Endocrine Deck 2 Flashcards
Biguanides
metformin (glucophage, glucophage XR)
Metformin glucose
Decreases glucose production in liver, decreases GI glucose absorption, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization
Does not stimulate insulin release for beta cells
Inhibits platelet aggregation and reduces blood viscosity
Biguanide patients may
loose weight. mostly weight neutral
Biguanide pharmacokinetics
Absorption: 50% to 60% after oral dosing; food decreases and delays absorption
Metabolism: no hepatic metabolism
Excreted by kidneys
Alcohol potentiates drug’s effect on lactate metabolism
Metformin is different than sulfonera because it does not
stimulate insulin release from beta cells.
Biguanides
Precautions and contraindications
Renal and hepatic disease
Biguanides withold
drug 48 hours before and after procedures involving iodine-based contrast mediums.
Biguanides watch
patients with vitamin B12 anemia/deficiency.
Biguanides are not recommended for children younger than 10 years of age.
Biguanides
ADRs Metabolic (lactic acid) acidosis risk! Lactic acidosis is rare, except in dehydration episodes. Renal disease: Watch patients at risk for metabolic acidosis. Liver disease: risk for lactic acidosis is increased.
GI ADRs usually resolve
in 2 weeks after starting dose
Biguanides rational drug slection
immediate release vs extended release
Type 2 DM: start with 500 mg twice/day and titrate up
If patients have not responded to 4 weeks of high dosing, consider adding oral sulfonylurea or other medication.
Biguanides monitoring
assess renal function, ketones, HbA1C before starting dosing; check every 6 months. Patient education
Administration
ADRs: report diarrhea lasting more than 2 days, dehydration
Lifestyle management
Usually not the source of any hypoglycemia
Alert imaging staff about drug presence
Alpha-Glucosidase Inhibitors examples
Acarbose (Precose), miglitol (Glyset)
Alpha-Glucosidase Inhibitors
Pharmacodynamics
Inhibit the absorption of carbohydrate from GI tract, lowering the BG levels after meals
Alpha-Glucosidase Inhibitors are not
monotherapy drugs
Alpha-Glucosidase Inhibitors hypoglycemia treatment
Hypoglycemia treated with dextrose (honey, corn syrup), not sucrose
Alpha-Glucosidase Inhibitors pharmacokinetics
Absorption: less than 2% of acarbose absorbed as active drug
Metabolized by intestinal bacteria and digestive enzymes (lots of gas production!)
Excreted by kidneys
Alpha-Glucosidase Inhibitors Precautions and contraindications
Should not be used in patients with inflammatory bowel disease, or in those at risk for bowel obstruction or renal impairment
Should not be used during pregnancy
Not to be used in pediatric population
Alpha-Glucosidase Inhibitors ADR
GI symptoms: flatulence, diarrhea, abdominal pain
Do not cause hypoglycemia
Alpha-Glucosidase Inhibitors Drug interactions
Acarbose: digoxin
Miglitol: propranolol, ranitidine
Alpha-Glucosidase Inhibitors
Clinical use and dosing
Initial dose is 25 mg 3 times per day.
Increase dose in 4 to 8 week intervals.
Alpha-Glucosidase Inhibitors
Patient education
Administration: should be taken with first bite of meal
ADRs: GI
Lifestyle: type 2 DM care
Thiazolidinediones examples
Pioglitazone (Actos), rosiglitazone (Avandia)
Thiazolidinediones
Pharmacodynamics
Improve target cell response to insulin by activating receptor cell proteins that improve insulin action
Increase utilization of insulin by liver and muscle cells and reduce liver glucose production
Thiazolidinediones
Pharmacokinetics
Absorption: rapid after oral dosing
Metabolism: liver via CYP2C8 and 3A4 to both active and inactive metabolites; substrate inhibits CYP2C8, CYP2D6, induces weakly CYP3A4
Greater than 99% protein bound
Excretion: in urine (15% to 30%) and feces as metabolites
Thiazolidinediones Precautions and contraindications
Chronic liver disease (heavy liver processing)
Fluid retention: exacerbates heart failure (HF)
FDA loosening restrictions, but still dangerous drug
Not approved for children younger than age 18 years.
Thiazolidinediones
ADRs
cardiovascular (CV) – edema, upper respiratory infection, headache, fatigue
Watch for signs of congestive heart failure (CHF), use with caution with patients with elevated liver enzymes
Increased risk of bladder cancer with pioglitazone use
Thiazolidinediones
Drug interactions
Birth control requiring higher dosing of oral contraceptives
Watch for drugs metabolized by CYP3A4: Coricidin, corticosteroids, ketoconazole
Thiazolidinediones
Monitoring:
liver enzymes at start of therapy, HgA1C
Rational drug selection
Thiazolidinediones
Careful selection of patient population
Monotherapy or combination with sulfonylureas, insulin
Initial dosing: 15 to 30 mg/day; maximum dosing: 45 mg/day
Strong recommendation for endocrine co-management
Thiazolidinediones Patient education: once-daily dosing
Administration, ADRs, lifestyle management
Meglitinides examples
Nateglinide (Starlix), repaglinide (Prandin)
Meglitinides increase
insulin release from beta cells by closing potassium channels, which leads to the opening of calcium channels, and it is the influx of calcium that releases the insulin.
Time in plasma is short, less than 2 hours, so these agents only lower postprandial BG levels.
Meglitinides precautions and contraindications
Precautions and contraindications
Liver impairment
Not approved in pediatric population
Meglitinide ADR
Hypoglycemia in vulnerable populations
Meglitinides
Drug interactions
CYP3A4 and CYP2C9 inducers increase meglitinide metabolism.
Antifungals (ketoconazole) and antimicrobials (erythromycin) inhibit metabolism, increasing risk for hypoglycemia.
Meglitinides
Rational drug selection: repaglinide
**For patients with postprandial hyperglycemia
Meglitinides
Monitoring and patient education
get baseline HbA1C, and recheck in 3 months
Patient education
Administration: no more than 30 minutes before a meal; hold if not eating
ADRs
Lifestyle management
DPP-4 Inhibitors known as
“Gliptins”
Sitagliptin (Januvia) and saxagliptin (Onglyza)
DPP-4 Inhibitors
Pharmacodynamics
Inhibits DPP-4
Breaks down GLP-1 and gastric inhibitory polypeptide, which are released in response to a meal
Leads to increase in the secretion of insulin and suppresses the release of glucagon by the pancreas
Promotes pre- and postprandial glucose levels
Promotes mild weight loss in obese patients with diabetes
DPP-4 Inhibitors Precautions and contraindications
Renal dysfunction
Pregnancy (check with obstetrician for necessity)
Not approved in children
DPP-4 Inhibitors you will see a side effect of
weight loss in obese patients
DPP-4 Inhibitors ADR
ADRs: GI, headache
Precautions and contraindications
DPP-4 Inhibitors
Renal dysfunction
Pregnancy (check with obstetrician for necessity)
Not approved in children
DPP-4 Inhibitors
Drug interactions
Angiotensin-converting enzyme inhibitors: increased risk of angioedema
Angiotensin-converting enzyme inhibitors: increased risk of angioedema
Monotherapy or in combination with other antidiabetic drugs
DPP-4 Inhibitors
Rational drug selection
Age: well-tolerated by older adults
Weight/obesity: patients may lose weight
Cost: more expensive than older drug families
DPP-4 Inhibitors
Monitoring
Renal function at baseline and annually
HbA1C every 3 months
DPP-4 Inhibitors
Patient education
Administration: taken once daily in the morning
ADRs: well-tolerated
Lifestyle: changes still needed
DPP-4 Inhibitors
Monitor for potential
thyroid medullary cancer concerns, especially in those with previous nodules
