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Pharmacology of drugs

act on nose (smell) and


tongue (taste)
Tri Widyawati, Aznan Lelo
Dep. Farmakologi & Terapeutik,
Fakultas Kedokteran
Universitas Sumatera Utara
KBK-SSS, Medan
Pharmacology of drugs act on
nose (smell) and tongue (taste)
Nasal decongestant
Menjelaskan aspek farmakologi nasal dencongestant
Obat yang mempengaruhi penciuman
Menyebutkan obat-obat yang dapat mempengaruhi penciuman
Menerangkan mekanisme kerja obat-obat yang mempengaruhi
penciuman
Obat-obat yang mempengaruhi pengecapan
Menyebutkan obat-obat yang dapat mempengaruhi
pengecapan
Menerangkan mekanisme kerja obat-obat yang mempengaruhi
pengecapan
Keterkaitan dosis dan pemaparan obat dengan terjadinya
gangguan pengecapan
Anatomy
Drugs for Allergic Rhinitis
& the Common Cold
Nasal Mucosa
dynamic structure, richly supplied with
vascular tissue, under control of the
autonomic nervous system.
the effects of sympathetic activation.
the effects of parasympathetic activation
What is the relevance of this statement to
pharmacotherapy of the upper respiratory
tract?
Correlation of Symptoms to
Inflammatory Mediators in AR
Symptoms Histamine Prostaglandin Leukotriene Bradykinin PAF
Tickling X X
Itching X X
Nose rubbing X X
Allergic salute X X
Sneezing X X
Nasal congestion X X X X
Stuffy nose X X X X
Mouth breathing X X X X
Snoring X X X X
Runny nose X X
Postnasal drip X X
Throat clearing X X

Rosenwasser L. Allergy Asthma Proc. 2007;28:10-15.


Pharmacotherapy
Medications used to treat allergic rhinits:
Antihistamines

Decongestants

AH-D combinations

Corticosteroids

Mast Cell stabilizers

Anticholinergics

Antileukotrienes
Nasal decongestant
Nasal congestion
Caused by vasodilatation
Reduce smell acuity
Nasal decongestant
Sympathomimetic
ex. PPA=phenyl-propanol-amine, etc
Topical and systemic
Topical
rebound phenomenon,
systemic effect
Decongestants
Oral or Intranasal Sympathomimetics
Most common
Alleviate nasal congestion of allergic rhinitis or the
common cold
Many available OTC
Ipratropium bromide anticholinergic
Caution/nursing consideration
Monitor pulse and B/P
Avoid within 2 hours of bedtime
Instruct regarding proper positioning and technique
for intranasal administration
Histamine and anti-histamine
What is histamine?
What two receptors interact with histamine?
Describe the difference between first-generation H1 receptor
antagonists and second generation H1 receptor antagonists.
Identify the prototype for each generation
What is another term used for H1-antagonist?
What is the mechanism of action of this class of drugs?
What are indications for OTC treatment with this class
of drugs?

H1 Receptor Antagonists
Contraindicated:
dysrhythmia, heart failure, HTN, sleep
disorders, asthma, narrow angle
glaucoma, urinary retention (e.g. BPH)
Can have paradoxical effect in children
(increased CNS stimulation instead of
drowsiness)
Must monitor elderly for safety
H1 Receptor Antagonists
Key Client Education
Report: chest pain, insomnia,
restlessness, visual changes, seizure
activity
Avoid driving until side effects are known
Avoid alcohol and other CNS depressants
Increase fluid intake to facilitate
expectoration of dry oral mucus
Antihistamines
First Generation
i.e.: Benadryl, Chlor-Trimeton (CTM)
Mechanism: inhibition of histamine (H1)
receptors.
Effect: reduce sneezing, nasal pruritus and
rhinorhea, but not congestion.
Note:
OTC
Work better in seasonal rhinitis.
Side Effects: anticholinergic activity --> adverse
CNS effects.
Antihistamines
Second Generation
i.e.: Claritin, Allegra, Zyrtec
Mechanism: inhibit histamine (H1) receptors.
Effect: same as First generation.
Note:
Nonsedating (Zyrtec is low-sedating)
Prescription only
Side effects: Seldane (Terenadine, now off
market) -- Black-box warnings related with
serious cardiac arrhythmias (w/ macrolide,
antifungals).
Decongestants (oral/topical)
i.e.: Sudafed (oral), Afrin (topical)
Mechanism: alpha-adrenergic agonist.
Effect: vasoconstriction restricts blood flow to
nasal mucosa decreasing nasal obstruction (no
influence on pruritis, sneezing or nasal
secretion).
Side effects:
Oral: HA, nervousness, irritability, tachycardia,
palpitations, insomnia.
Topical(nasal): prolonged use (>5-7 days) leads to
rhinitis medicamentosa
Ipratropium (intranasal)
i.e.: Atrovent (intransal)
Mechanism: inhibits muscarinic cholinergic
receptors.
Effect: reduces watery rhinorrhea (no effect on
nasal itching, sneezing or nasal congestion).
Note:
limited to control of watery secretions.
effective at reducing both cold-air and
gustatoryrhinitis.
Side effects: irritation, crusting, epistaxis.
Intranasal Glucocorticoids
Drug of choice for seasonal allergic rhinitis
Highly efficacious; Wide margin of safety
Use decongestant first
Prototype: fluticasone
Metered Spray Devise:
Shake
Clear nose
Avoid swallowing
Adverse effects:
Nasal irritation
Epistaxis
Corticosteroids (intranasal)
i.e.: Vancenase, Flonase
Mechanism:
reduce inflammation
suppress neutrophil chemotaxis
mildly vasoconstrictive
reduce intracellular edema
Effect: reduce nasal blockage, pruritis,
sneezing and rhinirrhea.
Actions of Various Nasal Preparations in
the Treatment of Rhinitis
Nasal Sneezing Itching Rhino- Conges
Preparation rhoea tion
Antihistamine +++++ ++++ +++ 0
Anticholinergic 0 0 +++++ 0
Corticosteroid +++++ +++++ +++ +++
Decongestant 0 0 + +++++
Mast cell +++++ +++ + 0
stabilizer
Anti-leukotriene +++ ++ 0 +++
SMELL
Smell

Central Olfactory Olfactory Receptor Neurons


Pathways Olfactory Transduction
Olfactory disorders
ANOSMIA a complete loss of smell
HYPOSMIA partial loss of smell
HYPEROSMIA enhanced smell sensitivity
distortion in odour perception
DYSOSMIA (includes parosmia &
phantosmia)
distortion of perception of
PAROSMIA
external stimulus
smell perception with no external
PHANTOSMIA
stimulus
Anosmia = loss of smell
Impaired smell is the partial or total loss of the sense of smell.
Causes
Drugs (such as amphetamines, estrogen, naphazoline,
phenothiazines, prolonged use of nasal decongestants,
reserpine)
Lead poisoning
Nasal decongestants
Nasal or sinus surgery
Natural aging process
Radiation therapy
Recent viral upper respiratory infection
Tracheostomy
Tumors of the nose or brain
CAUSES of OLFACTORY LOSS
Aetiology % patients
Head injury 19*
Post URI 17*
Nasal/sinus disease 16*
Idiopathic-nasal 17
Toxic exposure-nasal 5
Multiple 5
Congenital 2
Age 1
Idiopathic-oral 9
Miscellaneous-oral 6
Toxic exposure-oral 1
Zicam-induced hyposmia
Zicam is a zinc containing drug.
Zicam is an over the counter drug used as a
nasal spray to relieve symptoms associated with
colds and influenza.
While zinc is critical for maintenance of normal
smell function through its action as a cofactor in
carbonic anhydrase VI, given directly into the
nostrils at high concentrations, it can initiate
direct toxic destruction of the olfactory epithelium
with which it comes into contact in its spray form.
The associated nasal burning is another
manifestation of this local toxicity.
Chemotherapy as one of
Causes of Taste and Smell Loss
were found to be common during cancer
chemotherapy and
were related to socio-demographic rather
than clinical factors.
were also found to be closely related to
many other side effects of chemotherapy.
Diagnosis and type of chemotherapy
regimen did not predict causes
Carbonic anhydrase inhibitors
E.g. acetazolamide, methazolamide,
dichlorphenamide, dorzolamide, brinzolamide.
Uses: glaucoma, cystoid macular edema,
pseudotumour cerebri
Mechanism: aqueous suppression
Side effects: myopia, parasthesia, anorexia, GI
upset, headache, altered taste and smell, Na
and K depletion, metabolic acidosis, renal stone,
bone marrow suppression aplastic anemia
Contraindication: sulpha allergy, digitalis users,
pregnancy
Treatment
Systemic corticosteroids are potent anti-
inflammatory substances that act by
reducing the nasal mucous membrane,
allowing the odorant to reach the olfactory
neuroepithelium
Intranasal topical corticosteroids are a
reasonable alternative.
Taste
Taste bud receptors detect gustatory stimuli.
Receptors signal the five qualities of taste (humans):
sweet, salty, sour, bitter, umami (savory).
Taste buds are located on several kinds of papillae on
the tongue and in the pharynx and larynx. Taste buds
contain chemoreceptor cells arranged around a taste
pore.
These cells are innervated by taste afferent fibers of
cranial nerves VII, IX, X.
Taste fibers synapse in the nucleus of the solitary tract.
Higher pathways differ in different species, but
typically include thalamus, cortex, vomiting centers.
8 Basic Tastes, Many Sensations
Hedonic Tastes Taste Sensations
(1) Salty Astringent
(2) Sweet Electric taste
(3) Umami Alkaline taste
(4) Water Taste (Rolls) Alcohol taste
Aversive Tastes Orosensation (trigeminal)
(5) Bitter Touch
(6) Sour Temperature
Energy Tastes Pain
(7) Fatty acid taste? Pressure
Heat Taste
(8) Vanilloid receptor
Mechanisms of Taste Transduction
Transduction process
Taste stimuli (tastants)
Pass directly through ion channels (Na+)
Bind to and block ion channels (sour-H+)
Bind to G-protein-coupled receptors (bitter, sweet, umami)
Saltiness
Salt-sensitive taste cells
Special Na+ selective channel
Blocked by the drug amiloride
Sourness
Sourness- acidity low pH
Protons causative agents of acidity and sourness
Bitter, Sweet, Umami
G-protein coupled receptor
Activates Phospholipase C
Increases messenger inositol triphosphate (IP3)
Ca2+
Taste Disorders
Hypoguesia decreased taste sensation
Ageusia absence of the taste sensation
Caused by
head injuries,
damage to glossopharyngeal and facial
nerves.
Parageusia perversion of taste
Taste Disorders
A large number of substances and disease processes
may impact the sense of taste.
Toxic substances may cause taste dysfunction from their
effects on the gustatory system from the salivary gland,
to the taste bud, to the central neural pathways.
A number of external toxins, including industrial
compounds, tobacco, and alcohol, may adversely
affect taste, most commonly through local effects in the
oral cavity.
Blood-borne toxins, such as medications and those
present in autoimmune and other systemic disorders
(e.g. renal or liver failure), have access to all parts of the
gustatory system, and thus may exhibit varied effects on
taste function.
drug-induced taste alteration
Numerous drugs have the potential to adversely
influence a patient's sense of taste, either by
decreasing function or
producing perceptual distortions or
phantom tastes.
taste-related adverse effects
some cases are long lasting and cannot be quickly
reversed by drug cessation
significantly alter the patient's quality of life, dietary
choices, emotional state and compliance with
medication regimens.
antihypertensives, antimicrobials and
antidepressants
Drug-induced taste and smell disorders.
Incidence, mechanisms and management related primarily to treatment of sensory receptor dysfunction

Loss of acuity occurs primarily by drug


inactivation of receptor function through
inhibition of tastant/odorant receptor:
binding;
Gs protein function;
inositol trisphosphate function;
channel (Ca++,Na++) activity;
other receptor inhibiting effects; or
some combination of these effects
Drug-induced taste and smell disorders.
Incidence, mechanisms and management related primarily to treatment of sensory receptor dysfunction

Distortions occur primarily by a drug inducing


abnormal persistence of receptor activity (i.e.
normal receptor inactivation does not occur) or
through failure to activate:
various receptor kinases;
Gi protein function;
cytochrome P450 enzymes; or
other effects which usually
turn off receptor function;
inactivate tastant/odorant receptor binding; or
some combination of these effects.
Drug-induced taste and smell disorders.
Incidence, mechanisms and management related primarily to treatment of sensory receptor dysfunction

Treatment which inhibits sensory distortions


requires :
reactivation of biochemical inhibition at the
receptor or
inactivation of inappropriate stimulus receptor
binding and/or correction of other steps initiating
pathology including
dopaminergic antagonists,
gamma-aminobutyric acid (GABA)-ergic agonists,
calcium channel blockers and
some orally active local anaesthetic,
antiarrhythmic drugs.
Selected Medications that
Reportedly Alter Smell and Taste
Antibiotics Antihistamines and
Ampicillin decongestants
Azithromycin (Zithromax) Chlorpheniramine
Ciprofloxacin (Cipro) Loratadine (Claritin)
Clarithromycin (Biaxin) Pseudoephedrine
Griseofulvin (Grisactin) Antihypertensives and cardiac
Metronidazole (Flagyl) medications
Ofloxacin (Floxin) Acetazolamide (Diamox)
Tetracycline Amiloride (Midamor)
Anticonvulsants Betaxolol (Betoptic)
Carbamazepine (Tegretol) Captopril (Capoten)
Phenytoin (Dilantin) Diltiazem (Cardizem)
Antidepressants Enalapril (Vasotec)
Amitriptyline (Elavil) Hydrochlorothiazide (Esidix) and
Clomipramine (Anafranil) combinations
Desipramine (Norpramin) Nifedipine (Procardia)
Doxepin (Sinequan) Nitroglycerin
Imipramine (Tofranil) Propranolol (Inderal)
Nortriptyline (Pamelor) Spironolactone (Aldactone)
Selected Medications that
Reportedly Alter Smell and Taste
Anti-inflammatory agents Antipsychotics
Auranofin (Ridaura) Clozapine (Clozaril)
Colchicine Trifluoperazine (Stelazine)
Dexamethasone (Decadron) Antithyroid agents
Gold (Myochrysine) Methimazole (Tapazole)
Hydrocortisone Propylthiouracil
Penicillamine (Cuprimine) Lipid-lowering agents
Antimanic drug Fluvastatin (Lescol)
Lithium Lovastatin (Mevacor)
Antineoplastics Pravastatin (Pravachol)
Cisplatin (Platinol) Muscle relaxants
Doxorubicin (Adriamycin) Baclofen (Lioresal)
Methotrexate (Rheumatrex) Dantrolene (Dantrium)
Vincristine (Oncovin)
Antiparkinsonian agents
Levodopa (Larodopa; with
carbidopa: Sinemet)
Food Preparation and Texture
Taste and smell are very important factors that
influence food intake and can subsequently
affect the nutritional status of individuals.

Add flavor enhancers that amplify the intensity of


food odor
Appealing odors can help to enhance appetite
These may be useful for elderly adults with decreased
smell / taste
Garlic boosts Umami

Garlic aroma

Plain MSG
Medications that alter smell and taste
Antibiotics Anti-inflammatory agents
Ampicillin, Azithromycin, Colchicine, Dexamethasone, Gold,
Ciprofloxacin, Clarithromycin, Hydrocortisone, Penicillamine
Griseofulvin, Metronidazole, Antineoplastics
Ofloxacin, Tetracycline Cisplatin, Doxorubicin,
Antidepressants/Mood Stabilizer Methotrexate, Vincristine
Amitriptyline, Clomipramine, Antiparkinsonian agents
Desipramine, Doxepin, Levodopa, Sinemet
Imipramine, Nortriptyline Antipsychotics
Antihistamines and Clozapine , Trifluoperazine
decongestants Antithyroid agents
Chlorpheniramine, Loratadine, Methimazole, Propylthiouracil
Pseudoephedrine
Lipid-lowering agents
Antihypertensives/Cardiac Fluvastatin, Lovastatin, Pravastatin
Acetazolamide, Amiloride,
Betaxolol, Captopril, Diltiazem, Anticonvulsants
Enalapril, Hydrochlorothiazide, Carbamazepine, Phenytoin
Nifedipine, Nitroglycerin, Muscle relaxants
Propranolol, Spironolactone Baclofen, Dantrolene

ACE inhibitors one of the most common offenders