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Insulin and anti-diabetic Agents
April final
65
Pharmacology
Undergraduate 2
04/17/2012

Additional Pharmacology Flashcards

 


 

Cards

Term

What do the following cells secrete?

(a) Alpha cells

(b) Beta cells

(c) D cells

(d) PP F cells

Definition

(a) Glucagon

(b) Insulin 

(c) Somatostatin

(d) pancreatic polypeptide

Term
What are the 3 effects of glucagon?
Definition

Stimulates production of glucose in liver 

(gluconeogenesis)

Stimulates breakdown of glycogen  into 

glucose in skeletal muscles and liver cells 

(glycogenolysis)

Stimulates breakdown of triglycerides in 

adipose tissue and fatty acid release 

(lipolysis)

Term
4 Effects of Insulin
Definition

1. Accelerates glucose uptake and utilization by 

cells

2. Stimulates glycogen formation (glycogenesis)

3. Stimulates triglyceride formation in adipose 

tissue (lipogenesis)

4. Stimulates amino acid absorption and 

protein synthesis

Term

Normal blood glucose levels when 

(a) fasting

(b) 2 hours after meals (PP2)

Definition

(a) 70-110 mg/dl

(b)<180 mg/dl

Term

Abnormal blood glucose

– Hypoglycemia: 

– Hyperglycemia: 

• Impaired glucose tolerance: 

• Diabetes mellitus: 

Definition

- < 70 mg/dl

- >110 mg/dl

-110-180 g/dl

>180mg/dl

Term
Causes of secondary diabetes: 
Definition

Pancreatic disease: e.g., pancreatitis, tumor

– Endocrine disease: e.g., Cushing’s syndrome

– Drug induced: e.g., thiazide diuretics

– Infection: e.g., congenital rubella

Term
Gestational DM:
Definition
Pregnancy
Term
Clinical manifestations of DM: 
Definition

Polydipsia

• Polyuria + nocturia

• Glycosuria

• Complications

Term

Complications of DM

• Acute:

Definition

– Diabetic ketoacidosis (DKA)

– Hyperosmolar non-ketotic  (HONK) coma 

Term

Complications of DM

Chronic: 

Definition

Angiopathy:

• Microangiopathy:

– retinopathy - neuropathy - nephropathy

• Macroangiopathy:

– E.g., coronary artery disease (CAD)

Term
Other complications of DM: 
Definition
infection - skin complications
Term
Treatment of DM
Definition

Diet control

• Antidiabetic agents

• Treatment of complications

Term
Antidiabetic Agents
Definition

Insulin

• Oral hypoglycemic agents

Term
Indications of Insulin Therapy
Definition

Type I diabetes

• Type II diabetes:

– Inadequate control by oral hypoglycemic agents

– Stressful conditions: e.g., infection

– During pregnancy 

• Gestational diabetes

Term
Source of Insulin
Definition

• Bovine

• Porcine

• Human recombinant:

– Least antigenic

– Standardized to 100 U/ml

Term
Administration of source of insulin
Definition

Injection: SC, IV, IM

– Alternative methods: e.g., pump

Term

• Ultrashort-acting:

 
Definition
Insulin lispro & aspart 
Term

• Short-acting:

 
Definition
Regular (crystalline) insulin
Term
Intermediate-acting:
Definition

NPH (Neutral Protamine Hagedorn) insulin

– Lente insulin: reasonably soluble zinc preparation

Term
Long-acting:
Definition
Ultralente: poorly soluble zinc preparation
Term
Mixed types (combinations):
Definition
– Rapid onset & prolonged duration
Term

Insulin Regimens 

• Conventional therapy:

Definition

One or two injections per day

– Daily self monitoring of glucose 

– Lower risk of hypoglycemia

Term

Insulin regimens:

Intensive therapy

Definition

Multiple daily injections

– Daily self monitoring of glucose and dose adjustment

– Reduction in retinopathy, nephropathy, and 

neuropathy

– Higher risk of hypoglycemia (3-fold more than 

conventional regimen)

Term
Daily route of insulin: 
Definition
Subcutaneous
Term

Absorption of SC Insulin

• Highly variable:

Definition

Among different patients

– Between doses in same patient

Term
Factors affecting absorption of SC insulin: 
Definition

Blood flow to site of injection

– Site of injection:

• Abdomen > arm > buttock > thigh

– Depth of injection

– Exercise increases absorption

– Massage of the area increases absorption

Term
Alternatives to Insulin Injection (5)
Definition

Insulin pumps

• Insulin pens (insulin containing cartridges)

• Inhaled insulin

• Transdermal patches

• Oral formulas (designed to resist insulin 

digestion in the GIT)

Term
2 characteristics of Insulin pumps:
Definition

 

Indwelling catheter delivers basal insulin

Patient can program device to modify delivery rate

 

Term
What is a promising alternative to insulin injection?
Definition
Inhaled insulin  (Exubera)
Term

Exubera:

(a) Preparation

(b) powder

(c) delivery

Definition

(a) Short - acting insulin preparation

(b) fine dry powder

(c) Non-invasive insulin delivery

Term

What enters the blood faster? Inhaled insulin or SC injection?

Where must the drug reach?

Definition

Inhaled insulin

Alveoli in the lung

Term

Complications of Insulin Therapy

  • Systemic:

 

 

Definition

 

Hypoglycemia → most dangerous

Insulin allergy → rare with human insulin

Insulin resistance

 

Term

Complications of Insulin Therapy

Local

Definition

 

Lipoatrophy

Hypertrophy

 

Term

Oral Hypoglycemic Agents

(5)

Definition

 

Sulfonylureas

Biguanides

Meglitinides

Thiazolidinediones (TZDs, glitazones)

Alpha-glucosidase inhibitors

 

Term
Mechanism of action of sulfonylureas:
Definition

 

Inhibit K channels on β-cell → causing depolarization → ↑ calcium entry → ↑ insulin release

 

Term
Where do sulfonylureas potentiate insulin action?
Definition
At different tissues
Term

What do sulfonylureas require?

Which diabetes are they useful for?

Definition

Functional B cells to work

Only useful for type 2 not type 1

Term

What do sulfonylureas bind to?

(b) metabolised

(c) excreted

Definition

(a) Plasma proteins

(b) Liver

(c) Kidney

Term
Exaggerated effects of sulfonylureas are in:
Definition

(a) Elderly

(b) Renal disease

(c) Liver disease

Term
Where are sulfonylureas contraindicated?
Definition
Pregnancy. They can cross the placenta and have teratogenic effects.
Term
Which drugs increase hypoglycemic effects?
Definition

 

NSAIDs, coumarins, alcohol, MAO inhibitors, some antibacterials (sulfonamides, chloramphenicol)

Cimetidine (inhibits metabolism)

 

Term
Which drug inhibits insulin release?
Definition
Phenytoin
Term
What can mask the symptoms of hypoglycemia?
Definition
Beta blockers
Term
First generation sulfonylureas (least potent)
Definition
tolbutamide, chlorpropamide
Term
2nd generation sulfonylureas:
Definition
Glipizide, Glibenclamide, Ggliclazide
Term
3rd generation sulfonylureas:
Definition
Glimepiride
Term
Side effects of sulfonylureas:
Definition

Hypoglycemia (esp. chlorpropamide)

Gi disturbances

Jaundice

Allergic skin reactions

 

Term
Why does chlorpropamide have more side effects?
Definition
More side effects especially hypoglycemia because prolonged duration of action.
Term
Mechanism of action of biguanides:
Definition

Decrease gluconeogenesis in liver

Increase glucose uptake in skeletal muscles

Term
Indications of biguanides:
Definition

First choice drug in patients with Type 2 DB

Can be combined with sulfonylureas and insulin

Term
Advantage of biguanides:
Definition
Do not cause hypoglycemia as they do not alter insulin levels.
Term
Side effects of biguanides:
Definition

Anorexia: Dose dependent can be severe

Nausea, diarrhea, metallic taste

Lactic acidosis (acidification of blood)

Term
Contraindications of biguanides:
Definition
Renal disease
Term

What is the only approved form of biguanides?

What are its 2 forms?

Definition

Metformin (dimethylbiguanides)

 

 

  • 2 tablet forms:

          1. Glucophage™

 

  • Glucophage XR™ (extended-release tablets)

 

 

Term

What are meglinitides?

What are they similar to?

Duration of action?

Definition

Short acting insulin secretagogues.

Similar in action to sulfonylureas.

Half life is 1 hour.

Term
Indications of meglitinides:
Definition

Type 2 DM.

Can be combined with metformin.

Term
Side effects of meglitinides:
Definition
Hypoglycemia (rare)
Term

Examples of meglitinides:

 

Definition

repaglinide

nateglinide

Term
Mechanism of action of TZDs:
Definition

 

 

  • Activate a transcription regulator, PPARγ (peroxisome proliferator-activated receptor gamma) →

          1. modulate lipogenesis in adipocytes

 

  • improve glucose uptake in skeletal muscles

 

  • reverse insulin resistance

 

 

Term

Indications of TZDs:

 

Definition

 

Type 2 DM

Alone or combined with metformin, sulfonylurea

 

Term
Side effects of TZDs:
Definition

Congestive heart failure

Myocardial ischemia

May cause liver injury (monitor liver f unction)

Term
Example of TZDs:
Definition

 

Rosiglitazone???

 

Term
Alpha-glucosidase Inhibitors
Definition
Inhibits α-glucosidases in intestine → reduces absorption of carbohydrates

Not absorbed from intestine

Control post-prandial glucose levels not adequately controlled by diet and sulfonylureas

Side effects:

GI upset and flatulence

E.g., Acarbose
Term

What do you use for (a) Impaired insulin secretion

(b) Glucose uptake and utilisation

Definition

(a) Sulfonylureas and meglitinides

(b) Metformin and TZDs

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