Pharmacological Treatment of Diabetes Flashcards
**
Class of medications and examples
- Biguanides → Metformin (oral)
- Sulfonylureas → Tolbutamide, Glimepiride (oral)
- Thiazolidinediones → Pioglitazone, Rosiglitazone (oral)
- a-glucosidae inhibitors → Acarbose (oral)
- Meglitinides → Repaglinide, Nateglinide (oral)
- SGLT2 inhibitors → Canagliflozin, Dapagliflozin (oral)
- Insulin → Many, from rapid to long-acting (Inj.)
- GLP-1 analogs → Exenatide, Liraglutide (Inj.)
- DPP4 inhibitors → Sitagliptin, Saxagliptin (oral)
- TZIELD → teplizumab-mzwv (inj.)
biguanide mechanism
decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization
* metformin
* first line medication
biguanide advantages
decreases risk for diabetes related end-points
* reduce plasma TAG and LDL levels
* Dont see weight increases
* Can be used as mono therapy
* Lower costs
* Improves insulin sensitivity
biguanide disadvantages
risk is minimal
* GI disturbances
* lactic acidosis
* Cannot be used if impaired renal function and liver toxicity
* Biggest concern is hypoglycaemia
sulfonylureas mechanism of action
Primary is increase insulin secretion where it binds on beta cells receptors and similar mechanism to glucose (K+ATP channel closes, Ca opens etc.)
* bypass glucose metabolism and force insulin secretion
* tolbutamide
* glimepiride
sulfonylureas advantages
- low cost med
- No effect on plasma lipid levels
- no injections, oral med, start with small dose and titrate up
- Have huge and rapid effect, induces insulin excretion in a matter of seconds and reduces the plasma glucose
sulfonylureas disadvantages
- weight gain
- Can build a tolerance (around 10 years)
- At risk of hypoglycaemia
- Only beneficial for those with mild to moderate hyperglycaemia (??)
- Need functional beta cells
TZDs mechanismof action
Binds to PPARs as agonist ligand regulating insulin response primarly in fat metabolism but also glucose uptake in muscle and liver
* pioglitazone
* rosiglitazone
TZDs advantages
- Dont cause as much hypoglycaemia
- no contraindication with renal disease
- Increase in HDL
- Decreases plasma TAG
TZDs disadvantages
- Costly
- Weight gain
- increased LDL –> hypercholesterolemia
- Fluid retention —> Edema
- ALT increase —> hepatic toxicity
- Teratogen
a-glucosidae inhibitors mechanism of action
inhibit a-glucosidase enzymes in lumen of intestine that break down complex CHO so digestion of CHO is delayed and slows down entry of glucose to blood stream (↓ absorption) allowing more time for insulin to be released which helps manage post prandial
* acarbose
a-glucosidae inhibitors advantages
- less hypoglycaemic effect since it just delays/ prevents absorption of glucose
- No resistance over time
- No change in weight
- No change in LDL and HDL
- Original mode of action so can be used with another mode of action
a-glucosidae inhibitors disadvantages
- not as effective as monotherapy
- Effectiveness may be reduced if diet is already reduced in CHO
- GI disturbance because CHO reaches parts of colon not normally found in
Meglitinides mechanism of action
similar to sulfonylureas → Primary is increase in insulin secretion where it binds on beta cells receptors and similar mechanism to glucose (K+ATP channel closes, Ca opens etc. ). So bypass glucose metabolism and force insulin secertion
* Repaglinide
* Nateglinide
Meglitinides advantages
- low cost med
- No effect on plasma lipid levels
- no injections, oral med, start with small dose and titrate up
- Have huge and rapid effect, induces insulin excretion in a matter of seconds and reduces the plasma glucose
Meglitinides disadvantages
Similar to sulfonylureas
* weight gain
* Can build a tolerance (around 10 years)
* At risk of hypoglycaemia
* Only beneficial for those with mild to moderate hyperglycaemia (??)
* Need functional beta cells
SGLT2 Inhibitors mechanism of action
Acts directly on SGLT2 (sodium-glucose co-transporter) transporter in the kidney on the lumen side preventing reabsorption of glucose into blood stream so instead it goes into the urine and is excreted.
* Canagliflozin
* Dapagliflozin
SGLT2 Inhibitors advantages
- reduces body weight
- reduces blood pressure → not reabsoribing glucose so increases volume of urine to dilute and decrease body fluid overall and relieves the heart
- It improves glycemic control
- Reduces HbA1C
SGLT2 Inhibitors disadvantages
- May increase risk of infections
- can cause thirst
- dysuria - need to pee a lot
- UTI more likely
- Need kidney integrity which some diabetics in late stages have kidneys that dont work as well (contraindication)
Insulin mechanism of action
Different forms of insulin: rapid, longer acting, split dose regime, combination
* individualistic → person chooses what works best for them
* Got good at estimating how much they need
Insulin advantages
- may be useful for lowering very high fasting plasma glucose levels (>15.6 mmol/L)
- Can be used in gestational diabetes (oral is contraindicative)
Insulin disadvantages
- injection
- weight gain → coronary artery disease, hypertension, dyslipidemia
- risk of hypoglycemia (easy to be inadequately controlled)
GLP-1 analogs & DPP4 inhibitors mechanism of action
Both act on GLP-1 levels
* GLP-1 analogs: Exenatide, Liraglutide
* DPP4 inhibitors: Sitagliptin, Saxagliptin
What kind of hormone is GLP-1?
Glucagon-like peptide-1 (GLP-1) → an incretin hormone
* has similar gene to proglucagon but is cleaved differently in the intestine
