LSB384 Lecture Notes - Lecture 8: Glycosuria, Insulin Resistance, New Approach
Drugs for Diabetes
Drug Name
Mechanism of
Action
Action in Body
Clinical Use
Adverse Effects
Glucagon
Produced by
alpha cells of
pancreas
Opposite
effects of
insulin –
converts
glycogen to
glucose
Used to treat
severe
hypoglycemia
(unwanted
effect of some
anti-diabetic
drugs)
Insulin Replacement Therapy
Mimic
endogenous
insulin
Trying to match
kinetics of
endogenous
insulin (normal
prep and long-
acting)
Meal – insulin
injection, insulin
lispro
Fasting – insulin
glargine
Combination in
various
proportions
Endogenous
insulin injected
into portal vein
Hypoglycaemia
(sweating,
hunger,
palpitations,
tremor, anxiety,
convulsions,
coma)
Prevention:
regular
monitoring
Treatment: mild
– ingest glucose;
severe – IV
glucagon,
glucose
Insulin replacement therapy: drug interactions
Hypoglycemic
Ethanol inhibits gluconeogenesis
Aspirin increases pancreatic sensitivity to glucose, increases insulin secretion (additive
effect)
B-blockers inhibit effects of adrenaline at B2-adrenoceptors (inhibits gluconeogenesis)
Hyperglycemic
Adrenaline and B2-adrenoceptor agonists stimulate gluconeogenesis & glycogenolysis
Glucocorticoids increase effects of adrenaline at B2-adrenoceptors (widespread effects)
Metformin
Not clear –
inhibits
gluconeogenesis
Increases
sensitivity to
insulin (when
glucose uptake)
Anti-
hyperglycemic
(not
hypoglycemic)
Orally active
Used in DMT2
No weight gain
Hypoglycemic
effects rare
(because it is
anti-
hyperglycemic,
not
hypoglycemic)
GI disturbances
Gliclazide
Sulphonylureas
Blocks KATP
channel
Promotes
insulin
secretion
Oral
Not effective in
DMT1 (because
Hypoglycaemia
(enhanced by
alcohol)
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Document Summary
Trying to match kinetics of endogenous insulin (normal prep and long- acting) Opposite effects of insulin converts glycogen to glucose. Used to treat severe hypoglycemia (unwanted effect of some anti-diabetic drugs) Hypoglycaemia (sweating, hunger, palpitations, tremor, anxiety, convulsions, coma) Ingest glucose; severe iv glucagon, glucose. Aspirin increases pancreatic sensitivity to glucose, increases insulin secretion (additive effect) B-blockers inhibit effects of adrenaline at b2-adrenoceptors (inhibits gluconeogenesis) Adrenaline and b2-adrenoceptor agonists stimulate gluconeogenesis & glycogenolysis. Glucocorticoids increase effects of adrenaline at b2-adrenoceptors (widespread effects) Metformin effects rare (because it is anti- hyperglycemic, not hypoglycemic) May become less effective with time (progression of. Shouldn"t be used in patients with renal impairment (because drug efficacy depends on kidney"s ability to filter glucose) New approach peptide agonist at glp-1 receptors. Inhibitor of dipeptidyl peptidase-4 build up of glp 1 (glp1 is broken down / inactivated by dipeptidyl peptidase-4)