PHARMACOLOGY OF

ENT
Dept. of Pharmacology and Therapy
Medical Faculty
Universitas DIponegoro

DECONGESTANT, MUCOLYTICS,
ANTI-HISTAMINE, ANTITINNITUS & ANTI-VERTIGO

DECONGESTANT

Excessive nasal secretion, inflamed and swollen nasal mucosa

Decongestant
Decrease nasal congestion related to

common cold, allergic rhinitis, and sinusitis,

a condition that is caused by an
inflammatory response in the upper
respiratory tract

Types of decongestants
Adrenergic (alpha-adrenergic agonist)

largest group
Anticholinergic (parasympatolytics)
Corticosteroids

Preparations
Oral (systemic)
Topical (e.g. xylometazoline, phenylephrine,

oxymetazoline, naphazoline).
Inhaled (1-desoxyephedrine and propylhexedrine).

Oral decongestant
Prolonged effects
Less potent
No rebound congestion
Exclusively adrenergics
Side effects: nervousness, restlessness, tremor,

headache, insomnia, increase BP and HR, urinary

sphincter constriction, nausea, vomitting.
Example: pseudoephedrine, phenylpropanolamine (PPA)
and phenylephrine
Drug interactions: MAOI may increase blood pressure.
Sympathomimetic may increase toxicity it can decrease
effect of methyldopa, reserpine.

Topical decongestants:
Fast onset of action
Potent
Simple to use
Sustained use over several days could cause
rebound congestion make condition worse
Side effects:
Local irritation

Topical decongestants:
Adrenergic:

- Phenylephrine
- Oxymetazoline
- Pseudoephedrine
Intranasal steroids:
- Beclomethasone dipropionate
- Budesonide - Flunisolide
- Fluticasone - Triamcinolone
Intranasal cholinergic
- Ipratropium

Mechanisms of action
Adrenergic:
Stimulates -adrenergic (-adrenergic agonist)
Constriction of blood vessels, reducing its supply to the
nose, decrease the amount of blood in sinusoid vessels,
decrease mucosal edema.
Steroids:
Anti-inflammatory
Decrease inflammation, resulted in decrease congestion

Adverse effects
Adrenergics:

- Nervousness
- Insomnia
- Palpitation
- Tremor
- Etc.
be careful in patients with hypertension
Steroids:
- Local mucosal dryness & irritation

MUCOLYTICS

Layers of airway

Mucociliary blanket

Normal mucus physiology

Large molecule, 95% made up of water
Very hydrophilic

Pathologic mucus
Increased mucus production
Impaired mucus clearance
Thick, retained mucus

Infection or dehydration could cause thickening of the

mucus (gel layer). White blood cells, DNA, and cellular
debris add to the thickening. cant be moved by cilia.

Mucus secretion management

Increase the depth of sol layer (water, saline solution,

expectorant)
Alter consistency of gel layers (mucolytics)
Improve ciliary activity (bronchodilators, corticosteroid)

Mucolytics
Directly alter the structure of mucus
Dissolving, digesting, or liquefying mucus
Reducing the viscosity of mucus
The use of mucolytics in ENT problems:

- Sinusitis
- Rhinosinositis
- Otitis media with effusion
- etc.
Other use: Cystic Fibrosis, COPD, Bronchiectasis, other

Respiratory Infections

Mechanisms of Action:
Weakening inter-molecular forces that bind adjacent

glycoprotein chains disruption of inter-molecular

disulfide bonds (N-Acetylcysteine, Mesna)
Alteration of pH to weaken carbohydrate side chains of
glycoprotein (sodium bicarbonate)
Destruction of protein (proteolysis) contained in the
glycoprotein core breaking down of DNA in mucus
(dornase alpha)
Nondestructive Mucolytics: loosen mucus network by
charge shielding (low-molecular-weight dextran, and other
sugars or glycoproteins)

Mucolytic agents:
1. N-acetyl L-cysteine (NAC)
Treat thick, viscous secretion

Mucolytic agents:
N-acetyl L-cysteine (NAC)
- Smells bad because of the release of hydrogen
sulfide
- Dose & administration:
Aerosol, in 10% or 20% solution
Oral preparation
- Adverse reaction: nausea, vomiting,
bronchospasm, rhinorrhea, bronchorrhea
- Also works as anti-oxidant (anti-dote for
paracetamol overdose)
1.

Mucolytic agents:
2. Dornase alfa
- Clone of naturalhuman enzyme that digests
extracellular DNA
- Decreasing viscoelasticity of the secretion,
increasing airway clearing, decreasing the frequency and
severity of infections.
- 2.5 mg of 0.1% solution, iv, daily
- Side effects: voice alteration, laryngitis,
pharyngitis,
rash, chest pain

Mucolytic agents:
2. Dornase alfa

ANTIHISTAMINE

Histamine
Biologic amine
Receptor: histamine
G protein coupled receptors
H1, H2, H3 and H4

Histamine receptors

 H4:
Just found in 2000
Eosinophils, neutrophils, CD4T cells
Modulate the production of blood cells and cytokines
Potent antagonist: thioperamide

H1 receptor antagonist
Inverse agonist
Smooth muscle: inhibit constriction of respiratory smooth

muscle
Capillary permeability: block the increases capillary
permeability
Nerve ending: reduced the flare and itch (especially in
hypersensitivity reaction)
CNS: depress CNS (1st generation of antihistamine)

H1 receptor antagonist
Well absorbed from GI tract
Peak plasma concentration: 2-3 hours
Effect last 4-6 hours
Distributed widely including CNS
Extensively metabolized drugs: in liver, children >>
Excreted in urine

H1 receptor antagonist
Therapeutic uses:
Allergic disease: acute type of allergy (rhinnitis, urticaria,
conjunctivitist)
In anaphylactic: adjuvant role
Motion sickness, vertigo, sedation:
For milder case
Dymenhidrinate, pyperazines (cyclizine, meclizine), promathazine

Meniere disease

H1 receptor antagonist
Adverse effects:
Sedation
Dizziness, tinnitus, fatigue, blurred vision
Dryness of the mouth

H1 receptor antagonist
First generation:
Chlorpheniramine, diphenhydramine, doxylamine, hydroxyzine,
promethazine, cyproheptadine
Short to intermediate acting
More sedating, more antimuscarinic side effects
Second generation:
Weak sedating: cetirizine, acrivastine
Non sedating: loratadine, fexofenadine
Longer duration of action
Poor CNS entry (less lipid soluble), least sedating
No autonomic side effect

DRUGS FOR TINNITUS

Tinnitus
Perceived sensation of sound without a corresponding

external stimulus
Buzzing, hissing, ringing or combination
Continous, intermitten, or pulsatile

Tinnitus
Objective or subjective
Objective: rare, sound generated by internal biological sources i.e
vascular turbulence, pulsation, spasm in middle ear, can be heard
by external examiner
Subjective: common, phantom auditory sensation

Tinnitus
Acute or chronic
Acute: following acute hearing loss, < 3 months
Chronic :> 6 months
Prevalence: 25% of population
Risk factor:
Hearing loss
Increasing age
Male gender

Tinnitus: pathophysiology
Neuronal alteration in central system
neuronal firing rates, neuronal synchrony, and tonotopic
reorganization
alterations in GABAergic, glycinergic, and glutamatergic
neurotransmission
Gama band activity in auditory cortex ( alpha and theta
activity)

 Gambar di desktop
http://www.hilarymartinhiman.com/tag/mechanisms/

Acute tinnitus: treatment

Resolve spontaneously
Systemic or intratympanic steroids, vasodilators, and

antiviral agents
Otoprotectants: protect hair cell
4 g Mg aspartat daily
1200 mg NAC daily

Chronic tinnitus: treatment

Antidepressant
BDZ
Non BDZ
Antiglutamatergic compound
Dopaminergic-antidopaminergic drugs
Muscle relaxant
Other

Antidepresant
Reason: co occurant of depressive disorder
TCA : 100 mg amitriptylin
SSRI: sertraline, paroxetine

Benzodiazepine
Increase inhibitory neurotransmission
Beneficial effects on comorbid ansiety and insomnia
Alprazolam 1,5 mg daily
Clonazepam 0.5 mg+ Ginkgo biloba 40 mg daily

Non benzodiazepine anti convulsant

Carbamazepine:
reduced neuronal firing (through Na channel)
600-1000 mg/day
Gabapentin, pregabalin
reduced neuronal firing (through Ca channel)

Lamotrigine:
Valproic acid

Antiglutamatergics compound
Goal: reduce excitatory neurotransmission
Acamprosate :
blocks excitatory glutamatergic N-methyl-d-aspartate (NMDA)
receptors
333 mg 3x a day
Significant effect at 90 days
Caroverine :
Spasmolytic drug
Intravenously
160 mg, reduction in tinnitus loudness

Other drug: mematine, neraxamane, gacyclidine

Dopaminergics and anti dopaminergics drugs

Inhibitory function of cochlea
Dopamine antagonist: sulpiride
Selective D2 blocker
In combination with melatonine

Dopamine agonist: propamine

Muscle relaxant
Baclofen:
GABAA agonist
60 mg/day

Lidocaine
Reduction of tinnitus in 70% patients after intravenous

application of the voltage-gated sodium channel blocker

lidocaine.
Lidocaine :
Antiarrythmic drug
Poor bioavailability after oral intake
Short acting
Novel research: lidocaine patch

Other
Gingko biloba: vasodilating and antioxidant properties
Melatonin: regulating circadian rhythm, antioxidant protect

mitochondria protect against noise- and drug-induced

hearing loss
Misoprostol: Synthetic PGE1 analogue, a > 15-dB
reduction in tinnitus loudness
Zinc: important role in dorsal cochlear nucleus
Methylcobalamine considered home remedies, no
evidence based approved

Other treatment
Counseling
Cognitive behavioral therapy (CBT)
Sound therapies (environmental sound, hearing aids,

noise generators)

DRUGS FOR VERTIGO

Vertigo

Vertigo
Sensation of movement when no movement is actually

occurring.
Imbalance between two vestibular labyrinths
Main neurotransmitter:
Cholinergic
H1 histaminergic
GABA
Glutaminergics
Serotonin
Neurokinin type I

 Treatment goal:
Control acute episode
Speed up recovery
Prevent future episodes
Treatment:
Symptomatic
Specific

Treatment: Vestibular supressant:

Benzodiazepine:
act centrally via GABA-A receptors
SE: addiction, sedation, impaired memory, increased risk of falling
and impaired vestibular compensation
Long acting benzodiazepines are not helpful for relief of vertigo

Treatment: Vestibular supressant:

Anticholinergics:
Act on muscarinic receptors: M3 and M5
Increase motion tolerance
Centrally acting anticholinergic
Ineffective if administered after symptoms have already appeared
SE: dry mouth, dilated pupils, sedation, decreased alertness and

impaired attention.

Treatment: Vestibular supressant

Antihistamine:
H1 effect
Reduce motion sickness
Reduce severity of the symptoms
Promethazine: most effective

Drugs for vertigo

Other treatment for vertigo

Antiemetics:
Antihistamine meclizine has antiemetic properties
Droperidol and fentanyl: acute peripheral vertigo
Ca channel blocker:
inhibit the flow of calcium from the endolymph into the cells of the

crista ampullaris which trigger action potential

Flunarizine, cinnarizine