Give regular insulin in cases of diabetic emergency! (ketoacidosis, hyperosmotic coma)

It is the only form of insulin that can be administered IV

In pregnancy, no oral antidiabetic drugs are safe! The only drug you can use is insulin! (recall: administration is SC injection)

(Insulin does not cross the placenta.  Hypoglycemic drugs can, which will cause dangerous hypoglycemia in the neonate.)

Give Insulin to type I diabetics.

Type I diabetes has a lack of insulin due to pancreatic B-cell destruction.  Exogenous insulin replaces the b-cell function and restores insulin levels.

Metformin

(if not contraindicated)

Biguanides (metformin) and Thiazolidinediones (Pioglitazone, Rosiglitazone) do not cause hypoglycemia.

Alpha-glucosidase inhibitors (Acarbose, miglitol) do not normally cause hypoglycemia.

Acarbose and Miglitol are competetive inhibitors of alpha-glucosidase.  This enzyme is found on the brush border of the intestines, and is responsible for breaking complex sugars into simple sugars.  By decreasing the amount of monosaccharides in the intestine, the absorption of simple sugars is diminished.

Acarbose was one of the first drugs of this class.  Miglitol is used more often nowadays, as it is more potent.

The alpha-glucosidase inhibitors are acarbose and miglitol.  They commonly produce flatulence because the undigested sugars reach the colon where they are fermented by the gut flora!

they may also result in diarrhea and abdominal pain for the same reasons....

Glucose is taken up by GLUT2 transporters.  It is then converted into ATP.  Rising ATP levels in the pancreatic beta-cells cause the closure of K+ channels.  This causes depolarization of the cell.  Recall: the membrane potential is now less negative because the cell is less permeable to K+...
Upon depolarization, voltage gated Ca++ channels open, Ca++ enters the cell and stimulates vesicle release.  The vesicles are exocytosed, releasing the stored insulin.

Recall: sulfonylureas block the K+ channel, thereby depolarizing the cell and causing insulin release.  For this reason, they are known as insulin "secretagogues"

Insulin decreases lipolysis.  This is why insulin promotes weight gain.

Insulin also increases glucose uptake by tissues, increases glycogen synthesis by the liver and muscle cells, and increases FA synthesis.  (promotes storage of energy)

Please list these insulin preparations from fastest acting to slowest acting:

Regular insulin

Glargine insulin
NPH insulin

Lispro insulin

The ultra-rapid insulin preparation Lispro insulin

(other ultra-rapid insulins are Aspart and Glulisine)

Regular insulin is the only insulin that can be given IV.  All others are SC injection.  This makes regular insulin beneficial for diabetic emergencies.

Regular insulin must be injected at least 30 minutes before a meal.  Lispro insulin can be injected 5 minutes before eating. 

Lispro has a faster onset and shorter action, making it less likely to cause late post-meal hypoglycemia.

Think about diabetic ketoacidosis.  Treatment is with IV regular insulin and IV fluids.  Recall that in acidotic states, K+ is commonly lost, so KCl replacement therapy may also be called for, along with sodium bicarb to correct severe acidosis.

(acidosis -> H+ entry into cells to try to minimize the pH change -> K+ out of cells to maintain electroneutrality -> more K+ in plasma, more K+ filtered and lost in kidney)

Fluids are absolutely necessary because when insulin promotes glucose uptake into cells, water will follow and if the plasma volume/ECF is not replenished by giving fluids this reuptake into cells can lead to vascular collapse!

Sulfonylureas are oral hypoglycemic agents used in the treatment of type II diabetics that are not obese.  (metformin is preferred in obese patients).

They block the K+ receptor of pancreatic beta cells, causing the release of insulin, and are therefore known as insulin 'secretagogues'.

Chlorpropamide, Tolbutamide, Glyburide

Sulfonylureas can cause hypoglycemia, allergic reactions (sulfa drugs), and can cause weight gain.

It is therefore preferrable to give metformin to obese type II diabetics.

Metformin is a biguanide oral hypoglycemic agent.  It is used in type II diabetes patients that suffer from obesity (recall: sulfonylureas are contraindicated... they promote insulin release, which inhibits lipolysis and induces weight gain)

But recall: if this obese type II diabetic had COPD metformin would be contraindicated because it could more easily lead to lactic acidosis!

Metformin inhibits hepatic gluconeogenesis, reduces glucose absorption in the gut, promotes glucose uptake by skeletal muscle, and inhibits plasma glucagon.  These actions all lower the blood sugar levels!

Basically, think "how could blood sugar levels be lowered", and metformin does it

Recall that lactate can be shuttled into the gluconeogenesis pathway in the liver.  Metformin inhibits gluconeogenesis, thus causing lactic acid accumulation because this backed-up lactate is not being consumed by gluconeogenesis. 

Lactic acidosis is the most serious potential side effect of metformin therapy (can be fatal).  Therefore, anything that predisposes to lactic acidosis results in metformin being contraindicated.  Such conditions are: alcoholism, hypoxic conditions (COPD), septicemia, ACE inhibitor therapy etc.

the "_glitazones" are the thiazolidinediones.  They are insulin sensitizers, that increase target tissue sensitivity to insulin by binding to the Peroxisome proliferator activated receptor (PPAR), which is a transcriptional regulator of insulin-response genes.

Because they affect gene transcription, the thiazolidinediones have a delayed onset of action.

Rosiglitazone, Pioglitazone

Recall that alcohol metabolism utilizes NAD+ and inhibits gluconeogenesis.  It can therefore lead to hypoglycemia, especially when combined with insulin, which also promotes hypoglycemia.

Additionally, sulfonylureas like chlorpropamide and tolbutamide may cause a disulfiram-like reaction.

Please pair the drug name with its drug class:

Drugs: Tolbutamide, Pioglitazone, Miglitol, Metformin, chlorpropamide, Acarbose

Class: Alpha-glucosidase inhibitors, Thiazolidinediones, Biguanides, Sulfonylureas

Sulfonylureas = Tolbutamide, chlorpropamide

A-G inhibitors = Acarbose, Miglitol

Biguanides = Metformin

Thiazolidinediones = Pioglitazone

Glucagon increases heart rate and contractility.  It is therefore used sometimes to counteract beta-blocker overdose!

Glucagon relaxes the intestinal smooth muscle, which aids in x-ray visualization of the bowel.