diabetes pharmacology Flashcards
what is insulin
- it is a hormone secreted in the pancreas and acts on the liver
- it initiates increased glucose uptake by muscles, liver and adipose tissue
what is the release mechanism of insulin
The β‐ cells have K+ channels that are
regulated by intracellular ATP
When blood glucose increases more glucose
enters the β‐cells which increases the
intracellular ATP which closes the + ATP
channels
This depolarisation of the β‐ cell initiates an
influx of Ca2+ ions triggering insulin release
The insulin receptors are membrane spanning
glycoproteins
differences between human and synthetic insulin
- Human insulin absorbed slightly more rapidly from subcutaneous tissues and has a
slightly shorter duration of action - Less antigenic than bovine, but not porcine insulin
- There is no major difference in systematic activity between human and animal
insulin but any change in preparation should be monitored carefully
short acting regular insulin
- soluble insulins that may be human or animal
- only forms suitable or IV administration
- can be given IV in emergencies but half life of about 5 minutes when given via this route and the effect disappears in about 30 minutes
long acting insulins
- Absorption can be slowed by precipitating
the insulin into crystals (rhombohedral) or
particles of no uniform shape (amorphous)
and “suspending” these particles in solution - The insulin crystals or amorphous particles
are formed by complexing the insulin with
suitable zinc salts or with protamine - The size of the crystals or particles
determines the rate of absorption, onset and
duration - Suitable for subcutaneous administration
only!
insulin formulations
- Lantus is formulated at an acidic pH 4, where
it is completely water soluble - When subcutaneously injected (which may
cause stinging), most of the material
precipitates at the site of injection due to the
higher pH of the body fluids (7.35 -7.45) - A small amount diffuses into the
bloodstream and is immediately available for
use while the remainder is held in
subcutaneous tissue - Precipitated glargine will gradually dissolve
and diffuse into solution in the bloodstream,
and the basal level of insulin will be
maintained for up to 24 hours
what is hypoglycaemia
- the main complication of insulin therapy= insulin shock
due to - excessive insulin administration
- too much exercise in relation to insulin dose
- inadequate food intake in relation to insulin dose
- excessive sulphonylurea administration
treatment of type 2 diabetes
- where possible identify and treat eliminate underlying causes
- dietary changes, weight loss and exercise may be sufficient
- oral hypoglycaemic drugs
sulphonylurea class
- should only be used if dietary and exercise management unsuccessful
- stimulate basal insulin secretion by the pancreas- so must have functioning beta cells
- these drugs cause hypoglycemia
- promote weight gain
Biguanides- metformin
- Used in the treatment of NIDDM when diet,
exercise and sulphonylurea drugs have been
insufficient - Only works for patients with some residual
beta cell function - Decreases liver gluconeogenesis
- Increases glucose utilization by peripheral
cells - Also reduces LDL, VLDL and increases HDL
advantages, unwanted effects and lactic acidosis of metformin
advantages
- hypoglycemia not usually a problem
- lower incidence of weight gain than seen with sulphonylurea drugs
unwanted effects
- common effects are gastrointestinal- anorexia, diarrhoea, nausea
lactic acidosis
- may cause it
- renal and hepatic disease which decreases drug elimination
- hypoxic pulmonary disease which increases lactic acid production
- heart failure and shock which increases lactic acid production
