diabetes drugs
TRANSCRIPT
- DR.AKIF A.B
-GLUT-5 is also the main transporter of FRUCTOSE
Starch/SaccharidesIn diet
Decreases gastric emptying
Alpha glucosidase
Release of Insulin
Increases Ca entry
Depolarisation
ATP formed from glucose inhibitsATP-K+ channels
Stimulates GLUT-2 receptorsOn Beta islet cells
Glucose enters circulation
Releases Insulin& amylin
Stimulates Pancreas
Increases release of Incretin or GLP-1
Enters intestinalepithelial cells
Glucose
Increases GLUT-4 on surface of cells
Metabolised by DPP-4Enzyme
-Gliptins
-Acarbose
voglibose
+
ExenatideLiraglutide -
MeglitinidesSulfonylureas
Amylin analogue: Pramlinitide
-This drugs inhibits conversion of starch into glucose
accumulation of starch
S/E:Flatulence>Diarrhoea Prevents rise in glucose levelsDuring both prandial and post-Prandial levels (But not pre-Prandial)
Acarbose reduces fibrinogen levels but also several other markers of inflammation are reduced.
-Acarbose
-Voglibose
-Miglitol
Used as an add on drug in Type-2 DM
Absorbed in systemic circulation,hence dose is reduced In Renal Failure.
ULTRA-SHORT Short Intermediate Ultra long
Glulisine Regular NPH Glargine
Lispro Semi-lente Lente Detemir
Aspart
Onset=20minDuration=4min
Onset= 1hr
Duration=6-8hrs
Duration=16hrs
Smooth and peakless effect is caused by : Glargine & Detemir
Insulin increases K+ and Glucose uptake by cells and thus leads To Hypokalemia
Glargine has a acidic pH. So not mixed with other insulins
Other all Insulins are Neutral Insulins.
1st Generation 2nd Generation
Chlorpropamide Glybenclamide
Tolbutamide Gliclizide
Acetohexamide Glyburide
Causes Hepatotoxicity ( Mnemonic; T for tolbutamide and there are3Ts in hepatotoxicity)
Causes SIADH and Disulfiram like reaction
DISULFIRAM LIKE REACTION
1)Metronidazole
2)Chlorpropamide
3)Cephalosporins
-Insulin Secretagogues i.e they stimulate Insulin Release.
-Max. potency among sulfonylureas = Glyburide
-C.I. in = Liver disease
Renal Disease
Pregnancy/Lactation
-S/E: HypoglycemiaWeight Gain
-Causes maximum decrease in HbA1C levels ( 2nd : Biguanides) and increases C-peptide values
-Long acting(Max.; Chlorpropamide) and hence increases insulin for long timewhereas meglitinides are short acting.
-Short acting Insulin secretagogues.
-Hence used for Post-prandial Hyperglucemia
-Metabolised in liver and excreted in Kidney. Hence, dose to be reducedin both liver and renal failure.
-Rapeglinide
-Nateglinide
-Metformin = S/E: Vit. B12 deficiency
-Phenformin = S/E : Lactic acidosis
-Reduces gluconeogenesis
-Decreases hepatic glucose production
-Decreases insulin resistance
-Increases lipid oxidation = Decreases LDL levels
-Decreases gastric emptying
-Contra-Indication : Renal Failure
MC side effect of Metformin : Dyspepsia
1) Causes weight loss
2) PCOD
3) Metabolic Sx in HIV
4) Non alcoholic fatty Liver disease
Q. Only anti-daiabetic group which causes weight loss ??
Ans. Biguanides
Stimulates PPAR-@
Increase transcription factors for GLUT-4 Production
Increase GLUT-4 receptors on tissue cells
But still requires Insulin to bring glucose to cells so that glucose can be takenup by cells.
- They decreases Insulin Resistance
-Metabolised in Liver
-Safe in Renal Failure
1) Weight gain
2) Sodium and water retention
3) Macular edema
4) Increase risk of bone fracture in childrens.
-This inhibitors prevent glucose reabsorption and thus eliminates excessglucose in Urine
-Canagliflozin
-Dapagliflozin
-Empagliflozin
Decreases sodium and glucosereabsorption
Increase Glucose In Urine
UTI & Vaginal Infection
Glucose is a good media for bacterial growth
MC Side Effect
1) Bromocriptine
2) Colesevelam
3) Pramlintide : Amylin Analogue
Can be given in both Type1 and Type 2 DM
Qn. Anti-diabetic drug which can be given Sub-cutaneous
Ans. Pramlintide
Group Main Side Effect
Alpha glucosidaseInhibitor
Flatulence/Dyspepsia
SGLT-2 Inhibitors UTI & Vaginal infections
Gliptins Steven Johnson Sx
Thiazolidinediones Water retention/Macular edema
Insulin Hypoglycemia/ Lipodystrophy
Chlorpropamide SIADH/Disulfiram like reaction
Tolbutamide Hepatotoxicity
Metformin Vit. B12 deficiency
Phenformin Lactic acidosis
Meglitinides Hypoglycemia
1)Q. A 45-year-old woman presents to your office with a serum glucoseof 250 mg/dL and you diagnose diabetes mellitus type II. You intend to
prescribe the patient metformin, but you decide to order laboratory tests before proceeding. Which of the following basic metabolic panelvalues would serve as a contraindication to the use of metformin?
A. K+ > 4.0B. Na+ > 140C. HCO3- > 30D. Creatinine > 2.0
Metformin is absolutely contraindicated in patients with renal failuredue to the risk of lactic acidosis.
An elevated serum creatinine suggests a decrease in GFR and the presence of renal failure.
Metformin is a drug in the biguanide class used to treat diabetes mellitus type II. Metformin treats hyperglycemia by inhibiting gluconeogenesis.
Metformin carries no risk of hypoglycemia, but is known to occasionallycause lactic acidosis in patients with renal failure, liver dysfunction, CHF,alcoholism, and sepsis.
D. Creatinine > 2.0
2.Q.A 45-year-old African-American male presents to the family medicinephysician to assess the status of his diabetes. After reviewing the laboratory
tests, the physician decides to write the patient a prescription for miglitol andstates that it must be taken with the first bite of the meal.
Which of the following bonds will be most likely affected by taking miglitol?
1. Phosphodiester bonds2. Glycosidic bonds3. Peptide bonds4. Cystine bonds5. Hydrogen bonds
The bonds that will be most likely affected by taking miglitol areglycosidic bonds.
Miglitol is an alpha-glucosidase inhibitor that prevents the breakdownof disaccharides/polysaccharides into monomers by alpha-glucosidases
located along the intestinal brush border.
Miglitol prevents these bonds from being hydrolyzed. This delays sugar hydrolysis, resulting in a delayed glucose absorption. This is advantageous for patients with type II diabetes mellitus as it decreases postprandial hyperglycemia, thereby reducing insulin demand.
Common side effects of these inhibitors are upset stomach, diarrhea, andflatulence.
2. Glycosidic bonds
3.Q. A 60-year-old African-American female presents to your officecomplaining of dysuria, paresthesias, and blurry vision. Her body massindex is 37.2 kg/m2. Which of the following drugs would mostsignificantly increase the levels of C-peptide in the blood when administered to this patient?
1. Metformin2. Insulin3. Glipizide4. Acarbose
Glipizide is a second generation sulfonylurea that triggers release of insulin from pancreatic beta cells. Increased release of endogenous insulin results inelevated levels of C-peptide in the blood.
This patient's presentation is consistent with type II diabetes mellitus. Dysuria due to a urinary tract infection (the presence of glucosuria creates a good growth media for bacteria with subsequent increased risk of UTI), paresthesia due to diabetic neuropathy, blurry vision due to osmotic damage of the lens of the eye, and obesity are all associated with diabetes.
Glipizide is used in the treatment of diabetes type II only.
3. Glipizide
4.Q. A patient presents to the emergency room in an obtunded state.The patient is a known nurse within the hospital system and has no
history of any medical problems. A finger stick blood glucose is drawnshowing a blood glucose of 25 mg/dL.
The patient's daughter immediately arrives at the hospital stating that her mother has been depressed recently and that she found empty syringes in the bathroom at the mother's home. Which of the following is the testthat will likely reveal the diagnosis?
A. C-peptide levelB. 24 hr cortisol
C. Fasting blood glucoseD. Urine metanephrines
This patient is presenting with severe hypoglycemia likely secondary to exogenous administration of insulin.
C-peptide is the portion of pro-insulin that is cleaved away within the pancreatic beta cell.In normal physiology, c-peptide is present within the circulation in equimolar
concentrations with insulin. With the exogenous use of insulin, additional c-peptide is not present withinthe circulation.This scenario of hypoglycemia often occurs in individuals failing to
administer insulin correctly or in healthcare workers wishing to harmthemselves.
An insulin producing tumor should also be on the differential diagnosis forthese patients.
A. C-peptide level
5.Q. A simple experiment is performed to measure the breakdown of sucroseinto glucose and fructose by a gut enzyme that catalyzes this reaction. A glucose meter is used to follow the breakdown of sucrose into glucose.
When no enzyme is added to the sucrose solution, the glucose meter will have a reading of 0 mg/dL; but when the enzyme is added, the glucose meter will start to show readings indicative of glucose being formed. Which of the following diabetic pharmacological agents, when addedbefore the addition of the gut enzyme to the sucrose solution, will maintain a reading of 0 mg/dL?
1. Insulin2. Glyburide3. Metformin4. Acarbose
The gut enzyme that is added to the solution is most likely alpha-glucosidase. The only agent that will inhibit the enzyme from breaking down sucrose into glucose and fructose thus showing a 0 mg/dL reading on the glucose meter is acarbose.
Acarbose and miglitol are alpha-glucosidase inhibitors that prevent thebreakdown of disaccharides and polysaccharides into monomers byalpha-glucosidase located along the intestinal brush border.
This delays sugar hydrolysis resulting in a delayed glucose absorption.
This is advantageous for patients with type II diabetes mellitus as it decreases postprandial hyperglycemia, thereby reducing insulin demand.
Common side effects of these inhibitors are upset stomach, diarrhea, and flatulence.
4. Acarbose
6.Q. A 55-year-old male is hospitalized for acute heart failure. The patienthas a 20-year history of alcoholism and was diagnosed with diabetes mellitustype 2 (DM2) 5 years ago. Physical examination reveals ascites and engorgedparaumbilical veins as well as 3+ pitting edema around both ankles.
Liver function tests show elevations in gamma glutamyl transferase and aspartate transaminase (AST). Of the following medication, which most likelycontributed to this patient's presentation?
1. Glargine2. Glipizide3. Metformin4. Pioglitazone5. Pramlintide
Weight gain, edema (fluid retention), hepatotoxicity, and heart failure are toxicities associated with pioglitazone. The drug should not be administered to patients with heart failure or liver disease.
Pioglitazone and rosiglitazone are thiazolidinedione derivatives that reduce insulin resistance in patients with DM2. They are occasionally used as monotherapy for DM2 but are most often combined with other hypoglycemics. The drugs are also used to treat polycystic ovarian syndrome.
4. Pioglitazone
7.Q. A 53-year-old male presents to your office for a regularly scheduled check-up. The patient was diagnosed with type II diabetes mellitus two yearsago. To date, diet, exercise, and metformin have failed to control his elevatedblood glucose. Past medical history is also significant for hypertension.
The patient does not smoke or use cigarettes. Laboratory values show a hemoglobin A1c (HbA1c) of 8.5%. You decide to add sitagliptin to the patient’s medication regimen. Which of the following is the mechanism of action of sitagliptin?
1. Inhibits degradation of endogenous incretins2. Inhibits alpha-glucosidases at the intestinal brush border3. Activates transcription of PPARs to increase peripheral sensitivity to insulin4. Depolarizes potassium channels in pancreatic beta cells5. Increases secretion of insulin in response to oral glucose loads and delays
gastric emptying
Sitagliptin is a dipeptidyl peptidase 4 (DPP-4) inhibitor. This class of drugs acts to inhibit degradation of the endogenous incretins GLP-1 and GIP.
Incretins are a group of gastrointestinal hormones that increase the amount of insulin released from the beta cells of the islets of Langerhansafter eating.
They begin to act before blood glucose levels become elevated.
Incretins also inhibit glucagon release from alpha cells of the islets of Langerhans.
DPP-4 inhibitors block degradation of incretins and promote enhanced insulin secretion.
1. Inhibits degradation of endogenous incretins