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