ANTI-DIABETIC DRUGS Flashcards
Diabetes mellitus (DM) is defined as a ______geneous metabolic disorder characterized by (acute or chronic?) ______glycemia with relative disturbance of ————,________,________
heterogeneous
chronic
hyperglycemia
carbohydrate, fat and protein metabolism
There are two major types of DM and a number of minor types
Major types
Type 1/ _______ Dependent DM
Type 2/ __________ Dependent DM
Minor types
•____________ DM
•_______ Onset Diabetes of the _______
•_____________ DM
Insulin
Non Insulin
Gestational DM
Maturity ; Young
Secondary DM
PATHOPHYSIOLOGY
In a normal patient, Glucose metabolism is regulated by the hormone _________
And this is a polypeptide hormone made up of _____ amino acids
It is produced in the _________ Cells of the _________
It is secreted into circulation usually in response to _____ease in Glucose in the _________, usually (before or after?) a meal
INSULIN
51 amino acids
Beta Islet ; Pancreas
increase ; blood ; after
Function of Insulin after release includes
Enables _________ by tissues in the body
___________ Glycogen synthesis
___________ Gluconeogenesis and Glycogenolysis
___________ Lipogenesis
___________ Lipolysis
___________ Protein ______bolism
Glucose uptake
Stimulates
Inhibits
Stimulates
Inhibits
Stimulates
Anabolism
Hence absence or inactivity of Insulin would lead to
(Reduced or Increased ?) Uptake of Glucose by Tissues
(Reduced or Increased ?) Hepatic Glycogenosis and Gluconeogenesis
(Reduced or Increased ?) Lipolysis
(Reduced or Increased ?) Protein Catabolism
(Reduced or Increased ?) uptake of Glucose by tissues leads to accumulation of Glucose in the blood
Thus (ACUTE or CHRONIC?) HYPERGLYCEMIA
Reduced
Increased
Increased
Increased
Reduced
CHRONIC HYPERGLYCEMIA
ETIOLOGY
Type I Insulin-dependent diabetes mellitus (IDDM)
There is ____________ in pancreatic _______;
____________ (type _____) antibodies that ___________ are detectable in blood.
_________ INSULIN DEFICIENCY from ______
β cell destruction ; islets
Autoimmune (type 1A)
destroy β cells
Absolute; start
Type II Noninsulin-dependent diabetes mellitus (NIDDM)
Reduced ________ of ________ to ______ or ________
________ INSULIN DEFICIENCY at ______ stage
sensitivity ; peripheral tissues
insulin ; Insulin resistance
Relative ; later stage
Classification of hypoglycemic agents
A and B
B can be divided into C and D
A can be divided into E, F , G
A parenteral
B oral
C sulfonylureas
D Biguanides
E short acting
F intermediate acting
G long acting
INSULINS
Rapid
Insulin _______
Insulin _______
Insulin _______
Short acting
_______ Insulin
Intermediate acting
Neutral protamine Hagedorn/Insulin _______
Long acting
Insulin _______
Insulin _______
Rapid
Insulin Lipro
Insulin Aspart Insulin Glulisine
Short acting
Regular Insulin
Intermediate acting
Neutral protamine Hagedorn/Insulin isophane
Long acting
Insulin glargine
Insulin detemir
INSULIN
SOURCE
Naturally
Extracted from ______
– Artificially
Produced by ___________ technology using special strains of ___________ or _________ that have been genetically altered to ______________________________
PIGS
recombinant DNA technology
Escherichia coli ; yeast
contain the gene for human insulin
INSULIN
Binds to Insulin Receptor in the __________, __________ and __________
Insulin receptors are a type of __________ RECEPTOR
Activation of this receptor leads to the expression of unique glucose transporters on the membrane of the cells called __________
_______ expression causes an uptake of GLUCOSE from the blood
LIVER, SKELETAL MUSCLE and ADIPOSE TISSUE
TYROSINE KINASE RECEPTOR
GLUT; GLUT
INSULIN: PHARMACOKINETICS
Administered _____________
Insulin preparations vary primarily based on
________ and _____________
Metabolized in the _____ and _______ by _____________ ENZYME/ _____________
SUBCUTANEOUSLY
Onset; Duration of action
Liver and Kidney
INSULIN-DEGRADING ENZYME/ INSULIN PROTEASE
INSULIN: ADVERSE EFFECT
_____________
Weight _____
____________ at injection site
______kalemia
______/ _________ reaction
Edema
______ and _________ at Injection site
Hypoglycemia; gain
Lipodystrophy ; Hypokalemia
Allergic/ Hypersensitivity
Pain and Erythema
NON-Insulins
Insulin Secretagogues
____________
____________
Insulin Sensitizer
____________
____________/____________
Glucosidase Inhibitors
____________
____________
Meglitinide
Sulfonylurea
Biguanides
Thiazolidinediones/Glitazone
Acarbose
Miglitol
NON-Insulins
Insulin ________
Insulin _________
_________ Inhibitors
___________ Inhibitor
________ analogue
__________ ________
Secretagogues
Sensitizer
Glucosidase
Dipeptidyl Peptidase IV
Amylin
Incretin mimetic
NON-INSULINS
Dipeptidyl Peptidase IV Inhibitor
___________
Amylin analogue
__________
Incretin mimetic
___________
Sitagliptin
Pramlintide
Exenatide
Non-insulins: sulfonylureas
Examples
First Generation
___________
___________
___________
Second Generation
___________
___________
___________
Chlorpropamide
Tolbutamide
Acetohexamide
Glyburide
Glipizide
Glimepiride
Mechanism of action of SULFONYLUREAS
Insulin __________
Binds and Block ______________________________ of the pancreatic β cells
This causes _________ of the cell membrane
Leading to ___________
Eventually causing ____________
Extra-pancreatic effect: ↓ ______ ___________, ↑ peripheral ____ ___________
Insulin secretagogue
ATP- sensitive potassium channels
depolarization ; calcium influx
Insulin secretion
hepatic gluconeogenesis ; insulin sensitivity
Non-insulins : sulfonylureas
Adverse effect
________________
______ intolerance
Weight ______
______________ reaction
Granulocytopenic
_________ anemia
Hypoglycemia
Alcohol ; gain
Allergic skin
Hemolytic
NON-INSULINS: MEGLITINIDES
Examples
__________;________
Repaglinide
Nateglinide
NON-INSULINS: MEGLITINIDES
Mechanism of action
Insulin ___________
Binds and Block _______________of the pancreatic β cells
Causes _________ leading to ________________
Eventually causing Insulin _________
ATP-sensitive potassium channels
depolarization ;calcium influx
Insulin secretion
NON-INSULINS: MEGLITINIDES
Adverse effect
______________
Weight ______
________toxicity
Hypoglycemia
gain
Hepato
Non INSULINS: BIGUANIDES
Example
____________
Metformin
Non INSULINS: BIGUANIDES
Mechanism of action
Reduction in insulin __________ via modification of ______________________
–Inhibits _______________________(mGPD)
•Increases peripheral insulin _________ → ↑ peripheral _________ and glycolysis
Insulin resistance
glucose metabolic pathways
mitochondrial glycerophosphate dehydrogenase
insulin sensitivity
glucose uptake
NON-INSULINS: BIGUANIDES
Adverse effect
_________ ________
________/ _______ taste in the mouth
____________ deficiency
Weight ______
Lactic Acidosis
Dysgeusia/ Metallic taste in the mouth
Vitamin B12 deficiency
Weight loss
NON-INSULINS: THIAZOLIDINEDIONES
Examples
List 3
Pioglitazone
Troglitazone
Rosiglitazone
NON-INSULINS: THIAZOLIDINEDIONES
Mechanism of action
Bind and activates of the _________ factor ______ (_______________________________ of _______ type in the nucleus)
Lead to Increased glucose _________ and _____________ production
transcription
PPARγ
peroxisome proliferator-activated receptor
gamma
utilization
hepatic glucose production
NON-INSULINS: THIAZOLIDINEDIONES
Adverse effect
Weight _____
Increase risk of _________
Increased risk of _________
Edema
gain; Heart failure
Bone fracture
Non-INSULINS: INCRETIN MIMETICS
Examples
List 4
Exenatide
Liraglutide
Albiglutide
Dulaglutide
Non-INSULINS: INCRETIN MIMETICS
Mechanism of action
Binds to ___________________ (______) receptor
Lead to increase Insulin _______ and decrease ________ secretion
Glucagon Like Peptide-1 (GLP1)
Insulin secretion
Glucagon secretion
Non-INSULINS: INCRETIN MIMETICS
Adverse effect
Nausea
Vomiting
(Early or Late?) Satiety
___________
Weight ____
Early
Pancreatitis
Loss
Non insulins : DIPEPTIDYL PEPTIDASE INHIBITOR
Examples
List 3
Sitagliptin
Saxagliptin
Linagliptin
Non insulins : DIPEPTIDYL PEPTIDASE INHIBITOR
Mechanism of action
Binds and Inhibits the _____ enzymes that breaks down ______ or _______
Hence leads to ______________________
This leads to increase insulin _________ and decrease ________ secretion
DPP-4 enzymes
GLP-1 or Incretin
accumulation of Incretin
insulin secretion
glucagon secretion
DIPEPTIDYL PEPTIDASE INHIBITOR
Adverse effect
___________ upset
Arthralgia
_____ satiety
Risk of _______ infection
Risk of _______itis
Risk of _________ infection
Risk of _______ failure
Headache
Dizziness
Gastrointestinal upset
Early satiety
Urinary infection
Pancreatitis
Respiratory infection
Renal failure
Non-Insulins: GLUCOSIDASE INHIBITOR
Example
____________
_______________
Acarbose
Miglitol
Non-Insulins: GLUCOSIDASE INHIBITOR
Mechanism of action
Binds and inhibit _______________ (a brush border enzyme expressed by _________________ cells
This causes delayed and decrease intestinal glucose _________
Hence reduces _________ after ________
alpha-glucosidase
intestinal epithelial cells
intestinal glucose absorption
hyperglycemia
food ingestion
NON-insulins: GLUCOSIDASE INHIBITOR
Adverse effect
__________
_________
Abdominal _________
Diarrhea
Flatulence
Bloating
Abdominal discomfort
Non-insulins: AMYLIN ANALGOUE
Examples
_______________
Pramlintide
Non-insulins: AMYLIN ANALGOUE
Mechanism of action
Acting as an _______________
________ is a peptide hormone that is co-secreted with insulin
Hence pramlintide delays __________, decreases ________________ secretion, and improves ________.
amylinomimetic
Amylin
gastric emptying
postprandial glucagon
satiety
AMYLIN ANALGOUE
Adverse effect
Nausea
Anorexia
Vomiting.
Lol
Miscellaneous: GESTATIONAL DIABETES
__________
_____________
____________
Insulin
Glyburide
Metformin
