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Antiallergic drugs
ALLERGIC REACTIONSALLERGIC REACTIONS
• Frequency in UkraineFrequency in Ukraine – 35-45 % – 35-45 % from all from all adverse reactions of drugsadverse reactions of drugs
• Frequency in a world Frequency in a world – 10-15 % – 10-15 %
of populationof population
• 20 % 20 % healthy persons have gothealthy persons have got sensitization to drugssensitization to drugs
ALLERGENSALLERGENS
Animals skin, hear, fur
Drugs
Dust with mites
Wasp, beePollen of blooming
plants
Food products
Stevens-Johnson syndromeStevens-Johnson syndrome
Exfoliate dermatitis Exfoliate dermatitis ((LaiellLaiell’s’s syndrome syndrome))
Quincke's Oedema, Angioneurotic OedemaQuincke's Oedema, Angioneurotic Oedema
• oedema of the subcutaneous tissue, particularly of the lips, eyelids and genitalia, though any part of the body may be involved
• The tongue and larynx may also be affected, it may be life threatening
• Quincke's oedema may occur in urticaria, anaphylaxis, and serum sickness
• Etiologic factors include medications (e.g. penicillin, aspirin, phenytoin)
• infections and food related products for Quincke's oedema associated with urticaria
AntiallergicsAntiallergics – – drugs which stabilize membranes of mast drugs which stabilize membranes of mast
cells and basophilescells and basophiles
• Cetotifen Cetotifen ((ZaditenZaditen) – ) – orally orally
• Cromolin-sodium (Intal) Cromolin-sodium (Intal) – – by by inhalationsinhalations
• Nedocromil-sodiumNedocromil-sodium ( (TailedTailed) – ) – by by inhalationsinhalations
Leikotrien-inhibitor Leikotrien-inhibitor - - AccolatAccolat
KetotifenKetotifen ( (ZaditenZaditen), ), Cromolin-sodiumCromolin-sodium ( (IntalIntal), ), Nedocromil-sodiumNedocromil-sodium ( (TiladeTilade)),, AccolatAccolat
AntiallergicsAntiallergics – – drugs which stabilize membranes of drugs which stabilize membranes of
mast cells and basophilesmast cells and basophiles
slow down releasing of mediators of slow down releasing of mediators of hypersensitivity reactionhypersensitivity reaction
Only for Only for prophylaxis prophylaxis
of allergic reactionsof allergic reactions
Antihistamine drugsAntihistamine drugs
Structure of nucleus of Н1 histamine-receptors antagonists (H1 histamine-blockers)
CH2-CH2-N
R1
R1
CH3
CH3
Н1- Н1- ANTIHISTAMINES ACTIONANTIHISTAMINES ACTION
According to chemical structure blockers According to chemical structure blockers of of НН11 histamine-receptors are divided into histamine-receptors are divided into
derivatives of:derivatives of:
1) 1) ethylendiaminethylendiamin ( (suprastinsuprastin))2) 2) ethanolaminethanolamin ( (dimedrol, klemastindimedrol, klemastin))3) 3) piperasinpiperasin ( (cetyrisincetyrisin))4) 4) alkilaminsalkilamins ( (feniraminfeniramin))5) 5) phenothiasinphenothiasin ( (diprasin, teralen)diprasin, teralen)6) 6) oxycamoxycam ( (meloxycam, pyroxycammeloxycam, pyroxycam))6) 6) different structuredifferent structure ( (diasolindiasolin, , peritol, fenkarolperitol, fenkarol))
AntihistaminesAntihistamines
• 1 generation: dimedrol (difenhydramine), suprastin, diprazin (pipolfen), fencarol, diazolin, peritol, tavegil (clemastin)
• 2 generation: terfenadine, astemizol, loratadine (claritin)
• 3 generation: cetirizin (zyrtec), fexofenadine (telfast)
Comparative antiallergic activityComparative antiallergic activity
Н1 histamine blockers of 1st generation
diprasine>tavegil>dimedrol>suprastin>fenkarol>diasoline
Н1 histamine blockers of 2nd and 3rd generations
cetirizine>terfenadine=fexofenadine>
astemizole>loratadine
НН11--histamine blockers of 1st generationhistamine blockers of 1st generation
Н1Н1 histamine blockers of 2nd and 3rd histamine blockers of 2nd and 3rd generationsgenerations
1. 1. Nettle-rashNettle-rash2. 2. Hay feverHay fever3. 3. Vasomotor rhinitisVasomotor rhinitis4. 4. Contact dermatitisContact dermatitis5. 5. Angioneurotic edema Angioneurotic edema 6. 6. Serum sicknessSerum sickness7. 7. Anaphylactic shockAnaphylactic shock8. 8. Others Others
Indications for administration of Indications for administration of antihistamine drugsantihistamine drugs::
1) Depression of CNS (disorders of coordination, increased tiredness, dizziness, tremor, euphoria, nervousness, insomnia)
2) Disturbance of GI functioning : decreasing of appetite, nausea, vomiting, pain in epigastria, constipation of diarrhea
3) As a result of M-cholinoblocking activity – dryness of mucous membranes, eye disorders - blurred vision, impotence, ischuria, tachycardia, headache, psychosis
4) in case of repeated administration - tachyphylaxis
Side effects ofSide effects of Н Н11--histamine receptors blockers histamine receptors blockers of 1st generationof 1st generation
1) 1) BlockageBlockage Н Н11--histamine receptorshistamine receptors2) 2) Stabilizing mast cellsStabilizing mast cells3) 3) Decreasing histamine secretionDecreasing histamine secretion4) 4) Possessing anti-inflammatory activityPossessing anti-inflammatory activity
Properties of Properties of НН11- - histamine histamine
receptors blockers receptors blockers of 2nd and 3rd generations:of 2nd and 3rd generations:
Advantages of Н1-histamine receptors blockers of 2nd and 3rd generations over classical Н1-antagonists
1) High specificity and affinity to Н1-receptors2) Short onset
3) Long duration of action (over 24 hours)4) Absence of blockade of other types of receptors5) No penetrable through HEB in therapeutic doses
6) Absence of tachyphylaxis
Anti-inflammatory drugsAnti-inflammatory drugs(GCS and NSAIDs)(GCS and NSAIDs)
Groups of anti-inflammatory agents and mechanism of action:1) nonsteroidal anti-inflammatory drugs – NSAIDs, 2) glucocorticosteroids (GCS)
glucocorticosteroids L-
PhospholipasePhospholipaseАА22
Phospholipids
Arachidonic acid
Cyclic endoperoxydases
ProstaglandinsProstaglandins Thromboxan
InflammationInflammation PainPain FeverFever Vasoconstriction
Increasing of platelets aggregation
-
+
- depressing effect
- stimulating effect
NSAIDs
-CyclooxygenasesCyclooxygenases((COGCOG-1, -1, COGCOG-2, -2, COGCOG-3-3))
Classification of nonsteroid anti-inflammatory Classification of nonsteroid anti-inflammatory drugs according to mechanism of actiondrugs according to mechanism of action::
I.I. Selective inhibitors of COGSelective inhibitors of COG-1 (-1 (acetylsalicylic acid acetylsalicylic acid in small dosesin small doses))
II.II. Nonselective inhibitors of COGNonselective inhibitors of COG-1 -1 and COGand COG-2 -2 ((most of NSAIDsmost of NSAIDs))
III.III. Drugs with dominant influence on COGDrugs with dominant influence on COG-2-2 ((meloxycam, nimesulidmeloxycam, nimesulid))
IV.IV. High selective inhibitors of COGHigh selective inhibitors of COG-2-2 ((celecoxyb,celecoxyb, rofecoxybrofecoxyb))
Properties of nonsteroidal anti-Properties of nonsteroidal anti-inflammatory drugsinflammatory drugs
• Anti-inflammatory actionAnti-inflammatory action
indometacynindometacyn >> diclofenacdiclofenac >> meloxycammeloxycam >> nimesulidnimesulid >> pyroxycampyroxycam >> ketoprofenketoprofen >>
naproxennaproxen >butadion>butadion >> ibuprofenibuprofen >> acetylsalicylic acidacetylsalicylic acid
• Analgesic actionAnalgesic action
• AAntipyretic actionntipyretic action
Indications for administration ofIndications for administration ofnonsteroidal anti-inflammatory drugsnonsteroidal anti-inflammatory drugs
1. Rheumatism2. Infectious-allergic myocarditis3. Rheumatoid polyarthritis4. System lupus erythematosus 5. Anchilizing spondilitis (Bechterev’s disease)6. Gout 7. Deformating osteoarthrosis (DOA)8. Thrombophlebitis 9. Inflammation diseases of connective tissue,
osseous-muscular system10. Neuralgia 11. Meningoencephalitis12. Chronic bronchitis13. Virus hepatitis
Rheumatoid diseases
Doses in which NSAIDs are used as anti-Doses in which NSAIDs are used as anti-inflammatory agentsinflammatory agents
Drug Drug Daily dose (g)Daily dose (g) Frequency of Frequency of administration administration
per dayper day
Acetylsalicylic acidAcetylsalicylic acid 3,0-5,03,0-5,0 3-43-4
IbuprofenIbuprofen 1,2-3,21,2-3,2 3-43-4
Indometacin Indometacin 0,075-0,150,075-0,15 3-43-4
Diclofenac Diclofenac 0,075-0,150,075-0,15 2-32-3
Naproxen Naproxen 0,5-1,00,5-1,0 22
Piroxicam Piroxicam 0,020,02 11
MeloxicamMeloxicamRofecoxibRofecoxib
0,0075-0,0150,0075-0,0150,00,012125-0,055-0,05
1 1
Acetylsalicylic acidAcetylsalicylic acid
Aspirin Aspirin СС
Aspirin Aspirin
Butadion Butadion
Indometacin (methyndolIndometacin (methyndol))
Ibuprofen Ibuprofen ((brufenbrufen))
Piroxicam Piroxicam
Sodium diclofenacSodium diclofenac
Voltaren Voltaren
Diclofenac-sodiumDiclofenac-sodium
ІІndometacinndometacin
Nimesulid, MeloxicamNimesulid, Meloxicam
Celecoxib, RofecoxibCelecoxib, Rofecoxib
Side effects of nonsteroid anti-inflammatory drugsSide effects of nonsteroid anti-inflammatory drugsGastro-intestinal tract
Peptic ulcers and multiple micro-erosions Esophagitis and stricturesErosive damaging of large and small intestines
Kidney Reversible acute kidney insufficiencyWater-electrolyte disordersChronic kidney insufficiency and interstitial fibrosisInterstitial nephritisNephritic syndrome
Cardio-vascular system
Increasing of arterial hypertensionIncreasing of static cardiac insufficiencyIncreasing of stenocardia
Liver Increasing of transaminases levelLife-threatening liver insufficiency
CNS Headache, somnolenceconfusion, disorders of behavior aseptic meningitis
Blood system
ThrombocytopeniaHemolytic anemiaGranulocytopenia and aplastic anemia
Bones, joints Disorders of cartilages and subchondral tissue
Other Increasing of asthma and polypus of nose, skin rash
1) Administer simultaneously with gastric protectorssucralfat, misoprostol, ranitidin, famotidin,
omeprasol
2) Create and introduce NSAIDs which selectively inhibit COG-2
meloxycam, nimesulid, rofecoxib, celecoxib
Prevention of development of GI complications while administering
NSAIDs:
Directions of medical treatment Directions of medical treatment ofof rheumatoid diseasesrheumatoid diseases::
1)1)NSAIDsNSAIDs with the aim of depression of inflammatory process, pain, rigidness of muscles and joints, but don’t effect the currency of disease
2) 2) Basis drugsBasis drugs ((disease modifyingdisease modifying)) • Methotrexat, hydroxychloroquin, sulfasalazin, gold
containing drugs, penicillamin, • purin derivatives (asathioprin and mercaptopurin)• Alkilying drugs (chlorbutin and cyclophosphamid), • cyclosporin
3) 3) GCSGCS are administered if there’s a lack of effect of NSAIDs and basis drugs in case of very severe currency of inflammatory process