Anti-inflammatory - Glucorticoids Flashcards
explain the inflammation and its dynamic
-inflammation : its protective response to cell injury to eliminate the harmful agents by remove the damaged tissue and generate new one
-Dynamics of inflammation :
1- tissue injury
2-hormonal response : by V.d and increase the preamblity , Exudation
3-Cellular Response ( proliferation) : migration to inflammatory site , phagocytosis, tissue reparation
Explain the Eicosanoids , Df, synthesis , types , its receptors Cyclooxgnease ,
—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
explain the cyclooxgnase features
-— types of Cox and its effect :
1- Cox1 :
1-1: expressed in most normal tissue
1-2 physiological function :
gastric protection (pge2) , renal blood flow ( pge2) , platelets agg (TXA2)
1-3 pathological function: non
2– Cox2 :
2-1 expressed in the pathological condition: such as inflammation, carcinogenic
2-2 physiological function:
V.d , Anti agg
2-3 pathological function:
inflammation, fever , pain
explain the 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 Classification of Anti-inflammatory Drugs
-Starting from phospholipids (PL) transformed Archadonic Acids (AA) by Phospholipase (PL2) give Us steroid anti inflammatory drugs , then The Archdonic Acid ( AA ) transformed to Protsglandins (PGs) by Cox enzyme so Cox enzyme give us NSAID drugs , in the same time AA transformed by another substance which is Lipooxgnase (Lox ) and give us Leukotins drugs
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
explain The aspirin , Side effect , therapeutic use , contra indication
— 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
—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
Explain the Paracetamol Anti-dot
- 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
explain the Glucocorticoids ,Df , Secretion
—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)
Explain the Glucocorticoids, Classification of drug , pharmacokinetics, mechanism
—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
