Drug treatment of diabetes mellitus Flashcards

Question

What are some examples of sulfonylureas?

Answer 1

Glibenclamide Gliclazide Glipizide Glimepiride

Answer 2

Mechanism of action:  Receptors for sulfonylureas on the KATP channels  Block by sulfonylurea drugs of KATP channel activation  Depolarisation  Ca2+ entry  Insulin secretion

Answer 3

PK: ```  Oral absorption  High binding to plasma proteins  Renal excretion of the drugs or their active metabolites  Cross the placental barrier ```

Answer 4

```  Adverse drug reactions  Hypoglycemia, especially in patient with renal imparment  Weight gain –stimulate appetite  Gastrointestinal upsets  Allergic skin rashes can occur  Bone marrow toxicity although rare, can be severe. ```  Clinical use  Type 2 diabetes

Answer 5

 Drug interactions: ```  Drugs augmenting the hypoglycaemic effect (competition for metabolising enzymes, interference with plasma protein binding or with transport mechanisms for excretion):  Non-steroidal anti-inflammatory drugs  Coumarins  Alcohol  Some antibacterial drugs (including sulfonamides, trimethoprim and chloramphenicol)  Some imidazole antifungal drugs ```  Agents that decrease the action of sulfonylureas  Thiazide diuretics  Corticosteroids

Answer 6

Repaglinide Nateglinide • Much less potent than most sulfonylureas • Have rapid onset and offset kinetics • Short duration of action • Low risk of hypoglycemia • Administered shortly before a meal to reduce the postprandial rise in blood glucose in type 2 diabetic patients • Less weight gain than sulfonylureas.

Answer 7

```  Effects: Reduce hepatic glucose output. Increase glucose uptake into muscle, by enhancing the effectiveness of endogenous insulin. Decrease triglycerides. ```

Answer 8

 Mechanism of action: Thiazolidinediones bind to a nuclear receptor called the peroxisome proliferator-activated receptor-γ (PPARγ), which is mainly in adipose tissue, but also in muscle and liver. It is complexed with retinoid X receptor (RXR). ``` Thiazolidinediones cause the PPARγ-RXR complex to bind to DNA, promoting transcription of several genes with products that are important in insulin signalling. These include Glut-4. ``` PPARγ causes differentiation of adipocytes, increases lipogenesis and enhances uptake of fatty acids and glucose.

Answer 9

PK: Rapidly and nearly completely absorbed Metabolized in the liver ``` Adverse reactions: Weight gain and fluid retention:  Contraindicated in heart failure Increased risk of fractures with chronic use. ``` ``` Clinical use: In combination with metformin or with a sulfonylurea in patients whose blood glucose is inadequately controlled on one of these drugs ```

Answer 10

Acarbose  It delays carbohydrate absorption, reducing the postprandial increase in blood glucose.  Adverse effects:  Flatulence, loose stools or diarrhoea, and abdominal pain and bloating  Clinical use:  Like metformin, it may be particularly helpful in obese type 2 patients, and it can be co-administered with metformin.

Answer 11

Exenatide Other incretin mimetics: Liraglutide Dulaglutide Lixisenatide

Answer 12

 A synthetic version of exendin-4, a peptide found in the saliva of the Gila monster (a lizard disabling its prey by rendering them hypoglycemic).  Effects – mimics the effects of GLP-1, but is longer acting:  Increases insulin secretion  Suppresses glucagon secretion  Slows gastric emptying  Reduces food intake (by an effect on satiety) and is associated with modest weight loss.  Subcutaneous administration twice daily before the first and last meal of the day.  Adverse effects:  Hypoglycemia  Gastrointestinal effects  Pancreatitis (rare but sometimes severe)  Clinical use:  Type 2 diabetes in combination with oral drugs

Answer 13

Sitagliptin Vildagliptin Linagliptin Saxagliptin

Answer 14

```  Synthetic drugs that competitively inhibit dipeptidylpeptidase-4 (DPP-4), thereby potentiating endogenous incretins (GLP-1 and GIP). ```  Do not cause weight loss or weight gain.  Well absorbed from the gut.  Used for type 2 diabetes, usually in addition to other oral hypoglycemic drugs

Answer 15

Dapagliflozin Empagliflozin Canagliflozin ```  A novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors ```

Answer 16

 Mechanism of action:  Inhibition the transporter protein SGLT2 in the kidneys  Reduction of renal glucose reabsorption  Urinary glucose excretion  Reduction if blood glucose levels  The efficacy of glucuretics is independent of insulin secretion and action.  Used in the treatment of patients with type 2 diabetes.  An important addition to the therapeutic options for the management of type 2 diabetes, particularly when used as add-on therapy  Associated with reductions in body weight

Answer 17

 ADR:  Genital infections and urinary tract infections affecting about 8–9% of patients.  In clinical trials patients taking dapagliflozin had higher rates of breast cancer (nine cases versus none in comparator arms) and bladder cancer (nine cases versus one in placebo arm)

Drug treatment of diabetes mellitus Flashcards

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