Thyroid, diabetes, obesity etc. Flashcards
SGLT2 inhibitors (e.g. canagliflozin, dapagliflozin, empagliflozin)
Usage: Type 2 diabetes.
MOA: they promote glucose excretion into urine, thereby reducing the concentration of circulating hormones. The resulting glycosuria is associated with an osmotic diuresis and salt excretion.
Unwanted effects: natriuresis with diuresis can lead to increased urinary volume, hypotension, and dehydration.
Incretin mimetics (e.g. exenatide, liraglutide, semaglutide)
Usage: Type 2 diabetes.
MOA: GLP-1 agonists lower blood glucose after a meal by increasing insulin secretion, suppressing glucagon secretion, and lowering gastric emptying.
Biguanides (e.g. metformin)
Usage: type 2 diabetes.
MOA: the molecular target or targets through which biguanides act remain unclear, but their biochemical actions are described_
- Reduced hepatic glucose production, which is markedly increased in type 2 diabetes.
- Increased glucose uptake and utilization in skeletal muscle (reduced insulin resistance).
- Reduced carbohydrate absorption from the intestine.
- Increased fatty acid oxidation.
- Reduced circulating low-density and very-low density lipoprotein.
Unwanted effects: GI disturbances.
Sulfonylureas (e.g. tolbutamide, glibenclamide, gliclazide)
Usage: type 2 diabetes in early stages. They require functional beta cells.
MOA: acts on beta cells, stimulating insulin secretion and this reducing plasma glucose. High affinity of sulfonylureas are present on the Katp channels in the surface membranes of beta cells. Block by sulfonylurea drugs of Katp channel activation causes depolarization of beta cells, Ca2+ entry and insulin secretion.
Unwanted effects: generally well tolerated, but can cause hypoglycaemia.
Gliptins (e.g. sitagliptin)
Usage: Type 2 diabetes.
MOA: they competitively inhibit DPP-4, thereby lowering blood glucose by potentiating (increase the power of) endogenous incretins (GLP-1, GIP), which stimulate insulin secretion.
Side effects: usually well tolerated with a range of mild GI adverse effects; liver disease, heart failure, pancreatitis.
Thiazolidinediones (e.g. pioglitazone)
MOA: they act by enhancing the effectiveness of endogenous insulin, thereby reducing hepatic glucose output, and increasing glucose uptake into muscle. Thiazolidinediones bind to a nuclear receptor called PPAR-gamma, which is complexed with retinoid X receptor.
Unwanted effects: heart failure, bone fracture, oedema, and weight gain.
Orlistat
Usage: obesity.
MOA: In the intestine, orlistat reacts with serine residues at the active sites of gastric and pancreatic lipases, irreversibly inhibiting these enzymes and thereby preventing the breakdown of dietary fat to fatty acids and glycerol. It therefore decreases absorption of some of the dietary fat.
Radiodine
Usage: hyperthyroidism.
MOA: is taken up and processed by the thyroid in the same way as the stable form of iodide, eventually becoming incorporated into thyroglobulin. The isotope emits both beta and gamma radiation. The gamma rays pass through the tissue without causing damage, but the beta particles have a very short range; they are absorbed by the tissue and exert a powerful cytotoxic action that is restricted to the cells of the thyroid follicles, resulting in significant destruction of the tissue.
Side effects: hypothyroidism
Thioureylenes (carbimazole, propylthiouracil)
Usage: hyperthyroidism.
MOA: acts as competitive antagonist for tyrosine on the peroxidase iodinum complex. This decreases the output of hormones from the gland.
Unwanted effects: headaches, nausea, neutropenia (low concentration of neutrophils), agranulocytosis (low number of granulocytes).
Iodine/iodide
Usage: hyperthyroidism.
MOA: Temporarily inhibits the release of thyroid hormone (max effect 10-15 days). Inhibits iodination of thyroglobulin.
Side effects: allergic reactions.
Selective estrogen receptor modulators (SERMs) e.g. raloxifene, tamoxifen
Classified as selective estrogen receptor modulators (SERMs) because they can exhibit selective agonistic or antagonistic effects on estrogen receptors in different tissues.
Aromatase inhibitors e.g. anastrozole
Blocks the estrogen synthesis in the adrenal but not in the ovary.
Clomiphene
Inhibits estrogen binding to its receptor in the anterior pituitary, so preventing negative feedback and acutely increasing secretion of GnRH and gonadotrophins.
Ulipristal
Antiprogestogens.
Ulipristal is a selective progesterone receptor modulator (SPRM). It works primarily by inhibiting or delaying ovulation, thereby preventing the release of an egg from the ovary. Additionally, ulipristal may alter the endometrial lining, making it less receptive to implantation of a fertilized egg. It is used for emergency contraception within 120h of vaginal intercourse.
Cyproterone (anti-androgens)
A partial agonist. Cyproterone is a potent antiandrogen, meaning it blocks the effects of androgens (male hormones) in the body. It works by competitively inhibiting the binding of dihydrotestosterone (DHT) and testosterone to androgen receptors, thereby reducing the action of these hormones.
