112775
Metformin
- Dose 500-850mg 2G daily in divided doses with meals
, no therapeutic benefit of larger
doses, however max dose 3G
Daily.
- Start 500mg- 850mg OD
with main meal and
slowly titrate dose to
avoid GI side effects.
- Start 500mg- 850mg OD
with main meal and
slowly titrate dose to
avoid GI side effects.
- Type 2 Diabetes Monotherapy 1st line NICE. Dual therapy
with sulphonylurea and or insulin.
- Increased BMI
- Cardioprotective
- Contraindicated in Acute LVF ~ Increased risk of lactic acidosis
- Stop post MI, restart after 2 weeks if LVF stable and renal function OK.
- Lactic acidosis ~ Rarely
occurs except in extreme
illness and tissue hypoxia
acts as a trigger.
- Impaired renal
function.
- Tissue
hypoxia/MI/Sepsis.
- Withdraw for 48 hours post contrast
media and restart only when renal
function OK.
- Stop prior to planned
surgery/General Anaesthesia and
restart once eating and renal
function OK
- Increased risk with
acute alcohol
intoxication
- Impaired renal
function.
- Stop post MI, restart after 2 weeks if LVF stable and renal function OK.
- Contraindicated in Acute LVF ~ Increased risk of lactic acidosis
- Pharmacokinetics
- Oral bioavailability 50-60%
- Steady state after 24- 48 hrs
- Hydrophyllic
- Not metabolised, cleared by tubular secretion.
- Half life = 6.2 hours
- Oral bioavailability 50-60%
- No hypoglycaemia except in use with other OHAs
- Increased BMI
- Caution with poor renal function,
Review if Creatinine>130 or
GFR<45. Not if creatinine >150.
- When renal function impaired, renal clearance is decreased in
proportion to creatinine and therefore elimination half life is prolonged
leading to increased levels of metformin in plasma~ potential increase
risk of lactic acidosis
- When renal function impaired, renal clearance is decreased in
proportion to creatinine and therefore elimination half life is prolonged
leading to increased levels of metformin in plasma~ potential increase
risk of lactic acidosis
- Pharmacology
- Unclear mechanism of action.
- Potential mechanism =Disruption of respiratory chain oxidation in
mitochondria and activation of enzyme - Adenosine
Monophosphate(AMP) to Activated Protein Kinase (AMPK).Activation of
AMPK stimulates Adenosine Triphosphate (ATP) involved with
maintenance of cellular energy stores.
- In skeletal muscle AMPK
activation increases
glucose uptake and lipid
oxidation.
- In the liver AMPK activation inhibits
gluconeogenesis and lipid synthesis but
increases lipid oxidation.
- In Adipose tissue
AMPK activation
reduces lipolysis and
lipogenesis
- Therefore activation of AMPK in skeletal muscle, liver and
adipose tissue results in decreased circulating glucose, lipids and
ectopic fat collection, as well as increased insulin sensitivity.
- Increased insulin binding to
insulin receptors therefore
increased uptake of glucose
- Increased insulin binding to
insulin receptors therefore
increased uptake of glucose
- In skeletal muscle AMPK
activation increases
glucose uptake and lipid
oxidation.
- Potential mechanism =Disruption of respiratory chain oxidation in
mitochondria and activation of enzyme - Adenosine
Monophosphate(AMP) to Activated Protein Kinase (AMPK).Activation of
AMPK stimulates Adenosine Triphosphate (ATP) involved with
maintenance of cellular energy stores.
- Unclear mechanism of action.
- Biguanide
- Interactions~ H2 receptor antagonist cimetidine, increased plasma concentration of
metformin by reducing clearance by the kidneys, both cleared by tubular secretion and
compete for the same transport mechanism.
- First available in BNF in 1958, FDA approval in 1994
- Pregnancy NICE Guidance, safe and effective in pregnancy
- Unlicensed use for polycystic ovarian syndrome
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