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REAKSI
HIPERSENSITIVITAS
Noor Wijayahadi
Classification
Coombs and Gell classification
1-Type I - immediate ( atopic, or anaphylactic)
2-Type II - antibody-dependent sitotoksik
anemi hemolitik
3-Type III - immune complex serum
sickness
4-Type IV - cell-mediated or delayed
Allergy
Ig E mediated
(Type I
hypersensitivity)
Non Ig E
mediated
Terapi
ANTAGONIS KIMIAWI
ANTI HISTAMIN
STEROID
ANTAGONIS FUNGSIONAL
Bronkodilator adrenalin
POSISI SYOK
ABC (Airway-Breathing- Circulation)
VASOKONSTRIKTOR ADRENALIN
CEGAH REAKSI LANJUTAN STEROID
SUPORTIF:
CAIRAN
OKSIGEN
NB: MASA KERJA ALERGEN vs OBAT
Corticosteroids
1. Imunodepresan
2. Anti-inflamasi
Bentuk Sediaan
Glucocorticoids
Short acting
Intermediate acting
Long acting
Mineralocorticoids
Inhalant steroids
Topical steroids
Pharmacokinetics
Absorption: all are rapidly & completely absorbed
Transport:
Transcortin 75%
Albumin 5%
Free form 20%
Metabolism:
by liver enzymes, conjugation & excretion by urine
partly excreted as 17-ketosteroids.
t1/2 of cortisol 1.5 hours
Cortisol
Cortisone
1.0
5 mg tablet
100 mg/vial (i.m., i.v)
Topical; enema
0.8
0.8
5 mg tablet
25 mg/vial (i.m)
0.8
Prednisolone
0.3
5, 10 mg tablet
20 mg/vial (i.m, intrarti)
Methyl
prednisolone
Triamcinolone
4 mg Tab.,
10, 40 mg/ml for i.m. &
intrarticular inj.
Drug
AntiSalt retaining
inflam.
25
0.5 mg tab.
4mg/ml inj (i.m., i.v.)
Betamethasone
25
0.5, 1 mg tab.
4mg/ml inj (i.m., i.v.)
Paramethasone
10
2- 20 mg/day (oral)
Mineralocorticoids - Preparations
Drug
Antiinflammatory
Salt retaining
Preapartions &
dose
Fludrocortisone
10
150
DOCA
100
2.5 mg
sublingual
0.3
3000
Not used
clinically
Aldosterone
Fluticasone
propionate
Budesonide
Topical steroids
Drug
Topical preparation
Potency
Beclomethasone
dipropionate
0.025 % cream
Potent
Potent
Clobetasol propionate
0.05 % cream
Potent
Halcinonide
0.1 cream
Potent
Triamcinolone actonide
0.1 % ointment
Potent
Fluocinolone actonide
0.025% ointment
Moderate
Mometasone
Moderate
Fluticasone
0.05 % cream
Moderate
Hydrocortisone acetate
2.5 % ointment
Moderate
Hydrocortisone acetate
Mild
Topical Steroids
Benefits due to anti-inflammatory, immunosuppressive,
vasoconstrictor and anti-proliferative actions
Good response
Atopic eczema,
Allergic contact dermatitis,
Lichen simplex,
Primary irritant dermatitis,
Seborrheic dermatitis,
Psoriasis of face,
Varicose eczema
Slow response
Cystic acne
Alopecia areata
Discoid LE
Hypertrophied scars
Keloids
Lichen planus
Psoriasis of palm, sole,
elbow & knee
Topical Steroids
Penetration differs at different sites:
High: axilla, groin, face, scalp, scrotum
Medium: limbs, trunk
Low: palm, sole, elbow, knee
Therapeutic principles
frequent evaluation
Single dose: No harm
Few days therapy unlikely to be harmful
Incidence of side effects related to duration
of therapy
Use is only palliative (except replacement
therapy)
Abrupt cessation of prolonged high dose
leads to adrenal insufficiency
(contraindicated)
Siklus Sirkadian
Dosis
Goal of therapy:
To relieve pain or distressing symptom (e.g.,
rheumatoid arthritis): start with low dose
To treat life threatening condition (e.g., pemphigus):
initial dose must be high
Steroid withdrawal
Longer the duration of therapy, slower the withdrawal
Less than 1 week: withdrawal in few steps
Rapid withdrawal: 50% reduction of dose every day
Slow withdrawal: 2.5 5 mg prednisolone reduced at an interval
of 2-3 days
Others:
Superinfections
Delayed wound healing
Steroid arthropathy
Peptic ulcer
Live vaccines are dangerous
Contraindications
Infections
Hypertension with CCF
Psychosis
Peptic ulcer
Diabetes mellitus
Osteoporosis
Glaucoma
Pregnancy : (prednisolone preferred)
Body weight
X-ray of spine
Blood glucose
Examination of the eye
B.P.
Glucocorticoids antagonists
Mitotane: structure similar to DDT, used in
inoperable adrenal cancer
Target of Activity
Biologic DMARDs
Azathioprine
Name
Target of Activity
D-Penicillamine
Unknown
Adalimumab
TNF-
Hydroxychloroquine
T-lymphocytes?
Etanercept
TNF-
Infliximab
TNF-
Abatacept
CD28
Anakinra
IL-1
Rituximab
CD20
Tocilizumab
IL-6 receptor
IVIG*
Fc receptors
Leflunomide
Pyridine synthesis
Methotrexate
Sulfasalazine
Uncertain; multifactorial,
including impairment of lymphocyte
function and cytokine synthesis
Synthetic DMARDs
Methotrexate
Sulphasalazine
Chloroquine
Hydroxychloroquine
Leflunomide
HISTAMIN
&
AUTAKOIDS
Mediator
Perubahan Vaskular pada Inflamasi
Mediator perubahan aliran darah dan
permeabilitas vaskuler:
-
leukotrien B4
Eosinophil chemotactic factor of anaphylaxis
HISTAMIN
Komponen bisa/racun serangga/tumbuhan
Tersimpan di Mast Cell & Basofil
(di lokasi trauma: hidung, mulut, kaki)
Terlepas pada:
1. Respons Imun
Immediate (Type I) Allergic Reaction
Inflamasi akut
H1 ANTAGONIS
Gen 1: sedatif, blok reseptor otonom
Gen 2: <<sedatif ( distribusi di CNS<<)
- p.o. absorbsi cepat (peak 1-2 jam, durasi 4-6 jam)
- Metabolisme di hepar
- Efek:
- sedasi
- anti-nausea/ anti-emetik
- anti-Parkinson (Bromokriptin: anti-kolinergik)
- anti-kolinergik (Etanolamine, Etilendiamine)
- -adrenoceptor blocker: hipotensi postural
(Fenotiazin, Prometazin)
- Serotonin blocker (Siproheptadin)
- Anestesi lokal (Difenhidramin, Prometazin)
Penggunaan H1 antagonists
Allergic rhinitis e.g.chlorpheniramine, loratidine
Motion sickness eg. meclizine, chlorcyclizine
Hypnotic agents e.g.doxylamine, diphenhydramine
Pruritis e.g. hydroxyzine
Serum sickness- e.g. promethazine
Anti-emetics- e.g. promethazine
Antitussive e.g. diphenhydramine
Carcinoid tumors (serotonin-mediated)
cyproheptadine
Allergic conjuctivitis e.g. levocobastine
Drugs
Usual Adult
Dose
Anticholin
ergic
Activity
Comments
48 mg
+++
Dimenhydrinate (salt of
diphenhydramine)
(Dramamine)
50 mg
+++
Diphenhydramine
(Benadryl, etc)
2550 mg
+++
1.2525 mg
nd
Pyrilamine (Neo-Antergan)
2550 mg
2550 mg
Moderate sedation
15100 mg
nd
Marked sedation
Cyclizine (Marezine)
2550 mg
2550 mg
FIRST-GENERATION ANTIHISTAMINES
Ethanolamines
Carbinoxamine (Clistin)
Doxylamine
Ethylaminediamines
Piperazine derivatives
Alkylamines
Brompheniramine
(Dimetane, etc)
48 mg
Slight sedation
48 mg
1025 mg
+++
60 mg
Loratadine (Claritin)
10 mg
Longer action
Cetirizine (Zyrtec)
510 mg
Phenothiazine derivatives
Promethazine (Phenergan,
etc)
Miscellaneous
Cyproheptadine (Periactin, 4 mg
etc)
SECOND-GENERATION ANTIHISTAMINES
Piperidines
Fexofenadine (Allegra)
Miscellaneous
Toksisitas
mirip keracunan Atropin
eksitasi, konvulsi, koma
- Astemizole, Terfenadine aritmia
pada penderita hepar
interaksi dg ketokonazole, makrolid
juice anggur
dilarang di USA
H2 ANTAGONIS
- Cimetidine
- Ranitidine
- Famotidine
- Nizatidine
- Mengurangi sekresi HCl lambung
- Menghambat enzim hepar
Lipid Autacoids
EICOSANOIDS:
PROSTAGLANDINS
THROMBOXANES
LEUKOTRIENES