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Endocrinology > 28 Pharmacology of insulin and oral hypoglycemic drugs > Flashcards

28 Pharmacology of insulin and oral hypoglycemic drugs Flashcards

1
Q

Which of the following is false?

A. Preproinsulin is synthesized in endoplasmic reticulum
B. Proinsulin is a proteolytic cleavage product of preproinsulin in the ER
C. insulin is converted from proinsulin by 2 endopeptidases
D. insulin is stored in granules until the B chain is stimulated

A

B
should be in the Golgi body

C and D:

  • Conversion of proinsulin by 2 distinct endopeptidases
  • 2 chains (a chain and b chain)
  • Stored in granules (until b chain is stimulated to secrete insulin)
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2
Q

Which of the following about endogenous insulin is correct?

A. it is circulated in blood as a monomer
B. Its plasma half life is 1 minute
C. Hydrolysis is not involved during secretion
D: it is degraded in the kidneys

A

A

B: 5-6 minutes plasma half life
C:
Hydrolysis of disulphide bonds between A&B chains by glutathione insulin transhydrogenase (insulinase)

D: by the liver

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3
Q

Which of the following about exogenous insulin is false?

A. In the presence of K+, insulin dimers associate into hexamers and diffuse slowly into blood
B. there is variable duration of action
C. They are metabolized mainly by the kidneys
D. Dimers in solution due to H-bonding between C-termini of B chains and like-monomers are readily diffused into blood

A

A

should be Zinc ions

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4
Q

What type of insulin preparation do isophane insulin (NPH) and Lentes insulin belong to?

A

They belong to intermediate acting insulin preparations

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5
Q

What is the name of the insulin preparation who is more longer acting than isophane insulin (NPH) and Lentes insulin ?

A

Ultralente insulin

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6
Q

Give the 3 names of the insulin analogues which is ultrashort acting.
Explain briefly why they can attain around 15 minutes onset time.

A
  1. Insulin Lispro 利士浦
  2. Insulin Aspart “Asgard”
  3. Insulin glulisine 姑呢曬
    好快
    There is no dimerization following subcutaneous injection, therefore is more easily absorbed.
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7
Q

What are the therapeutic advantages of fast acting insulin analogues over regular insulin?

A
  1. Reduce prevalence of hypoglycemia

2. Improved glucose control

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8
Q

Give the 3 names of insulin analogue which is long acting.

A
  1. Insulin Glargine 架賤
  2. Insulin Detemir (Detergent + mirror)
  3. Insulin Degludec （爹 glue decade）

好耐

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9
Q

What is the advantages of long acting insulin analogues to short acting ones?

A
  • sustained peakless absorption profile that spans 24 hours
  • better basal insulin replacement during night and between meals
  • less variability and lower hypoglycemic incidence
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10
Q

Explain the following side effects of insulin preparations/ analogues?
A. insulin edema
B. Lipohypertrophy
C. Hypoglycemia (how is it dealt with?)

(allergy may also occur sometimes)

A

A. Initial transient blurring of vision and edema of feet (will diminish after a week)

B: Benign proliferation of subcutaneous adipose tissues at recurrent injection site; due to lipogenic effect of insulin

C. Overdose, missed meal or excess exercise;
treated by replenishing glucose/ injection of glucagon in severe cases

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11
Q

List the 5 main types of oral anti-diabetic agents (insulin secretagogues) .
What are their main goals respectively?

A
  1. Sulphonylurea (insulin secretion)
  2. Meglitinides (insulin secretion) （mag-glitter-nights)
  3. Biguanides (increase insulin sensitivity) (big-關-nights)
  4. Thiazolidinedione derivatives (increase insulin sensitivity) (泰雅soli dindione）
  5. Alpha-glucosidase inhibitors (reduce glucose absorption)

(SMTBA shaw management business association)

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12
Q 
What drug class do glipizide, glibenclamide and gliclazide belongs to?
What is their action?
A

They are sulphonylurea.
Tolbutamide: 1st generation
the others 2nd generation, more potent

Action:
bind to SUR1 on K+ ATP channel to close it, Ca2+ channels thus open to release insulin

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13
Q

What are the possible drug interactions for sulphonylurea?

A
  • Enhanced by drugs that compete for metabolizing enzyme

- NSAIDS, MAOI, alcohol, antibacterial and antifungals

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14
Q

Which of the 2 drug class will cause weight gain as a side effects? How the causes of weight gain different?

A

Sulphonylurea: weight gain due to stimulated appetite

Thiazolidinedione (Glitazones): weight gain due to fluid retention

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15
Q

Give examples of Meglitinides.

Give one precaution upon administration.

A

Repaglinide (Rep.a.戒奶)
Nateglinide ; (Nat.e 戒奶)
Contraindicated in patients with liver disease

extra information:
- Rapidly and completely absorbed from GI tract
- Rapid onset with short half life 
- When taken prior meal, = insulin 
Prandial glucose regulation
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16
Q 
What drug class does Metformin belong to?
How does it increase insulin sensitivity?
A

Biguanides;

it increases GLUT4 thus muscular glucose uptake and utilization

17
Q

Which of the following about metformin is correct?

A. It is a kind of Meglitinide
B. It does not cause hypoglycemia
C. It does not cause insulin release from beta cells
D. It reduces gluconeogenesis by activation in hepatocytes of AMP-activated protein kinase (AMPK)
E. It increases LDL and VLDL
F. It is contraindicated in patients with liver disease,alcoholism/ before X-ray examinations

A

All of the above except A and E

A: it is a kind of biguanide
B: it decreases LDL and VLDL, thus reduce atheroma

18
Q

Which drug could cause potentially fatal lactic acidosis? Why?

A

Metformin (Biguanide)
- accumulation of lactate in patient with renal diseases (reduced drug elimination) or cardiac diseases (increased anaerobic metabolism)

19
Q

Name the drug that belongs to the drug class Glitazone (thiazolidinedione). What are its actions?

A

Pioglitazone.

  • act on peroxizome proliferator-activated receptor-gamma in nucleus (PPARgama)
  • Modulate the transcription of insulin responsive genes involved in control of glucose and lipid metabolism
  • Enhances action of insulin
20
Q

Which of the following about pioglitazone is correct?

A. It is 99% protein bound
B. It has rapid and almost complete absorption
C. Metabolites are eliminated mainly in kidneys
D. Once daily improves fasting and postprandial hyperglycemia
E. It is contraindicated in patients with liver disease and with active bladder cancer
F. It strengthened bones

A

All except C and F
C: in bile
F: Increased risk of bone fracture due to reduced osteoblast formation

21
Q 
Which of the following are side effects of pioglitazone?
A. Fluid retention
B. Increased risk of bone fracture
C. Weight gain
D. Decline triglycerides
E. Slight increase in cholesterol 
F. Reduction in hemoglobin concentration 
G. Abdominal bloating and diarrhea
A

All except G

Should be side effect of Acarbose (a-glucosidase inhibitors)

22
Q

Name a drug that belongs to the drug class a-glucosidase inhibitors. What is its main action?

A

Acarbose.

It reduces glucose absorption, thus allowing sluggish insulin secretion to catch up with carbohydrate absorption

23
Q

Which of the following drugs has/have no risk of hypoglycemia?

A. Pioglitazone 
B. Metformin
C. Tolbutamide
D. Glibenclamide 
E. Acarbose
A

B and E

24
Q

What is the side effect of using acarbose?

A

Abdominal bloating and diarrhea.

25
Q

What are the 2 new anti-diabetic drugs?

What are their main functions?

A
  1. Incretin mimetics: restore first-phase insulin secretion and promote beta cell proliferation and islet neogenesis
  2. SGLT 2 inhibitors: reduce reabsorption of glucose in kidneys
26
Q

What drugs are Exenatide and Liraglutide? Give 2 side effects.

A

They are glucagon-like peptide (GLP-1) mimetics.

  • nausea, vomit, diarrhea
  • hypoglycemia if sulphonylurea is used
27
Q

Give examples of Dipeptidyly peptidase-4 (DPP-4) inhibitors . What are their uses?

A

Sitagliptin; (sit啊）
Gliptins: Vildaliptin （view啊) , Saxagliptin (Sax啊)

  • inhibit DDP-4 formation thus prolongs the half life of GLP-1 and GIP
28
Q

What are the side effects of Sitagliptin; Gliptins: Vildaliptin, Saxagliptin ?

A
  • No risk of hypoglycemia

- Increased incidence of pancreatitis, nasopharyngitis, arthralgia and back pain

29
Q

What drug class does Canagliflozin and Empagliflozin belong to? This drug shall not be given to what type of patients?

A

SGLT 2 inhibitors.

Patients with kidney disease (because there will be no effect)

30
Q

Sequence the duration of onset of action of the below sulphonylurea:

Glipizide, Gliclazide, Tolbutamide, Glibenclamide

A

Tolbutamide < Glicazide < Glipizide < Gliberclamide

Endocrinology (11 decks)

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