Drugs used in the treatment of metabolic diseases

Question 1

Secretion and synthesis , Regulation of synthesis of Insulin:

Answer 1

Exclusively produced from pancreatic b cells

Synthesized as pro-insulin, cleaved to form insulin and connecting peptide (C-peptide_

Secretion tightly regulated by glucose and other nutrients

Short half-life

Question 2

Insulin synthesis

Answer 2

Preproinsulin→ Proinsuiln→ (Cleavage of C-peptide)

Question 3

Secretion of insulin

Answer 3

Insulin is rapidly released from the granules of pancreatic

β‐cells in postprandial states

Question 4

The major metabolic actions of insulin in its target tissues

Answer 4

Facilitate glucose uptake and utilization in the skeletal
muscle, heart and adipocytes

Stimulate glycogen synthesis and storage in the liver and skeletal muscle

Inhibit glucose production in the liver

Increase protein synthesis and lipogenesis

Question 5

Four principal types of insulin preparations

Answer 5

Short acting Regular Human Insulin

Rapid onset and ultrashort‐acting Insulin Lispro, Insulin Aspart,
Insulin Glulisine and inhaled insulin

Intermediate acting Neutral Protamine Hagedorn (NPH)

Long acting Insulin Glargine, Insulin Detemir, Insulin Degludec

All the insulin preparations are produced by recombinant DNA
technology using special strains of E. coli or yeast

Question 6

Human Regular Insulin

Answer 6

A short‐acting soluble crystalline zinc
insulin made by recombinant DNA
techniques

Self‐aggregate in antiparallel fashion to
form dimers that stabilize around zinc
ions to create hexamers

The hexameric nature causes delayed
onset and prolongs time to peak actions

Its effect appears within 30 min, peaks
between 2‐3 hours and lasts 5‐8 hours

It can be administered intravenously

Particularly useful for the management
of diabetic ketoacidosis and when insulin
requirement is changing rapidly (postsurgery
and acute infection)

Question 7

Limitations of using Regular Insulin for bolus injection

Answer 7

Slow onset of action, due to self aggregation
→Inconvenient administration (20‐40 min prior to meal)
→→Risk of hypoglycemia if meal is further delayed
Mismatch with postprandial hyperglycemia peak

Long duration of activity
→Up to 12 hours
Potential for late postprandial hypoglycemia

Question 8

Rapid‐onset and ultrashort‐acting Insulin Lispro

Answer 8

Produced by reversing the two amino acids near the carboxyl terminal of the B‐chain (Proline 28 and Lysine 29)

Present as monomers

Rapid acting ~10‐15 min onset; peak effect 30‐60 min

2‐4 hours duration of action

Taken JUST before meal;

Closely mimics endogenous postprandial insulin secretion;

Provides improved postprandial glucose control without risk of hypoglycemia between meal

Question 9

Rapid‐onset and ultrashort‐acting Insulin Aspart

Answer 9

Produced by the substitution of the B‐chain proline 28 with a negatively charged aspartic acid.

Rapidly breaks into monomer after subcutaneous injection;

Rapid onset: 10‐20 min; Peak effect: 1 hour.

Duration: 2‐4 hours

Question 10

Intermediate acting insulin: NPH

Answer 10

Neutral protamine Hagedorn (NPH) insulin: a mixture of insulin
and protamine (a positively charged polypeptide)

Insulin bound to zinc and protamine ‐ slowly dissolve in body
fluids

Facilitates control of glycaemia over an extended period ‐ peak
effect 4‐10 hours

Effective duration 10‐18 hours

Question 11

Long‐acting Insulin Detemir (Levemir)

Answer 11

A fatty‐acid moiety(myristic acid) is added to the)the lysine amino acid at position B29;

Threonine in position B30 of the B chain has been omitted

In the circulation, the fatty acid causes it to bind to albumin, thereby causing the slow release and extended circulating life

Question 12

Insulin pump: continuous subcutaneous insulin

infusion device

Answer 12

Major components

the pump itself (including
controls, processing module, and batteries)

a disposable reservoir for
insulin (inside the pump)

a disposable infusion set,
including a cannula for
subcutaneous insertion (under the skin) and a tubing system to interface the insulin reservoir to the cannula.

Question 13

Complications of insulin therapy

Answer 13

Hypoglycemia !!!
Manifestations: confusion, weakness, bizarre behavior, coma…
Treatment: glucose administration

Insulin allergy and immune resistance: seldom happens in nowadays due to the improvements in insulin preparation

Lipodystrophy at injection sites: can be corrected by multi‐site
injection

Question 14

Multiple insulin injection sites

Answer 14

Sites rotated to prevent
lipodystrophy

Insulin injected near the
stomach works fastest,
while insulin injected
into the thigh works
slowest. Insulin injected
into the arm works at
medium speed.

Question 15

Nurse’s responsibility for Insulin administration

Answer 15

Check medication order

Check the correct insulin type and dose

Ensure correct timing

Supervise administration technique

Documentation

Question 16

Key Points of using insulin for treatment of diabetes

Answer 16

attempting to keep the blood glucose relatively normal yet
avoiding hypoglycemia and ketoacidosis

balancing the dose and timing of insulin injections with the
content of meals and the amount of physical activity

requiring that the patient be educated about their disease and
monitor blood glucose levels at home