DM

Question 1

Jncretins exs.

Answer 1

GLP-1 and GIP

Question 2

Fxns of GLP-1 & GIP(only works on insulin)

Answer 2

 Released in response to ingested nutrients  Stimulate insulin production and synthesis  Stimulate glucose uptake in the liver & adipocytes
 Decrease glucose production in the liver
 Increase β-cell proliferation

Actions of incretins are terminated by dipeptidyl peptidase-4 (DPP-4)

Question 3

GLP-1

Answer 3

 Inhibits glucagon secretion
 delays gastric emptying

Question 4

What is DM? + it’s characterised by…?

Answer 4

 Reduced (or absent) secretion of insulin often coupled with ‘insulin resistance’ causes
diabetes mellitus
 Characterised by a high blood glucose
concentration: hyperglycaemia

Question 5

Type 1 Diabetes is?

Answer 5

 Absolute deficiency of insulin resulting from
autoimmune destruction of pancreatic β cells  Insulin is essential for its treatment

Question 6

Type 2 Diabetes

Answer 6

 Insulin resistance
 Impaired insulin secretion
 Excess glucagon

Question 7

DM drugs

Answer 7

 Insulin
 Metformin
 Sulfonylureas
 Thiazolidinediones
 Glucagon-like peptide 1 (GLP-1) mimetics
 Dipeptidyl peptidase-4 (DPP-4) inhibitors
 Sodium-glucose co-transporter 2 inhibitors (SGLT-2i)

Question 8

Insulin tx MoA

Answer 8

• first line in T1D
• About one third of patients with T2D ultimately benefit from insulin
• May also be used during intercurrent events short-term ex. Infections, MI, operation
• Recombinant human insulins now more commonly used

Question 9

Insulin tx
- safe to use in?
- RoA

Answer 9

-Safe to use during gestational diabetes, not controlled on diet
- Destroyed in GI tract -»> Given parenterally (SC, IV, IM)

Question 10

Main problem in using insulin:

Answer 10

wide fluctuations in plasma
concentration and thus in blood glucose

Question 11

INSULIN PREPARATIONS

hexameric vs monomeric insulin

Answer 11

• Different formulations vary in timing of peak effect and duration of action (affect hexameric vs monomeric insulin)
  
  • Chemical modifications to insulin
  • Dosage formulation modifications
    • Amorphous, insoluble crystals for long-acting preparations

*Hexameric takes longer to work and take longer to work

Question 12

Soluble insulin
RoA

Answer 12

 IV in emergency treatment of hyperglycemic emergencies
(diabetic ketoacidosis)
 Used immediately before the start of a meal
Take 30 mins before you eat

Question 13

Short-acting insulin exs.

Answer 13

Example: lispro, aspart, glulisine

Question 14

Short-acting insulin preparations
Effects+ when to administer

Answer 14

 Rapid and short-lived effects compared to endogenous insulin
 Injected before a meal

Question 15

Long-acting insulin exs.

Answer 15

Examples: neutral protamine hagedorn (NPH; insulin isophane); glargine; determir; degludec

Question 16

Long-acting insulin MoA

Answer 16

 Provide a more constant basal insulin supply
 Mimic physiological post-absorptive basal ins

Question 17

Dosage regimens of Insulin

Answer 17

Dosage regimens may vary
 Multiple daily injections
 Rapid-acting analogues given with meals
 Basal insulin analogues injected once daily (often at night)

Question 18

Main AE of insulin tx
+ it’s complication

Answer 18

The main undesirable effect of insulin is hypoglycaemia
 Common and can cause brain damage or sudden cardiacdeath

Question 19

Treatment of hypoglycaemia:

Answer 19

sweet drink/snack or IV glucose
or IM glucagon if the patient is unconscious

Question 20

Other AE of insulin

Answer 20

 Weight gain
 Lipohypertrophy at injection site
 Allergy to human insulin is unusual but can occur
 Insulin resistance as a consequence of antibody formation is rare

Question 21

Metformin MoA

Answer 21

Mechanism of action at molecular level is unclear
 Activation of AMP-dependent protein kinase (AMPK)
 Activated when cellular energy stores are reduced

Question 22

Biochemical action Of Metformin

Answer 22

 Reduces hepatic glucose production (gluconeogenesis) -> Inhibits expression of genes important in gluconeogenesis
 Increases glucose uptake and utilisation in skeletal muscle (i.e. reduces insulin resistance)
 Reduces carbohydrate absorption
 Increases fatty acid oxidation
 Reduces circulating LDL and VLDL
 Metabolic changes may be associated with weight loss

Question 23

AE of Metformin

Answer 23

 Less propensity to cause hypoglycaemia
 Dose-related gastrointestinal disturbances (e.g. anorexia, diarrhoea, nausea)
 Lactic acidosis is rare but potentially fatal
 Long-term use may interfere with absorption of vitamin B12

Question 24

CI of Metformin regarding Lactic acidosis

Answer 24

 Should not be given routinely to patients with severe renal (excreted unchanged in urine) or hepatic disease, hypoxic pulmonary disease, shock or decompensated heart failure
 Reduced drug elimination or reduced tissue oxygenation predisposes patients to lactic acidosis

Question 25

Metformin clinical use

Answer 25

 Drug of first choice in the majority T2D
patients, especially obese patients
- Unless contraindicated (e.g. significant renal or
hepatic dysfunction) [you can use if it’s just Mild renal/hepatic dysfxn]
- May reduce risk of cardiovascular events and death
- May promote weight loss

 May be combined with other drugs in dual
or triple therapy