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Characterized by high levels of blood glucose that result from either action of insulin now the two most commonly encountered types of diabetes insulin production and the second is type 2 in which there is insulin is insulin and how does it work well it all starts with the food that we eat following a meal when the blood glucose levels rise beta cells of the pancreas insulin
Receptor and stimulates glucose uptake by our cells now under the glycogen many other cells quickly break down absorbed glucose to make atp a think of insulin as a key for entrance of glucose into cells which either use happens when blood glucose levels fall too low well if that’s the case alpha glucagon glucagon simply has the opposite effect of insulin so for into glucose
Which is then released into the bloodstream group of agents i would like to discuss is insulin and it’s analogs so human the amino acid sequence of human insulin can also be altered to produce insulin is a polypeptide it is susceptible to degradation in the gastrointestinal subcutaneous injection insulin preparations are generally divided into we have rapid and short acting
Insulins preparations that fall into this considered as rapid-acting producing peak effect in as quickly as 30 minutes group is regular insulin which is considered as short-acting with peak hours now you may wonder what gives these analogs the ability to act quickly so-called hexamers that is six insulin molecules bound together these hexamers therefore they must first
Separate into single insulin molecules before amino acid sequence of insulin molecules to make them less likely to aggregate intermediate acting insulin preparation that falls into this category is nph insulin has a little slower onset of action it produces peak effect lasting effects are accomplished simply by addition of zinc and protamine to outcome is delayed absorption
And thus longer duration of action finally we into this category are the following insulin detemir with a peak effect next insulin glargine which doesn’t produce peak effect due to its steady which also doesn’t produce peak effect and lasts beyond 24 hours and again all molecule in case of insulin detemir fatty acid side chain was added to the release into the bloodstream
Insulin glargine on the other hand was modified the subcutaneous tissue that slowly releases insulin into the bloodstream in subcutaneous tissue that serve as a depot from which insulin is surprisingly hypoglycemia or low blood glucose is the most common one which can develop at the site of repeated insulin injections now let’s analog used in treatment of diabetes that
Is synthetic amylin so first of secrete insulin but also another peptide hormone called amylin glucagon secretion and to promote satiety available on the market is pramlintide one of the biggest benefits of hypoglycemia is still there other common are nausea and modest weight loss now let’s move on to the last group of incretins are a group of metabolic hormones that are
Secreted from the gut more insulin the two primary incretin hormones are glucagon-like peptide-1 short so in theory increasing concentrations of these hormones would actually quite limited as a result of rapid inactivation by the were able to develop glp-1 mimetics that are resistant to degradation by liraglutide in addition to stimulating insulin secretion glp-1 mimetics
Slow often experience weight loss some common side effects also include gi problems associated with the use of glp-1 mimetics this is thought to be due to i would like to discuss a class of drugs closely related to glp-1 mimetics hormones is to simply inhibit dpp-4 enzyme which is responsible for the hormones we increase insulin secretion decrease gastric emptying and reduce
Linagliptin saxagliptin and sitagliptin side effects of dpp-4 inhibitors nasopharyngitis and headache now let’s move on to another class of oral antidiabetic agents that is sulfonylureas so in order to understand how dependent insulin secretion from pancreatic beta cells so available once inside the cell glucose gets metabolized to create a bunch of atp channels thus blocking
The inflow of potassium this in turn leads to voltage-gated calcium channels and then influx of calcium finally increased membrane leading to insulin release so now what sulfonylureas do is they bind to and inhibit the activity of atp-sensitive potassium channels this just ultimately insulin secretion other actions of sulfonylureas include production example of drugs that
Belong glipizide some of the common side effects reported with sulfonylureas are protein bound and most are extensively metabolized in the liver by cytochrome move on to another class of oral antidiabetic agents that is glinides secretion from pancreatic beta cells however they accomplish that by binding kinetics than sulfonylureas as a result they have a more rapid onset
And shorter primarily postprandial hyperglycemia example of drugs that belong to this class are nateglinide and repaglinide common side effects include to sulfonylureas now let’s move on to another class of oral antidiabetic mechanism of action of biguanides is not entirely understood that being said the reduction of hepatic glucose production additionally biguanides appear
To slow enhances peripheral glucose uptake the only biguanide that’s currently are limited to gi tract and include nausea vomiting diarrhea and loss of hepatic uptake of lactate it may increase risk of lactic acidosis failure or renal impairment now let’s move on to another class of oral called peroxisome proliferator-activated activated this receptor binds to dna triggering
Expression and repression of well as insulin signal transduction this leads to effects such as increased inhibition of hepatic glucose production additionally thiazolidinediones in fatty acid concentrations in turn leads to increased uptake and pioglitazone and rosiglitazone now when it comes to side effects in addition to this increase is especially pronounced with the use
Of pioglitazone in part because of its effects not only on ppar-gamma but also on ppar-alpha as you may which promote the formation of hdl may also increase ldl levels however this increase appears to be limited only to larger less atherogenic ldl particles as for the other with weight gain and fluid retention leading to peripheral edema few cases of of oral antidiabetic
Agents that is sodium-glucose cotransporter-2 inhibitors responsible for about 90% of glucose reabsorption inhibition of thus reduced levels of blood glucose furthermore this increase in glucose and small reduction in blood pressure and weight loss drugs that belong to this class include canagliflozin and dapagliflozin when it comes to side urinary tract and genital infections
Now antidiabetic agents that is alpha-glucosidase inhibitors so first in the intestinal brush border that is responsible for breaking down inhibitor blocks this enzyme the absorption of glucose is delayed include acarbose and miglitol now one of the biggest effects which include abdominal cramps bloating flatulence and diarrhea and and as always stay tuned for more
Transcribed from video
Pharmacology – DRUGS FOR DIABETES (MADE EASY) By Speed Pharmacology
