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

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

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 Ampicillin Azithromycin (Zithromax) Ciprofloxacin (Cipro) Clarithromycin (Biaxin) Griseofulvin (Grisactin) Metronidazole (Flagyl) Ofloxacin (Floxin) Tetracycline Anticonvulsants Carbamazepine (Tegretol) Phenytoin (Dilantin) Antidepressants Amitriptyline (Elavil) Clomipramine (Anafranil) Desipramine (Norpramin) Doxepin (Sinequan) Imipramine (Tofranil) Nortriptyline (Pamelor) Antihistamines and decongestants Chlorpheniramine Loratadine (Claritin) Pseudoephedrine Antihypertensives and cardiac medications Acetazolamide (Diamox) Amiloride (Midamor) Betaxolol (Betoptic) Captopril (Capoten) Diltiazem (Cardizem) Enalapril (Vasotec) Hydrochlorothiazide (Esidix) and combinations Nifedipine (Procardia) Nitroglycerin Propranolol (Inderal) Spironolactone (Aldactone)

Selected Medications that Reportedly Alter Smell and Taste

Anti-inflammatory agents Auranofin (Ridaura) Colchicine Dexamethasone (Decadron) Gold (Myochrysine) Hydrocortisone Penicillamine (Cuprimine) Antimanic drug Lithium Antineoplastics Cisplatin (Platinol) Doxorubicin (Adriamycin) Methotrexate (Rheumatrex) Vincristine (Oncovin) Antiparkinsonian agents Levodopa (Larodopa; with carbidopa: Sinemet) Antipsychotics Clozapine (Clozaril) Trifluoperazine (Stelazine) Antithyroid agents Methimazole (Tapazole) Propylthiouracil Lipid-lowering agents Fluvastatin (Lescol) Lovastatin (Mevacor) Pravastatin (Pravachol) Muscle relaxants Baclofen (Lioresal) Dantrolene (Dantrium)

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

SMELL

Smell

Central Olfactory Pathways

Olfactory Receptor Neurons

Olfactory Transduction

Olfactory disorders
ANOSMIA
HYPOSMIA

a complete loss of smell

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
Head injury Post URI Nasal/sinus disease Idiopathic-nasal Toxic exposure-nasal Multiple Congenital Age Idiopathic-oral Miscellaneous-oral Toxic exposure-oral

% patients
19* 17* 16* 17 5 5 2 1 9 6 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

Treatment
Systemic corticosteroids are potent antiinflammatory 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
(1) Salty (2) Sweet (3) Umami (4) Water Taste (Rolls)

Taste Sensations

Astringent Electric taste Alkaline taste Alcohol taste

Touch Temperature Pain Pressure

Aversive Tastes
(5) Bitter (6) Sour

Orosensation (trigeminal)

Energy Tastes
(7) Fatty acid taste?

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

Garlic boosts Umami

Garlic aroma

Plain MSG

Smell in infants & Smell and ageing