K46 Pharmacology of Drugs Act on Smell Dan Taste

7/28/2019 K46 Pharmacology of Drugs Act on Smell Dan Taste

1/26

Pharmacology of drugsact on nose ( smell ) andtongue ( taste )

Tri Widyawati, Aznan Lelo

Dep. Farmakologi & Terapeutik, Fakultas Kedokteran

Universitas Sumatera UtaraKBK-SSS Medan


2/26


3/26

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


4/26

Drug-induced taste and smell disorders. Incidence, mechanisms and management related primarily to treatment of sensory receptor dysfunction

Loss of acuity occurs primarily by druginactivation of receptor function throughinhibition 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


5/26

Drug-induced taste and smell disorders. Incidence, mechanisms and management related primarily to treatment of sensory receptor dysfunction

Distortions occur primarily by a drug inducingabnormal 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.


6/26

Drug-induced taste and smell disorders.Incidence, mechanisms and management related primarily to treatment of sensory receptor dysfunction

Treatment which inhibits sensory distortionsrequires :

reactivation of biochemical inhibition at thereceptor or

inactivation of inappropriate stimulus receptor binding and/or correction of other steps initiatingpathology including dopaminergic antagonists,

gamma-aminobutyric acid (GABA)-ergic agonists, calcium channel blockers and some orally active local anaesthetic, antiarrhythmic drugs.


7/26


8/26

Selected Medications thatReportedly Alter Smell and Taste Anti-inflammatory agents

Auranofin (Ridaura)ColchicineDexamethasone (Decadron)Gold (Myochrysine)HydrocortisonePenicillamine (Cuprimine)

Antimanic drug Lithium

Antineoplastics Cisplatin (Platinol)Doxorubicin (Adriamycin)Methotrexate (Rheumatrex)Vincristine (Oncovin)

Antiparkinsonian agents Levodopa (Larodopa; withcarbidopa: 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)


9/26

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


10/26


11/26

Smell

Central OlfactoryPathways

Olfactory Receptor Neurons Olfactory Transduction


12/26

ANOSMIA a complete loss of smell

HYPOSMIA partial loss of smell

HYPEROSMIA enhanced smell sensitivity

DYSOSMIAdistortion in odour perception(includes parosmia &phantosmia)

PAROSMIA distortion of perception of external stimulus

PHANTOSMIA smell perception with no externalstimulus

Olfactory disorders


13/26

Anosmia = loss of smellImpaired 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


14/26

CAUSES of OLFACTORY LOSSAetiology % patients

Head injury 19*Post URI 17*Nasal/sinus disease 16*

Idiopathic-nasal 17Toxic exposure-nasal 5Multiple 5Congenital 2

Age 1Idiopathic-oral 9Miscellaneous-oral 6Toxic exposure-oral 1


15/26

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 withcolds and influenza.

While zinc is critical for maintenance of normalsmell function through its action as a cofactor incarbonic anhydrase VI, given directly into thenostrils at high concentrations, it can initiate

direct toxic destruction of the olfactory epitheliumwith which it comes into contact in its spray form.The associated nasal burning is another manifestation of this local toxicity.


16/26

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 tomany other side effects of chemotherapy.

Diagnosis and type of chemotherapyregimen did not predict causes


17/26

Treatment

Systemic corticosteroids are potent anti-inflammatory substances that act byreducing the nasal mucous membrane,allowing the odorant to reach the olfactoryneuroepithelium

Intranasal topical corticosteroids are areasonable alternative.


18/26

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 onthe tongue and in the pharynx and larynx. Taste budscontain chemoreceptor cells arranged around a tastepore.

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 typicallyinclude thalamus, cortex, vomiting centers.


19/26


20/26

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 (IP 3) Ca 2+


21/26

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


22/26

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 industrialcompounds, tobacco, and alcohol , may adverselyaffect taste, most commonly through local effects in theoral cavity.

Blood-borne toxins , such as medications and thosepresent in autoimmune and other systemic disorders (e.g.renal or liver failure), have access to all parts of thegustatory system, and thus may exhibit varied effects ontaste function.


23/26

drug-induced taste alteration

Numerous drugs have the potential to adverselyinfluence 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, dietarychoices, emotional state and compliance withmedication regimens.

antihypertensives, antimicrobials andantidepressants


24/26

Garlic boosts Umami

Garlic aroma

Plain MSG


25/26

Smell in infants & Smell and ageing


26/26

K46 Pharmacology of Drugs Act on Smell Dan Taste

Documents

Transcript of K46 Pharmacology of Drugs Act on Smell Dan Taste