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Introduction
In our clinical practice while treating diabetic patients, we may have to use various other
drugs for other associated medical problems. Those drugs while tackling the offending problem may at time affect the diabetic part of the patient. These drugs may either convert an IGT to overt Dm, may convert a controlled DM patient to suddenly uncontrolled state. So we must keep in mind these factors while treating a patient of DM & at time just by decreasing the dose or withdrawal of these drugs may smoothen the Diabetic control of patient.
Classification of drugs causing DM :-
Drugs causing DM may be classified into following categories depending on their
prototype class :-
1. Hormonal preparations eg. Glucagon, Growth Hormone, Corticosteroids, Androgens,
Contraceptives, Thyroxine.
2. Drugs used in Cardiovascular medicine eg. Catecholamines (Epinephrine, Norepi
Nephrine Clonidine) or drugs releasing Catecholamines, Diuretics (Thiazides + Loop),
Encainide, Nifedipine, Diazoxide.
3. CNS drugs eg. Phenytorn, L-dopa, Atropine, Pyridostigmine, Bromoc rip tine.
4. Respiratory drugs eg. Theophylline, R'cin, Salbutamol.
5. Other eg. L-Asparaginase, Cyclosporine, Niacin, Nalidinic acid, Pen tami dine.
Mechanism of DM production
Drugs may produce hyperglycemia or DM by either increased intestinal glucose
absorption. Decreased glycogenesis, increased glycogenolysis, increased gluconeogenesis. Inhibition of Insulin release, increased insulin resistance by means of receptor or post-receptor defect, or by causing direct pancreatic damage.
i. Androgens cause it by increasing insulin resistance and increased GH release.
ii. Atropine acts by its vagolytic action causing decreased insulin release.
iii. b-blockers 2 inhibits insulin release & increases GH (growth hormone) release.
iv. Cortico steroids 5 increases gluconeogesis, increases glucose formation by synthesis
of G6 phosphatase, Fl-6 di-phosphatase, PEP Carboxykinase enzymes. Steroids also
decreases glucose uptake by skin adipose tissue, fibroblasts by translocation of glucose
transporter units from plasma membrane to intracellular location.
v. CatecholaminesS through 1 & 2 receptor activation causes phosphorylase enzyme
activation which cause glycogenolysis. They also inactivates glycagon synthetase
enzyme causing inhibition of glycogenesis, increases glucagon release from pancreas,
decreases insulin secretion 2 from b-cells of pancreas, increases GH release, causes
hypokalemia which decreases insulin
vi. Oral contraceptives 6, 7 increases insulin resistance by decreasing hepatic insulin
receptors, decreased peripheral insulin receptors causing post receptor changes'. In
addition estrogen's increases GH release.
vii. Cyclosporine, Niacin & Nalidixic acid causes IGT, Encainide, causes hyperglycemia.
Diazoxidel prolongs opening of K+ channels 10 which decreases insulin release2,
decreases peripheral glucose utilization increases gluconeogenesis, increases
catecholamines release. DiureticslS causes hypokalemia which decreases conversion
of pro-insulin & thiazides also causes direct islet cell damage.
viii. Dopaminergic drugs eg. L-dopa, Bromocriptime, Apmorphine increases GH release4.
ix. GlucagonlO causes phosphorylase activation & glycagon synthetase inhibition to
increase glycogenolysis, increases gluconeogenesis by PEP carboxykinase activation,
decreases glycolysis by inhibition of phosphofructokinase enzyme, increased
somatostatin release which inhibits insulin release.
x. GH11 cause hyperglycemia through IGFS, increases hepatic glucose output, blocks
action of receptor bound insulin causing insulin resistance.
* L-Asparaginasel inhibits insulin release!2 and also causes direct pancreatic damage
while Tacrolimust (macrolide lactone antibiotic and immuno stimulant) also causes IGT &
DM9.
* Nifedipine decreases insulin release and increases insulin resistance because decrease
K+ due to mind diuretic effect. Phenytoin 13 also inhibits insulin release and R'cin 16
because intestinal glucose absorption while pentamidinel cytolyses the b- cells which
later inhibits insulin secretion and pyridostigmine causes GH release.
* Theophylline being PDE inhibitor activates CAMP which inhibits glycogenesis, increases
glycogenolysis, increases gluconeogenesis and increases glucagon release. While
Salbutamol and terbutaline by b-receptor stimulation on pancreatic cells increases
glucagon release and also acts by increasing cAMP.
* Thyroid 14 hormonal preparations causes increased glucose absorptions from GIT,
increases glycogenolysis, increases gluconeogenesis, causes post receptor defect and
inhibits insulin degradation.
Clinical implications of diabetogenic drugs
With the use of many of these drugs in patients of DM, the control of Dm may become
very difficult because of associated hyperglycemia produced by these drugs. Even a previously well controlled DM may become uncontrolled inspite of adequate diet control and antidiabetic therapy, because of use of concomitant diabetogenic drugs and if a DM patient suddenly becomes uncontrolled then one must look for diabetogenic factors including drugs rather than directly increasing the OHA or insulin dose because at times just withdrawal of these diabetogenic drugs or decreasing their dose may completely control the diabetic status. And lastly one must be cautions in using these drugs in patients with IGT or patients with a strong family history of DM.
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