💊Pharmacology💊 - Diabetes Flashcards
What is the correct series of therapeutic steps when prescribing medications?
- Identify the patients problem
- Specify the therapeutic objective
- Select a drug on the bases of comparative efficacy, safety, cost and suitability
- Discuss choice of medication with patient(/carer) and make shared decision
- Write a correct prescription
- Counsel the patient on appropriate use of the medication
- Make appropriate arrangements for follow up
What are the diagnostic options for investigations for diabetes?
Blood tests:
HbA1c
Fasting glucose
Random glucose
Postprandial glucose
What problems does this woman have?
A 72 year old woman, Mrs Wallace, attends a GP appointment for a routine health check. Her BMI is 31, her blood pressure is 144/92mmHg, and a brief history reveals her mother dies of diabetes, although Mrs Wallace reports no polyuria, polydipsia or weight loss. Her GP a routine NHS health check. During a follow up appointment, Mrs Wallace’s blood tests reveal the following: HbA1c is 65 mmol/mol, LDL-cholesterol 5.18 mmol/L, HDL-cholesterol 0.8 mmol/L, and triglycerides 6.53 mmol/L. Urinalysis shows glycosuria but no ketones. Her blood pressure is 148/91HHmg. A further appointment confirmed the elevated HbA1c.
Type 2 diabetes
Dyslipidemia
Hypertension
High BMI
All risk factors for CVD
All largely asymptomatic - T2DM is quite insidious
What are the normal thresholds for HbA1c, HDL, LDL, triglycerides?
HbA1c threshold for diagnosis is 48
HDL >1mmol/L
LDL <2.6mmol/L
Triglycerides <1.7mmol/L
What are the therapeutic objectives for Mrs Wallace? (high BMI, blood glucose+HbA1c, dyslipidemia, hypertension)
Lower BMI
Lower HbA1c
Improve lipid profile
Lower blood pressure
What is the first step of T2DM management?
Standard release Metformin (500mg/day, oral)
What is the first intensification of T2DM management?
If HbA1c rises to 58mmol/mol:
Consider dual therapy of metformin with 1 of the following:
DPP-4 inhibitor
Pioglizatone
SU (sulphonylurea)
SGLT-2 inhibitor
What is the second intensification of T2DM management?
If HbA1c rises to 58mmol/mol, and first intensification has insufficient effect:
Insulin based treatment
OR
Triple therapy:
Metformin, DPP-4 inhibitor, SU
Metformin, Pioglitazone, SU
Metformin, Pioglitazone/SU, SGLT-2 inhibitor
Support patient to aim for HbA1c of 53
Mrs Wallace visits her GP for the firsts time about her T2DM, what treatment should she receive?
Standard release Metformin (500mg/day, oral)
Despite her HbA1c, she is the first line treatment as this is her first attempt at treatment, therefore would be inappropriate to go down a route of treatment which serves as an “intensification” at this point
What consequences does the molecular structure of metformin have on its absorption?
Has a pKa of 12.4
Meaning even in the most alkaline of tissue, will be in its charged form
Not easily absorbed
How is metformin absorbed, if it is in its charged form in all tissues?
Active transport protein
Organic cation transporter (OCT-1) is expressed in hepatocytes, enterocytes and proximal tubules
Why are the locations of the OCT-1 transporters significant for the pharmacokinetics of metformin?
Action of metformin: Liver is site of action (inhibits hepatic gluconeogenesis), OCT-1 enhances distribution to the liver
Absorption of metformin: metformin is absorbed in the small bowel after being taken orally
Elimination of metformin: OCT-1 transporters in proximal tubules allow transport into renal cells, and then excretion into the filtrate
What side effects are patients vulnerable to with DPP-4 inhibitors?
Upper respiratory tract infections
What side effects are patients vulnerable to with Pioglitazone?
Heart failure
What side effects are patients vulnerable to with Sulphonylurea?
Weight gain
What is the series of events that leads to DKA?
Liver cells are surrounded by glucose that is unable to enter cells because of lack of insulin, so ketones are made as an alternative energy source, leading to acidosis
