hypoglycaemics Flashcards
Discuss risk assessment of metformin overdose
Lactic acidosis in a patient on therapeutic metformin usually occurs in the context of acute rneal failure or severe sepsis and is associated with a mortality exceeding 50%
- Metformin overdose is usually benign but severe lactic acidosis is reported. The threshold dose of concern remains undefined but is thought to be >10g
- lactic acidosis is more likley to develop following acute overdose if there is pre-existing impairment of renal function or if cardiovascular toxicity of co-ingestants results in impaired renal perfusion
- The prognosis for severe lactic acidosis from metformin overdose remains good provided there is early recognition and instituion of HD
Discuss TM and TK of metfromin
TM: metformin inhibits gluconeogenesis reduces hepatic glucose output and stimulates peripehral glucose uptake. The chief agent of toxicity is lactate. Metformin can produce a type b (non aerobic) lactic acidosis possibly by changing the intracellular redox protentional and increasing cellular pdocution and by inhibiting hepatic uptake of lactate
TK: Rapidly and well absorbed following oral administration whith peak levels occuring at 2 hours. It is not metabolised and eliniantion is entierly dependent on renal excretion.
Discuss clinical features of metformin overdose
- Acute metformin overdose is usually asymptomatic
- lactic acidosis if it develops manifests some hours following overdose with worsening non specific features including altered sensorium nausea vomting diarrhoea dyspnoea tachycardai hypotension and cool peripheries
- Lactic acidosis may progress to coma shock and death
- hypoglycaemia if it develops at all is usually minor and easily corrected by dextrose administration
- Patietn who develop lactic acidosis on therapeutic metformin present unwell with a history of progressively worsening clinical features as described above.
Discuss management of metformin overdose
Resus
ABCD
- Sodium bicarbonate can be used to control severe acidosis
D: charcoal orally if within 2 hours of greater than 10 grams of metformin
E: HD not only rapdily corrects acidosis but also removes metformin from circulation thus preventing further lactate production it is urgently indicated in
-any unwell patient with alctic acidosis from therapeutic administration
–worsening lactic acidosis following acute overdose where signs of clinical instablity are present or emerging
-HD may need to be prolonged >15 hours
A: nil antidotes available
D:
Discuss risk assessment of sulfonylureas
Glibenclamide, gliclazide, glimepiride and glipizide
Acute sulfonylurea overdose results in profound and prolonged hypoglycaemia with onset usually within 8 hours of ingestion. Hypoglycaemia can also occur at therapeutic doses particularly in the setting of pre-existing renal dysfunction. Although initial control of hypoglycaemia requires administration of concentrated glucose solutions, early administration of the specific antidote octreotide greatly simplifies subsequent management
Risk assessment
- acute poisoning with sulfonylureas can result in profound hypoglycaemia
- ingestion of single tablet can produce hypoglycaemia in a non diabetic patient
- Likley to be prolonged and relapse is common following initial resolution that follows glucose administration
- elderly patients are at particular risk of sulphonylurea-induced hypoglycaemia, particularly those with imparied renal or hepatic funciton
- Hypoglycaemic response is more severe in the non diabetic patient
- onset of hypoglycaemia may be delayed up to 8 hours followin overdose
Children - ingestion of one tablet of any sulfonylurea is sufficient to cause profound potentially fatal hypoglycaemia in a child. Onset is usually wihtin 8 hours but may be delayed up to 18 .
Discuss TM and TK of sulfonhylurea
TM: Stimulate endogenous insulin release from the pancreatic beta cells through the inhibition of K efflux. overdose results in a hyperinsulinaemic staet.
TK: Sulfonylureas are rapidly and completely absorbed with a peak serum level occuring wihtin 4-8 hours. Volumes of distribution are variable but mostly small. They are metabolised in the liver to actiave and inactive metabolites which underog renal excretion.
Discuss management of sulfonylurea overdose
RESUS
ABCD
-Administer concentred IV glucose 50mls 50% to adults in IV boluses and children 5ml/kg of 10%
-Maintian euglycaemia by administration of glucose
D: oral activated charcoal can be given where the patient presents wihtin 1 hour of acute overdose providing mental state permits
E: Not clinically useful
A: Octreotide is the specific antidote for sulfonylurea induced hyperinsulinaeami. Give adults a 50 mic IV bolus followed by 25 mic/hour continous infusion for at least 24 hours. Give children 1mic/kg IV followed by 1 mic/kg/hour
D: All children with suspected sulfynurea ingetion require observation for 18 horus.
-All adults with confirmed or suspected require observation for clinical features of hypoglcyaemia and monitoring of BGLs with bedside testing for at least 8 hours.
-If requiring glucose and ocreotide can be dsicharged when stable for 12 hours
DIscuss risk assessment of insulin overdose
Deliberate self administrated insulin overdose causes profound and prolonged hypoglycaemia that may result in life threatening seizures coma and permanent neurological injury
Risk assessment
- Hypoglcyaemia may last for days and require prolonged treatement and monitoring
- the severity and duration of hypoglcyaemia is unpredictable is not dependent on the insulin preparation and correleates poorly with dose injfected.
Discuss TM and TK of insulin overdose
TM: Insulin is released from the beta pancreatic islet cells at a low basal rate.
TK: In OD the PK of insulin change. The duration of action is extended (can be days) and does not depend on the type of insulin preparation used. Instead it is determined by the slow and earratic release from sub cut adipose tissue at the injection site, in additiion to the prolonged clearance of the absorbed insulin.
DIscuss clinical features of insulin overdose
-Features are those of hypoglycaemia and are usually evident within 2 hours of administration
ANS
- Nasuea and vomiting m
- diaphoresis
- tachycardai and palpitations
CNS:
- Agitation and tremor
- confusion and visual disturbancess
- seizures
- hemiplegia
- coma
DIscuss IX of insulin overdose
BGL every 15 minutes during resus and then stretching to 2 horus during maintenance.
-EuC serum phosphate and MG: detect and treat hypokalaemia, hypophosphataemia and hypomagnesaemia
Insulin and c-peptide levels are helpful in the stremely rare circumstance where it is necessary to excldue an endogenous hyperinsulinaemic state
Discuss management of insulin overdose
Resus
ABCD
-IF BGL <4 administere 50 mls 50% or 2ml/kg 10% for kids
-Likley need ongoing therapy start 10% glucose infusion at 100ml/hour and monitor bedside BGL frequently
-If not adequate Central access for concentrated glucose will be required.
-Likley need supplemental K as per DKA
D: nil
E: nil
A: nil
D: Patients who are well within normal BGLs for 6 horus followin exposure can be discharged hom
