Oral Hypoglycemic Drugs

ORAL HYPOGLYCEMIC DRUGS

Q. 1 A 75-yrs-old woman with diabetes is taking an oral antidiabetic drugs. One day she goes without eating for 18 h. Her serum glucose concentration is 48 mg/dL (hypoglycemic) upon arrival at the emergency department, where she is deemed to be in critical condition. Which of the following drugs most likely aggravated this fasting hypoglycemia? 
 A Acarbose
 B Glyburide
 C Metformin
 D Pioglitazone
Q. 1 A 75-yrs-old woman with diabetes is taking an oral antidiabetic drugs. One day she goes without eating for 18 h. Her serum glucose concentration is 48 mg/dL (hypoglycemic) upon arrival at the emergency department, where she is deemed to be in critical condition. Which of the following drugs most likely aggravated this fasting hypoglycemia? 
 A Acarbose
 B Glyburide
 C Metformin
 D Pioglitazone
Ans. B

Explanation:

Glyburide

Glyburide is a second-generation sulfonylurea oral hypoglycemic. Of the main groups or chemical classes of oral

antidiabetic agents, these are the ones typically associated with causing hypoglycemia, whether from overdose or as a rather expected response in some patients, particularly before meals. Normally carbohydrates from a meal trigger insulin release; when blood glucose levels are low, as after the 18-h fast this patient experienced, physiologic insulin release would be low too. However, even in a fast-induced hypoglycemic state a sulfonylurea will release insulin

and drive blood glucose down even further.

The elderly are particularly susceptible to sulfonylurea-induced hypoglycemia. Part of this may relate to diet. However, expected age-related falls of renal and/or hepatic function can reduce elimination of these drugs, thereby increasing their serum levels and their effects unless dosages are reduced accordingly.

This propensity for preprandial hypoglycemia is shared by the meglitinides, repaglinide and nateglinide because they, too, increase pancreatic insulin release.

The thiazadolinediones (glitazones) seldom cause symptomatic hypoglycemia because they do not release insulin. The same applies to metformin, the biguanide; and acarbose (with, along with miglitol, is an aglucosidase inhibitor). Because of a longer half-life, compared with glipizide, a sulfonylurea is more likely to cause preprandial hypoglycemia. Glipizide is contraindicated in patients with liver disease because it is metabolized in the liver. Care

should be taken in the elderly because of their propensity to develop hypoglycemia, which is perhaps due to

decreased hepatic and renal function that is evident in this patient population. Metformin, acarbose, and pioglitazone do not produce serious hypoglycemic reactions.


Q. 2

False about pioglitazone ‑

 A

 It PPARy agonist

 B >It metabolized in liver
 C >Not given in case of diastolic dysfunction
 D

It acts on insulin gene and even in absence of insulin helps in metabolism of carbohydrate

Q. 2

False about pioglitazone ‑

 A

 It PPARy agonist

 B >It metabolized in liver
 C >Not given in case of diastolic dysfunction
 D

It acts on insulin gene and even in absence of insulin helps in metabolism of carbohydrate

Ans. D

Explanation:

It acts on insulin gene and even in absence of insulin helps in metabolism of carbohydrate [Ref: Harrison 17/e p. 2300; KDT 6/e p 269, 270; Katzung 11/e p 742-743]

km                                                                                                              • Pioglitazone belongs to Thiazolidinediones

Other drugs of this group are Troglitazone, Rosiglitazone

  • It is an oral antihyperglycemic agent that acts primarily by decreasing insulin resistance.

Pioglitazone deceases insulin resistance in the muscles, adipose tissues and in the liver resulting in increased L                                               insulin dependent glucose disposal and decreased hepatic glucose output.

Mechanism of action

  • Pioglitazone is a potent and higly selective agonist for peroxisome proliferator activated receptor gamma (PPAR

PPAR receptors are, found in tissues important. for insulin action such as adipose tissue, skeletal muscle and liver. – PPAR is .found in highest level in adipose tissue.

Activation of PPAR7 nuclear receptors modulates the transcription of a number of insulin responsive genes  involved in the control of glucose and lipid metabolism.

Pioglitazone appears to reduce insulin resistance by enhancing fatty acids storage and possibly by increasing adinopectin levels.

In animal models of diabetes pioglitazone reduces the hyperglycemia, hyperinsulinemia and hypertriglyceridemia which are characteristic of insulin resistant states.

  • Pioglitazone depends on the presence of insulin for its mechanism of action.

–                                                              Since piogletazone acts by enhancing the effect of circulating insulin it does not lower blood glucose in persons that lack endogenous insulin,

– Circulating insulin level decrease with the use of pioglitazone indicating decrease in insulin resistance.

  • Thiazolidinediones are considered euglycemics.

-The overall response is similar to sulfonylureas and biguanide monotherapy.

–                                                              Because their mechanism of action involves gene regulation, the thiazolidinediones have a slow onset and offset of activity over weeks or even months.

– Combination therapy with sulfonylurea or insulin may lead to hypoglycemia.

Metabolism of Pioglitazone

  • Pioglitazone is extensively metabolized in liver by hydroxylation and oxidation.

aiims pgmee answers & explanations – May 2011

  • Multiple CYP isoforms are involved in the metabolism of pioglitazone. – The cytochromes p450 isoforms primarily invove are :

 -CYP2 C8

– CYP 3A4 (to a lesser degree)

  • Liver function should be monitored in patients receiving thiazolidinediones even though pioglitazone and rosiglitazone rarely have been associated with hepatotoxicity.
  • Originally three member of thiazolidinedione family were introduced

– Pioglitazone

– Rosiglitazone

– Troglitazone (This was withdrawn from the market due to an increase incidence of drug induced hepatitis).

  • The withdraw! of troglitazone has also led to concerns of other thiazolidinediones also increasing the incidence of hepatitis and potential liver failure.
  • Because of this FDA, recommends two to three months checks of liver enzyme for the first year of thiazolidinedione therapy, to check for this rare but potentially catastrophic complication.

– Till date newer thiazolidinediones have been free of this problem.

  • Thiazolidinediones should not be used in patients with NewYork Heart association class III or IV failure.
  • The main side effect of all thiazolidinediones is water retention leading to edema.Sometimes there is significant water retention leading to decompensation of potentially previously unrecognized heart failure.
  • herefore thiazolidinediones should be prescribed with both caution and patient warnings about the potential ,for water retention/weight gain especially in patients with decreased ventricular function.

Q. 3 New drug effective in post prandial sugar control is:
 A Acarbose
 B Metformin
 C Sulfonylurea
 D Repaglinide
Q. 3 New drug effective in post prandial sugar control is:
 A Acarbose
 B Metformin
 C Sulfonylurea
 D Repaglinide
Ans. D

Explanation:

Repaglinide

Quiz In Between


Q. 4 True about cause of Lactic Acidosis is that it is mainly caused by intake of:
 A Biguanides
 B Glibenclamide
 C Tolbutamide
 D Chlorpropamide
Q. 4 True about cause of Lactic Acidosis is that it is mainly caused by intake of:
 A Biguanides
 B Glibenclamide
 C Tolbutamide
 D Chlorpropamide
Ans. A

Explanation:

Biguanides


Q. 5

Following are the properties of Biguanides, EXCEPT:

 A

Decrease hepatic gluconeogenesis

 B

Not contraindicated in renal dysfunction

 C

Can be used along with sulfonylureas

 D

Don’t stimulate insulin Release

Q. 5

Following are the properties of Biguanides, EXCEPT:

 A

Decrease hepatic gluconeogenesis

 B

Not contraindicated in renal dysfunction

 C

Can be used along with sulfonylureas

 D

Don’t stimulate insulin Release

Ans. B

Explanation:

Biguanides are contraindicated in patients with renal failure, congestive heart failure, alcoholism and hepatic diseases.

Ref: Richard Finkel, Michelle Alexia Clark, Pamela C. Champe, Luigi X. Cubeddu (2009), Pharmacology, 4th Edition, Lippincott Williams and Wilkins Publications, United States Page 292


Q. 6

All the statements regarding pioglitazone are true, EXCEPT:

 A

It is a PPARy agonist

 B

It is metabolized in liver

 C

Not given in case of diastolic dysfunction

 D

It acts on insulin gene and even in absence of insulin helps in metabolism of carbohydrate

Q. 6

All the statements regarding pioglitazone are true, EXCEPT:

 A

It is a PPARy agonist

 B

It is metabolized in liver

 C

Not given in case of diastolic dysfunction

 D

It acts on insulin gene and even in absence of insulin helps in metabolism of carbohydrate

Ans. D

Explanation:

Pioglitazone is a thiazolidinedione.

It acts as selective agonists for the nuclear peroxisome proliferator receptor gamma and enhance the transcription of several insulin responsive genes.

Activation of genes regulate fatty acid metabolism and lipogenesis in adipose tissue contribute to insulin sensitizing action.

Pioglitazone is metabolized by CYP2C8 and CYP3A4.

Pioglitazone when given in hypertensive patients were found to have an enhancement of left ventricular diastolic function, so its avoided in cases of diastolic dysfunction.

Quiz In Between


Q. 7

An obese patient presented in the casualty in an uncon­scious state. His blood sugar measured 400mg%, urine tested positive for sugar and ketones; drug most useful in management is:

 A

Glibenclamide

 B

Troglitazone

 C

Insulin

 D

Chlorpropamide

Q. 7

An obese patient presented in the casualty in an uncon­scious state. His blood sugar measured 400mg%, urine tested positive for sugar and ketones; drug most useful in management is:

 A

Glibenclamide

 B

Troglitazone

 C

Insulin

 D

Chlorpropamide

Ans. C

Explanation:

This patient is a clear case of diabetic ketoacidosis, with presence of increase in blood sugar (diabetic) and presence of sugar and ketones in urine (ketoacidosis). This cannot be reverted without use of insulin.
 
Ref:  Harrison’s Principle of Internal Medicine, 16th Edition, Page 2160

Q. 8

A patient presents with symptoms of Hypoglycemia. Investigations reveal decreased  blood glucose and increased Insulin levels. C-peptide assay is done which shows normal levels of C-peptide. The most likely diagnosis is:

 A

Insulinoma

 B

Accidental sulfonylurea ingestion

 C

Accidental exogenous Insulin administration

 D

Accidental Metformin ingestion

Q. 8

A patient presents with symptoms of Hypoglycemia. Investigations reveal decreased  blood glucose and increased Insulin levels. C-peptide assay is done which shows normal levels of C-peptide. The most likely diagnosis is:

 A

Insulinoma

 B

Accidental sulfonylurea ingestion

 C

Accidental exogenous Insulin administration

 D

Accidental Metformin ingestion

Ans. C

Explanation:

For the production of insulin enzymes in the pancreatic beta cells cleave the proinsulin molecule into insulin and C peptide, which are both present in insulin granules and are released in equimolar amounts when insulin is secreted into blood stream.

In accidental exogenous Insulin administration, beta cell function is normal, and the release of endogenous insulin as well as C peptide is suppressed by the low circulating glucose level.

Ref: Joslin’s diabetes mellitus By Elliott Proctor Joslin, C. Ronald Kahn page1160; Clinical endocrinology By Ashley Grossman page 534; Problem solving in clinical medicine: from data to diagnosis By Paul Cutler page 204; Criminal poisoning: clinical and forensic perspectives By Christopher P. Holstege page 94


Q. 9

A pregnant, diabetic female on oral hypogly-cemics is shifted to insulin. All of the following are true regarding this, except :

 A

Insulin does not cross placenta

 B

During pregnancy insulin requirement increases and cannot be provided with sulphonylureas

 C

Tolbutamide crosses placenta

 D

Tolbutamide causes PIH

Q. 9

A pregnant, diabetic female on oral hypogly-cemics is shifted to insulin. All of the following are true regarding this, except :

 A

Insulin does not cross placenta

 B

During pregnancy insulin requirement increases and cannot be provided with sulphonylureas

 C

Tolbutamide crosses placenta

 D

Tolbutamide causes PIH

Ans. D

Explanation:

Ans. is d i.e. Tolbutamide causes PIH

Quiz In Between


Q. 10

A lady with 12 wks of pregnancy having fasting blood glucose 170 mg/dl, the antidiabetic drug of choice is :

 A

Insulin

 B

Metformin

 C

Glipizide

 D

Glibenclamide

Q. 10

A lady with 12 wks of pregnancy having fasting blood glucose 170 mg/dl, the antidiabetic drug of choice is :

 A

Insulin

 B

Metformin

 C

Glipizide

 D

Glibenclamide

Ans. A

Explanation:

Ans. is a i.e. Insulin

Fasting blood glucose 170 mg/dl, in a pregnant female indicates diabetes (Fasting blood glucose > 126 mg/dl is frankly abnormal and indicates diabetes).

In such cases insulin should be started as it is the only antidiabetic drug which can be used during pregnancy. (except for glyburide which is not given in options).


Q. 11

Sulfonylurea is shifted to insulin in pregnant lady because :

 A

Sulphonylurea causes PIH

 B

Increases demands during pregnancy not com­pensated by sulfonyl urea alone

 C

Insulin does not cross placenta

 D

Sulfonylurea depletes insulin from fetus-beta cell of pancreas

Q. 11

Sulfonylurea is shifted to insulin in pregnant lady because :

 A

Sulphonylurea causes PIH

 B

Increases demands during pregnancy not com­pensated by sulfonyl urea alone

 C

Insulin does not cross placenta

 D

Sulfonylurea depletes insulin from fetus-beta cell of pancreas

Ans. C

Explanation:

Insulin does not cross placenta


Q. 12

Oral hypoglycemic used in diabetes are

 A

Tolbutamide

 B

Troglitazone

 C

Bigunides

 D

All

Q. 12

Oral hypoglycemic used in diabetes are

 A

Tolbutamide

 B

Troglitazone

 C

Bigunides

 D

All

Ans. D

Explanation:

Ans. is ‘a’ i.e., Tobutamide; ‘b’ i.e., Troglitazone; ‘c’ i.e., Bigunides

Quiz In Between


Q. 13

Which of the following does not cause hypoglycemia?

 A

Insulin

 B

Glimerpiride

 C

Metformin

 D

Gliclazide

Q. 13

Which of the following does not cause hypoglycemia?

 A

Insulin

 B

Glimerpiride

 C

Metformin

 D

Gliclazide

Ans. C

Explanation:

Ans. is ‘c’ i.e., Metformin


Q. 14

Glipizide, the oral hypoglycaemic drug acts by ‑

 A

Improving insulin resistance

 B

Inhibiting brush border enzyme

 C

Helps in insulin secretion

 D

Increased glucose uptake by fat cells

Q. 14

Glipizide, the oral hypoglycaemic drug acts by ‑

 A

Improving insulin resistance

 B

Inhibiting brush border enzyme

 C

Helps in insulin secretion

 D

Increased glucose uptake by fat cells

Ans. C

Explanation:

Ans. is ‘c’ i.e., Helps in insulin secretion


Q. 15

If a diabetic patient being treated with an oral hypoglycemic agent, develops dilutional hyponatremia-which one of the following could be responsible for this effect –

 A

Chlorpropamide

 B

Tolazamide

 C

Glyburide

 D

Glimepiride

Q. 15

If a diabetic patient being treated with an oral hypoglycemic agent, develops dilutional hyponatremia-which one of the following could be responsible for this effect –

 A

Chlorpropamide

 B

Tolazamide

 C

Glyburide

 D

Glimepiride

Ans. A

Explanation:

Ans. is ‘a’ i.e., Chlorpropamide

o Cholorpropamide causes cholestasis, dilutional hyponatremia, intolerance to alcohol (disulfiram like reaction).

Quiz In Between


Q. 16

Oral hypoglycemic which causes cholestatic jaundice-

 A

Tolbutamide

 B

Glibenclamide

 C

Glipizide

 D

Chlorpropamide

Q. 16

Oral hypoglycemic which causes cholestatic jaundice-

 A

Tolbutamide

 B

Glibenclamide

 C

Glipizide

 D

Chlorpropamide

Ans. D

Explanation:

Ans. is ‘d’ i.e., Chlorpropamide


Q. 17

Flushing is common in patient taking which of the following oral hypoglycemic drug with alcohol-

 A

Chlorpropamide

 B

Phenformin

 C

Glibenclamide

 D

Tolazamide

Q. 17

Flushing is common in patient taking which of the following oral hypoglycemic drug with alcohol-

 A

Chlorpropamide

 B

Phenformin

 C

Glibenclamide

 D

Tolazamide

Ans. A

Explanation:

Ans. is ‘a’ i.e., Chlorpropamide

o Chlorpropamide causes disulfiram like reaction with alcohol.


Q. 18

Biguanides acts by following except

 A

↑Insulin release from pancreas

 B

↑ Glycolysis

 C

↓ Gluconeogenesis

 D

↑ Insulin binding to its receptors

Q. 18

Biguanides acts by following except

 A

↑Insulin release from pancreas

 B

↑ Glycolysis

 C

↓ Gluconeogenesis

 D

↑ Insulin binding to its receptors

Ans. A

Explanation:

Ans. is ‘a’ i.e., ↑ insulin release from pancreash

Biguanides acts by :

o Suppress hepatic gluconeogenesis and glucose output from liver major action.

o Enhance insulin mediated glucose disposal in muscle and fat (Increased peripheral utilization of glucose) by enhancing GLUT-I transport from intracellular site to plasma membrane.

o Retartd intestinal absorption of glucose.

o Promote peripheral glucose utilization by enhancing anaerobic glycolysis.

Quiz In Between


Q. 19

Deaths from lactic acidosis in diabetes mellitus is associated with therapy with which one of the following-

 A

Metformin

 B

Tolbutamide

 C

Phenformin

 D

Glipizide

Q. 19

Deaths from lactic acidosis in diabetes mellitus is associated with therapy with which one of the following-

 A

Metformin

 B

Tolbutamide

 C

Phenformin

 D

Glipizide

Ans. C

Explanation:

Ans. is ‘c’ i.e., Phenformin


Q. 20

Which one of the following statements about biguanides is not true –

 A

Don’t stimulate insulin release

 B

Don’t stimulate insulin release

 C

Renal Dysfunction is not a contraindication for their use

 D

Renal Dysfunction is not a contraindication for their use

Q. 20

Which one of the following statements about biguanides is not true –

 A

Don’t stimulate insulin release

 B

Don’t stimulate insulin release

 C

Renal Dysfunction is not a contraindication for their use

 D

Renal Dysfunction is not a contraindication for their use

Ans. C

Explanation:

Ans. is ‘c’ i.e., Renal dysfunction is not a contraindication for their use

o Biguanides are contraindicated in hypotensive states, cardiovascular, respiratory, hepatic and renal disease and in alcoholics because of increased risk of lactic acidosis.

About other options

o Biguanides do not cause insulin release.

o Their major action is to suppress hepatic gluconcogenesis (Decreased hepatic glucose production).

o Biguanides may be combined with sulfonylureas and thiazolidinediones in type 2 DM in whom oral monotherapy is ineffective.


Q. 21

New drug for increasing sensitivity of cells to insulin‑

 A

Glibenclemide

 B

Venalafaxine

 C

Pioglitazone

 D

Glipizide

Q. 21

New drug for increasing sensitivity of cells to insulin‑

 A

Glibenclemide

 B

Venalafaxine

 C

Pioglitazone

 D

Glipizide

Ans. C

Explanation:

Ans. is ‘c’ i.e., Pioglitazone

Thiazolidinediones (Pioglitazone, Rosiglitazone) has insulin sensitizing action.

Quiz In Between


Q. 22

Thiazolidinedione is associated with increased risk of-

 A

Heart failure

 B

Pulmonary fibrosis

 C

Myocarditis

 D

Renal dysfunction

Q. 22

Thiazolidinedione is associated with increased risk of-

 A

Heart failure

 B

Pulmonary fibrosis

 C

Myocarditis

 D

Renal dysfunction

Ans. A

Explanation:

Ans. is “a’ i.e., Heart failure

Thiazolidinediones (glitazones) can precipitate CHF.


Q. 23

Antidiabetic used safely in renal failure

 A

Metformin

 B

Glimeperide

 C

Glibenclamide

 D

Rosiglitazone

Q. 23

Antidiabetic used safely in renal failure

 A

Metformin

 B

Glimeperide

 C

Glibenclamide

 D

Rosiglitazone

Ans. D

Explanation:

Ans. is ‘d’ i.e., Rosigtitazone


Q. 24

Management for an obese patient with NIDDM include‑

 A

Glibenclamide

 B

Diet therapy + exercise

 C

Diet therapy + exercise + Metformin

 D

b and c

Q. 24

Management for an obese patient with NIDDM include‑

 A

Glibenclamide

 B

Diet therapy + exercise

 C

Diet therapy + exercise + Metformin

 D

b and c

Ans. D

Explanation:

Ans. is “b’ i.e., Diet therapy + exercise; ‘c’ i.e., Diet therapy + exercise + Metformin

Quiz In Between


Q. 25

An obese NIDDM patient present with FBS = 180 mg% and PPBS = 260 mg%. Initial management should include:

 A

Glibenclamide

 B

Diet therapy + exercise

 C

Diet therapy + exercise + metformin

 D

b and c

Q. 25

An obese NIDDM patient present with FBS = 180 mg% and PPBS = 260 mg%. Initial management should include:

 A

Glibenclamide

 B

Diet therapy + exercise

 C

Diet therapy + exercise + metformin

 D

b and c

Ans. D

Explanation:

Answer is B >C (Diet therapy + exercise > Diet therapy + exercise + metformin):

The initial management of an asymptomatic type H DM with fasting blood glucose < 200mg/dl should include dietry/ life style modification and exercise. Oral hypoglycemics (Metformin) should be added if blood glucose level are not controlled with diet and exercise.

As the question has specifically asked about the initial therapy in this case, ‘option B’ with diet and exercise is the better choice of the two.


Q. 26

Treatment of 42 year old obese man with blood glucose 450 mg, urine albumin 2+sugar 4+ketone 1+ is

 A

Insulin

 B

Glibenclamide

 C

Glipizide

 D

Metformin

Q. 26

Treatment of 42 year old obese man with blood glucose 450 mg, urine albumin 2+sugar 4+ketone 1+ is

 A

Insulin

 B

Glibenclamide

 C

Glipizide

 D

Metformin

Ans. A

Explanation:

Answer is A (Insulin):

Presence of sugar and ketones in urine and the presence of hyperglycemia (400 mg Glucose) suggests a diagnosis of Diabetic ketoacidosis. The treatment of choice in Diabetic ketoacidosis is Insulin.


Q. 27

Hypoglycemic unawareness that occurs in diabetic patients when transferred from oral hypoglycemics to insulin, is due to :

 A

Autonomic neuropathy

 B

Insulin resistance

 C

Lipodystrophy

 D

Somogi phenomenon

Q. 27

Hypoglycemic unawareness that occurs in diabetic patients when transferred from oral hypoglycemics to insulin, is due to :

 A

Autonomic neuropathy

 B

Insulin resistance

 C

Lipodystrophy

 D

Somogi phenomenon

Ans. A

Explanation:

Answer is A (Autonomic neuropathy):

Hypoglycemic unawareness refers to a loss of warning symptoms that alert individuals to the presence of hypoglycemia and prompt them to eat and’abort the episode.

Hypoglycemic unawareness can be attributed to two factors :

  1. Autonomic neuropathy
  2. Loss of catecholamine response to hypoglycemia : This means that patients with repeated attacks of hypoglycemia lose their capacity to release epinephrine and norepinephrine in response to hypoglycemia. (increase release of glucogon in response to hypoglycemia is lost very early in type I Diabetes

Thus type I patients overtreated with insulin may be unaware of critically low levels of blood glucose because of an adaptive blunting of their alarm systems owing to repeated episodes of hypoglycemia.

Quiz In Between


Q. 28

Lactic acidosis is not seen in

 A

Methanol poisoning

 B

Respiratory failure

 C

Circulatory failure

 D

Tolbutamide

Q. 28

Lactic acidosis is not seen in

 A

Methanol poisoning

 B

Respiratory failure

 C

Circulatory failure

 D

Tolbutamide

Ans. D

Explanation:

Answer is D (Tolbutamide) :

Oral hypoglycemics of the biguanide group (Metformin & Phettfelrmin) are known to cause Lactic acidosis. It is not a complication of sulfonylureas such as Tolbutamide, Chlorpropamide etc.

Lactic acidosis

  • Lactic acid is produced from pyruvate when oxidative metabolism is reduced and glycolysis is increased.
  • Lactic acidosis occurs when the rate of production of lactic acid from pyruvate in muscle, skin brain and erythrocytes exceeds the rate of removal by liver and kidney.

The ingestion of methanol (wood alcohol) causes metabolic acidosis and its metabolites formaldehyde and formic acid cause severe optic nerve and central nervous system damage. Lactic acide, Aceto-acids and other unidentified organic acids contribute to the acidosis.


Q. 29

In the management of diabetes mellitus, lactic acidosis is commonly caused by which of the following:

March 2005

 A

Tolbutamide

 B

Glipizide

 C

Pioglitazone

 D

Metformin

Q. 29

In the management of diabetes mellitus, lactic acidosis is commonly caused by which of the following:

March 2005

 A

Tolbutamide

 B

Glipizide

 C

Pioglitazone

 D

Metformin

Ans. D

Explanation:

Ans. D: Metformin

Medicinal and toxic causes of lactic acidosis

  • Acetaminophen
  • Alcohols and glycols (ethanol, ethylene glycol, methanol, propylene glycol)
  • Antiretroviral nucleoside analogs (zidovudine, didanosine, lamivudine)
  • Beta-adrenergic agents (epinephrine, ritodrine, terbutaline)
  • Biguanides (phenformin, metformin)
  • Cocaine
  • Cyanogenic compounds (cyanide, aliphatic nitriles, nitroprusside)
  • Sugars and sugar alcohols (fructose, sorbitol, and xylitol),
  • Salicylates
  • Strychnine
  • Sulfasalazine
  • Valproic acid
  • Diethyl ether, 5-fluorouracil
  • Halothane, propofol
  • Isoniazid

Q. 30

True statement regarding mechanism of action of sulfonylureas is:           

March 2008, September 2010

 A

Increased peripheral utilization of glucose

 B

Reduce hepatic glucose output

 C

Act on SURI receptors on pancreatic beta cell membrane

 D

Transcription of genes regulating glucose metabolism

Q. 30

True statement regarding mechanism of action of sulfonylureas is:           

March 2008, September 2010

 A

Increased peripheral utilization of glucose

 B

Reduce hepatic glucose output

 C

Act on SURI receptors on pancreatic beta cell membrane

 D

Transcription of genes regulating glucose metabolism

Ans. C

Explanation:

Ans. C  Act on SURI receptors on pancreatic beta cell membrane

Sulfonylureas (Tolbutamide/ chlorpropamide/Glibenclamide) bind strongly to plasma proteins. Sulfonylureas are only useful in Type II diabetes, as they act on SURI receptors on pancreatic beta cell membrane, stimulating endogenous release of insulin. They work best with patients over 40 years old, who have had diabetes mellitus for under ten years. They cannot be used with type I diabetes, or diabetes of pregnancy. They can be safely used with metformin or -glitazones. The primary side effect is hypoglycemia.

Meglitinides (Repaglinide/ nateglinide) help the pancreas produce insulin and are often called “short-acting secretagogues.” They act on the same potassium channels as sulfonylureas, but at a different binding site. By closing the potassium channels of the pancreatic beta cells, they open the calcium channels, hence enhancing insulin secretion

Biguanides (Metformin) reduce hepatic glucose output and increase uptake of glucose by the periphery, including

skeletal muscle. Although it must be used with caution in patients with impaired liver or kidney function, metformin, a biguanide, has become the most commonly used agent for type 2 diabetes in children and teenagers. Amongst common diabetic drugs, metformin is the only widely used oral drug that does not cause weight gain

Thiazolidinediones (TZDs) (rosiglitazone) bind to PPARd, a type of nuclear regulatory protein involved in transcription of genes regulating glucose and fat metabolism. These PPARs act on Peroxysome Proliferator Responsive Elements (PPRE). The PPREs influence insulin sensitive genes, which enhance production of mRNAs of insulin dependent enzymes. The final result is better use of glucose by the cells.

Quiz In Between


Q. 31

Which of the following drug does not cause hypoglycemia:         

September 2008, March 2013

 A

Tolbutamide

 B

Glibenclamide

 C

Metformin

 D

Chlorpropamide

Q. 31

Which of the following drug does not cause hypoglycemia:         

September 2008, March 2013

 A

Tolbutamide

 B

Glibenclamide

 C

Metformin

 D

Chlorpropamide

Ans. C

Explanation:

Ans. C: Metformin

Metformin is an oral anti-diabetic drug in the biguanide class.

It is the first-line drug of choice for the treatment of type 2 diabetes, particularly in overweight and obese people and those with normal kidney function

When prescribed appropriately, metformin causes few adverse effects—the most common is gastrointestinal upset — and, unlike many other anti-diabetic drugs, does not cause hypoglycemia if used alone.

Lactic acidosis can be a serious concern in overdose.

Metformin helps reduce LDL cholesterol and triglyceride levels and is not associated with weight gain, and is the only anti-diabetic drug that has been conclusively shown to prevent the cardiovascular complications of diabetes.


Q. 32

An oral hypoglycemic agent used to treat obesity is:

September 2008

 A

Tolbutamide

 B

Glipizide

 C

Gliclazide

 D

Metformin

Q. 32

An oral hypoglycemic agent used to treat obesity is:

September 2008

 A

Tolbutamide

 B

Glipizide

 C

Gliclazide

 D

Metformin

Ans. D

Explanation:

Ans. D: Metformin

Agents used for treating obesity

  • Orlistat reduces intestinal fat absorption by inhibiting pancreatic lipase. Orlistat may cause frequent, oily bowel movements (steatorrhea), but if fat in the diet is reduced, symptoms often improve.
  • Sibutramine is an anorectic or appetite suppressant, reducing the desire to eat. Sibutramine may increase blood pressure and may cause dry mouth, constipation, headache, and insomnia.
  • Rimonabant is a recently developed anti-obesity medication. It is cannabinoid (CB1) receptor antagonist that acts centrally on the brain thus decreasing appetite. It may also act peripherally by increasing thermogenesis and therefore increasing energy expenditure.
  • In people with Diabetes mellitus type 2, the drug metformin can reduce weight.
  • olestra is a sucrose polyester which can be used as a cooking medium in place of fat.
  • Leptin analogues are under investigation.

Q. 33

All of the following are true regarding adverse effects of chlorpropamide except:  

March 2010

 A

Sensitizes the kidney to ADH action

 B

Less incidence of hypoglycemia

 C

More incidence of weight gain

 D

Disulfiram like reaction may occur

Q. 33

All of the following are true regarding adverse effects of chlorpropamide except:  

March 2010

 A

Sensitizes the kidney to ADH action

 B

Less incidence of hypoglycemia

 C

More incidence of weight gain

 D

Disulfiram like reaction may occur

Ans. B

Explanation:

Ans. B: Less incidence of hypoglycemia

Chlorpropamide is a long-acting sulphonylurea.

It has more side effects than other sulphonylureas and its use is no longer recommended.

Like other sulphonylureas, chlorpropamide acts to increase the secretion of insulin, so it is only effective in patients who have some pancreatic beta cell function.

It can cause relatively long episodes of hypoglycemia; this is one reason why shorter-acting sulfonylureas such as gliclazide or tolbutamide are used instead. The risk of hypoglycemia makes this drug a poor choice for the elderly and patients with mild to moderate hepatic and renal impairment.

Chlorpropamide and other sulphonylureas encourage weight gain, so they are generally not favored for use in very obese patients. Metformin is considered a better drug for these patients. Sulfonylureas should be avoided in patients with hepatic and renal impairment, patients with porphyria, patients who are breastfeeding, and patients with ketoacidosis. Not indicated for patients more than 65 years of age.

It may cause facial flushing after the ingestion of alcohol.

It may increase secretion of antidiuretic hormone (ADH), which can lead to hyponatremia.

Quiz In Between


Q. 34

Which of the following is true of biguanides:

September 2011

 A

Cause little or no hypoglycemia

 B

Stimulates pancreatic beta cells

 C

Completely metabolized

 D

Promotes hepatic gluconeogenesis

Q. 34

Which of the following is true of biguanides:

September 2011

 A

Cause little or no hypoglycemia

 B

Stimulates pancreatic beta cells

 C

Completely metabolized

 D

Promotes hepatic gluconeogenesis

Ans. A

Explanation:

Ans. A: Cause little or no hypoglycemia

Metformin does not lower blood sugar in normal subjects

By itself, it does not produce hypoglycemia in diabetics. However it potentiates the hypoglycemic action of insulin and sulfonylureas

Biguanide

Examples of biguanides:

– Metformin – widely used in treatment of diabetes mellitus type 2

– Phenformin – withdrawn from the market in most countries due to toxic effects

– Buformin – withdrawn from the market due to toxic effects

– Proguanil – an antimalarial drug

  • Biguanides do not affect the output of insulin, unlike other hypoglycemic agents such as sulfonylureas and meglitinides.
  • Therefore, not only are they effective in Type 2 diabetics but they can also be effective in Type 1 patients in concert with insulin therapy.
  • The mechanism of action of biguanides is not fully understood.
  • However, in hyperinsulinemia, biguanides can lower fasting levels of insulin in plasma.
  • Their therapeutic uses derive from their tendency to reduce gluconeogenesis in the liver, and, as a result, reduce the level of glucose in the blood.
  • Biguanides also tend to make the cells of the body more willing to absorb glucose already present in the blood stream, and there again reducing the level of glucose in the plasma.
  • The most common side effect is diarrhea and dyspepsia, occurring in up to 30% of patients.
  • The most important and serious side effect is lactic acidosis, therefore metformin is contraindicated in renal insufficiency.
  • Renal functions should be assessed before starting metformin.
  • Phenformin and buformin are more prone to cause acidosis than metformin; therefore they have been practically replaced by it.
  • However, when metformin is combined with other drugs (combination therapy), hypoglycemia and other side effects are possible.

Q. 35

Rosiglitazone mechanism of action is ‑

 A

Acts as PPAR gamma agonist

 B

Inhibitor of alpha glucosidase

 C

Acts as amylin analogue

 D

Acts as dipeptidyl peptidase inhibitor

Q. 35

Rosiglitazone mechanism of action is ‑

 A

Acts as PPAR gamma agonist

 B

Inhibitor of alpha glucosidase

 C

Acts as amylin analogue

 D

Acts as dipeptidyl peptidase inhibitor

Ans. A

Explanation:

Ans. is ‘a’ i.e., Acts as PPAR gamma agonist

Rosiglitazone

  • It is oral antidiabetic drug
  • They are selective agonists for nuclear peroxisome proliferator activator receptor gamma (PPAR gamma) expressed in the fat and muscle cells.
  • It enhances transcription of several insulin responsive genes.
  • Reverse insulin resistance by enhancing GLUT 4 expression and translocation.

Q. 36

Mechanism of action of sulfonylureas is ‑

 A

Insulin release

 B

Alpha glucosidase inhibitor

 C

PPAR y inhibitor

 D

Insulin sensitizer

Q. 36

Mechanism of action of sulfonylureas is ‑

 A

Insulin release

 B

Alpha glucosidase inhibitor

 C

PPAR y inhibitor

 D

Insulin sensitizer

Ans. A

Explanation:

Ans. is ‘a’ i.e., Insulin release

Sulfonylureas act by

  • Sulfonylurease provoke a brisk release of insulin from pancreas.
  • They act on the so called “Sulfonylurea receptors” (SUR1) on pancreatic β-cell membrane – cause depolarization by reducing conductance of ATP sensitive K+ channels. This enhances influx of Ca+2 → degranulation.
  • They do not cause hypoglycemia in pancreatectomized animals and type 1 diabetes (Presence of at least 30% of functional β-cells in essential for their action).
  • A minor action reducing glucagon secretion by increasing insulin and somatostatin release has been demonstrated.

Extrahepatic action

  • On chronic administration they sensitize the target cells (especially the liver) to the action of insulin.
  • On chronic administration their action on pancrease (to release insuline) declines due to down regulation of sulfonylurea receptors.
  • But glycemic control is maintained due to extrahepatic action.

Quiz In Between


Q. 37

Increased insulin secretion from beta cells is doneby ‑

 A

Metformin

 B

Pramlidine

 C

Repaglinide

 D

Pioglitazone

Q. 37

Increased insulin secretion from beta cells is doneby ‑

 A

Metformin

 B

Pramlidine

 C

Repaglinide

 D

Pioglitazone

Ans. C

Explanation:

. Ans. is ‘c’ i.e., Repaglinide 

  • Oral hypoglycemic drugs may be divided into two groups:‑

1. Group 1

  • These drugs reduce plasma glucose by stimulating insulin production, therefore called insulin secretogogues.
  •  Hypoglycemia is a well known side effect.

Examples are:

  1. Sulfonylureas: first generation (chlorpropamide, tobutamide); second generation (Glimipiride, glyburide, glipizide, gliclazide).
  2. Megalitinnide/D-phenylalanine analogues: Nateglinide, Rapaglinide.

2. Group 2

  • These drugs reduce blood glucose without stimulating insulin production, therefore are insulin non-secretogogues.
  • These durgs do not cuase hypoglycemia when used alone and can cause hypoglycemia, only when used with other oral hypoglycemics.

Examples are:

  1. Biguanides: Metformin, Phenformin
  2. Thiazolidinediones: Rosiglitazone, Pioglitazone, Troglitazone.
  3. a-glucosidase inhibitors: Acarbose, miglital.

Q. 38

Thiazolidinedione is associated with increasedrisk of‑

 A

Heart failure

 B

Pulmonary fibrosis

 C

Myocarditis

 D

renal dysfunction

Q. 38

Thiazolidinedione is associated with increasedrisk of‑

 A

Heart failure

 B

Pulmonary fibrosis

 C

Myocarditis

 D

renal dysfunction

Ans. A

Explanation:

Ans. is ‘a’ i.e., Heart failure 

Thiazolidinediones

  • They are selective agonists for the nuclear peroxisome proliferator – activated receptor y(PPAR-y) which enhances the transcription of several insulin responsive genes.
  • They tend to reverse insulin resistance by stimulating GLUT-4 expression and translocation entry of glucose into muscle and fat is improved.
  • Hepatic gluconeogenesis is also suppressed.
  • Fatty tissue is a major site of their action.
  • Pioglitazone lowers serum triglyceride and HDL without change in LDL level (Rosiglitazone does not has this effect).

 Thiazolidinediones cause following adverse effects

  • Plasma volume expansion, edema, weight gain, headache, myalgia and mild anemia.
  • Few cases of hepatic dysfunction and some cardiovascular events have been reported – CHF may be precipitated → they are contraindicated in liver disease and in CHF.
  • Rosiglitazone has been found to increase the risk of fracture, especially in elderly women.
  • Glitazones with insulin can precipitate CHF  → avoid such combination.
  • These drugs prevent type 2 DM in prediabetics.

Q. 39

Drug used in post prandial sugar control is?

 A

Alfa glucosidase

 B

Biguinides

 C

Sulfonylurea

 D

Repaglinide

Q. 39

Drug used in post prandial sugar control is?

 A

Alfa glucosidase

 B

Biguinides

 C

Sulfonylurea

 D

Repaglinide

Ans. D

Explanation:

Ans. is ‘d’ i.e., Repaglinide

Quiz In Between


Q. 40

Which of the following drugs used to treat type-II diabetes mellitus causes weight loss 

 A

Metformin

 B

Glimepiride

 C

Repaglinide

 D

Gliclazide

Q. 40

Which of the following drugs used to treat type-II diabetes mellitus causes weight loss 

 A

Metformin

 B

Glimepiride

 C

Repaglinide

 D

Gliclazide

Ans. A

Explanation:

Ans. is ‘a’ i.e., Metformin

  • Effect of antidiabetic drugs on weight
  1. Increased : Sulfonylureas, insulin, pioglitazone
  2. Decreased : Metformin, GLP-1 antagonists, pramlinitide
  3. No effect: DPP-4 inhibitors

Quiz In Between



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