HISTAMIN

&
AUTAKOIDS

Mediator Perubahan Vaskular pada Inflamasi

Mediator perubahan aliran darah dan
permeabilitas vaskuler:
-

vasoactive amina (histamin, serotonin)

vasoactive peptida (bradykinin)
vasoactive lipid (prostaglandin, leukotrien)

Mediator kemotaksis leukosit

-

leukotrien B4
Eosinophil chemotactic factor of anaphylaxis

Penyebab Cedera Jaringan pada

Inflamasi dan Penyakit Autoimmune
Pembentukan reactive oxygen species (O2-,
H2O2, HOCl) and enzime proteolitik
(kolagenase, elastase) oleh sel fagosit
Cytotoxic complement proteins
Respons imun seluler dan humeral
Pelepasan sitokin pro-inflamasi

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

2. Respon Kimia (gol. Amine: morfin)

EFEK: - Triple Response: merah, edema, nyeri

- Shock anafilaktik
- Rangsang ujung saraf tepi
nyeri, gatal
H1
- Vasodilatasi + edema jaringan
nadi
tensi
- Bronkokonstriksi provocatif test
- Kontraksi otot polos:
H2
GI
: peristalsis
diare
Uterus : aborsi
Lambung: sekresi HCl
- Pengelolaan:
1. Antagonis Fisiologis: epinefrin
2. Antagonis Reseptor : CTM, Burimamide anti-H2
3. Release Inhibitor: Cromolin, Nedocromil

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)

H1 Antagonists Generasi I vs. II

Generasi-1 antagonis reseptor H1 tidak spesifik
- diphenhydramine muscarinic receptors
- Promethazine dopamine, muscarinic, 1
- Cyproheptadine serotonergic receptors

Generasi-2 antagonis reseptor H1:

-

Spesifik pada H1 receptors

Tidak menembus blood-brain barrier sedasi kurang
Half-lives lebih panjang
Indikasi utama: allergic rhinitis
Astemizole, Terfenadine aritmia

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

+++

Slight to moderate sedation

Dimenhydrinate (salt of
diphenhydramine)
(Dramamine)

50 mg

+++

Marked sedation; anti-motion

sickness activity

Diphenhydramine
(Benadryl, etc)

2550 mg

+++

Marked sedation; anti-motion

sickness activity

1.2525 mg

nd

Marked sedation; now available

only in OTC "sleep aids"

Pyrilamine (Neo-Antergan)

2550 mg

Moderate sedation; component

of OTC "sleep aids"

Tripelennamine (PBZ, etc)

2550 mg

Moderate sedation

Hydroxyzine (Atarax, etc)

15100 mg

nd

Marked sedation

Cyclizine (Marezine)

2550 mg

Slight sedation; anti-motion

sickness activity

Meclizine (Bonine, etc)

2550 mg

Slight sedation; anti-motion

sickness activity

FIRST-GENERATION ANTIHISTAMINES
Ethanolamines
Carbinoxamine (Clistin)

Doxylamine
Ethylaminediamines

Piperazine derivatives

Alkylamines
Brompheniramine
(Dimetane, etc)

48 mg

Slight sedation

Chlorpheniramine (ChlorTrimeton, etc)

48 mg

Slight sedation; common

component of OTC "cold"
medication

1025 mg

+++

Marked sedation; antiemetic

Moderate sedation; also has

antiserotonin activity

60 mg

Lower risk of arrhythmia

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

Penggunaan Klinis Antihistamin

- Reaksi Alergi: rinitis, urtikaria
asma ? (tidak efektif)
- Motion sickness
- Gen 1: difenhidramin/ dimenhidrinat, prometazin
sikloserin, meclizine: less sedatif
- Obat lain : skopolamin
- + efedrin/amfetamin: >>efek
- Nausea/Vomiting pd kehamilan
piperasin : teratogenik

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

Penggunaan Klinis H2 Antagonists

Ulkus Gastric dan duodenal
Reflux Gastroesofagus
Esofagitis Erosif
Heartburn

Lipid Autacoids

EICOSANOIDS:

PROSTAGLANDINS
THROMBOXANES
LEUKOTRIENES

Prostaglandins (PGE2) and

Inflammatory pain sensitization
PGE2 inhibit a glycine receptor (GlyR
alpha3) in its action regulating central
inflammatory pain sensation.
GlyR alpha3 is expressed in the superficial
layers of the spinal cord dorsal horn.

Indications for Prostaglandin

analogues
Alprostadil- maintains a patent ductus
arteriosus in the fetus; useful in treating
erectile dysfunction
Misoprostil a PGE2 analogue used to
treat NSAID-induced gastritis
Carboprost; Dinoprostone
abortafacients, may be used to induce
labor
Lantanoprost used in treating
glaucoma

Aspirin (Acetyl Salicylic Acid)

Asetilasi COX Irreversibel
hambat enzim permanen
Salicylate inhibitor kompetitif COX
Dose-dependent
efek tergantung besarnya dosis

Steroid

Dr Noor Wijayahadi

The anterior pituitary :

thyroid stimulating hormone (TSH)
adenocorticotrope hormone (ACTH)
growth hormone (GH)
follicle stimulating hormone (FSH)
luteinizing hormone (LH)
prolactin (PRL).
Specific releasing hormones from the
hypothalamus regulate the release
posterior pituitary:
Antidiuretic hormone (ADH) or vasopressin
directly released in the bloodstream by neurons
originating from the supraoptic nucleus

Ketoconazole

Some Therapeutic Indications for the Use of Glucocorticoids in Nonadrenal

Disorders.
Allergic
reactions

Angioneurotic edema, asthma, bee stings, contact dermatitis,

drug reactions, allergic rhinitis, serum sickness, urticaria

Collagenvascular
disorders

Giant cell arteritis, lupus erythematosus, mixed connective

tissue syndromes, polymyositis, polymyalgia rheumatica,
rheumatoid arthritis, temporal arteritis

Eye diseases

Acute uveitis, allergic conjunctivitis, choroiditis, optic neuritis

Gastrointestinal
diseases

Inflammatory bowel disease, nontropical sprue, subacute

hepatic necrosis

Hematologic
disorders

Acquired hemolytic anemia, acute allergic purpura, leukemia,

autoimmune hemolytic anemia, idiopathic thrombocytopenic
purpura, multiple myeloma

Systemic
inflammation

Acute respiratory distress syndrome; (sustained therapy with

moderate dosage accelerates recovery and decreases mortality)

Infections

Gram-negative septicemia; (occasionally helpful to suppress

excessive inflammation)

Inflammatory
conditions of
bones and
joints

Arthritis, bursitis, tenosynovitis

Neurologic
disorders

Cerebral edema (large doses of dexamethasone are given

to patients following brain surgery to minimize cerebral
edema in the postoperative period), multiple sclerosis

Organ
transplants

Prevention and treatment of rejection

(immunosuppression)

Pulmonary
diseases

Aspiration pneumonia, bronchial asthma, prevention of

infant respiratory distress syndrome, sarcoidosis

Renal
disorders

Nephrotic syndrome

Skin diseases

Atopic dermatitis, dermatoses, lichen simplex chronicus

(localized neurodermatitis), mycosis fungoides,
pemphigus, seborrheic dermatitis, xerosis

Thyroid
diseases

Malignant exophthalmos, subacute thyroiditis

Miscellaneous Hypercalcemia, mountain sickness

Some Commonly Used Natural and Synthetic Corticosteroids for General Use

Agent

Anti-inflam

Topi Saltcal
Retain
ing

Equi
Oral
Dose
(mg)

Forms Available

20

Oral, injectable,
topical

Cortisone

0.8

0.8

25

Oral, injectable,
topical

Prednisone

0.3

Oral

Prednisolone

0.3

Oral, injectable,
topical

Methylprednisolo 5
ne

Oral, injectable,
topical

Oral, injectable

Short- to mediumacting
glucocorticoids
Hydrocortisone
(cortisol)

Meprednisone2

Intermediateacting
glucocorticoids
Triamcinolone

Paramethasone2

10

Fluprednisolone

15

Betamethasone
Dexamethasone

53

Oral, injectable,
topical

Oral, injectable

1.5

Oral

2540

10

0.6

Oral, injectable,
topical

30

10

0.75

Oral, injectable,
topical

Fludrocortisone

10

10

250

Oral, injectable,
topical

Desoxycorticost
erone acetate

20

Long-acting
glucocorticoids

Mineralocorticoid

Injectable, pellets

Glucocorticoids for Oral & Parenteral Use

Betamethasone (Celestone)
Oral: 0.6 mg tablets; 0.6 mg/5 mL syrup
Betamethasone sodium phosphate (Celestone Phosphate)
Parenteral: 4 mg/mL for IV, IM, intralesional, or intra-articular injection
Cortisone (generic, Cortone Acetate)
Oral: 5, 10, 25 mg tablets
Parenteral: 50 mg/mL solution
Dexamethasone (generic, Decadron, others)
Oral: 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6 mg tablets; 0.5 mg/5 mL elixir; 0.5 mg/5 mL, 0.5
mg/0.5 mL solution
Dexamethasone acetate (generic, Decadron-LA, others)
Parenteral: 8 mg/mL suspension for IM, intralesional, or intra-articular injection; 16 mg/mL
suspension for intralesional injection
Dexamethasone sodium phosphate (generic, Decadron Phosphate, others)
Parenteral: 4, 10, 20 mg/mL for IV, IM, intralesional, or intra-articular injection; 24 mg/mL
for IV use only
Hydrocortisone [cortisol] (generic, Cortef)
Oral: 5, 10, 20 mg tablets
Hydrocortisone acetate (generic)
Parenteral: 25, 50 mg/mL suspension for intralesional, soft tissue, or intra-articular injection
Hydrocortisone cypionate (Cortef)
Oral: 10 mg/5 mL suspension
Hydrocortisone sodium phosphate (Hydrocortone)
Parenteral: 50 mg/mL for IV, IM, or SC injection
Hydrocortisone sodium succinate (generic, Solu- Cortef)
Parenteral: 100, 250, 500, 1000 mg/vial for IV, IM injection

 Methylprednisolone (generic, Medrol)

Oral: 2, 4, 8, 16, 24, 32 mg tablets
Methylprednisolone acetate (generic, Depo- Medrol)
Parenteral: 20, 40, 80 mg/mL for IM, intralesional, or intra-articular inj
Methylprednisolone sodium succinate (generic, Solu-Medrol)
Parenteral: 40, 125, 500, 1000, 2000 mg/vial for injection
Prednisolone (generic, Delta-Cortef, Prelone)
Oral: 5 mg tablets; 5, 15 mg/5 mL syrup
Prednisolone acetate (generic)
Parenteral: 25, 50 mg/mL for soft tissue or intra-articular injection
Prednisolone sodium phosphate (Hydeltrasol, others)
Oral: 5 mg/5 mL solution
Parenteral: 20 mg/mL for IV, IM, intra-articular, or intralesional injection
Prednisolone tebutate (generic)
Oral: 5 mg/5 mL liquid
Parenteral: 20 mg/mL for intra-articular or intralesional injection
Prednisone (generic, Meticorten)
Oral: 1, 2.5, 5, 10, 20, 50 mg tablets; 1, 5 mg/mL solution and syrup

 Triamcinolone (generic, Aristocort, Kenacort)

Oral: 4, 8 mg tablets; 4 mg/5 mL syrup
Triamcinolone acetonide (generic, Kenalog)
Parenteral: 3, 10, 40 mg/mL for IM, intra-articular, or intralesional inj
Triamcinolone diacetate (generic)
Parenteral: 25, 40 mg/mL for IM, intra-articular, or intralesional injection
Triamcinolone hexacetonide (Aristospan)
Parenteral: 5, 20 mg/mL for intra-articular, intralesional, or sublesional
Mineralocorticoids
Fludrocortisone acetate (generic, Florinef Ace- tate)
Oral: 0.1 mg tablets
Adrenal Steroid Inhibitors
Aminoglutethimide (Cytadren)
Oral: 250 mg tablets
Ketoconazole (generic, Nizoral)
Oral: 200 mg tablets (unlabeled use)
Mitotane (Lysodren)
Oral: 500 mg tablets