Anti-Diabetic , Antithyroid Flashcards
Df of Diabetes mellitus , Insulin
-its clinical syndrom by distrubnce of carbohydrate , Fat , and proteins metabolism duo to either A insulin dificincy or insulin Resistance
-insulin: its substance that contain a 2 polypeptide chain connected by desulfed bond and its metabolized by insulinse in the liver and kidney
type of insulin , insulin secretion , insulin receptor , insulin mechanism
—types of insulin:
1- traditional ( animal ) : prepared from animal such as pork and beef , animal insulin may contain animal proteins that could cause allergy and its more antigenic
2-human insulin : its identical to human insulin and its prepared by recombinant DNA technology , its less antigenic and rare development of insulin resistance
—insulin secretion: glucose enters B cells which lead to increase the ATP closure of ATP-dependent k channel which lead to opening of voltage gated C+2 channel which increase the calcium influx and insulin release
—insulin receptor : A tyrosine kinase receptor consist of 2 extracellular (a) and 2 subunits of Beta
—mechanism : binding of insulin to the alpha subunit cause activation of tyrosine kinase enzyme which triggers a series of intercellular effects lead to increase the number of glucose transporters ( GLUT4 ) in the cell membrane and increase the transporter of glucose to cell
Types of DM , explain the Endogenous and Exogenous Insulin
——diabetes mellitus has 2 types
—DM Type 1 :
-pathophysiology : its autoimmune condition against the pancreatic B cells , that damaged pancreas doesn’t make insulin
-onset: under age of 30
-insulin therapy: essentially required
-oral drugs : not required
—DM type 2 :
-pathophysiology : the pancreas usually produces insulin , but either is the amount is not sufficient, or the body cells are resistant to it
-onset: above the Age of 30
-insulin therapy : only 20% of the patients
-oral drugs : required
—Endogenous insulin : the pancreas release insulin to the portal vein to the liver which is cleared 50% of the insulin and the rest is distributed to the all over the body and cleared by receptor-mediated uptake
—Exogenous insulin : insulin is not giving orally bcs its rapidly destroyed by the GIT enzyme’s its commonly given SubCotenous or IV in emergency
explain the Insulin , insulin analogs
- regular insulin
-group : short acting
-onset : 0-30 min
-duration : 5-6 h
its the safest insulin in emergency for example used in hyperglycemic coma I.V
2- insulin Aspart
-group : short acting
-onset : 5-10 min
-duration : 3 h
its insulin analog , created by replacement of proline to aspart and the result its fast acting and short duration insulin’s bcs its monomer
3- insulin isophane
-group : intermediate acting
-onset : 1-3 hour
-duration : 12-24 h
its created by replacement of the zinc with protein for the fishes called protamine and its positive charge and bind with insulin molecules ionic bond which lead to take the body long time time to break this bond , and its hexomor
4-insulin glargine
-group : long acting
-onset : 1-3 h
-duration : 12-24 h
its created by adding 2 more molecules of argin to the insulin which made the insulin 53 amino acid instead of 51 which lead to longer duration
explain the pharmacological effect of insulin
1-increase glucose transporter in insulin-dependent tissue in Sk muscles and fat tissue
2-stimulation of glycolysis : break down the glucose
3-stimulation of glycogen synthesis: glycogen is the stored form of glucose
4-inhibition of glaconeogensis in the liver : gluconeoginsis is process in the liver which is making glucose from breaking down of lipids or proteins
5-stimulate pintos phosphate pathway ( PPP ) : its pathway generally regulate the body cell tissue , in glucose its metabolize 30% of glucose by this pathway
6- increase the protein synthesis: by activating of mechneray increase EIFs
7-stimulation of Fat synthesis : which is gone decrease the glucose
8-inhibition of lipolysis
explain the PPP pintose phosphate pathway
this pathway start with
1- glucose-6-phosphate: the NADPa enters and get out with NADPH + H+ which called glucos 6 phosphate dehydrogenase = 6-phosphoglucon-delta-lactos
2- 6-phosphoglucon-delta-lactose : the H2O enters and get out with H+ which result of =
6-phosphogluconate
3- 6-phosphogluconate : the NADP enters and get out with NADPH + H+ which result of =
Riblose 5-phosphate
explain the Therapeutic uses , adverse effect of insulin
—therapeutic uses :
1-T1DM
2-T2DM : in some cases
2.1 after fail of oral drugs
2.2 if the patient got stress conditions such as surgery, infection, pregnancy
3-hyperglycemia coma
4-hyperkalemia : bca insulin and glucose can shift the potassium from blood to tissue
—adverse effect :
systemic >
1-hypoglycemia: its most common
2-hypoklamia
3-hypersensitive reaction
4-insulin resistance
locally >
1-local allergy : maybe bcs the animal insulin
2-lipids dystrophy
3-local infection
explain the Insulin resistance, causes and mechanism of IR
—DF: its failure of the body cells to respond to either endogenous or exogenous insulin , As result of large doses of insulin to get the desired response
—causes and mechanism of each :
1- pre-receptor defect ( immunological) : duo to formation of Antibodies against insulin
2-receptor defect : duo to down regulation of insulin receptor in >
2.1 metabolic syndrome: its combination of obesity, hyper cholesterol , heart disease
2.2 pregnancy
2.3 sever infection
3- post-receptor defect : abnormal signal transductions duo to genetic defect in one or more of the tyrosine kinase chains of events
4-local insulin resistance: its duo to injection of the insulin in the same site
explain the , Oral drugs , mechanism of action of each , uses , side effect
1- family of Sulfonyurea
-drug: Glibnclamid tab 0,007 ( stimulate insulin secretion)
-mechanism of action : it has 2 type of mechanism>
1.1 pancreatic: binding to the SUR1 receptor on B cells and blocked of ATP-dependent K+ channel which lead to depolarization bcs Ca2+ and increase the insulin secretion
1.2 Extrapancreatic : they increase the insulin receptor sensitivity
-side effect :
1-hypoglycemia
2-increase apitite and weight gain
3-allergic recation
4- renal failure > contraindications
-uses : T2DM
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2- family of megletunds
-drug: Repaglinide Tab 0,0005 ( stimulate insulin section)
-mechanism of action :the has the same mechanism of sulfynurea
-uses : T2DM used for patient with allergies from sulf or has renal failure
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3- family of Bigunaides
-drug: metformin tab 0,5
-mechanism of action : Stimulate of AMP-dependent protein kinase of hepatocytes which lead to inhibition of gluconeognesis in the liver , and increase the insulin receptor sensitivity
-pharmacological effect :
no risk of hypoglycemia
-side effect :
1-nausea
2-dihrria
3-lactic acidosis: duo to increase of Anarobic glycolysis
-uses : T2DM , wight loss
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4- family of Thiazolidinis
-drug: Rosiglitazone tab 0,5(insulin sensteiser)
-mechanism of action : its act on nuclear gene called Perixisom-prolifratir-activated-receptor-gamma ( PPAR-y) bind to this gene in liver and adipose tissue , and increase insulin resistance
-pharmacological effect :
they have slow onset because the mechanism involves gene regulation
-side effect :
1-heptoroxic
2-wight gain
-uses : to improve insulin resistance in T2DM
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5- family of incretin ( glucagon like peptide 1 )
GLP-1
-drug: Exenatide Amp
-mechanism of action : they increase the insulin secretion by binding to B cells and forcing it to secrete it , and decrease the glucagon , and slow the gastric emptying and decrease apitite
-side effect :
1- nausea 2-vomiting 3-pencreatits
-uses : in T2DM and should be giving before eating by 60 min
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6- family of Dipeptidly peptdens 4 inhibitor ( Dpp-4)
-drug:Saxagliptin tab 0,0025
-mechanism of action : they inhibt the DPP-4 enzyme which is responsible for proteolysis of incretin so its decrease the GLP-1 may improve B-cells function and decrease the glucagon secretion
-side effect :
1- nausea 2- headache
-uses : for T2DM usually combined with metformin
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7- family of sodium-glucose cotransporter 2 inhibitor ( SGLT-2 )
-drug: Dapagoiflozin tab 0,005
-mechanism of action : increase the urine glucose and sodium secretion
-pharmacological effect :
1- decrease Bp
2-body wight loss
-side effect :
1-polyuria
2-hypotension
3-hyperkalimia
-uses : in T2DM in case of the patient has renal or haptic failure and cant take metformin
Explain the synthesis of thyroid hormones
—synthesis of thyroid glands :
start with activating Uptake of iodide, then oxidation with peroxides enzyme and indentation of tyrosine of theyroglobin to form MIT and DIT
then condensation of MIT and DIT Nd formation of T3 and T4 , then proteolysis of thyroglobulin, then secretion of T3 and T4 into blood stream
—NB! the secretion of T4 and T3 stimulate by TSH , most of T3 is drived from peripheral dioidenation of T4 in the peripheral tissue
-B blockers and corticoids inhibit the peripheral conversation of T4 to T3
explain the thyroid drugs
—they are used to treat hypothyroidism
—Drugs group :
1-Levothyroxine
2-Liothyronine
all tabs
—hypothyroidism: its clinical syndrome results from high levels of thyroid hormones
-clinical types :
1-Graves disease: its an autoimmune disease in which there abnormal Antibodies > activating TSH receptor in the thyroid gland which lead to enlargement or the gland and softness
2-toxic multinudular goiter : the treatment is usually surgical
—management:
1-graves disease: usually medication
2-multiple nodular goiter : surgical
explain the Antithyroid drugs
-Drug : Thiamazole tab 0,005
-mechanism of action: they inhibit the oxidation of Iodides by inhibition of peroxides enzyme
-side effect :
1-agranulocytosis, bone marrow depression
2-hypothyroidism with increased the size of vesicularty of the gland
3-hepatotoxic
4-hypersensitive reaction
explain the Radioactive therapy
- radioactive tab
-pharmacokinetics:
absorbed orally , selectively accumulation of in the thyroid gland
-mechanism: its accumulation selectively in the thyroid gland
-use’s: thyrotoxic , thyroid cancer
