Hormonal drugs ( Insulin drugs )
Hormonal drugs
(1) Pancreatic hormones
Pancreas is an exo- and endocrine organ. It releases hormones into blood: insulin and glucagon.
Insulin
Diabetes mellitus (DM) is a clinical syndrome caused by absolute or relative insulin deficiency, leading to metabolic disorders: chronic hyperglycemia and glycosuria, suppression of the synthesis of proteins, lipids, vascular disease (diabetic angiopathy), neuropathy and pathological changes in various organs and tissues.
Type 1 diabetes is an insulin-dependent one and it makes 5-10% of total diabetic diseases characterized by the destruction of the β-cells of Langerhans’ islets, whereas α-cells that produce glucagon and D-cells producing somatostatin are preserved. Type 2 diabetes, insulin-dependent, is 90-95% of the total number of cases of diabetes. It is associated with the decrease in insulin secretion due to decreased activity of β- cells and / or the development of resistance to insulin.
Insulin drugs
Currently used:
1. Recombinant (genetically engineered, biosynthetic) drugs of human insulin;
2. Semisynthetic human insulin drugs obtained from pig’s insulin;
3. Monocomponent (highly-purified) insulin drugs, obtained from pig pancreas (monocomponent pig’s insulin).
Classification of insuling drugs according to the duration of action
1. The short-acting drugs:
A. Human insulins: Actrapid HM, Humulin R, insuman P
B. The insulin analogs of ultra-short action: Humalog, NovoRapid or insulin aspart
2. The drugs of average duration:
Human insulin: Protaphane HM, Monotard HM, Humulin N, Insuman-basal
3. The long-acting drugs:
Human insulin: Ultratard HM, Humulin-ultralente
4. Mixed insulin:
Humulin 70/30
Pharmacodynamics of insulin drugs
The mechanism of action. Insulin is synthesized as a proinsulin in β- cells of Langerhans’ islets and in the secretory granules it turns into insulin. The granules are released by exocytosis. One distinguishes basal (constant) insulin secretion (approximately 1 UA per hour) and the secretion of insulin stimulated by the increase in glucose level in plasma during food intake (1.5 units per 10 g of carbohydrate). Insulin stimulates cell membrane receptors conjugated with tyrosine kinase. Therefore insulin:
1. promotes the absorption of glucose into cells of tissues (except CNS) – mainly by skeletal muscles, adipose tissue. This activates the cytoplasmic membrane translocation in transport systems for glucose – GLUT;
2. reduces the intensity of hepatic gluconeogenesis;
3. stimulates the formation of glycogen and its storage in liver and muscles;
4. activates protein and lipid synthesis, inhibits their catabolism.
Duration of action of insulin drugs
Insulin drugs of short action
Drugs: Actrapid HM, Humulin-regular, normal-insulman and others. The onset of action is in 15 - 30 min., the peak of action – 2-4 hours, duration of action – 6-8 h. Usually administered S/C 20-30 min before meal. If necessary – I/M or I/V. The drugs are administered with the help of special insulin syringes or pen-syringes in which an insulin drugs is contained in a special cartridge (Penfill).
Insulin drugs of ultra-short action
Insulin lispro, insulin aspart, insulin Humalog are characterized by more rapid onset of action - 10 - 15 min. after administration and a short duration of action - 3 - 4 hours. The disadvantage of these drugs is the need for frequent repeated injections.
Insulin drugs of average duration of action
hey are called the drugs of prolonged type of action. In the drugs like Lente the slowdown of absorption speed of insulin is associated with the presence of zinc-insulin crystals of various sizes. In NPH-insulin drugs (basal-insuman, protofan) a protein called protamine is used. It is obtained from salmon milt.
Depending on the prolongator, they can be:
1. insulins such as lente and ultralente
2. NPH (neutral protamine of Hagedorn) – insulins.
Drugs: Insulin isophane (human biosynthetic) – suspension of insulin with protamine. Synonyms: Insuran NPH Insumanbazal HT Protafan NM NM Protafan Penfill, Humulin NPH.
Zinc insulin (human biosynthetic) – combined suspension. Zinc insulin suspension. Synonyms: Monotard HM, Humulin L.
Insulin isophane (human semisynthetic). Synonyms: Brinsulmidi H, Pensulin HC. Insulin-zinc (human semisynthetic) – combined suspension. Synonyms: Brinsulmidi B, Insulidd L.
Insulin isophane (porcine monocomponent). Synonyms: Pensulin SS, Protaphane MC.
Insulin-zinc (porcine monocomponent) – combined suspension. Insulinisophane (porcine monocomponent) – compound suspension. Synonyms: Brinsulmidi IR, Insulin-Long SMC.
The onset of action of the drugs of the average duration is in 2 - 2.5 hours after administration; maximum action is in 8-10 h., duration of action - 18 - 24 hours. The drugs have their pH level close to the pH of body tissues and they are hardly destroyed at the injection site, while retaining activity.
NPH insulins can be mixed in the same syringe with a short-acting drugs without changing the pharmacokinetics of the component parts. But insulin drugs such as Lente must not be mixed in the same syringe with a short-acting drugs.
These drugs are similar in properties and usage with the corresponding drugs of recombinant insulin.
Insulin drugs of prolonged action
Suspension of crystalline insulin-zinc (biosynthetic human). Synonym – Ultratard HM. Only S/C administration. The onset of action is in 4 hours and peak action is in 8 - 12 hr., The duration of action is 24 - 48 hours.
Insulin-glargine (Insulinglargin; Lantus) is a recombinant peak-less human insulin analog. Duration of action – 24 hours.
Insulin drugs of combined action
The combination of insulin or short-acting insulin drugs with isophane-insulin provides rapid and long action.
Biphasic insulin (human biosynthetic). Synonyms: Mixtard 30 HM, Mixtard 30 HM Penfill, Humulin M3. S/C administration. The onset of action is in 30 min., peak of action is in 2 - 8 hr., the duration of action is 18 - 20 hours.
Insulin aspart dvuhfaznyy.Insulinaspartbiphasic. Synonyms: NovoMix 30 Penfill, NovoMix 30 FlexPen. S/C administration. The onset of action is in 10 - 20 min., The peak of action is in 1 - 4 hrs. The duration of action is in 24 hours.
Indications
According to the requirements of the Pharmacological Committee of the Ministry of Health it is recommended to use:
• recombinant or biosynthetic human insulin for the treatment of children, teenagers and pregnant women suffering from diabetes;
• human insulin for the treatment of adult patients with type 1 diabetes;
• human insulin and possibly monocomponent porcine insulin drugs for insulin-demanding patients with type 2 diabetes.
The schemes of DM treatment with different insulin drugs
Currently, there are several different treatment regimens for DM:
1. Short-acting insulin (Actrapid, Humulin-regular, insuman-Rapid, etc.) is administered before the main meals (breakfast, lunch, dinner) and insulin od average duration of action (monotard, Protaphane, Humulin NPH, insuman-basal and etc.) - before breakfast and before bedtime (at 10 or 11 pm).
2. Short-acting insulin (Actrapid, Humulin-regular, insuman-Rapid, etc.) is administered before main meals (breakfast, lunch, dinner), and at night at 11 pm. - Ultratard HM or Humulin-ultralente. Instead of long-acting insulin, some patients may use average-acting insulin at the same time (11 pm).
In this regimen the administered long-acting insulin drug imitates the basal insulin secretion, and short-acting insulin administered 30 min. before meal provides an additional peak of insulin increase in the blood, which coincides in time with the postprandial (after meal) hyperglycemia.
These schemes are often complemented by the administration of 1 - 2 injections of short-acting insulin if necessary before lunch and afternoon tea.
Complications of insulinotherapy
1. Hypoglycemia. The most common complication of insulin therapy. Often occurs as a result of delayed food intake, exercise, or as a result of excessively high doses of insulin.
2. Insulin allergy. Often occurs when using animal insulins.
3. Insulin resistance. IgG neutralizes the effects of insulin to some degree. In most patients its titer is low. Sometimes, especially in obese patients or patients treated with animal insulins the titer of antiinsulin IgG is increased. This leads to increased resistance and insulin dose. The shift to highly purified human insulins reduces the insulin doses.
4. Lipodystrophy at the injection site. Atrophy of subcutaneous fat can be developed. At present it is rarely noticed because of the creation of highly purified human insulin injection that are injected directly to the site of atrophy, and on the contrary, it often leads to tissue repair.
