Question

Oral medications

Which oral antidiabetic agent can accumulate to toxic levels with renal impairment?

What else can cause it to accumulate to toxic levels?

What can occur when the drug rises to toxic levels?

What would it look like?

Which oral and injectable antidiabetic agents are most likely to cause hypoglycemia?

Why?

Should patients be monitored for hypoglycemia even if they aren’t on these drugs?

What would you see in a patient who is having an adverse effect from pioglitazone (Actos)?

What medications are hormone related (help the body’s natural response to glucose)?

What do these hormones do?

Answer 1

Which oral antidiabetic agent can accumulate to toxic levels with renal impairment?

Biguanides group of oral antidiabetic agents can accumulate to toxic level with renal impairement. For example- Metformin . Its elimination ia almost occur by kidney and in kidney impairment metformin build up in blood and cause intoxication. Another example of biguanide is Phenformin , but it was withdrawn from many country as it more easily develops toxicity than metformin.

What else can cause it to accumulate to toxic levels?

Accumulation of metformin can be caused by renal impairments. Apart from that Old age, Chronic therapy with doses above 2 gram per day , Heart failure . These condition generally leads to decraese renal perfusion or renal clearance and accumulate metformin.

What can occur when the drug rises to toxic levels?

Metformin associated lactic acidosis can occur when the drug rises to toxic level.

What would it look like?

Lactic acidosis includes symptoms like nausea, vomiting. Kussmaul breathing (labored and deep) and generalized weakness, muscle pain, burning sensation.

Which oral and injectable antidiabetic agents are most likely to cause hypoglycemia?

Oral antidiabetic agent cause hypoglycemia are Sufnonylureas (Glibenclamide, Glimepiride , Gliclazide) and D-Phenylalanine analogue or Meglitinide analogue (Repaglinide , Nateglinide ).

Sulfonylureas are most potent for developing hypoglycemic condition whereas Meglitinide analogue are short acting and less potent for developing hypoglycemia.

Insulin injections are most likely to cause hypoglycemia.

Why ?

Sulfonnunylureas and meglitinide analogue increase insulin secretion. They act on beta cells of islets of Langerhans, cause depolarization by reducing conductance of ATP sensitive K+ channel. this enhance Ca++ into the cell and lead to degranulation (insulin release). Injectable insulin is the insulin hormone itself. Excess insulin cause excess decrease of blood glucose level and if it lowers than normal blood level , the condition known as hypoglycemia.

Should patients be monitored for hypoglycemia even if they aren’t on these drugs?

Patient should be monitored for hypoglycemia even if they are not under insulun or sulfonylurea or biguanude analogue treatment. Hypoglycemia is a emergency condition and needs immediate management. For example Metformin monotherapy even can cause severe hypoglycemia in some patient. Controlling blood glucose at a stable level with parfect medication is very tough thing and almost impossible with static dose of mediaction and without monitoring. This is because principle dietary component is carbohydrate. Blood glucose level vary many times in a day following food intake , body requirement etc. Medication may be overdose or insufficient following this condition. And this often leads to hypoglycemic condition . So often monitoring is highly recommended.

What would you see in a patient who is having an adverse effect from pioglitazone (Actos)?

Adverse effect from pioglitazone are - edema (due to plasma volume expansion), weight gain, headache, myalgia, mild anemia.

What medications are hormone related (help the body’s natural response to glucose)?

And What do these hormones do?

1. There are various recombinant forms of human insulin used as parenteral medication (injection)

Hormone is Insulin : function is decreasing blood glucose by increase its peripheral utilization, protein synthesis , lipolysis and decrease hepatic gluconeogenesis, glucogenolysis .

example of insulin medications are - Insulin aspart, isophane, regular soluble insulin etc

2. Sufonylureas (described earlier) - insulin stimulator

3. Meglitinide analogue and D-phenylalanine derivative (described earlier) - insulin stimulator

4. Thioazolidinediones ( eg : Pioglitazone, Rosiglitazone) - activate insulin responsive gene that regulate carbohydrate and lipid metabolism. Thus sensitize peripheral tissue to insulin.

5. Pramlintide (synthetic analogue of amylin) decreases glucagon secretion.

Function of insulin is stated earlier. Function of glucagon is just opposite to insulin that is increasing blood glucose level by antagonising insulin action.