IC11 Pharmacology of Selected Drugs for Endocrine Disorders

Question 1

What is the cause of diabetes & what is the difference between the 2 types?

Answer 1

cause

high glucose levels aka hyperglycemia

type 1

pancreas no longer working, unable to produce insulin

type 2

insulin is released by glucose levels are still not well-regulated

Question 2

List the symptoms of diabetes

Question 3

What is the MOA of metformin?

Answer 3

• inhibits gluconeogenesis (synthesis of glucose from non-carbohydrate based substrates) → ↑AMP-activated protein kinase
• may enhance tissue sensitivity to insulin
• outcome ↑glucose uptake into tissues

Question 4

What are the clinical uses of metformin?

Answer 4

• T2DM (alone or w other oral hypoglycemic agents)
• useful in obese patients due to added benefit of ↓appetite = regulate weight

Question 5

How is the absorption of metformin?

Answer 5

• oral
• F ~40 to 60%
• DOA of 8 to 12h

Question 6

How is the distribution of metformin?

Answer 6

• rapidly distributed
• minimal plasma protein binding = expect large V of >5-8L
• t1/2 = 3h

Question 7

How is metformin metabolised?

Answer 7

NA

Question 8

How is metformin excreted?

Answer 8

excreted unchanged in urine

• 🥖avoid in patients w renal insufficiency (t1/2 ↑ in these)
• in non-renally impaired, monitor kidney function

Question 9

What are the adverse effects of metformin?

Answer 9

• anorexia
• GI disturbances (diarrhea → weight loss, vomiting & indigestion) so take w or after meal
• ­↑risk of Vit B12 malabsorption → B12 deficiency
• 🥖caution in patients w renal problems or lactic acidosis (hepatic & CV disease)

Question 10

How does lactic acidosis happen with metformin?

Answer 10

• gluconeogenesis blocked → lactate prevented from being broken down into glucose
• so [lactate] ↑ = lactic acidosis

Question 11

List 3 advantages of metformin

Answer 11

• does not result in hyperinsulinemia or hypoglycemia
  & most PO agents, unlike metformin, carry danger of over lowering glucose
• helps w weight loss
• improves lipid levels

Question 12

What is the MOA of glipizide aka sulphonylureas?

Answer 12

• 2nd gen insulin secretagogues
• stimulate pancreatic β cells to secrete insulin → acute ↓blood glucose
  🥖 need functioning β cells
• main target is pancreatic β cell ATP-sensitive potassium (KATP) channel, which has a major role in controlling the β cell membrane potential
• SU binds to SU receptor proteins (subunits of KATP channels aka SUR)
• inhibits KATP channel-mediated K+ efflux → Ca2+ channels depolarize, causing them to open → Ca2+ influx → trigger fusion of vesicles containing insulin stores → released(calcium dependent exocytosis of insulin granules from the pancreatic β cells)

Question 13

How is the absorption of glipizide?

Answer 13

• oral
• F >95% (delayed w food intake)
• onset of action 0.5h
• DOA is 12-24h

Question 14

How is the distribution of glipizide?

Answer 14

• binds extensively (~99%) to plasma proteins (primarily albumin)
• t1/2 of 4h

Question 15

How is glipizide metabolised?

Answer 15

90% by liver via hydroxylation

Question 16

How is glipizide excreted?

Answer 16

• urine & feces
• <10% excreted unchanged
• the rest are metabolites (action prolonged in patients w renal disease)
• renal disease → ↓excretion of parent compound → glipizide plasma levels may ↑
• monitor to prevent over lowering glucose levels

Question 17

What are the adverse effects of glipizide?

Answer 17

• hypoglycemia
  more in elderly, ↓renal function, DDI
• weight gain
  & most DM patients are already obese