DM PHARMACOLOGY Flashcards
What do you understand by Diabetes Mellitus?
Diabetes mellitus is a spectrum of metabolic disorders arising from myriad pathogenic mechanisms, which results in hyperglycemia
pathogenesis of DM (4)
Both genetic and environmental factors contribute to its pathogenesis, which involves;
insufficient insulin secretion,
reduced responsiveness to endogenous or exogenous insulin,
increased glucose production, or
abnormalities in fat and protein metabolism
Tissues that are critical for regulation of blood glucose are (5)
liver,
skeletal muscle
fat,
specific regions of the brain
the pancreatic islet
The insulin receptor is expressed on ?
virtually all mammalian cell types
With insulin receptor binding, cell membranes become permeable to?
glucose which facilitates its entry into the cells. Increased cell permeability also allows for amino acids, fatty acids and electrolytes to enter cells
how does insulin increase the amount of body protein?
increasing uptake of amino acids into cells resulting to protein synthesis within the cells
counter hormones to insulin/ Hormones that raise blood glucose levels include? (6)
1)Cortisol
2)Glucagon
3)Growth hormone
4)Epinephrine
5)Estrogen
6)Progesterone
Mechanism of action of insulin; insulin binding to its receptor results in: (5)
1) Activation of insulin-dependent glucose transport processes in adipose tissue and muscle
2) Inhibition of adenylyl cyclase-dependent processes (lipolysis,proteolysis, glycogenolysis)
3) Intracellular accumulation of potassium and phosphate (which are linked to glucose transport in some tissue)
4) Increased cellular amino acid uptake, DNA and RNA synthesis
5) Increased oxidative phosphorylation
Insulin Formulations; Insulin was previously being extracted from ? and whats the difference with human insulin
previously being extracted from cattle or pig pancreas
Bovine (B) insulin; from cattle especially cow, differs from human insulin in three amino acid residues
while, porcine (S) insulin in one, but their action is very similar to human.
which insulin is purer and carries less risk of allergy?
using recombinant DNA technology in vitro manufacturing of human insulin
what are the Two approaches are used to modify the absorption and pharmacokinetic profile of insulin?
1) based on formulations that slow the absorption of insulin following subcutaneous injection e.g. NPH; Neutral Protamine Hagedorn
Protamine from fish sperm, which helps to delay its absorption into the bloodstream, resulting in an extended duration of action compared to regular/rapid-acting insulins.
2) The other approach is to alter the amino acid sequence or protein structure of human insulin so that its ability to bind to the insulin receptor is retained, but its behavior in solution or following injection is either accelerated or prolonged compared to native/regular insulin i.e. insulin analogues
Preparations of insulin are classified according to ?
to their duration of action, that is
i)short acting and,
ii) long acting
In the short acting there’s, the very rapid-acting insulins and regular insulin,
examples of the very rapid-acting insulins (3)
1)aspart,
2)glulisine and
3)lispro
Likewise, formulations with a longer duration of action
1)degludec
2)detemir
3)glargine
Stable combinations of short-acting and long-acting insulins provide ? a
convenience by reducing the number of daily injections
whats inhaled insulin
Inhaled insulin:
Inhaled insulin (Afrezza) is formulated for inhalation. It is not widely used
Used in combination with a long-acting insulin and has a more rapid onset and shorter duration than injected insulin analogues
Adverse events include cough and throat irritation. It should not be used in individuals who smoke
list the insulin delivery routes (5)
Subcutaneously
IV and IM (not suitable for long-acting)
Continuous Subcutaneous Insulin Infusion (short-acting insulin only)
Nasal delivery (rare)
Adverse effects of insulin (5)
Hypoglycaemia
Modest weight gain
Allergic reactions to recombinant human insulin or because of sensitivity to a component added to insulin in its formulation e.g protamine, zinc
Atrophy of subcutaneous fat at the site of insulin injection (lipoatrophy)
Enlargement of subcutaneous fat depots (lipohypertrophy)
Indications for Insulin therapy
Main treatment in type 1 DM
Many patients with Type 2 DM (adjunct to oral anti-diabetic therapy)
Indications for insulin use in type 2 DM include
Acute infections
Pregnancy
Surgical operations
Burns
Myocardial infarction
DKA(Diabetic Ketoacidosis) and HHS(Hyperosmolar Hyperglycemic
State)
Diabetic foot ulcer
Anti-diabetic Medications Broadly classified into ?
Insulin secretagogues and other glucose-lowering agents
Insulin secretagogues, use and examples
used to stimulate insulin release
Examples of insulin secretagogues include sulfonylureas, meglitinides, GLP-1agonists (Glucagon-like peptide-1), and inhibitors of DPP-4 (Dipeptidyl peptidase-4)
