Week 5: Diabetes (2) (pharmacology) Flashcards
(51 cards)
1
Q
Type 1 diabetes mellitus
Diagnosis
A
- Fasting glucose >6.9 mml/L or random plasma glucose >11 mmol/L
- Plasma or urine ketones
- HbA1C >48 mmol/mol
- A single raised plasma glucose without symptoms not sufficient for diagnosis ( would need several blood tests in the absence of symptoms)
- *Diagnostic factors**
- Rapid onset symptoms
- Polyuria (nocturia)
- Polydipsia (needing to wake at night for water)
- Weight loss
- Fatigue/lethargy
- Generalised weakness
- Blurred vision
2
Q
Glucose vs HbA1c
A
- Glucose = an immediate measure of glucose levels in blood mmol/L
-
Haemoglobin A1c- glycated haemoglobin
- % of RBC with sugar coating
- Reflects average blood sugar over last 3 months (mmol or %)
3
Q
Diabetic ketoacidosis (DKA) Biochemical triad of
A
- Hyperglycaemia
- Ketonemia
- Acidosis
4
Q
DKA predominantley found in
A
- T1DM
- Common in children on diagnosis
5
Q
When to suspect DKA
A
- Blood glucose >11 mmol AND
- Polydipsia
- Polyuria
- Abdominal pain
- Acetonic breath
- Confusion
- Lethargy
- Visual disturbances
- Symptoms of shock
6
Q
precipitating factors for DKA
A
- Infection
- Trauma
- Non-adherence to insulin treatment
- DDIs
7
Q
diagnosis of DKA
A
- Blood glucose >11mmol (may not always be present = euglycemia)
- Test for ketones in blood and urine
8
Q
DKA treatment
A
- Initially i.v.i fluid (with potassium) and then i.v.i soluble insulin
9
Q
Therapeutic insulins
A
- Historically bovine and porcine (immunogenicity concerns)
- Now use human insulin
- Recombinant DNA (bacteria/yeast)
- Protein therefore must given parenterally to avoid digestion
- Usually formulation in 100 units/mL
- Due to obesity and insulin resistance there are higher doses (300 and 500 units/mL(
- NEVER abbreviate units or international units → dangerous mistake could be made
10
Q
Emerging therapeutics
A
- Immunotherapy- monoclonal antibodies for high risk group
- Delay progression
- Islet transplantation
- Islet cell regeneration
- Inhaled insulin
- Pharmaceutical challenge
- SGLT-2 inhibitors
- TI and TII DM and other CVDs
11
Q
Pharmacokinetics of insulin therapy
A
- Routine delivery= subcutaneous injection in upper arm, thighs, buttocks, abdomen
- Emergency e.g. DKA= i.v.i (IV infusion)
Half life of insulin in plasma is short (5 mins) therefore we need to slow absorption via a few methods
12
Q
Half life of insulin in plasma is short (5 mins) therefore we need to slow absorption via a few methods:
A
- For bovine and porcine insulins adding protamine and/or zin complex – used less now
- Delays dissolving
- Soluble (neutral) insulin forms hexamers
- Delaying absorption from site of injection
- [plasma] insulin will be highest after 2-3 hours (dosing 15-30 min prior to meals)
- Insulin analogues
- Recombinant modifications- a few amino acid changes
- Changes PK and not PD
13
Q
Effects of different insulin available
A
14
Q
prescribing insulin
A
Prescribing insulin
- Many preparations available
- Combinations often prescribed
- Short and long-acting mixtures
- May take them separately
- Basal bolus dosing- common
- Methods of injecting
- Syringes
- Pens
- Pumps
- Inhalers?
15
Q
drug class of insulin
A
hormonal drug
16
Q
mOA of insulin
A
- Insulin binds to insulin receptor
- Causes cascade of events which causes GLUT4 receptors to translocate from the cytoplasm to the membrane
- GLUT4 increases uptake of glucose into the cell lowering blood glucose
17
Q
ADR insulin
A
Adverse drug response
- Hypoglycaemia
- Lipodystrophy
- Lipohypertrophy or
- lipoatrophy
18
Q
Basal bolus dosing
A
A common dosing schedule for young active TIDM patients which provides some flexibility if adherence is good
- Basal- long acting e.g. glargine
- Given once a day
- Bolus- rapid acting e.g. aspart
- Given before meals
19
Q
management of T@DM
A
Management
- Lifestyle
- Education
- Weight loss
- Initially non-insulin therapies
- May form part of treatment plan in poorly managed or later stage disease
- Treatment with hypoglycaemic agents
- Can cause weight gain- makes adherence to sustained successful therapy a challenge
- Treatment of comorbidities
20
Q
classes of glucose lowering drugs
A
sulphonylureas
biguanides
glitazones
dipeptidyl peptidase-4 DDP (gliptins)
SGLT-2 (gliflozins)
GLP-1 receptor agonists (incretin mimetics)
1
21
Q
biguanides example
A
metformin
22
Q
sulphonylureas example
A
glicazide
23
Q
glitazone example
A
pioglitazone
24
Q
DDP-4 inhibitor example
A
saxagliptin
sitagliptin
25
SGLT-2 inhibitors
canagliflozin
26
GLP-1 receptor agonist
exenatide
liraglutide
27
metformin
biguanide
* First line treatment for T2DM
28
metformin MOA
* Reduces hepatic glucose production by inhibiting gluconeogenesis
* Some gluconegenic activity remains so hypoglycaemia risk reduced
* Also: suppresses appetite to limit weight gain
29
ADR metformin
nausea
vomiting
diarrhoea
30
metformin contraindication
* eGFR \<30 mL/min
* excreted unchanged by kidneys
* alcohol intoxication
31
metformin DDI
**Drug-drug interaction**
* ACEi (drugs which impair renal function)
* Diuretics (drugs which impair renal function)
* NSAIDs (drugs which impair renal function)
* Loop and thiazide like diuretics which increase glucose so can reduce metformin action
32
gliclazide
sulfonylureas
used
* Typically in combination with other agents or a first line option if metformin contraindicated
33
gliclazide MOA
* Inhibit ATP-dependent K+ channels causing membrane depolarisation
* Causes calcium into the cell
* Stimulate B cell pancreatic insulin secretion by blocking
* NEED PANCREATIC FUNCTION TO WORKA
* Can cause weight gain through anabolic effects of insulin
34
ADR glicazide (SU)
* Mild GI upset
* Nausea
* Vomiting
* Diarrhoea
* Hypoglycaemia (works at low [glucose])
35
contraindication gliclazide (SU)
* Hepatic disease
* Renal disease
* Caution of those at risk of hypoglycaemia
36
DDI gliclazide (SU)
* Other hypoglycaemic agents
* Loop and thiazide like diuretics (increase glucose so can reduce SU action)
37
dapagliflozin
SGLT-2 inhibitor
**Uses**
* adjunct to insulin in T1DM (high BMI)
* T2DM as an add on therapy
* Modest weight loss, hypoglycaemic risk is low
38
MOA of gliflozins
* **Competitive reversible inhibition of SGLT-2 in PCT**
* Decrease glucose absorption from tubular filtrate
* Increase glucose excretion
39
ADR gliflozins
* UTI (sugar urine)
* Genital infections
* Thirst
* Polyuria
40
contraindication gliflozins
* Risk of DKA in T1DM
* Possible hypotension
41
DDI gliflozins
* Antihypertensives
* Other Hypoglycaemic agents
42
**Physiological effect of GLP-1 (incretin hormone)**
* **In the pancreas**
* Increases insulin secretion
* Decrease glucagon secretion
* Increase insulin biosynthesis
43
**Drugs which target GLP-1 actions**
* Dipeptidyl peptidase- 5 (DPP-4) inhibitors (Gliptins)
* Glucagon-like peptide-1 (GLP-1) receptor agonists (incretin mimetics)
44
sitagliptin
Dipeptidyl peptidase- 5 (DPP-4) inhibitors (Gliptins)
45
MOA of gliptins e.g. DPP-4 inhibits
* Prevent incretin (GLP-1) degradation – increasing plasma incretin levels
* Glucose dependent so postprandial action
* Will not stimulate insulin secretion at normal blood glucose- lower hypoglycaemic risk
* Supress appetite- due to GLP-1 action in satiety
* Weight neutral
* Given subcutaneously like insulin – protein therefore would be digested if given enterally
46
ADR gliptins
1. GI upset
2. Small pancreatitis risk
47
contraindications gliptins
1. Avoid in pregnancy
2. History of pancreatitis
48
DDI gliptins
1. Other hypoglycaemic agents
2. Drugs increase glucose can oppose gliptin action- thiazide like and loop diuretics
49
exenatide
GLP receptor agonist- incretin mimetic
50
mode of action of exenatide (GLP-1)
* Increase glucose dependent synthesis of insulin secretion from B cells by activating GLP-1 receptors (resistance to degradation by DPP-4)
* Subcutaneous injection
* Promotes satiety- possible weight loss
51
ADR exenatide
* GI upset
* Decreased appetite with weight loss
