Diabeetus Flashcards
Type 1 diabetes
insulin-dependent, loss of beta cells. 5-10% of diabetics
Type 2 diabetes
insulin-independent, decreased response to insulin, 85-90% of diabetics
Type 3 diabetes
caused by gene mutations
Type 4 diabetes
gestational diabetes (4% of all pregnancies)
Central goal of DM therapy
correct hyperglycemia and maintain BGL near normal range. preventing, delaying, or reducing complications, minimizing side effects of therapy, and improving quality of life
non-pharmological approaches to treatment
diet and exercise: large reduction in type 2 incidence
what stimulates insulin release?
glucose, which stimulates depolarization of beta cells through closing K+ channels, causing the opening of Ca2+ channels
what does insulin do?
stimulates the production of triglycerides in adipose tissue, stimulates the production of glycogen in liver cells, and stimulates the production of protein in muscles
types of insulin
rapid acting, short acting, intermediate acting, and long acting
rapid-acting
peak in 30 min-2 hrs, can be injected or inhaled
inhaled insulin (Exubera)
used in combination with other insulin in Types 1 and 2 or alone in Type 2. contraindicated in smokers, not recommended for asthma or COPD patients. side effects are cough, shortness of breath, hypoglycemia
oral hypoglycemic agents
Sulfonylureas and meglitinides; act to increase the levels of insulin
sulfonylurea mechanism of action
block K+ channels, causing beta cell depolarization
prototypical sulfonylureas
tolbutamide (1st gen,~8hr duration) and glyburide (2nd gen, ~12-24 hr duration)
sulfonylurea contraindications
sulfa drug alerrgy, pregnancy, major stress (surgery, trauma, infection)
sulfonylurea side effects
hypoglycemia, weight gain, rash, elevated liver enzymes, allergic reaction
Meglitinides mechanism
inhibition of K+ channel at a different site from sulfonylureas
prototypical meglitinides
repaglinide, nateglinide
meglitinide pharmacokinetics
rapid onset and short duration, intended to be taken after meal
meglitinide side effects
diarrhea, allergic reactions, headache. less chance of hypoglycemia than sulfonylureas
antihyperglycemic agents
biguanides, alpha-glucosidase inhibitors, thiazolidinediones. act without changing insulin levels
biguanide mechanism of action
inhibit production of glucose in liver, increase sensitivity to insulin, decrease GI glucose absorption. comparable to sulfonylureas in efficacy
prototypical biguanide
metformin
metformin side effects
metallic taste, nausea/diarrhea, reduced absorption of B12 and folic acid
metformin pharmacokinetics
little binding to plasma proteins, no active metabolites
advantages of metformin
no hypoglycemia or increased weight
a-glucosidase inhibitor prototype
acarbose
acarbose mechanism
competitive inhibition of intestinal alpha-glucosidase, reduction in starch digestion and glucose absorption
acarbose side effects
bloating and flatulence. can cause hypoglycemia in combo with insulin, treatable with glucose
acarbose contraindications
intestinal diseases exacerbated by gas (ulceration, inflammatory bowel disease)
thiazolidinediones prototypes
risigilitazone, pioglitazone
thiazolidinedione mechanism of action
agonist for PPAR-gamma, increases insulin sensitivity in muscle, liver, and adipose tissue, and increases insulin’s action on glucose and lipid metabolism. reduces A1c by 1.0-1.5%
pharmacokinetics of thiazolidinediones
take 3-6 weeks to reach maximum effect
thiazolidinediones side effects
weight gain, fluid retention, some liver toxicity
thiazolidinedione contraindications
heart failure; rosigilitazone can cause MI (43% increase in MIs in one study) and CHF
new drugs
sitagliptin, exenatide, pramlintide
sitagliptin mechanism
inhibition of DPP4, an enzyme that leads to increased insulin production and decreased glucagon production
sitagliptin pharmacokinetics
rapid absorption (PO), little metabolism (79% excreted whole in urine), hl of 11.8-14.4 hr. used as sole therapy or in combo with metformin or thiazolidinediones
sitagliptin side effects
none, no hypoglycemia or weight gain
exenatide mechanism
enhances glucose dependent insulin release, suppresses elevated glucagon secretion, slows gastric emptying
decreases HbA1c by .4-.8% and 2 hr PPG bt 63-71 mg/dl
exenatide pharmacokinetics
subQ, used in combo with sulfonylureas and/or metformin
exenatide side effects
indigestion, diarrhea, weight loss (1-3 kg)
pramlintide mechanism
synthetic analog of amylin, a hormone co-secreted with insulin that slows gastric emptying, suppresses glucagon secretion after meals, and modulates appetite
decrease H1c by .5%, 1.5 kg weight loss
pramlintide pharmacowhatever
SubQ before meal