Insulin and oral Anti-diabetic drugs Flashcards
1
Q
Classification of the insulin preparations?
A
Insulin preparations:
- Short/rapid acting IP’s
- Intermediate IP’s
- Long acting IP’s
- Insulin combinations
- Insulin analogues
- Very short acting insulin analogues
- Long acting insulin analogues
- Ultra long acting insulin analogues.
2
Q
Pharmacodynamics of insulin preparations?
A
- Short/rapid acting: This functions to “mimic” the normal post pradinal insulin release. Normal insulin is administered 30 mins before a meal, but due to the rapid nature of this preparation it is administered 15 mins before meal.
- Intermediate acting insulin preparation: NPH (Neutral protamine hagedorn) is a complex structure comprised of protamine that reduces the solubility of the insulin preparation, prolonging its action. Used for Fasting control of glucose in type 1 and type 2 diabetes. Only administered subcutaneously. (Taken subcutaneously because insulin is a polypeptide, would be degraded by GIT if orally taken.
- Long acting insulin preparation: Produces a precipitation at the site of injection, causing a prolonged insulin release and gradual glucose internalisation. An example is “Insulin detemir, which is strongly associated to albumin, causing a slow dissociation. They should only be administered subcutaneously.
- Insulin combinations: Reduces the number of daily injections required for the patient, makes it more difficult to adjust doses.
- Insulin analogues: Human insulin is produced via a DNA recombinant process using E.coli and yeast, which are genetically modified for producing the gene for human insulin. If insulin itself is modified it can lead to the production of insulins with varied pharmacokinetic properties (onset of action, duration of activity). ADR’s - Hypoglycaemia, local injection site reactions and lipidodystrophy ( abdnormal degenerative condition of the body adipose tissue).
3
Q
Classification of the “Oral hypoglycaemic drugs?”
A
- Sulphonylureas
- Glinides
- Biguanides
- Alpha-glucosidase inhibitors
- Thiazolidinediones
- Dipetidyl-peptidates 4 inhibitors
- Sodium glucose co transport 2 inhibitors
4
Q
Pharmacokinetics of the oral hypoglycaemic drugs?
A
- Sulphonylureas: Oral absorption, bound to serum proteins, undergoes hepatic metabolism. urinary and fecal excretion.
- Glinides: Administration before meal favours a good oral absorption. Hepatic metabolism by CYP 3A4 into inactive metabolites.
- Biguanides: Good oral absorption, is not bound to plasma proteins. not metabolised and undergoes urinary excretion.
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- Alpha glucosidase inhibitors : “ACARBOSE” “MIGLITOL” are metabolised by the intestinal bacteria, metabolites are absorbed and excreted in the urine.
- Thiozolidinedione: (GLITAZONES) “PIOGLITAZONES” and “ROSIGLITAZONE, active metabolites of PIOGLITAZONE are excreted in the bile/feces. metabolites of ROSIGLITAZONE are lost in the urine.
- Dipetidyl peptidates 4 inhibitors: (LIPTINS) “ALOGLIPTIN”, “SITAGLIPTIN” undergo urinary excretion, “SAXOGLIPTIN” is metabolised by CYP3A4 isoenzyme into active metabolite and “LINAGLIPTIN” is eliminated via the enterohepatic system.
- Sodium glucose co transporter 2 inhibitor: Once daily in the morning. “CANAGLIFLOZIN” undergoes glucuronidation into inactive metabolite. 1/3 eliminated in urine and 2/3 in the feces.
5
Q
Pharmacokinetics of the “Incretin mimetics”? (TIDES)
A
Mostly administered subcutaneously, “LIRAGLUTIDE” has good plasma protein binding, allowing for a long half life. Taken once daily. “EXENATIDE” is eliminated via glomerular filtration and has a much shorter half life compared to liraglutide. Due to this it must be taken twice daily.
6
Q
Pharmacodynamics of the “Oral hypoglycaemic drugs”?
A
- Sulphonyureas: Function to inhibit the ATPase K+ channels, which leads to the exocytosis of insulin.
- Glinides: Have the same function to block the ATPase K+ channels, but has a faster onset of action compared to the sulphnoyureas.
- Biguanides: Function to reduce the hepatic gluconeogenesis, slow down intestinal absorption of sugars and increase peripheral uptake and utilisation of glucose.
- Alpha glucosidase inhibitrors: Acarbose and miglitol function to reversible block the alpha glucosidase enzymes found in the brush border of the intestines, reducing the rate of uptake of carbohydrates (slows conversion of carbohydrates to glucose/sugars), resulting in lower post pradinal glucose levels.
- Thiozolidindiones: Lower insulin resistance by acting as agonists “peroxisome proliferator activated receptor gamma”, which induces transcription for insulin responsive genes, reducing the resistance of insulin.
- Dipeptidyl peptidates 4 inhibitors: Inactivation of incretin hormones, via binding/inhibition of DPP-4 enzyme.
- Sodium-glucose cotransporter 2 inhibitors: The physiological function of the sodium glucose co transporter channel is for the reabsorbtion of filtered glucose in the tubular epithelium. Blockage of these channels by the inhibitors increases their excretion and lowers blood glucose concentration.
7
Q
Incretin mimetics pharmacodynamics? (TIDES)
A
Liraglutide and exenatide function to
- reduce gastric emptying time
- reduce post pradinal glucagon secretion,
- enhance satiety (fullness)
- Promote beta cell proliferation for the increased secretion of the insulin.
8
Q
Adverse drug reactions of the oral hypoglycaemic drugs?
A
- Sulphonyureas: Hypoglycaemia (excessive insulin) and hyperinsulinemia. (exocytosis action of the sulphonyureas)
- Glinides: hypoglycaemia and weight gain
- Biguanides: Gastrointestinal adverse effects. (It has 3 main functions).
- Alpha-glucosidase inhibitor: Flatulence, diarrhea and abdominal cramping.
- Thiozolidinediones: Liver toxicity and increase subcutaneous fat.
- Dipeptidyl peptidates 4 inhibitors: Nasopharngitis and headaches
- Sodium glucose co transporter 2 inhibitors: Female genital mycotic infections.
9
Q
Adverse effects of the incretin mimetics ?
A
Nausea, vomiting and constipation.
