FARMAKOLOGI THT

dr.Sufi desrini M.Sc

Nasal Congestion

Nasal congestion is one of the most frequent symptoms in URT disorders, such as allergic rhinitis, rhinosinusitis, nonallergic rhinitis, and nasal polyposis

Nasal congestion is also common symptom in otitis media and asthma

Mucosal inflammation is the central pathophysiological mechanism that contribute congestion,incl increased venous engorgement, increased nasal secretion and edema

Nasal Congestion (cont)

Inflammation can reduce the physical sie of the nasal passages

Inducing vasodilatation, increasing BF and increasing vascular

permeability

Engorgement of nasal venous sinusoids,

swelling of inferior & anterior turbinates and

obs of nasal airflow

Figure 1. Allergic sensitization

Figure 2. Early Phase of allergi inflammation

Figure 3. Late phase of allergic inflammation

Figure 4. Allergic cascade of symptoms of allergic rhinitis

Pharmacotherapy

H1-antihistamines

Intranasal Glucocorticoids

Decongestans

Chromones (Amnivisnaga)

Anticholinergics

Antileukotrienes

Allergen-Spesific Immunotherapy

H-1 Antihistamines

inverse agonists

Antihistamines stabilise the inactive form and shift the equilibrium in the opposite direction.Thus, the amount of histamine-induced stimulationof a cell or tissue depends on the balance betweenhistamine and H1 antihistamines.

H-1 Antihistamines(Cont1)

Common H1- receptor antagonists

First generation Second generation*

Hydroxyzine Cetirizine

Diphenhydramine Loratadine

Chlorpheniramine Desloratadine

Promethazine Fexofenadine

Levocetirizine

*Two earlier developed agents, astemizoleand terfenadine, werewithdrawn in 1986 because of cardiac toxicity adverse effects.

H-

onset of effect occurs within 1-3 hours;

Duration of action varies from several hours to 24 hours,

First-generation antihistamines and some ofthe second-generation agents are oxidativelymetabolisedby the hepatic cytochromeP450 system,the exceptions being levocetirizine, cetirizine, and fexofenadine.

H-

Levocetirizineand cetirizineare excretedlargely unchanged in urine and fexofenadineis excretedmainly in the faecesbut also the urine

Concomitant administration of probenicidreduces the totalbody and renal clearance of fexofenadine

The bioavailability of fexofenadinemay be altered by simultaneousconsumption of grapefruit juice (reduced rateand absorption of the drug by almost 30%).

bahan kuliah THT\daftar obat rhinitis alergi.docx

bahan kuliah THT/daftar obat rhinitis alergi.docx

Nasal Decongestant

Nasal decongestants are vasoconstrictivedrugs extremely useful as nonprescription medication. Both oral and topical dosage forms are often chosen as therapy in the common cold.

Mechanism of action:

Nasal decongestants belong to the pharmacological class of sympathomimeticamines. Decongestant stimulates alpha-adrenergic agonist, by constriction of blood vessels, reducing its supply to the nose, decrease the amount of blood in sinusoid vessels and decrease mucosal edema.

Types of nasal decongestant:

Internally or systemic decongestant: (e.g. pseudoephedrine, phenylpropanolamine (PPA) and phenylephrine ).

Topical decongestant: drops or sprays (e.g. xylometazoline , phenylephrine , oxymetazoline , naphazoline).

Inhaler: (1 -desoxyephedrine and propylhexedrine ).

Systemic nasal decongestant:

Mechanism of action:

Potent direct acting alpha -adrenergic stimulator with weak beta -Adrenergic activity, causes vasoconstriction of the arterioles of the nasal mucosa and conjunctive, activates the dilator muscle of the pupil to causes contraction, and produce systemic arterial vasoconstriction.

Side effect of systemic decongestant:

CNS effect: Nervousness, restlessness, headach and insomnia.

CV effect: increase blood pressure and increase heart rate.

Urinary sphincter constriction

Examples of systemic decongestant:

PseudoephedrinePhenylpropanolamine (PPA)phenylephrine

PhenylephrineHCLPseudoephedrine

For Symptomatically relief of nasal and

nasopharyngeal mucosal congestion and relief of redness of the eye due

to irritation.

Its symptomatically relief of nasal congestion due to

common cold, upper respiratory allergies and it

promotes nasal or sinus drainage.

Indication

CNS: nervousness, irritability, restlessness, headache.

CV: 9blood pressure and heart rate is irregular and palpitation.

GIT : nausea, vomiting.

Neuromuscular and skeletal: weakness, tremor.

CNS: nervousness, irritability, restlessness, headache and insomnia.

CV: 9blood pressure and heart rate is irregular and palpitation.

GIT : nausea, vomiting.

Neuromuscular and skeletal:weakness, tremor.

Side effect