride
(p. 687)
Regardless of what the glucose level is – high, normal, or low, sulfonylureas will…..
….make it go lower.
p. 687
Sulfonylureas are contraindicated in….
….impaired renal or liver function.
p. 687
The first first-generation sulfonylurea was linked to an increased risk of…
….morality from sudden cardiac death.
In regards to prescribing of meglitinides, patients who do not respond to sulfonylureas will….
….not respond to meglitinides either.
What is different about the meglitidines compared to sulfonylureas?
They are more short-acting, and are taken with each meal (15 min prior).
(p. 688)
What is the advantage of using meglitinides in patients with renal disease?
They are metabolized by the liver and excreted in the bile, therefore they are safe to use in patients with impaired renal function.
Because of possible hypoglycemia, it is imperative that patients on meglitinides…..
….eat no later than 30 minutes after taking the drug.
p. 688
What drugs belong to the thiazolidinediones (TZD)?
pioglitazone
rosiglitazone
(p. 688)
What is the mechanism of action of thiazolidinediones?
Activation of a specific receptor type in the cell nucleus, knows as peroxisome proliferator-activated receptor gamma (PPAR gamma). By activating PPAR gamma, TZDs turn on insulin-responsive genes that help regulate carbohydrate and lipid metabolism.
Overall, they increase glucose uptake by skeletal muscle and adipose tissue and decrease glucose production by the liver.
(p. 689)
pioglitazone (Actos) and in particular, rosiglitazone (Avandia) are associated with…
….myocardial infarction and sudden cardiac death.
p. 689
What are the side effects of the TZDs?
retention of fluid resulting in edema and weight gain, increased risk of fractures
What drugs are alpha-glucosidase inhibitors?
acarbose (Precose)
miglitol (Glycet)
What is the mechanism of action of alpha-glucosidase inhibitors?
Alpha-glucosidase is an enzyme located on the brush border of cells that line the intestine. These drugs inhibit this enzyme, and thereby slow digestion of carbohydrates, which reduces the postprandial rise in blood glucose.
(p. 690)
Alpha-glucosidase inhibitors should be administered with….
….the first bite of each meal.
What are the common adverse effects of the alpha glucosidase inhibitors?
Flatulence, cramps, abdominal dissension, borborygmus, and diarrhea.
With long term therapy, these drugs can cause liver dysfunction.
(p. 690)
Which drugs are considered GLP-1 receptor antagonists?
glucagon-like peptide-1
exenatide (Byetta)
liraglutide (Victoza)
dulaglutide (Trulicity)
albiglutide (Tanzeum)
What is the mechanism of action of the GLP-1 receptor antagonists?
These drugs are considered incretin mimetics. Incretin mimetics activate receptors for GLP-1, and thereby cause the same effects as endogenous incretins. That is, they slow gastric emptying, stimulate glucose–dependent release of insulin, inhibit postprandial release of glucagon, and suppress appetite.
(p. 692)
What is the black box warning for the GLP-1 receptor antagonists?
increased risk for medullary thyroid carcinoma
What is the recommended dosing for the GLP-1 receptor antagonists?
Injected BEFORE a meal. Some of them are daily, some are BID.
Which drug class do you NOT want to combine with the GLP-1 receptor antagonists?
Dipeptidyl peptidase-4 (DPP-4) inhibitors (also called gliptins)
What form do the DPP-4 inhibitors come in, and name three of these drugs.
oral
saxagliptin (Onglyza)
sitagliptin (Januvia)
linagliptin (Tradjenta)
What are some of the more serious adverse effects of DPP-4 inhibitors (gliptins)?
pancreatitis, including fatal necrotizing and hemorrhagic pancreatitis
hypersensitivity reactions such as Stevens-Johnson syndrome, anaphylaxis, etc.
(p. 690)
What does SGLT stand for?
sodium-glucose co-transporter
What is the mechanism of action of the SGLT-2 inhibitors?
SGLT-2 is a high capacity, low-affinity transporter expressed chiefly in the kidney that accounts for approximately 90% of glucose reabsorption in the kidney. SGLT-2 inhibitors have been shown to block the reabsorption of filtered glucose, leading to glucosuria. This mechanism of action has proven clinically useful in patients with type II diabetes in terms of improving glycemic control. In addition, the glucosuria associated with SGLT-2 inhibition is associated with caloric loss, thus providing a potential benefit of weight loss.
(p. 691)
Name 3 drugs that are SGLT-2 inhibitors.
canagliflozin (Invokana)
dapagliflozin (Farxiga)
empagliflozin (Jardiance)
SGLT-2 inhibitors are contraindicated in….
….moderate renal insufficiency.
What are the adverse effects of SGLT-2 inhibitors?
female genital fungal infections, vaginitis, urinary tract infections, and increased urination sometimes resulting in dehydration.
