Antidiabetics 1

Question 1

Pharmacotherapy of Type 2 Diabetes?

Answer 1

• Pharmacotherapy for type 2 DM includes a
number of noninsulin hypoglycemic agents.
• Most type 2 diabetics don’t require exogenous
insulin for survival but many need it to achieve
optimum health.
• 20% of type 2 diabetics in the USA take insulin.

Question 2

Pharmacotherapy of Type 1 Diabetes?

Answer 2

• Type 1 DM patients have virtually no insulin
secretion.
• They must rely on exogenous insulin injected
SC to control hyperglycemia and avoid
ketoacidosis.

Question 3

What is Insulin?

Answer 3

• Small protein with mw of 5808 in humans.
• 51 amino acids arranged in 2 polypeptide chains
connected by disulfide bonds.

Question 4

The secretion of insulin by  cells is stimulated by:

Answer 4

• Glucose. The most important stimulus for
insulin secretion.
• Amino acids.
• Gastrointestinal hormones (Incretins).
Released after the ingestion of food.

Question 5

The Incretin Effect, what is it?

Answer 5

• Glucose given orally results in higher insulin levels than glucose given IV.
• This is because incretins, released by the gut, enhance insulin secretion.

Question 6

Describe the Insulin Receptor?

Answer 6

• The insulin receptor consists of two covalently linked
heterodimers.
• Each contains an alpha subunit and a beta subunit.
• The alpha subunit is extracellular and contains the recognition site for insulin.
• The beta subunit spans the membrane and contains a
tyrosine kinase.
• When insulin binds to the alpha subunit, the tyrosine kinase is activated in the beta subunit.
• This leads to phosphorylation of tyrosine residues on the beta subunits and of cytoplasmic proteins.

Question 7

Effects of Insulin on Its Targets?

Answer 7

Increases
Amino acid uptake by muscle
Glycolysis
Fatty acid synthesis and storage as TG in adipose tissue
Glycogen Synthesis in liver and muscle
Glucose entry in muscle and adipose tissue

Decreases
gluconeogenesis

Question 8

Sources of Insulin?

Answer 8

• Human insulin has largely replaced insulin
isolated form beef or pork pancreas.
• Human insulin is produced by recombinant DNA
technology using strains of E coli or yeast.

Question 9

Preparations of Insulin?

Answer 9

• Rapid-acting, with very fast onset and short duration.
• Short-acting, with rapid onset of action.
• Intermediate-acting.
• Long-acting, with slow onset of action and long duration.

Question 10

There are three injected, rapid-acting insulin analogs, what are they?

Answer 10

• Insulin Lispro
• Insulin Aspart
• Insulin Glulisine

Question 11

Rapid acting insulin: importance of hexamers?

Answer 11

• Native insulin monomers are associated as hexamers in currently available insulin preparations.
• These hexamers slow the absorption of insulin.
• This led to the development of short-acting insulin analogs that don’t form hexamers.

Question 12

Rapid acting Insulin Lispro amino acid replacements?

Answer 12

Insulin Beta chain: 28-proline, 29-lysine

Lispro Beta chain: 28-lysine, 29-proline

Question 13

Rapid acting Insulin Aspart amino acid replacements

Answer 13

Insulin beta chain: 28-proline

Aspart beta chain: 28-aspartate

Question 14

Rapid acting Insulin glulisine amino acid replacement?

Answer 14

insulin beta chain: 3-aspartate, 29-lysine

Glulisine beta chain: 3-lysine, 29- glutamic acid

Question 15

Rapid-Acting Insulins: Uses?

Answer 15

• Rapid-acting insulins are given to mimic the
prandial release of insulin.
• They are usually given along with a longer
acting insulin to assure proper glucose control.
• Given SC.
• Given 15 minutes before a meal.
• Also suitable for IV.

Question 16

Short-acting Insulins overview?

Answer 16

Regular insulin
• Short-acting soluble crystalline zinc insulin.
• Should be given 30 minutes before a meal.
• Given SC
• Given IV in emergencies.

Question 17

Intermediate-acting Insulins overview?

Answer 17

Neutral protamine Hagedorn (NPH)
• Also called Isophane Insulin.
• Suspension of crystalline zinc insulin combined
with protamine.
• Should only be given SC.
• Used for basal control.
• Usually given along with rapid- or short-acting
insulin for mealtime control.

Question 18

What are the injected three long acting insulin analogs?

Answer 18

• Insulin Glargine
• Insulin Detemir
• Insulin Degludec

Question 19

Long acting insulin Glargine amino acid differences?

Answer 19

insulin alpha chain 21-asn
Glargine: 21- glycine

Glargine beta chain- 2 arg AA extended onto end of beta chain

Question 20

Insulin Analogs vs

Human Insulin Preparations

Answer 20

• Regimens based on rapid- and long-acting
insulin analogs improve HbA1C levels, and
reduce hypoglycemia compared with regimens
with regular insulin and NPH insulin.

Question 21

How is insulin administered?

Answer 21

• The standard mode of insulin therapy is SC
injection.
• Insulin can be administered using conventional
disposable needles and syringes, portable pen
injectors, and pumps.

Question 22

When is Insulin Given IV?

Answer 22

• IV infusions of insulin are used in:
• Patients with ketoacidosis
• During the perioperative period
• During labor and delivery
• In intensive care situations.
• Regular human insulin is used for IV therapy.

Question 23

Inhaled insulin preparation ae, contraindications, pk, and overview?

Answer 23

• Dry powder formulation of regular human insulin.
• After inhalation peak levels are reached in 12-15
minutes and decline to baseline in 3 hours.
• Adverse effects: cough, throat pain, hypoglycemia.
• Pulmonary function should be monitored.
• Contraindicated in patients with asthma, COPD, and smokers.

Question 24

goal of insulin therapy?

Answer 24

The goal of insulin therapy is to replace the
basal insulin (overnight, fasting, and between
meals) as well as prandial insulin.

Question 25

Two methods are used to achieve a similar

pattern of insulin release:

Answer 25

• Basal-Bolus Insulin Regimens

* Insulin Pump Therapy

Question 26

describe basal bolus insulin regimens?

Answer 26

• One daily shot of a long acting insulin analog to
provide basal coverage
• Doses of a rapid acting analog to provide
coverage for each meal.
• The long-acting insulin can be given at bedtime
or in the morning.
• If patients skip a meal, they omit a premeal
bolus.
• If they eat a larger meal than usual, they
increase the premeal bolus.
• Similar dose adjustments can be made to
accommodate snacks, exercise patterns, and
acute illnesses.

Question 27

describe the insulin pump therapy and which types on insulins are used with the pump?

Answer 27

• The use of an insulin pump is the best way to mimic normal insulin secretion.
• It consists of a battery-operated pump and a
computer that programs the pump to deliver predetermined amounts of insulin.
• Glulisine, lispro, or insulin aspart is used in the
insulin pump

Question 28

AE of insulin?

Answer 28

Hypoglycemia
• Most serious and common adverse reaction to
overdose.
• Risk of hypoglycemia with rapid-acting insulin
analogs is less than with regular insulin.
• Risk of hypoglycemia with long-acting insulin
analogs is less than with NPH insulin.

Question 29

How is hypoglycemia managed?

Answer 29

• Mild hypoglycemia in a conscious patient:
orange juice, glucose or any sugar-containing
beverage or food.
• Severe hypoglycemia with unconsciousness or
stupor: IV glucose infusion.
• If IV therapy is not available: glucagon SC or IM.

Question 30

Drugs That Cause Hypoglycemia?

Answer 30

• Ethanol
• beta-blockers
• Salicylates

Question 31

Drugs That Cause Hyperglycemia?

Answer 31

• Epinephrine
• Glucocorticoids
• Atypical antipsychotics
• HIV protease inhibitors
• Phenytoin
• Clonidine
• Ca2+-channel blockers
• Diuretics

Question 32

Management of Diabetes in

Hospitalized Patients?

Answer 32

• Insulin is the cornerstone of treatment of
hyperglycemia in hospitalized patients.
• Oral antidiabetic agents should be discontinued
during acute illness and replaced with insulin.
• Oral agents can be restarted on discharge.