hormones i protein-peptide: i protein-peptide: 1. hypothalamus 2. pituitary gland 2. pituitary gland...

HormonesHormones

I I Protein-peptideProtein-peptide:: 1. 1. Hypothalamus Hypothalamus 2. 2. Pituitary glandPituitary gland 3. 3. Parathyroid glandsParathyroid glands 4. 4. Pancreas Pancreas 5. 5. IntestinalIntestinal II II Derivatives of amine acidsDerivatives of amine acids:: 1. 1. Thyroid glandThyroid gland – – derivatives of thyroninderivatives of thyronin 2. 2. Medulla of suprarenal glandsMedulla of suprarenal glands – – catecholaminescatecholamines

IIIIII SteroidSteroid::

1. 1. Adrenal cortexAdrenal cortex 2. 2. Sex glandsSex glands

Feedback regulation in endocrine systemFeedback regulation in endocrine system

Hormones and hormonal drugs of Hormones and hormonal drugs of protein and polypeptide structureprotein and polypeptide structure

PancreasPancreas

Langergans isletsLangergans islets

Regulation of insulin secretion by glucoseRegulation of insulin secretion by glucose

Mechanism of insulin secretionMechanism of insulin secretion

to insuline

Influence of insulin on Influence of insulin on metabolismmetabolism

Type of metabolism

Stimulation Depression

Carbohydrate Synthesis of glycogen (in liver and muscles)Transport of glucose into a cell GlycolysisPhosphorilation of glucose

Glycogenolysis Glyconeogenesis Glycosilyting of proteins

Fat Synthesis of triglyceridesSynthesis of fatty acids Income of glucose in adipocytesActivity of lipoprotein lipase

Lipolysis Production of keton bodies

Protein Synthesis of proteinsAbsorption of amine acids

Disintegration of proteins

Nucleonic acids

Synthesis of cyclic nucleotides (c-AMP and c-GMP)

Absorption of nucleonic acidsSynthesis of RNA and DNABiosynthesis of ribonucleotides

1 Lung Cancer, 2 Criminality, 3 Stroke, 4 Breast Cancer, 5 Same Sex Attraction, 6 Leukemia, 7 Malformation, 8 Alzheimer’s, 9 Ulcerative Colitis, 10 Rheumatoid Arthritis, 11 Alcoholism, 12

Schizophrenia, 13 Depression, 14 Suicide attempt, 15 Diabetes type I, 16 Divorce, 17 Crohn’s disease, 18 Asthma, 19

Hypertension, 20 Co twin is best friend, 21 Diabetes type II, 22 Autism, 23 Opposite Sex Attraction, 24 Phenylketonuria

diabetes epidemicdiabetes epidemic

• The rate of new diabetes cases nearly doubled in the The rate of new diabetes cases nearly doubled in the United States in the past 10 yearsUnited States in the past 10 years

Worldwide:Worldwide:• 2007 - 2007 - 246 246 billionsbillions, ,

tilltill 2025 – 380 2025 – 380 millions patientsmillions patients • 90% 90% of patients – diabetes of patients – diabetes 2 type2 type

• tilltill 20 2019 annual profit from antidiabetic drugs – 19 annual profit from antidiabetic drugs – 29 billions $29 billions $

• Diabetes experts said the findings show there is no Diabetes experts said the findings show there is no end in sight to the diabetes epidemic and end in sight to the diabetes epidemic and

• it will get worse before it gets betterit will get worse before it gets better

Complications Associated With DiabetesComplications Associated With Diabetes

• Atherosclerosis:Atherosclerosis: Heart attacks and strokes related to the development of atherosclerotic plaques in the vessel lining

• Retinopathy:Retinopathy: With resultant loss of vision as tiny vessels in the eye are narrowed and closed

• Neuropathies:Neuropathies: With motor and sensory changes in the feet and legs and progressive changes in other nerves as the oxygen is cut off

• Nephropathy:Nephropathy: With renal dysfunction related to changes in the basement membrane of the glomerulus

• NASHNASH: non-alcoholic steatohepatitis: non-alcoholic steatohepatitis

Complications Associated With DiabetesComplications Associated With Diabetes

RetinopathyRetinopathy

normalnormal

Insulin drugsInsulin drugs Group Onset Duration of

actionTrade names Routs of

introduction

1. Simple (short duration of action)

20-40 min 4-6-8 hours Iletin, Insul-rapid, Humalog, Humalin R, Actrapid

S.c., i.m.,

i.v.

2. Medium (moderate) acting (on neutral protamine of Hagedorne - NPH

1-1,5 hour 12-14 hours Insuman, Humulin N

S.c., i.m.

3. Long acting (contain Zinc)

6-8 hours 24 hours (till 36 hours)

Insulin-Zn-suspension, Ultratard n-m

S.c., i.m.

4. Standard mixtures of drugs of 1st group with NPH-insulins

20-60 min Till 18 hours Insuman Comb: 30% / 70%, 25% / 75%, 20% / 80%, 10% / 90%

S.c., i.m.

Types of Insulin DeliveryTypes of Insulin Delivery

• PastPast– Subcutaneous injectionSubcutaneous injection

• PresentPresent– Subcutaneous injection, insulin jet Subcutaneous injection, insulin jet

injector, insulin pen, extended insulin injector, insulin pen, extended insulin pump, long-acting insulinpump, long-acting insulin

• FutureFuture– Implantable insulin pump, insulin patch, Implantable insulin pump, insulin patch,

inhaled insulin (?), oral insulin (?)inhaled insulin (?), oral insulin (?)

Subcutaneous Subcutaneous injectioninjection

Insulin pumpInsulin pump

Indication for usage of insulin drugsIndication for usage of insulin drugs:: Patients with diabetes mellitusPatients with diabetes mellitus::

1.1. Absolutely indicated in case of diabetic coma and Absolutely indicated in case of diabetic coma and precomaprecoma

2.2. Diabetes mellitus of I type if diet therapy and other Diabetes mellitus of I type if diet therapy and other sugar decreasing means aren’t enough effectivesugar decreasing means aren’t enough effective. .

3. 3. Diabetes of any type if it is accompanied by Diabetes of any type if it is accompanied by complicationscomplications ( (ketoacidosis, infection, gangrene etc.)ketoacidosis, infection, gangrene etc.)

4.4. Surgeries + DMSurgeries + DM5.5. Pregnancy + DMPregnancy + DM

Other casesOther cases::

- In case of long-lasting exhausting illnesses.- In case of heart, liver, kidney diseases the drugs are administered with glucose or

as a component of polarizing mixture.- Shock therapy of schizophrenia.

TREATMENT OF HYPERGLYCEMIC TREATMENT OF HYPERGLYCEMIC KETOACIDIC COMAKETOACIDIC COMA

1.1. Introduction of insulinIntroduction of insulin ((only insulin of short action is only insulin of short action is usedused) )

• intravenously dropplyintravenously dropply counting 0,1 0,1 UU//kgkg of body weight of body weight per hourper hour. First two hours – with the speed of 8 U/hour. If the initial glycemia is higher than 33,3 mmol/lл insulin dose in first hour is increased till 16 U. In case of decreasing of sugar level on 25-50 % from the initial level the speed of introduction of insulin is correspondingly decreased on 25-50 %. If glycemia is lower than 16,6 mmol/l insulin should be introduced with the speed of 4 U/hour. In case of decreasing of sugar level lower than 11 mmol/l, it is recommended to transfer to subcutaneous introduction of the drug every 6-8 hours.

• Glycemia should not be decreased faster than 5 mmol/l/hour, otherwise it is possible to promote brain edema. The level of glycemia should be examined The level of glycemia should be examined every every 30-60 30-60 minutesminutes..

TREATMENT OF HYPERGLYCEMIC TREATMENT OF HYPERGLYCEMIC KETOACIDIC COMAKETOACIDIC COMA

2. Elimination of dehydration and dehydration and hypovolemiahypovolemia: intravenous dropping introduction of liquids: during 1st hour 1 l of 0,9 % NaCl (better – Ringer’s solution) is introduced, during the next 2 hours – 500 ml of 0,9 % NaCl each hour, and after not more than 300ml/hour. In case of decreasing of glycemia level lower than 14 mmol/l, 0,9 % NaCl should be substituted by 5-10 % glucose solution

TREATMENT OF HYPERGLYCEMIC TREATMENT OF HYPERGLYCEMIC KETOACIDIC COMAKETOACIDIC COMA

3. Acidosis correction3. Acidosis correction – solution of sodium hydrocarbonate (if pH lower than 7,1)

4. Correction of electrolyte disorders4. Correction of electrolyte disorders: after 2 hours from beginning of treatment intravenous dropping introduction of КСІ dosed 2 g/hour should be started under the constant control of potassiumemia

TREATMENT OF HYPERGLYCEMIC TREATMENT OF HYPERGLYCEMIC KETOACIDIC COMAKETOACIDIC COMA

5. Symptomatic treatment5. Symptomatic treatment: for correction of blood pressure only introduction of mesatone is possible, since other adrenomimetics stimulate glycogenolysis and increase sugar level in blood

TREATMENT OF TREATMENT OF HYPOGLYCEMIC COMAHYPOGLYCEMIC COMA

• Intravenous bolus introduction of Intravenous bolus introduction of 20-50 20-50 mlml of of 40 % 40 % glucose (dextrose) solutionglucose (dextrose) solution. .

• If the condition doesn’t improve, afterIf the condition doesn’t improve, after 10-20 10-20 minutes minutes the injection should be repeatedthe injection should be repeated. .

• In case of absence of effect - intravenous dropping In case of absence of effect - intravenous dropping infusion of infusion of 5 % 5 % glucose solutionglucose solution should be started should be started. .

• Correction of blood pressure and stimulation of Correction of blood pressure and stimulation of glycogenolysisglycogenolysis – – adrenalinadrenalin hydrochloride hydrochloride. .

• Prophylaxis and treatment of brain edemaProphylaxis and treatment of brain edema – – mannitmannit, , glucocorticosteroidsglucocorticosteroids

SYNTHETIC ANTIDIABETIC SYNTHETIC ANTIDIABETIC PREPARATIONSPREPARATIONS

(taken orally)(taken orally)

Derivatives of sulfonylureaDerivatives of sulfonylurea – – 4 4 generationsgenerations

ІІ ( (appeared in theappeared in the 50- 50-ss) – ) – chlorpropamidchlorpropamid, , butamidbutamid, , bucarbanbucarban; ;

ІІІІ ( (introduced afterintroduced after 1967) – 1967) – glybenclamidglybenclamid ((maninilmaninil); );

ІІІІІІ – – glymeperidglymeperid ( (amarylamaryl););

ІУІУ – – repaglynidrepaglynid

Possible mechanism of hypoglycemic action of derivatives of sulfonylurea

butamid, chlorpropamidbutamid, chlorpropamid

Block ofBlock of ATPATP--dependent dependent К+ -К+ -canals ofcanals of --cellscells

Depolarization of membranes ofDepolarization of membranes of --cellscells

Opening of potential-depending Opening of potential-depending Са Са 2+2+ - -canals ofcanals of --cellscells

Entering of Entering of Са Са 2+2+ intointo --cellscells

Secretion of insulinSecretion of insulin

Classification of biguanidesClassification of biguanides

1.1. PhenilethylbiguanidsPhenilethylbiguanids ( (phenphorminphenphormin););

2.2. ButhylethylbiguanidsButhylethylbiguanids ( (buphormin-buphormin-glibutidglibutid););

3.3. Dimethylbiguanids Dimethylbiguanids ((methphorminmethphormin – – glucophageglucophage))

Mechanism of action of biguanidesMechanism of action of biguanides

Mechanism of sugar-decreasing action of biguanidsMechanism of sugar-decreasing action of biguanids – – influence of peripheral tissuesinfluence of peripheral tissues: :

1.1. increasing of action of endogen insulin due to increasing of action of endogen insulin due to increasing increasing of quantity and sensitivity of insulin receptorsof quantity and sensitivity of insulin receptors; ;

2. 2. decreasingdecreasing of absorption of glucose in intestines, of absorption of glucose in intestines, blockade of gluconeogenesisblockade of gluconeogenesis; ;

3. 3. increasingincreasing of synthesis of glycogen in liverof synthesis of glycogen in liver; ; 44. . increasingincreasing of glucose metabolismof glucose metabolism till stage of lactate in till stage of lactate in

musclesmuscles..

Biguanides depress lipogenesis and stimulate lipolysis, Biguanides depress lipogenesis and stimulate lipolysis, which leads to body weight loss in obese patientswhich leads to body weight loss in obese patients

GlitazonesGlitazones --ТІАТІАZOLIDINDIONESZOLIDINDIONES

• Increase susceptibility of peripheral Increase susceptibility of peripheral tissues to insulintissues to insulin

• TroglitazoneTroglitazone – 1– 1st preparation with high st preparation with high hepatotoxicity hepatotoxicity

• Rosiglitazone and Rosiglitazone and PioglitazonePioglitazone – – are widely used, are widely used, especially for insulin resistance, diabetes 2especially for insulin resistance, diabetes 2

Sites of Action of Drugs Used to Treat Sites of Action of Drugs Used to Treat DiabetesDiabetes

Hormonal preparations Hormonal preparations of thyroid glandof thyroid gland

Thyroid GlandThyroid Gland

parathyroids

Front view Posterior view

Types of Thyroid DysfunctionTypes of Thyroid Dysfunction

• HHypothyroidismypothyroidism– UnderactivityUnderactivity

• HyperthyroidismHyperthyroidism– OveractivityOveractivity

Struma (goiter) and Struma (goiter) and hyperthyroidismhyperthyroidism

HypothyroidismHypothyroidism

ThyrotoxicosisThyrotoxicosis

Congenital hypothyroidismCongenital hypothyroidism(physical and mental retardation (physical and mental retardation

– nanism - pygmy, idiotism– nanism - pygmy, idiotism

Drugs of thyroid hormonesDrugs of thyroid hormones

Name Contents, origin Onset Duration of action

Way of introduc-tion

Thyreoidine Thyreoidine (Thyroxin(Thyroxin + + threeiodthyronin)threeiodthyronin) extract from extract from thyroid glandthyroid gland

2-3 2-3 daysdays 3-4 3-4 weeksweeks OrallyOrally

Threeiodthyronin Threeiodthyronin (liothyronin) (liothyronin)

Synthetic Synthetic 4-8 4-8 hourshours 8-10 8-10 daysdays Orally Orally

Levothyroxin-Levothyroxin-sodium sodium ((L-L-thyroxin-sodiumthyroxin-sodium))

Synthetic Synthetic 3-4 3-4 daysdays ((max.max. 8-10 8-10 daysdays))

6–8 h6–8 h

2-4 2-4 weeksweeks

peak 24–peak 24–48 h48 h

6-7 days6-7 days

Orally Orally

IV IV

LL -- thyroxinthyroxin

ThyreocombThyreocomb((thyroxinthyroxin + + threeiodthyroninthreeiodthyronin))

Thyreotom Thyreotom ( (thyroxinthyroxin + + threeiodthyroninthreeiodthyronin))

Antithyroid drugsAntithyroid drugs

1)1) Depression of production of TTHDepression of production of TTH -- iodineiodine -- diiodithyrosine diiodithyrosine ( (dithyrinedithyrine))2)2) Depression of synthesis of hormones in thyroid glandDepression of synthesis of hormones in thyroid gland -- mercasolilmercasolil -- propilthiouracyl propilthiouracyl

3)3) Disturbance of absorption of Disturbance of absorption of ІІ22 by thyroid glandby thyroid gland -- potassium perchlorate potassium perchlorate

4)4) Destroying cells of thyroid gland follicles Destroying cells of thyroid gland follicles -- radioactive iodine radioactive iodine (І (І131131) )

Adverse Effects of Iodine Adverse Effects of Iodine SolutionsSolutions

• Hypothyroidism

• Iodism (metallic taste and burning in the mouth, sore teeth and gums, diarrhea, cold symptoms, and stomach upset)

• Staining of teeth

• Skin rash

• Development of goiter

Calcium Control in the BodyCalcium Control in the Body

Parathyroid Dysfunction• Hypoparathyroidism

– The absence of parathormone– Most likely to occur with the accidental

removal of the parathyroid glands during thyroid surgery

• Hyperparathyroidism – The excessive production of parathormone– Can occur as a result of parathyroid tumor or

certain genetic disorders

Hormones of pituitary gland

Deficit of GHDeficit of GH

Overproduction of GHOverproduction of GH

Posterior pituitary hormonesPosterior pituitary hormones