Drugs affecting Blood Sugar

 

a) Drugs which reduce blood glucose

Insulins – These are versions of normal insulin which are given by subcutaneous injection.

There are many different forms of insulin, which have different half-lives:
o Insulin glulisin + insulin aspart + insulin lispro – these are rapidly acting [RAPID]

o Regular insulin – this is a recombinant form of human insulin.
– Must deliver to patients using an insulin syringe, as in normal syringe there are 100units/ml [REGULAR]

o Neutral Protamine Hagedorn – this is intermediate acting. It is a suspension of insulin-zinc complexes with protamine which slows absorption [INTERMEDIATE]

o Ultralente insulin + Detemir + Glargine – long acting. They have changes to the amino acid sequence which delays absorption [LONG]

 

Side effects:
– Overdose can result in hypoglycemia
– Hypokalemia
– Weight gain + lipodystrophy (fat build up) at the injection site

 

Metformin
This reduces gluconeogenesis and increases peripheral insulin sensitivity.
– Also acts to decrease the intestinal absorption of glucose
– It does not depend of functioning ß-cells as it exerts most its effects at the liver
– Taken as a tablet and safe to use if breastfeeding
– Metformin is good in that it rarely causes hypoglycemia or weight gain on its own.

 

Side effects:
– Lactic acidosis in renal failure patients due to decreased drug excretion or in liver failure patients
– GI upset –> if this occurs, switch to the modified release tablet

 

Sulphonylureas – These drugs bind to the SUR1 receptor on KATP channels on the beta-cells closing them, mainly increasing insulin release and also increasing tissue insulin sensitivity

1st generation:
o Tolbutamide – this is a short acting sulphonylurea
o Chlorpropamide – long acting which used in the treatment of Neurogenic diabetes insipidus as it potentiates ADH action at V2 receptors.
– However, it is long acting and has highest chance of hypoglycemia, produces SIADH and has disulfiram-like reactions with alcohol.

2nd generation:
o Glipizide – this is an intermediate acting drug.

3rd generation:
o Glimepiride – this is a long acting sulphonylurea.

These drugs are very useful in treating type II diabetes but are not effective against type 1 diabetes.

 

Side effects:
– Hypoglycemia – proportional to how long the drug acts for
– Weight gain
– Not used in pregnancy as can cross the placenta
– Some can cause SIADH leading to hyponatreamia
– People develop tolerance due to downregulation of sulphonylurea receptors.

 

MeglitinidesRepaglinide
These drugs also block KATP channels causing an increase in insulin secretion.
– It is a very fast acting drug which is used to limit post-prandial hyperglycemia
– Also used in people with sulpha-drug allergies

 

Side effects: Hypoglycemia + Weight Gain

 

ThiazolidinedionesPioglitazone + Rosiglitazone (-glitazone)
These PPAR-y agonists increase tissue sensitivity to insulin and activate hormone adiponectin
– They also act on muscle and fat to increase glucose uptake and lipogenesis
– Therefore they reduce plasma glucose but do not cause hypoglycemia.

 

Side effects: Exacerbate congestive heart failure due to fluid retention
– Osteoporosis – Bladder Cancer – Weight Gain

 

Alpha-glucosidase inhibitorsAcarbose + Miglitol
These inhibit amylase and glucoside enzymes which break down starch in the intestines
– Therefore, act to reduce the absorption of glucose into the bloodstream

 

Side effects: Flatulence –> Not used in IBD or Liver cirrhosis

 

IncretinsExenatide + Liraglutide
These are synthetic versions of GLP-1 which reduce appetite, taken by subcutaneous injection
– Acts by increasing insulin secretion, decreasing glucagon secretion and decreasing appetite

 

Side effects: Sickness + Pancreatitis – Also cause weight loss

 

DPP-4 inhibitorsSitagliptin, Saxagliptin (-gliptin)
-These inhibit the DPP-4 enzyme which breaks down the incretins GLP-1 and GIP

 

Side effects: Indirectly cause sickness + pancreatitis – Also cause weight loss

 

Amylin analogPramlintide
This is a polypeptide stored and secreted by B-cells which acts with insulin to reduce blood sugar
– Treats type 1 and 2 diabetes by slowing gastric emptying and decreasing glucagon secretion.

 

SGLTI (selective sodium glucose transporter 2 inhibitor)Empagliflozin (-gliflozin)
– Blocks glucose reabsorption in the kidneys to promote excretion of excess glucose in urine

 

Side effects: Genital infections/UTI due to increased glucose in urine + Diabetic Ketoacidosis

 

b) Drugs which increase blood glucose

Glucagon
This is a hormone which is made by the alpha cells of the pancreas and is gluconeogenic
– It used to rescue people from hypoglycaemic crisis acting to increase the serum glucose concentration
– Has minimal side effects

Diazoxide
This is a potassium channel opener that binds and opens ATP-sensitive K+ channels in the -cells causing hyperpolarization –> inhibits insulin release.
– Used to treat hypoglycemia secondary to an insulinoma
– Also used as a potent vasodilator used in hypertensive emergency

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