Diabetes II - Diabetes and Insulin Pharmacology Flashcards
1
Q
All diabetes medications (reference only)
A
2
Q
Metformin
A
- Biguanide medication
- First-line therapy for Type II Diabetes, started in all of these patients unless there is a contraindication
- Major contraindication is anything that puts patients at risk of lactic acidosis
- Activates AMP Kinase in the liver, inhibiting gluconeogenesis, fatty acid synthesis, and cholesterol synthesis
- Net effect is to lower hepatic glucose production
- Side effects include mild nausea or diarrhea, transient and can be minimized by taking it with food, starting at a low dose, and increasing the dose slowly
3
Q
Sulfonylureas
A
- Glipizide, glyburide, glimepiride
- Bind to the SUR1 subunit (the sulfonylurea receptor) of the ATP-dependent potassium channel on the β-cell
- Close this channel, resulting in depolarization, calcium mobilization, and release of insulin
- Major side effect is risk of hypoglycemia due to elevated baseline insulin
4
Q
Meglitinides
A
- Repaglinide, nateglinide
- Also act on ATP-dependent potassium channel on the β-cell, same as sulfonylureas
- Similar side effects
- Shorter half life than sulfonylureas
- Sometimes used in individuals with erratic meal patterns, so they can take the agent only if they are about to eat
*
5
Q
Gliptins
A
- Dipeptidyl peptidase-4 (DPP-4) inhibitors
- Sitagliptin, saxagliptin, linagliptin, and alogliptin
- DPP-4 is the enzyme that inactivates GLP-1
- Prolong the half-life of GLP-1
- Lead to increased insulin secretion and suppression of glucagon secretion when blood glucose is high
- These agents are weight-neutral and not associated with hypoglycemia
- Generally very well tolerated
6
Q
GLP-1 receptor agonists
A
- Act directly on the GLP-1 receptor on pancreatic islet cells to increase insulin secretion in response to rising blood glucose and suppress glucagon production
- Most GLP-1 agonists are injected subcutaneously. Semaglutide also available orally
- Generally cause weight loss
- Side effects of nausea, early satiety, abdominal discomfort, diarrhea, and constipation
7
Q
Glifozins
A
- SGLT-2 inhibitors
- SGLT-2 is located in the S1/S2 segment of the proximal renal tubule and is responsible for 90% of glucose reuptake in the nephron
- These drugs work by decreasing the “renal threshold” for glucose excretion into the urine
- The glycosuria draws water with it into the urine, leading to a mild diuretic effect
- Main side effects are dehydration and genitourinary infections
- Euglycemic ketoacidosis is a rare but important risk
8
Q
SGLT-1 and SGLT-2
A
9
Q
Thiazolidinediones (TZDs)
A
- PPARγ agonists
- Promote fatty acid uptake and storage in adipose tissue rather than in skeletal muscle or liver, making muscle and liver more insulin sensitive
- Suppresses liver glucose production
- Favor insulin sensitivity at the muscle and liver by stimulating the energy-regulating enzyme AMP kinase
- Main side effects are weight gain and fluid retention, with possible heart failure
- Contraindicated in patients w/ Hx heart faiure
10
Q
Selecting the right medication for a patient just diagnosed with Type II Diabetes
A
- Start with metformin unless contraindicated by heart failure, stage 4 or 5 chronic kidney disease, liver cirrhosis, hypoxemia, or active alcohol abuse
- The choice of second agent depends on patient-specific factors and preferences
- In general, 2 or even 3 non-insulin agents can be combined, but once the patient is switched to insulin, sulfonylureas should be stopped
11
Q
During pregnancy, increases in levels of certain hormones produced by the placenta (progesterone, human placental lactogen) cause ___. There is also an increase in ___.
A
During pregnancy, increases in levels of certain hormones produced by the placenta (progesterone, human placental lactogen) cause insulin resistance. There is also an increase in ketogenesis.
12
Q
Risk factors for gestational diabetes mellitus
A
- Obesity
- Increased age
- Certain ethnicities (South Asians, East Asians, African-Americans)
- History of polycystic ovarian syndrome (PCOS), hypertension, or GDM
- History of unexplained stillbirth or a child with a birth weight >4 kg
- Family history of diabetes mellitus
13
Q
Diagnosing gestational diabetes mellitus
A
- Diagnosis is made by screening tests such as an oral glucose tolerance test, usually at the end of the second trimester (24-28 weeks of gestation)
- Near-universal screening is currently practiced
14
Q
Complications of gestational diabetes mellitus
A
- Poorly controlled pre-existing diabetes is associated with birth defects, mostly cardiac (TGA, VSD, ASD), neural tube defects (caudal regression, spina bifida, anencephaly), and genitourinary abnormalities.
- Fetal risks are due to exposure of the fetus to the elevated glucose levels, with resulting elevated fetal insulin levels. These include a range of abnormalities: Macrosomia, polyhydramnios, preterm delivery, hypoglycemia, hyperbilirubinemia, and many more.
- Maternal risks include perineal laceration, preeclampsia, UTI, and worsening diabetic complications
15
Q
Treating gestational diabetes mellitus
A
- Goal of treatment is to restore and retain a reference range of fasting blood glucose and post-prandial glucose
- Achieved with dietary modification or insulin
- Metformin and glyburide, a sulfonylurea, are also approved for pregnancy
- Women diagnosed during pregnancy should be screened again 6 weeks after delivery w/ glucose tolerance test
- Women should then be screened anually for diabetes, as these women are at higher risk of diabetes in the future
16
Q
Factors in choosing the right diabetes medication
A
17
Q
AMPK Signaling
A
Remember that metformin is an AMPK agonist!
