1st Zatchot Flashcards
Explain the Eicosanoids , Df, synthesis , types , its receptors Cyclooxgnease , effect of cyclooxgnase
—Eicosanoids: they are fatty acids derivatives
—Synthesis of Eicosanoids:
its start from phospholipids (PL) transformed to Arachonic Acid (AA) by Phospholapes A2 (PL2) then it have 2 pathway
1-with help of cyclooxgynes (cox) generate :
1-1 Prostaglandins (PGs)
1-2 Thromboxan A2 (TXA2)
2-with help of Lipooxgnase (Lox) generate:
2-1 Liukutmins (LTs)
—types : we have 3 types according to the synthesis :
1-PGs 2-TXA2 3-LTs
— receptor of Cyclooxgnease : first we should know that the Cox only effect the PGs and TXA2 and by that we have 2 types of Cox
–effect of cyclooxgnase :
they are two groups harmful and functional
1-Functional consist of : PGe1 , PGe2, PGi2 :
in >
-B.V : physiological V.D
-Edema : +
-bronchi: B.D
-Uterus : in non pregnancy > relaxtion
in pregnancy > contraction ( near full term )
- renal blood flow : increase
- platelets: PGi2 is Specially decrease the Agg
— harmful group Consist of : PGf2â ,TXA2 , LTB4
in >
-B.V : V.C except LTB4 inflammatory V.D
-Edema : - , except LTB4 inflammatory Edema
-bronchi: B.C
-Uterus : Uterus Contraction
- renal blood flow : decrease
- platelets: TXA2 is Specially increase the Agg
explain The NSAID Prototype
—Drug : Acetylsalicylic Acid Tab 0,05
— Pharmacokinetics:
1- Absorption: is good bcs the drug is Acidic and the stomch HCL is acidic also
2-elimination : its dual root of elimination according to the dose
—mechanism of Action :
Aspirin is non-selective and irreversible Cox enzyme inhibitor leading to inhibit both of PGs and TXA2
NB! the only different between the aspirin and its derivatives its they are reversible and Aspirin is not
—Pharmacological effect and mechanism of each:
1-Analgesic Action : mechanism
1-1 prephrally effect : decrease the synthesis of PGs in prephral tissue
1-2 centrally : decrease the synthesis of PGs in subcortical sites ( hypothalmus and thalamus )
2-Antipyretic: : its not hypothermic but it decreases the elevated temperature Ex:39 to 37
-mechanism:
2-1 decrease the synthesis of PGE2 in hypothalamus
2-2 decrease the hypothalamic response to interleukin
2-3 Coutenous V.D which increase the sweating
3- Anti inflammatory effect :mechanism > by inhibition of Cox enzyme 1 and 2 its decrease the synthesis of PGs and TXa and possible other inflammatory substances
3-1 decrease the inflammatory cell division
3-2 decrease the capillary preamability
3-3 decrease the Hyaluronuides enzyme
3-4 stabilise lysosomes membrane of inflammatory cells
— Side effects :
1- respiratory system:
1-1low toxic dose : produce metabolic acidosis
1-2high toxic dose : produce acidly together with inhibition of R.c leads to death from sever acidosis
1-3increase risk of asthma
2- GIT effect : produce 2 types of gastric ulcer
2-1 acute gastric ulcer : ion trap of aspirin in case of empty stomach
2-2 chronic gastric ulcer : when ingestion of small doses for several years
3- hepatic effect : produce 2 types of hepatic injury
3-1 mild haptic injury : ita dose dependent and asympathomitc there may be increase of serum which is (SGOT and SGPT )
3-2 sever hepatic injury: children under 16 shouldn’t use aspirin bcs its related to Ray syndrome which is liver failure and Encephalopathy
4- hematological effect : by inhibition of Cox its inhibit the platelets agg irreversibly which lead to risk of bleeding
5- kidney: NSAIDs prevent synthesis of PGE2 which responsible for sodium which lead to salt and water retention and Edema
—- Therapeutic Use :
1- As analgesic: for mild or moderate pain
2- As Anti inflammatory
3- Antipyretic
— Contra indication :
1- GIT disorders : such as Peptic ulcer or gastritis
2-hematological disorders: hemophilia
3- Chronic renal disorders: may aggregate the renal failure
4- Gout : small dose may inhibit the uric acid Execration
5-before surgery: risk of uncontrollable bleeding
6-children under 16 : ray syndrome
Explain the Aspirin interaction
1- Aspirin Antagonist the Urine execration so i. patient with Gout disease which need to execrate the urine and use drug Probenecid they anatagoinse each other
2-Aspirin can replace the Anticoagulant drugs such as Heparin
3-Aspirin Antagonize Anti-acids and decrease the Aspirin Absorption in stomch
Explain the NASIDa drugs derivatives selective and non selective
—non selective
1- drug : Diclofenac Tab and Amp
> its less gastric irritation but more nephrotoxic / wildly used for rheumatoid pain
2- drug : Ibuprofen tab or oint 5%-30.0
> its more safe on children but study showed that women under 30 who used it have relatively hypertension from this drug
3- Drug : Indomethacin tab , Oint , Supp , eyedrops
> its the most potent Cox inhibitor but relatively more nephrotoxic
> the most useful for indomethacin is for ductus arterioles
—— Cox2 inhibitors
- they are 2 drugs
-1- Celecoxib Caps
-2- Meloxicam tab or amp
- mechanism: they inhibit Cox 2 enzyme reversibly
- pharmacological effect : Antipyretic, analgesic, Anti inflammatory
- side effect :
1- gastric irritation less frequent
2- renal side effect : more frequent
3- thrombotic complications : increase duo to increasing the platelets agg
explain the Paracetamol , the Paracetamol Anti-dot , paracetamol intraction with alcohol
—Drug : Paracetamol tab 0.5
—Pharmacokinetics:
1- Absorption: Complete
2-Distribution : goes to all body tissue
3-Metabolism: in liver by
3-1 glucuronic acid 60%
3-2 Sulfate 35%
3-3 hydroxolation by CYP450 , and form toxic form NABQ N-Acetyl-P-Bezoqinon ( can cause liver damage )
— mechanism: has less effect on Cox in peripheral tissue duo peripheral inactivation , Study showed its work centrally on Cox3
—Pharmacological effect :
1- Analgesic
2-Antipyretic
—Side effect :
- Forming Toxic form NABQ
N-Acetyl-P-Benzoqenon which bind to cellular proteins Around the central vein in the hepatocytes and cause > hepatocellular necrosis
—Therapeutic use :
1-Analagisc
2-Antipyretic
–first of all the paracetamol is is very safe and its the first line for children and women who’s in pregnancy
—Antidote: Sulfhydryl > N-AcetylCysteine which contains sulfhdryl form glotatheion to wash the toxic form which is N-Acetyl-P-Benzoqinon
–intaction :
The paracetamol–alcohol interaction is complex; acute and chronic ethanol have opposite effects in human chronic ethanol causes induction of hepatic microsomal enzymes and increases paracetamol hepatotoxicity as expected (ethanol primarily induces CYP2E1 and this isoform is important in the oxidative metabolism of paracetamol).
explain the Glucocorticoids ,Df , Secretion ,, Classification of drug , pharmacokinetics, mechanism
—Df: its natural in the body ( Cortisol ) , and its synthesis of circadian rhythm in morning 8am- 16pm
— Secretion : from hypothalamus by corticotrophen releasing hormone (RH) to pituitary gland and then another hormone secreted ACTH adreno corticotrophen releasing hormone to adrenal Cortex to secret Cortisol
NB! once it’s enough the Cortisol gland send A negative feed back to Pituitary gland and hypothalamus to stop secreting the previous hormones
(RH and ACTH)
—Classification:
1-Drug: Hydrocortisone ( natural ) tab,oint,Amp AntiF= 1 SW=1
2-Drug: Prednisolone tab,oint,Amp AntiF=4 SW=0,3
3-Drug: Triamcinolone tab,oint,Amp AntiF= 5 SW=0
4-Drug:Dexamethasone , tab,Eye,Amp AntiF= 30 SW=0
5-Drug: Betamethasone oint,Amp
AntiF= 30 SW=0
6-Drug: Beclomethasone Aerosoli
AntiF= 30 SW=0
—pharmacokinetics:
1-Absorption : All glucocorticoids are absorbed completely
2-Distribution: 85% bind to globin and 10% bind to albumin
3-Metabolism: by the liver CYP450 and execration by kidney
—mechanism: glucocorticoids bind to cell surface receptor then cytoplasm receptor ( carrier ) transferred to nucleus where it interacts with DNA the. transcription Activated and results of RNA
Explain the Glucocorticoids Pharmacological effect
—Pharmacological effect :
1-metabolic effect :
1-1 Carbohydrates metabolism: decrease the peripheral glucose utilization which lead to hyperglycemia
1-2 Protein metabolism: increase the proteolysis which lead to decrease muscle mass and then limbs
1-3 Fat metabolism: Increase lipolysis with redistribution of fat which lead to moon face with buffalo hump ( cushing syndrome )
1-4 salt and water retention: which lead to hypoklamia
2- immunological effect :
-Anti inflammtory , anti immunological
2-1 they inhibt B cells function : which lead to decrease Antigen-Antibody reaction
2-2 they inhibit T cell function : which lead to decrease inflammatory mediators and cytokines
2-3 inhibit macrophages activity and stabilize lysosomes membrane
2-4 inhibit mast cells : which lead to decrease Histamine release and capillary permeability
2-5 they inhibit PLsA2 enzyme: which lead to decrease synthesis PGs and LTs
3-CVS :
3-1 hypertension: duo to
salt and water retention and increase sensitivity pf BV and heart to circulating catecholamines
3-2 Antishock : duo to hypertensive and CVS effect , and anti inflammatory action
4- haematological effect :
4-1 increase RBCs and neutrophils and decrease lymphocytes and eosinophils
4-2 increase coagulation factors and plasma lipids
5- CNS effect : initial euphoria followed by depression
6- Eye effect : increase IOP
7- effect on bone : decrease bone matrix bcs the bone has proteins and the glucocorticoids are catabolic of protein
8- effect of growth : growth retardation bcs bones and , decreasing the growth hormone
Explain the Glucocorticoids , side effect , Therapeutic use , contraindications
—Adverse effect :
1-immune suppurations; leading to flaring of infection
2-hypertension: duo to SW retention
3-hyperglycaemia
4-peptic ulcer: duo to decrease synthesis of PGs
5-increase IOP which have high risk of glaucoma
6-osteoporosis
7-thrombosis: bcs PLs decrease
8-withdrawal symptoms
—therapeutic uses :
1-inflammatory disease: bcs it decrease PLA2
2-Autoimmune disease: bcs decrease B cells
3- Allergic disease: ex asthma , bcs its decrease histamine release
4-organ transplantation: bcs its immune suppression ( Dexamethason)
5- adrenal inefficiency : (hydrocortisone)
6-anaphylactic shock : bcs its decrease histamine release and do SW to correct the pressure
7-Cerebral edema : Dexamethason bcs it has no SW effect
8-Stamulation of lung maturation in the fetus : betamethasone / lung maturation in fetus is regulated by fetus secretion of cortisol , when the fetus should be delivered per-term we use the glucocorticoids to reduce the incidence of respiratory destress syndrome ( lack of surfactant in fetus alveoli)
we choose betamethasone bcs most of it is free part which allows the drug to cross the placenta and reach the fetus
— Contraindication :
1- Presence of viral infection : especially TB
2-DIabetus mellitus
3-hypertension and heart failure: bcs they cause SW retention
4-peptic ulcer : they decrease the synthesis of PGE2 and I2 which protect the stomach
5-in early pregnancy : may cause cleft palate
Df of Diabetes mellitus , Insulin , 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 which lead to»_space;>
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 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 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, DF,causes and mechanism of IR , Oral drugs , mechanism of action of each , uses , side effect
—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
—–oral drugs :
1-family of Sulfonyurea
-drug: Glibenclamide 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
-———————————
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
-———————————
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
-———————————
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
———————————-
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
————————————
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
———————————
7- family of sodium-glucose cotransporter 2 inhibitor ( SGLT-2 )
-drug: Dapagliflozin 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 , Antithyroid drugs
—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
—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
—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
–uses : thyrotoxic
explain DF , Complains , Predesposing factors , pathophysiology , Classification of Drugs for BA
-DF : its chronic inflammatory disease reversible episodes of airway obstruction, with symptoms of broncho spasm, mucosal edema , increase bronchial mucosa secretion,
-Complains :
1-wheezing 2-coughing 3-shortness of breath
-pre disposing factors:
1-genetical factors
2-environmental factors
3-Drugs thats induced BA such as : B blocker , cholinimaitics , PGF2A , Morphine > vigal stimulation
-pathophysiology: Frequent exposer to allergic stimulate, Cause infiltration of the bronchial wall by activating inflammatory substance such as : PGS , LTs , adenosine , histamine all of these getting out from Mast cells
> which lead to :
1-hypertrophy of air way smooth muscles
2-increase muscos secretion
-there are 4 types : 1 and 2 is the primary way
1-bronchodilator : B2 agonist, muscranic blockers
2-Antiiflmatory drugs : Glucocorticoids
3-Prophylactic drugs
4- Antitussive , mucolitic , Expectoran
————
Explain the B2 Agonist for treating BA , Methylxanthines , The glucocorticoids For BA , prophylactic drugs , Antitussive
— Drugs : B2
1- short acting
1.1Salbutamol tab, aears
1.2 Fenoterol
2- long acting :
2.1 Formoterol Caps
2.2 Salmeterol Aers
— mechanism: by activating the B2 receptor it will increase the CAMP which lead to broncho dilation , and suppress of inflammatory mast cells , mediators secretion and reducing of Ach reales from Nerve Ending
—uses : Quick relief , long term controlling of BA in combaination with Glucocorticoids
-side effect :
1- tolerance
2-tremors
3-hypoglycemia
————————————————–
-Drugs : Methylxanthines
1-Theophylline Tab
2-Aminophylline Amp
-mechanism:
1- Adenosine ( A1) receptor: these drugs blocks A1 receptor which lead ti broncho dilation , CNS stimulate , decrease mediator’s that secreted by Mast cells , Increase AV conductivity,
2- they inhibit Phosphodiesterase PDE3 and PDE4 which lead to accumulation of CAMP leading to :
1-B.D
2- increase cardiac conductivity, relaxation of most smooth muscle
-pharmocokintics :
1- absorption : full absorption 90-100%
2-metabolism: in the liver Cyp450 ~ CYP1A2 and metabolite to Cafien
3- cleared by smoking bcs its microsomal inducer
4- decrease cleared by microsomal inhibitor ~ Erythromycin
-side effect : nausea, vomiting , dyspepsia , durisis stimulation
-uses : Chronic BA theophylline
Acute BA aminophylline Amp
——————————————————-
- Drugs : glucocorticoids
- there is two types
1-local effect drugs :
1.1 Beclomethasone
1.2 budesonide
1.3 Fluticasone all aresol
2-systematic effect :
2.1 Prednisolone Tab , Amp
—mechanism: bind to cell surface receptors to the cytoplasm receptor carrier then transferred to nucleus where it interacts with DNA then transcription which results of RNA which lead to decreese the synthisis of Pgs and other inflammatory mediators
—systemic Pharmacological effect : mentioned in crticoids
- local pharmacological effect :
1-reducing the inflammation and hyper reactivity of bronchi
2-reducing frequency and severity of BA
—uses :
-local drugs : BA inflammatory
-systematic drugs : Sever asthma ~ asthmatic status IV
———————————————————
- prophylactic drugs
we have 3 families of these drugs
1-Luktraines
2-Mast cells stabilizer
3-MABs
———
1- Leukoutraines inhibitors
-Drugs :
1-Zafirlukast tab
2-Montelukast tab
-mechanism: they inhibit LTD4 receptor which is responsible for :
1-plasma exudation
2-mucous secretion
3-Esionphilis recurmnet
4- B. C
-uses : as adjuvant drugs For BA, and ita a replacement for Glucocorticoids in children bcs the glucocorticoids cause growth retardation
———-
2-Mast cells stebiliazer
-Drug : Cromoglicic acid ~ Caps for inhalation
-mechanism: they block Ca2+ entry to the mast cell which lead to membrane stiblazation and inhibit the degranulation
-Pharmacokinetics: poorly absorbed in GIT
-uses : only for pervntation
- side effect : Res tract irritation
——
3- Monoclonal antibodies MABs
-Drugs : Omalizumab Amp S.c
-mechanism: its antagonist of IGE which is binding to the mast cell , and degranulation , so this drug inhibit the Ige
-Drug : benralizumab Amp S.c
-mechanism : Via its Fab fragments, benralizumab specifically binds to IL-5Rα, thereby preventing the interaction between IL-5 and its receptor
- Uses : As adjuvant drug For BA
———
-Antitussive : can be used to treat dry cough
-Drug ( central acting ) :
1-Codeine ( opioid )
2-butamirat ( non opioid )
-drug ( peripheral acting )
1-Prenoxdiazin ( non opioids)
