Insulin and Oral antidiabetics Flashcards
Routes of administration of insulin?
subcutaneous, intramuscular, intravenous
Clinical uses of Insulin?
T1 Diabetes, Hyperglycemic diabetes emergencies (DKA/HHS), chronic T2 DM, gestational DM (not so impt to know) + hyperkalemia at late stages
Adverse effects of Insulins?
- Hypoglycemia (extreme opposite of the intended effect)
- Rebound hyperglycemia (Somogyi effect)
- Allergy due to anti-insulin IgE antibodies (body creates antibodies towards insulin)
- Insulin resistance (down regulation of insulin receptors)
What is the drug class related to Insulin secretagogues?
Sulfonylureas
What are the 2 drug class of Insulin sensitisers?
Biguanides (Metformin) and Thiazolidinediones (Rosiglitazone, Pioglitazones**) –> the -zones
What are the few drug class related to insulin sparing agents?
SGLT2 inhibitors, Alpha-glucosidase (Acarbose), GLP-1 receptor agonists (Exenatide, -glutides like Liraglutides), DPP-4 inhibitors (Sitagliptins, -gliptins)
What’s the indication of Sulfonylureas? Explain MOA of Sulfonylureas simply and give examples of them
Indication: T2 DM
- increase insulin release/secretion from pancreatic beta cells
- reduction of serum glucagon concentrations
Some examples: (-amides)
Glibenclamide, Tolbutamide, Chlorpropamide
Adverse effects of Sulfonylureas
Hypoglycemia,
Gastrointestinal irritations/upsets, weight gain, Allergic skin rash, bone marrow damage, increase in CVS death
what is an example of Biguanides? what is it often called in toxicity? (x-toxic) –> what is X?
What is its indications?
Metformin.
Nephrotoxic since its excreted by the kidneys
T2 DM, insulin resistance
MOA of Biguanides?
- Increases insulin sensitivity by increasing insulin receptor density
- direct stimulation of glycolysis in tissues, with increased glucose removal from blood
- decreased hepatic and renal gluconeogenesis
- slowing glucose absorption from the GIT
- decrease in plasma glucagon levels
Contraindications of biguanides?
Anorexia
hepatic and renal disease
alcoholicism patient
conditions r/t tissue anoxia
Side effects of biguanides?
Anorexia (low BMI patients), GI effects (nausea, vomitting, abdominal pain, diarrhoea), decreased vitamin B12 absorption
Indications of Thiazolidinediones (Tzds)? Give the examples of them
T2 DM. Rosiglitazone, Pioglitazone (-zones)
PPAR-gamma heterodimerise w another transcription factor (Retinoid X receptor (RXR)),
Tzds bine to PPAR-gamma- Rxr complex so complex binds DNA and promotes several genes transcriptions
MOA of thiazolidinediones
- Decrease hepatic glucose output
- increase glucose uptake into muscle tissues and adipocytes
- decrease triglyceride levels in blood, and enhancing uptake of fatty acids and glucose, + lipogenesis.
Side effects of Thiazolidinediones??
Who should not use Tzds?
Hypoglycemia (w. sulfonylurea and insulin), weight gain, fluid retention (edema), hepatotoxicity
Contra: liver disease, heart failure patients
Give the indication of Alpha-glucosidase inhibitors and an example of this class of drug.
Used for T2 DM. Acarbose, a pseudo, tetrasaccharide
MOA of alpha-glucosidase?
How should a patient take this drug?
delay digestion of specific polysaccharides (carbohydrates) and absorption of sugars into the gut.
Take it before meals.
Side effects of alpha glucosidase?
GI Sx: Flatulence, diarrhoea, increased liver enzymes*
Give examples of GLP-1 Receptor agonists and DPP-4 Inhibitors.
Indicated for?
GLP1: Exenatide, and -glutides (Liraglutides, Dulaglutides, Albiglutides)
DPP4 Inhibitors: -gliptins (Sitagliptin, Linagliptin, Alogliptin, saxagliptin, vildagliptins) –> remember the first 2 and the suffix if u cant remember the rest
Used for T2 DM
MOA for DPP4 inhibitors and GLP1 receptor agonists??
GLP1: increases incretin action, increasing GLP1 and GIP hormones,
1. increasing insulin release, increased cellular glucose uptake
2. decreased glucagon release, decreased glucose production hence decreased hepatic glucose output
DPP4:
increases incretin action
DPP4 enzyme deactivates GLP1 and GIP,
MOA:
- decreased glucagon release –> decrease glucose production –> decreased hepatic glucose output
- decreased gastric emptying
Both drugs work on the same pathway
Side effects for GLP1 and DPP4?
GLP1: Weight loss, GI problems, risk of pancreatitis (?)
DPP4: GI and flu Sx (headaches, runny nose, sore throat, nasopharyngitis, nausea, stomach pain, diarrhoea)
Indications for Sodium Glucose Cotransporter 2 inhibitors?
Give example of such drugs.
Indicated for t2 DM, but good for diabetic patients with CVS disorders (Chronic heart failure)
-Gliflozin drugs
(e.g. Dapagliflozin, Empagliflozin, Canagliflozin)
MOA of SGLT2 inhibitors?
Blocks the reabsorption of glucose in the proximal convoluted tubule (PCT) in the kidneys by blocking the sodium-glucose cotransporter pump. Hence, increased glucose excretion (in the urine) and decreased blood glucose levels
Other mechanisms:
-increased insulin sensitivity and uptake of glucose in muscle cells
-decrease gluconeogenesis
-improved first phase insulin release
Drawbacks/ Adverse effects of SGLT2 inhibitors?
increased genital infections and increased urinary tract infections
