Drugs Used in Diabetes Flashcards
Pathology behind Type 1 DM?
loss of pancreatic B cells > absolute dependence on insulin
Pathology behind Type 2 diabetes?
decreased response to insulin
Which type of diabetes is ketoacidosis prone?
Type 1 DM
Name some basal insulin forms.
glargine, determir, degludac
Name some meal time insulin medications.
lispro, regular, aspart, glulisine
What are some factors/drugs that can increase insulin release?
increased by glucose, sulfonylureas, M-agonists, B2 agonists
What are some factors that can decrease insulin release?
a2 agonists
What are the symptoms associated with diabetic ketoacidosis?
polyuria, polydipsia, nausea, fatigue, dehydration, Kussmaul breathing, “fruity” breath
What is the best treatment for diabetic ketoacidosis?
regular insulin IV, fluid and electrolyte replacement
Do most basal forms of insulin have a peak?
no
MOA of glargine.
insulin binds to the transmembrane receptors which activate tyrosine kinase to phosphorylate tissue-specific substrates
What is the DOC for Type II diabetes?
metformin
Does metformin cause hypoglycemia or weight gain?
no
MOA metformin.
may involve inc. tissue sensitivity to insulin and/or dec hepatic gluconeogenesis
Indications for metformin.
mono therapy or combinations for treatment of Type II DM
S/E metformin use?
possible lactic acidosis, GI distress
Name a drug class that metformin has synergistic activity with?
sulfonylureas
Acarbose MOA.
inhibits a-glucosidase in brush borders of SI > dec formation of absorbable carbs > dec postprandial glucose > dec demand for insulin
What are the S/E of acarbose?
GI discomfort, flatulence, diarrhea; recent concern over potential hepatotoxicity
What is a way to tell if diabetic medication has potential to cause hypoglycemia vs if it doesn’t?
If the target in the diabetes medication is glucose > there is not a risk of hypoglycemia;
If the target in the diabetes medication is insulin; then it has potential to cause hypoglycemia
What is the MOA of sulfonylureas? How do they affect glucagon release?
- Normally K+ efflux in pancreatic B cells maintains hyper-polarization of membranes; insulin is release only when depolarization occurs
- Acute action of sulfonylureas is to block K+ channels> depolarization > insulin release
- dec glucagon release
- inc. insulin receptor sensitivity
Glucagon is released from what pancreatic cells?
alpha cells
How does glucose act as an insulinogen?
glucose increases intracellular ATP > closure of K+ channels > membrane depolarization> inc Ca2+ influx > insulin release
Repaglinide MOA?
stimulates insulin release from pancreatic beta cells
Indications for repaglinide.
adjunctive use in Type 2 diabetes - administer just before meals due to short half-life
Which GLUT type usually bring glucose into the Beta pancreatic cell?
GLUT 2
Indications for 1st generation sulfonylureas?
they were discontinued because had long t1/2 which increased the risk for hypoglycemia
What are the second generation sulfonylureas?
glipizide, glyburide
Would you decrease doses of glipizide in hepatic or renal dysfunction? (Which one would you decrease it in?)
hepatic dysfujnction
Would you decrease the dose of glyburide in hepatic or renal dysfunction?
dec dose in renal dysfunction
S/E of sulfonylurea use?
Hypoglycemia
weight gain
What are some important adverse drug interactions to consider when using sulfonylureas?
inc. hypoglycemia with use of cimetidine, insulin, salicylates, sulfonamides, have A/E with first generation sulfonylureas.
Symptoms of hypoglycemia.
lip/tongue tingling, lethargy, confusion, sweats, tremors, tachycardia, coma, seizures
What is the best treatment for hypoglycemia?
oral glucose (or eat some candy), IV dextrose if unconscious, or glucagon (IM or inhalation)
What is the MOA of the thiazolidinediones?
- bind to nuclear peroxisome proliferator activating receptors (PPARy) involved in transcription of genes responsible for insulin regulation
- sensitization of tissue to insulin,
- plus dec hepatic gluconeogenesis and triglycerides
- and inc. insulin receptor numbers
Name the TZD drugs? What is the suffix to remember them?
“glitazones”
pioglitazone
rosiglitazone
Is PPARy also implicated in the MOA for fibrates?
PPARa
so alpha type is the difference
S/E of using TZDs?
less hypoglycemia than sulfonylureas, but weight gain and edema have been reported
Be able to reproduce a table on the modes of action of drugs covered in this chapter and the organs implicated in their MOA?
MOA Exenatide?
GLP1 is an incretin released from the SI. It augments glucose-dependent insulin secretion.
This drug is a long acting GLP-1 receptor full agonist
Indications for Exenatide.
used in combination with other agents in Type 2 diabetes
S/E of exenatide?
nausea, hypoglycemia when used with oral sulfonylureas
MOA of the gliptins? Name a drug in this group?
sitagliptin
MOA: inhibits dipetidyl peptidase (DPP-4) thereby inhibiting inactivation of GLP-1
Pramlintide MOA.
a synthetic version of amylin that slows rate at which food is absorbed from intestines.
Decrease glucose production and decreases appetite
Indication for pramlintide?
type 1 and type 2 diabetes
What is the suffix for the SGLT -2 inhibtors? Name a drug in this class.
“gliflozins”
canagliflozin
GLP-1 agonist common suffix and drug names in this class?
“glutides”
liraglutide, exenatide
MOA canagliflozin.
blocks SGLT-2 in the proximal tubule, increasing glucose excretion
S/E of the SGLT-2 inhibitors?
UTIs
SGLT-2 stands for what?
sodium-glucose cotransporter 2
Drugs to think of when thinking of diabetic nephropathy treatment?
ACE, ARBs
Drugs to think of when thinking of treating diabetic neuropathy symptoms?
TCAs (to a lesser degree), gabapentin
Drugs to think of when thinking of gastroparesis related to diabetes?
metoclopramide, erythromycin (macrolide; macrolides stimulate motilin receptors)
