Antidiabetics Flashcards
hallmark of untreated T1 DM is elevated levels of blood ___ and ___
patients have virtually no insulin secretion → must rely on _____ injected
hallmark of untreated T1 DM is elevated levels of blood glucose and ketone bodies
patients have virtually no insulin secretion → must rely on exogenous insulin injected
Type ___ DM is the most common form of the disease (over 90% of adults with DM have this type)
Type 2 DM is the most common form of the disease (over 90% of adults with DM have this type)
in T2 DM, insulin secretion is enough to restrain ____
there is hyperglycemia but no ____
in T2 DM, insulin secretion is enough to restrain ketogenesis
there is hyperglycemia but no ketoacidosis
The secretion of insulin by B cells is stimulated by (3)
- Glucose (most important stimulus)
- Amino acids
-
Gastrointestinal hormones (Incretins)
- released after food ingestion
describe the image below
Incretin Effect - glucose given orally results in higher insulin levels than given IV because incretins released by gut enhance insulin secretion
describe the mechanism of insulin secretion
Hyperglycemia results in high ATP levels → close ATP-dependent K+ channels → membrane depolarization and opening of voltage-gated calcium channels → Ca2+ influx causes pulsatile insulin exocytosis
describe the insulin receptor and where they are found
consists of two covalently linked heterodimers, each containing an a subunit and a ß subunit
found in liver, muscle, adipose tissue
Insulin is inactivated by the enzyme ____, which is found mainly in the ___ (60%) and ___ (40%)
(ratio is reversed in insulin-treated diabetics receiving SC injections)
The half-life of circulating insulin is ____
Insulin is inactivated by the enzyme insulinase, which is found mainly in the liver (60%) and kidney (40%).
(ratio is reversed in insulin-treated diabetics receiving SC injections)
half-life of circulating insulin is 3-5 min
describe the effects of insulin
list the 3 injected, rapid-acting insulin analogs
Lispro
Aspart
Glulisine
Rapid-acting insulins mimic the ___ release of insulin
they have greater control of postprandial plasma glucose (PPG) and associated with less risk of ____
Given with a longer acting insulin to assure proper glucose control
Rapid-acting insulins mimic the prandial release of insulin
they have greater control of postprandial plasma glucose (PPG) and associated with less risk of hypoglycemic episodes
Given with a longer acting insulin to assure proper glucose control
Rapid-acting insulins should be injected ____
Peak serum levels seen ____ after injection
(50-120 minutes for regular insulin)
DOA is about ____
Rapid-acting insulins should be injected 15 min before a meal
Peak serum levels are seen ~ 1 hr after injection
(50-120 minutes for regular insulin)
DOA is about 3-4 hrs
Short-acting insulin: ____
Short-acting soluble human ____
Should be given ____ before a meal
Usually given SC (or IV in emergencies)
Short-acting insulin: Regular insulin
Short-acting soluble human crystalline zinc insulin
Should be given 30 minutes before a meal.
Usually given SC (or IV in emergencies)
Intermediate-Acting Insulin: ____
crystalline zinc insulin combined with __
what kind of appearance does this have?
Given __ only
Neutral protamine Hagedorn (NPH)
also called Isophane Insulin
crystalline zinc insulin combined with protamine
cloudy appearance
Given SC only
NPH is used for ___ control
usually given with ___ for ___ time control
NPH is used for basal control
usually given with rapid/short-acting insulin for meal time control
list long-acting insulin
Glargine
Detemir
Degludec
Glargine modifications make it more ____ in acidic pH, but precipitates in ____ pH after SC injection
It cannot be mixed with ____
Glargine modifications make it more soluble in acidic pH, but precipitates in neutral pH after SC injection
It cannot be mixed with short acting insulin
Detemir modifications increase _____ in SC tissue and fatty acid chain binds reversibly to ____
Detemir modifications increase self-aggregation in SC tissue and fatty acid chain binds reversibly to albumin
What is the benefit of Glargine and Detemir?
How do they differ in administration?
they have a lower risk of hypoglycemia than NPH insulin
Glargine: 1x/day
Detemir: 2x/day
when Degludec is injected SC, it forms ____ and binds to circulating ____ which delays its absorption
how does Degludec differ from Glargine/Detemir in absorption and administration?
when Degludec is injected SC, it forms multihexamers and binds to circulating albumin which delays its absorption
DOA > 42 hrs - does not have to be administered at the same time each day (unlike Glargine and Detemir)
onset and duration of different Insulins
- rapid: 1 hr peak
- short: 3 hr peak
- intermediate: 5 hr peak
- long: 24 hr (no peak)
Properties of Currently Available Preparations
rapid and long-acting insulin analogs improve ___ levels, and reduce ____ compared with regimens with regular insulin and NPH insulin
rapid and long-acting insulin analogs improve HbA1C levels, and reduce hypoglycemia compared with regimens with regular insulin and NPH insulin
The standard mode of insulin therapy is ___
When is it given IV?
The standard mode of insulin therapy is SC injection
IV: ketoacidosis, perioperative period, during labor and delivery, intensive care situations
describe inhaled insulin
Peak level at 12-15 min and decline to baseline in 3 hrs
AE: cough, throat pain, hypoglycemia.
Pulmonary function should be monitored
Contraindicated: asthma, COPD, smokers
two methods used to achieve physiological pattern of insulin release
- Basal-Bolus Insulin Regimens
- Insulin Pump Therapy
Basal-Bolus Insulin Regimens
- 1 shot/day of long-acting insulin for basal coverage (at bedtime or morning), and
- doses of rapid-acting analog for each meal
- skip a meal? omit a premeal bolus
- eat a larger meal than usual? increase the premeal bolus
an insulin ___ is the best way to mimic normal insulin secretion
consists of a battery-operated pump and a computer that programs the pump to deliver ____
an insulin pump is the best way to mimic normal insulin secretion
consists of a battery-operated pump and a computer that programs the pump to deliver predetermined amounts of insulin
what drugs are used in the insulin pump?
rapid-acting: Glulisine, Lispro, or Aspart
___ is the most serious and common adverse reaction to insulin overdose
there is ___ risk with rapid-acting insulin analogs than with regular or NPH insulin
Hypoglycemia is the most serious and common adverse reaction to insulin overdose
there is less risk with rapid-acting insulin analogs than with regular or NPH insulin
describe management of mild and severe hypoglycemia
-
Mild hypoglycemia in a conscious patient
- orange juice, glucose, any sugar-containing beverage or food
-
Severe hypoglycemia with unconsciousness or stupor
- IV glucose infusion (if not available: glucagon SC or IM)
list other drugs that can cause hypoglycemia
- Ethanol - inhibits gluconeogenesis
- B-blockers - blocks effects of catecholamines on gluconeogenesis and glycogenolysis, masks sympathetically-mediated symptoms of hypoglycemia (eg tremor and palpitations)
- Salicylates - enhance pancreatic B-cell sensitivity to glucose potentiating insulin secretion
list other drugs that can cause hyperglycemia
- Epinephrine - increased glycogenolysis and glucagon
- Glucocorticoids - prednisolone, dexamethasone, beclomethasone, budesonide, flunisolide, fluticasone
- Atypical Antipsychotic
- HIV Protease inhibitors
- Phenytoin
- Clonidine
- CCBs - verapamil, diltizaem, nifedipine, amlodipine
- Niacin - causes insulin resistance → caution in diabetic pts
- Diuretics - Thiozides: hydroclorothiozide, metolazone, chlorthalidone
describe management of diabetes in hospitalized patients
- Insulin = cornerstone treatment of hyperglycemia in hospitalized patients
- Oral antidiabetic agents should be discontinued during acute illness and replaced with insulin (can be restarted on discharge)
