Type 2 Diabetes Flashcards by Aisha Farah

Classification of Type 2 diabtes

insulin resistance with relative insulin deficiency

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Classes of Drugs used in Type 2 diabtets

Insulin Secretagogues
Insulin Sensitizers
a-Glucosidase Inhibitor
Dipeptidyl Peptidase IV Inhibitors: DPP-IV
Glucagon-like Peptide-1 GLP-1 Mimetic
Sodium-glucose co-transporter 2 SGLT2 inhibitors

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Function of Insulin Secretagogues

Increase basal and/or postprandial insulin levels

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The action of Insulin Secretagogues depend on

Functional B cells

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Which are the Insulin Secretagogues

Sulfonylureas
Meglitinides

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Dosing of the Sulfonylureas

1-2 times daily

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Dosing of Meglitinides

3-4 times daily

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AEs of Insulin Secretagogues

Weight gain
Hypoglycemia

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Insulin Secretagogues cause a reduction in

Microalbuminuria

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Which are the 2nd gen Sulfonylureases

Gibenclamide
Gliclazide
Glipazide
Glimepiride

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Which are the long acting Sulfonylureas

Gibenclamide
Glimepiride
DOA: 24 hrs

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Which are the short acting Sulfonylureas

Glipizide
Gliclazide
DOA: 12-24

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MOA of Sulfonylureas

Incr. Insulin secretions
Decr. Hepatic clearance of insulin
decr. Glucagon levels

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CIs of Sulfonylureas

Significant Hepatic/renal impairment–> incr. T1/2 of drug

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AEs of Sulfonylureas

Hypoglycemia
NV
Headache
Allergic skin rxn
Minor Disulfiram-like rxns
Cardiotoxicity

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DIs with Sulfonylureas

Aspirin + Sulphonamides: potentiate effecrs of Sulfonylureas
-Hepatic enzyme inducers
-Corticosteroids
-Oral contraceptives
–> decr. effects of Sulfonylureas
B-Blockers mask signs of hypoglycemia

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Which are the Meglitinides?

Repaglinide
Nateglanide

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MOA of Meglitinides

Bind to ATP dependent K channels causing insulin release
*have no effect on lipids

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Can Meglitinides be used with the Sulfonyureases

Nope, they Incr. insulin secretions

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Repaglinide can be combined with

Metformin
Thiazolidine-diones

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AEs of Repaglinide

Hypoglycemia
URTIs
Weight gain
Bronchitis
Headache

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MOA of Nateglinide

Rapid onset action: 3x more than Repa..
–> incr. early phase of insulin release
Rapid-off action: 5x more than Repa
–> insulin return to pre-prandial levels 3-4 hrs
–> decr. risk of postprandial hypoglycemia

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AEs of Nateglinide

Nausea
diarrhea
Mild Hypoglycemia
*no increase in body weight

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What are Thiazolidinediones

They are insulin sensitisers= enhance effects of insulin
-decr. glucose ouptout in liver
-incr. glucose uptake and incr. insulin sensitivity in mucsles

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MOA of Thiazolidinediones

Are agonists at Peroxisome Proliferator-activated receptor-γ (PPARγ) --> induce insulin genes

The induction of insulin genes cause

incr. expression of glucose transporter Rs --> decr. glucose output by incr. glucose uptake by incr. glucose sensitivity in muscles

Why is the therapeutic effect of Thiazolidinediones delayed

Bcos they work at the gene transcription levels --> induce insulin genes and decr. peripheral resistance of insulin *ddelayed for 4-12 wks

Name a Thiazolidinedione

Pioglitazone

Effects of Pioglitazone

Decr. Trigs and FFA levels Incr. HDL levels No effect on LDL levels Decr. rsk of Hypoglycemia

Therapeutic uses of Pioglitazone

Monotherapy

Pioglitazone can be used in combination with

Sulfonylureases Metformin Injected insulin

AEs of Pioglitazone

Fluid retention--> Oedema Weight gain Anemia CVD Incr. riks of Cardiac ischaemia

What is Metformin

Its a insulin sensitiser

MOA of Metformin

Incr. insulin sensitivity decr. hepatic glucose production, fasting insulin Decr. Trigs, FFA, LDL leves Incr. HDL levels Decr. risk for developmeny of macrovascular complications

Name a Metformin agent

Biguanides

Where does Metformin act

Liver: decr. glucose output Muscle: incr. glucose uptake

Uses of Biguanide (metformin)

1st line drug in Type 2 diabetes

Biguanide can be used in combination with

Sulfonylureases Meglitinide Thiazolidinediones Insulin or a-glucosidase inhibitor

AEs of Biguanide

GI disturbances such as: -abdominal discomfort -diarrhea -Metallic taste -mild anorexia Lactic Acidosis

CIs of Biguanide

Renal impairment Hepatic disease Alcohol use Predisposition to CV, collapse, acute CHF, sever infection History of Lactic Acidosis

Name an a-glucosidase inhibitor

Acarbose

MOA of Acarbose

inhibits the breakdowm of CHO comples in SI--> delays CHO absorption inhibits glucoamylase>sucrase>maltase>dextranase

Benefits of taing Acarbose

decr. postprandial hyperglycemia no effect on lipids or insulin levels

AEs of Acarbose

GI disturbances Dose-dependent toxicity

CIs of Acarbose

Inflammatory bowel disease GI obstruction Cirrhosis

Acarbose can combined with

Insulin Metformin SUlfonylureases --> has an additive effect

What are incretins

Are a group of GI enzymes that cause an icrease in the amount of insulin released from B-cells --> Enhance GLP-1 activity= insulin enhanced

Function of Dipeptidyl Peptidase IV

Breakdown/inactivates GLP-1

What are DPP4 Inhibitors

They are incretin enhancers thus they inhibit the DPP-IV enzyme

Effect of DPP4 inhibitors

they extend the action of insulin while suppressing release of glucagon

Which are the DPP4 inhibitors

Sitagliptin Vildagliptin Saxagliptin

DPP4 inhibitors can be combined with

Insulin Metformin Slufonylureases --> have an additive effect

AEs of DPP4 inhibitors

GIT discomfort Peripheral oedema Liver dysfunction

Cautions when using DPP4 inhibitors

Renal impairment

Which are the GLP-1 mimetics

LEDS Liraglutide Exenatide Dulaglutide Semaglutide

MOA of GLP-1 mimetics

are incretin mimietics exhibit GLP-1 actions incr. insulin secretion decr. glucagon secretion

Admin of GLP-1 mimetics

SC L: 1x daily E: 2x daily s: 1x daily

Effects of GLP-1 mimetics

May promote weight loss CVS benefits

AEs of GLP-1 mimetics

Hypoglycemia NV Rash Pancreatitis

CIs in GLP-1 mimetics

Type 1 diabetics (as functional B-cells are required and they dont have these) Ketoacidosis Severe renal Impairment PREGNANCY

Function of Sodium-glucose co-transporter 2 SGL2 inhibitors

they prevent kidneys from reabsorbing glucose back into blood --> kidneys can remove excess glucose

Which are the SGL2 inhibitors

CDE Canagliflozin Dapagliflozin Empagliflozin

MOA of SGL2 inhibitors

are competitive selective inhibitors of SGL2 thus prevent the kidneys from reabsorbing glucose into blood

SGL2 inhibitors can be used with

Metformin Pioglitazone Sitagliptin

Admin SGL2 inhibitors

orally once a day before 1st meal

CIs with SGL2 inhibitors

Renal impairment PREGNANCY LACTATION

AEs of SGL2 inhibitors

Incr. risk of gental_urinary tract infections Hypotension