CPT10 - Diabetes Flashcards
4 features of insulin therapy for type 1 diabetes
Site of Administration
Basal-Bolus Dosing
Contraindications/Side Effects x3
Cautions x2
1.) Site of Administration - SC injections in the:
- upper arms, thighs, buttocks, and abdomen
- must rotate site to prevent lipodystrophy
- IV for emergency treatment
2.) Basal-Bolus Dosing - long-rapid acting dosing
- glargine: basal (long acting) dose taken at night time
- aspart (or Humulin S): bolus dose taken 15-30 mins before meals
3.) Contraindications/Side Effects
- hypoglycaemia, renal impairment (hypoglycaemic risk)
- lipodystrophy (lipohypertrophy or lipodystrophy)
4.) Cautions
- ↑dose with steroids, other hypoglycaemic agents
4 pharmacokinetic features of insulin injections
Formulation
Metabolism and Elimination
Absorption
Dosing
1.) Formulation - given paraenterally (injections)
- protein so needs to avoid digestion from the gut
2.) Metabolism and Elimination - by the liver and kidneys
- half-life is roughly 5 minutes in plasma
3.) Absorption
- soluble insulins form hexamers which delays absorption from the injection site (overcomes short half life)
- protamine and zinc can be used to modify absorption
4.) Dosing - rapid acting taken 15-30 mins before meals
- due to insulin [plasma] greatest 2-3hrs after injections
4 features of using biguanides to treat type 2 diabetes
Drug Name
Mechanism x2
Effect on Weight
Side Effects x3
Caution x2
1.) Drug Name - metformin
2.) Mechanism - ↓hepatic production of glucose via:
- ↓gluconeogenesis and glycogenolysis
- ↑glucose utilisation in skeletal muscle
3.) Effect on Weight - weight loss
- supresses appetite
4.) Side Effects
- GI upset (nausea, vomiting, diarrhoea)
- renal impairment (stop if eGFR < 30ml/min)
- lactic acidosis (rare)
5.) Caution
- nephrotoxic drugs: ACEi, NSAIDs
- thiazide-like diuretics: ↑glucose, reducing efficacy
5 physiological effects of glucagon-like peptide (GLP-1, incretin)
Pancreas
Brain
Stomach
Liver
Muscle
1.) Pancreas - ↑insulin secretion, ↓glucagon secretion
- also ↑insulin biosynthesis
2.) Brain - supresses appetite –> ↓food intake
3.) Stomach - ↓gastric emptying which decreases postprandial glycaemia
4.) Liver - ↓glucose production (indirectly)
5.) Muscle - ↑glucose uptake (indrectly)
5 features of using dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) to treat type 2 diabetes
Drug Names x2
Mechanism x2
Effect on Weight
Side Effects x3
Caution x2
1.) Drug Names - sitagliptin, saxagliptin
2.) Mechanism - ↑[plasma] incretin (GLP-1) levels
- prevents incretin (GLP-1) degradation
- incretins are glucose dependent –> ↑insulin secretion at low BG levels so has a low hypoglycaemic risk
3.) Effect on Weight - weight neutral
- slightly supresses appetite
4.) Side Effects
- GI upset, pancreatitis (rare)
- avoid in pregnancy
5.) Caution
- thiazide-like: ↑glucose
- other hypoglycaemic agents
5 features of using GLP-1 receptor agonists (incretin mimetics) to treat type 2 diabetes
Drug Names x2
Mechanism
Effect on Weight
Side Effects x3
Caution x1
1.) Drug Names - exenatide, liraglutide
2.) Mechanism - ↑insulin synthesis and secretion
- they are not degraded by DPP-4
- requires SC injections
3.) Effect on Weight - weight loss
- supresses appetite
4.) Side Effects
- GI upset, GORDs
- stop if eGFR < 30ml/min
5.) Caution - other hypoglycaemic agents
5 features of using sulfonylureas (SU) to treat type 2 diabetes
Drug Name
Mechanism
Effect on Weight
Side Effects x3
Caution x3
1.) Drug Name - gliclazide
2.) Mechanism - ↑ß-cell pancreatic insulin secretion
- blocks ATP-dependant K+ channels
- ↓hyperpolarisation –> ↑membrane depolarisation –> Ca2+ influx –> exocytosis of inuslin granules
3.) Effect on Weight - weight gain
- due to the anabolic effects of insulin
4.) Side Effects
- GI upset: nausea, vomiting, diarrhoea
- hypoglycaemia: SU overdose will lead increased insulin levels and increased C-peptide (proinsulin cleaved in to insulin and C-peptide)
- hypersensitivity reactions (rare)
5.) Caution
- hepatic and renal impairment
- thiazide-like diuretics: ↑glucose
- other hypoglycaemic agents
5 features of using thiazolidinediones (glitazones) to treat type 2 diabetes
Drug Names x2
Mechanism x2
Effect on Weight
Side Effects x5
Caution x1
1.) Drug Names - pioglitazone, rosiglitazone
2.) Mechanism - ↓hepatic production of glucose
- activation of PPAR-gamma –> gene transcription causing glucose to be converted into triglycerides
- ↑insulin sensitisation in muscle and adipose
3.) Effect on Weight - weight gain
- due to fat cell differentiation (e.g. CT –> fat cells)
4.) Side Effects
- hypoglycaemia
- GI upset, bladder cancer
- fluid retention, CVD concerns
- fracture risk
5.) Caution - other hypoglycaemic agents
5 features of using SGLT-2 inhibitors (gliflozins) to treat type 2 diabetes)
Drug Names x2
Mechanism
Effect on Weight
Side Effects x2
Caution x2
1.) Drug Names - dapagliflozins and canagliflozins
- can be used in type 1 diabetes (DKA risk)
- preferred in any patient with established/high risk of CVD
2.) Mechanism - ↓glucose absorption in PCT
- leads to increased urinary glucose excretion
3.) Effect on Weight - modest weight loss
- low risk of hypoglycaemia
4.) Side Effects
- polyuria and polydipsia
- UTI and genital infections (bacteria love glucose) inc Fournier’s gangrene
5.) Caution
- antihypertensives and other hypoglycaemic agents
NICE guidelines for management of type 2 diabetes w/ metformin
Standard Treatment
First Intensification
Second Intensification
1.) Standard Treatment - if HbA1c >48mM (6.5%)
- lifestyle modification for 3 months, if ineffective:
- metformin (modified-release if standard not tolerated)
- target: <48mM
2.) First Intensification - HbA1c >58mM (7.5%)
- metformin + DPP-4i/pioglitazone/SU/SGLT-2i
- target: 53mM (7.0%)
3.) Second Intensification - HbA1c still >58mM, options:
- metformin + SU + DPP-4i/pioglitazone/SGLT-2i
- metformin + SGLT-2i + pioglitazone
- metformin + SU + GLP-1 agonist (last resort, if BMI >35)
- if triple therapy doesn’t work, consider insulin treatment
NICE guidelines for treating type 2 diabetes w/out metformin
1.) Standard Treatment - if HbA1c >48mM (6.5%)
- DPP-4i or pioglitazone or SU
- SGLT-2i if others are not appropriate
2.) First Intensification - HbA1c >58mM (7.5%)
- any 2 of: DPP4i/pioglitazone/SU
3.) Second Intensification - HbA1c still >58mM
- insulin-based treatment
