Laboratory Phar Olfaction and taste.pptx

Pharmacology Laboratory

1. TRANSDUCTION SENSORY CELLS TRASLATING CHEMICAL, ELECTROMAGNETIC, AND MECHANICAL STIMULI INTO ACTION POTENTIALS THAT OUR NERVOUS SYSTEM CAN MAKE SENSE OF “EACH SENSE WORK IN THIS WAY”

2. Our vision functions with the help of photoreceptors, cells that detect light waves, while our senses of touch, hearing, and balance use mechanoreceptors that detect sound waves and pressure on the skin and in the inner ear. But our sense of taste, or gustation, and smell, or olfaction, are chemical senses. They call on chemoreceptors in our taste buds and nasal passages to detect molecules in our food and the air around us.

3. Tastes and smells Tastes and smells are powerful at activating memories, triggering emotions, and alerting us to danger. They also help us enjoy the small things that make life worth living…like pizza Now, the process starts by sniffing molecules up into the nose. This means that for you to be able to smell something, the odorant must be volatile , or in a gaseous state to get sucked up into your nostrils. The harder and deeper you sniff, the more molecules you vacuum up, and the more you can smell it. Most of these molecules are filtered out on the way up the nasal cavity, as they get caught by the protective nose hairs, but a few make it all the way to the back of the nose and hit the olfactory epithelium.

4. olfactory system olfactory system is a small yellowish patch of tissue on the roof of the nasal cavity. The olfactory epithelium contains millions of bowling pin-shaped olfactory sensory neurons surrounded by insulating columnar supporting cells. So these airborne pizza molecules -- many of which are just broken-off parts of fats and proteins -- land on the olfactory epithelium and dissolve in the mucus that coats it. Once in the mucus, they’re able to bind to receptors on the olfactory sensory neurons, which, assuming they hit their necessary threshold, fire action potentials up their long axons and through your ethmoid bone into the olfactory bulb in the brain. Each olfactory neuron has receptors for just one kind of smell. And any given odorant, like pizza, is made up of hundreds of different chemicals that you can smell, like the thymol of the oregano, the butyric acid of the cheese.

5. after each smell-specific neuron is triggered, the signal travels down its axon where it converges with other cells in a structure called a glomerulus . “a tangle of fibers that serves as a kind of a transfer station, where the nose information turns into brain information”. Inside the glomerulus, the olfactory axons meet up with the dendrites of another kind of nerve cell, called a mitral cell , which relays the signal to the brain. So for each mitral cell, there are any number of olfactory axons synapsing with it, each representing and identifying a single volatile chemical. As a result, every combination of an olfactory neuron and a mitral cell is like a single note, and the smell coming off of pizza triggers countless of those combinations, forming a delicious musical chord of smells

6. Scientists estimate that our 40 million different olfactory receptor neurons help us identify about 10,000 different smells, maybe even more. So, once a mitral cell picks up its signal from an olfactory neuron, it sends it along the olfactory tract to the olfactory cortex of the brain. From there the smell hits the brain through two avenues: One brings the data to the frontal lobe where they can be consciously identified, like oh, melted mozzarella. the other pathway heads straight for the emotional ground control -- the hypothalamus, amygdala , and other parts of the limbic system . This emotional pathway is fast, intense, and quick to trigger memories. If the odor is associated with danger, like the smell of smoke, it quickly activates the sympathetic system’s fight or flight response

7. Molecular interactions of drug signaling with olfactory signaling 400 Olfactory receptors, coupled to Gs and Golf proteins, sense thousands of different odors by combinatorial coding. Binding of odorant molecules leads to the activation of olfactory receptors and to an increase in intracellular cAMP levels. Opioids activate Gi protein-coupled receptors, leading to a decrease in intracellular cAMP levels, and thus decrease olfactory function by raising olfactory thresholds .

8. Molecular interactions of drug signaling with olfactory signaling Cannabinoids activate Gi protein-coupled receptors, leading to reduced intracellular cAMP levels, and thus also decrease olfactory function by raising olfactory thresholds Theophylline leads to an increase in intracellular cAMP levels by blocking phosphodiesterase -mediated cAMP degradation, and thus improves olfactory function

9. Measurement of Olfactory Function

10. Measurement of Olfactory Function 1- Psychophysical Methods of Olfactory Testing The basic principle of psychophysical testing of olfaction is to expose a subject to an olfactory stimulus and to interpret the responses or reactions of the tested subject. The most valuable advantage in this procedure compared to objective testing methods in daily clinical life is the rapidity which allows psychophysical tests to serve as quick screening tools for olfactory dysfunction

11. Measurement of Olfactory Function subject has to identify the odor from a list of descriptions of odors (e.g. the subject gets rose odor to smell, and is asked whether the perceived odor was ‘‘banana,’’ ‘‘anis,’’ ‘‘rose,’’ or ‘‘lilac’’) Most tests are based on the identification of 16 to 40 odors – the more items tested the more reliable the results. Identification tests are known to have a cultural connotation that a certain population ( ex: Northern American’s) will identify but not other population ( ex: Asians ) .

12. Measurement of Olfactory Function 2- Electro- Olfactogram (EOG) Electro- olfactograms (EOG) are electrical potentials of the olfactory epithelium that occur in response to olfactory stimulation. The EOG represents the sum of generator potentials of olfactory receptor neuron (ORN).

13. Do you think we can use animal models to estimate impairment in senses caused by medications ? How is that ?

14. Olfactory Test The Olfactory Test is a sensory assay used to measure the olfactory ability, degree of social interest, and perception of social novelty in rodent models of CNS disorders. The nonsocial olfactory test employs water and synthetic odorants The social olfactory test uses water and urine samples from other animals.

15. Olfactory Test Cotton swabs dipped in odorant solution are placed in centrifuge tubes with holes drilled around the base at regular intervals, thus preventing the animal from chewing or sitting on the cotton swab. Subjects are exposed multiple times to three different odorants in a clean cage free of bedding. Trials are videotaped and later scored for the amount of time spent sniffing the odorant , defined as nose contact with the centrifuge tube .

16. Olfactory Test No odor ( control )

17. Olfactory Databases Olfactory Receptor Database (ORDB) is a repository of genomics and proteomics information of odors OdorDB stores information related to odorous compounds, specifically identifying those that have been shown to interact with olfactory receptors OdorModelDB disseminates information related to computational models of olfactory receptors (ORs). 

18. ANOSMIA IS THE COMPLETE LOSS OF SMELL

19. Anosmia Causes Nasal congestion from a cold, allergy, sinus infection, or poor air quality is the most common cause of anosmia. Nasal polyps -- small noncancerous growths in the nose and sinuses that block the nasal passage. Injury to the nose and smell nerves from surgery or head trauma. Exposure to toxic chemicals , such as pesticides or solvents. Certain medications , including antibiotics, antidepressants, anti-inflammatory medication, heart medications, and others. Cocaine abuse. Old age . Like vision and hearing, your sense of smell can become weaker as you age. In fact, one's sense of smell is most keen between the ages of 30 and 60 and begins to decline after age 60. Certain medical conditions , such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, nutritional deficiencies, congenital conditions, and hormonal disturbances. Radiation treatment of head and neck cancers.

20. Anosmia Treatments If nasal congestion from a cold or allergy is the cause of anosmia, treatment is usually not needed, and the problem will get better on its own. Short-term use of over-the-counter decongestants may open up the nasal passages so that can breathe easier. If the cause is an infection , need antibiotics , or another medical condition may be to blame. If a polyp or growth is present, surgery may be needed to remove the obstruction and regain your sense of smell. If you suspect a medication is affecting your sense of smell, talk to your doctor and see if there are other treatment options available that won't affect your ability to smell. However, never stop taking a medication without first talking with your doctor. If you smoke , quit. Smoking can dull the senses, including the sense of smell.

21. Taste and the effect of smell As the food is chewed, air is forced up the nasal passages, so the olfactory receptor cells are registering information at the same time as the taste receptors are, so both smelling and tasting happens simultaneously. So, it’s true that having a bad cold, or just holding the nose, the sense of taste is impaired.

22. Taste as soon as taking a bite of pizza, all of the sensory information in there is quickly sorted by the ten thousand or so taste buds covering the tongue, mouth, and upper throat. Most taste buds are packed deep down between the fungiform papillae -- those little projections that make your tongue relatively rough. Taste sensations can be grouped into : Sweet حلو , Salty مالح , Sour حامض , Bitter مُر , Umami لذيذ ,

23. Taste buds Each bud has 50 to 100 taste receptor epithelial cells which register and respond to different molecules in the food. Notice that these are specialized epithelial cells, not nervous tissue, so they still have to synapse to sensory neurons that carry information about the type and amount of taste back to the brain. These epithelial receptor cells come in two major types: Gustatory cells -- or the kind that actually do the tasting, Basal cells -- the stem cells that replace the gustatory cells after burnt. Basal epithelial cells are extremely dynamic and replace the gustatory cells every week

24. Taste buds Every gustatory cell projects a thread-like protrusion of the cellular membrane called a gustatory hair , which runs down to a taste pore , a small hole .

25. In order to taste a bite of pizza, those food chemicals, or tastants , must dissolve in saliva so they can diffuse through those taste pores, and bind to receptors on those gustatory cells, and then trigger an action potential. each tastant is sensed differently

26. Pathway Once an action potential is activated, that taste message is relayed through neurons via the seventh, ninth, and tenth cranial nerves to the taste area of the cerebral cortex , at which point your brain makes sense of it all, and begins releasing digestive enzymes in your saliva and gastric juices in your stomach to help you break that food down so you can use it.

27. Measurement of Taste Taste sensitivity depends on the number of taste receptors on taste buds and the number of taste buds on the tongue . To measure this, scientists use a wafer that contains a drop of a chemical called 6-n-propylthiouracil, or PROP , which has a nasty bitter taste . Placing this on the human tongue can send a super-taster through the roof, while non-tasters just taste the paper.

28. Measurement of Taste

29. Artificial flavors in medication Artificial flavors are used in medicine to mask or impart taste to medications . A flavor , as used in the pharmaceutical industry for inactive ingredients, refers to natural or artificial tastes, which may include fragrances and colors of the flavoring. Flavors are used for orally consumed products such as syrups, chewable tablets, suspensions, or gums that impart beneficial therapeutic effect, as well.

30. Artificial flavors in medication We mainly use them to optimize the taste of oral medications in children and enhance the adherence to it . Many parents are faced with the daily challenge of getting their children to take a medicine. The unpleasant flavor of the medicine can thwart the benefits of even the most powerful drug, and failure to consume medication may do the child harm, and in some cases, may be life-threatening. Although there are no easy solutions to this dilemma, children’s acceptance of many medicines can be improved by applying the knowledge gained from basic research in the chemical senses.

31. Artificial flavors in medication

32. Artificial flavors in medication Antibiotics , especially penicillin-type antibiotics, have a distinct odor and bad taste. Antihistamines and decongestants taste bitter, too. BUT, in few medications especially supplements formulated for kids as chewable candy ( multivitamins ), parents have to assume a certain amount of responsibility for keeping the medications out of the reach of kids to overcome constipation or systemic toxicity due to overdosing some vitamins or minerals .

33. Taste masking methods 1- Organoleptic Methods This is the simplest and most convenient method of taste-masking. It involves adding a combination of sweeteners ( sucralose , aspartame) and flavors (orange, mint) to mask the unpleasant taste of low to moderately bitter actives

34. Taste masking methods 2- Polymer coating A simple option which is direct coating that provides a physical barrier over the drug particles with a composition that is insoluble in the mouth. Hydrophobic or hydrophilic polymers, lipids, and sweeteners can be used as coating materials, alone or in combination to produce a single or multi-layer coat. EX : Methacrylic acid and methacrylic ester copolymers

35. Taste masking methods 3- Microencapsulation I s a technology with a long history in the pharmaceutical industry, and taste-masking represents an expanded area of its application. In principle, microencapsulation provides the opportunity to encapsulate the bitter active and thus prevent its contact with taste buds. EX : Microcaps ® and Advatab ® in compressed ODT  4- Complexation Cyclodextrins have been extensively used for taste-masking bitter drugs by forming inclusion complexes with the drug molecule.

36. Artificial flavors in medication

37. Taste in diagnosis May a certain taste ( if present ) aids the diagnosis of a medical condition ? Yes Metallic Taste A metallic taste in the mouth is a relatively common side effect of medications. Dozens of different drugs produce changes in the sense of taste as a side effect, that can include the perception of a metallic taste. Examples include many antibiotics and some  antihistamines . In the majority of these cases, the condition is only temporary and resolves once the medication is discontinued.  Cancer chemotherapy  medications may also produce a metallic taste in the mouth as a side effect.

38. What causes Metallic taste ? Some common medical conditions that can cause metallic taste in the mouth include ear or upper respiratory infections such as sinusitis, as well as head injury or conditions that damage the central nervous system (CNS). A history of  radiation therapy  to the head and neck can also cause a metallic taste in the mouth.  Pregnant  women sometimes experience an alteration in the sense of taste, particularly in the early stages of pregnancy

39. Taste disorder The most common taste disorders are: Phantom taste perception , which is a lingering, often unpleasant taste even though you have nothing in your mouth. Hypogeusia , a reduced ability to taste sweet, sour, bitter, salty, and savory (umami). Dysgeusia is a condition in which a foul, salty, rancid, or metallic taste sensation will persist in the mouth. Ageusia is the inability to detect any tastes, which is rare.

40. What causes taste disorders? Some people are born with taste disorders, but most develop them after an injury or illness; especially head injuries. Upper respiratory and middle ear infections . Radiation therapy for cancers of the head and neck. Exposure to certain chemicals , such as insecticides and some medications “metronidazole”, including some common antibiotics and antihistamines. Some surgeries to the ear, nose, and throat (such as middle ear surgery) or extraction of the third molar (wisdom tooth). Poor oral hygiene and dental problems.

41. Treatment If a certain medication is the cause, stopping or changing your medicine may help eliminate the problem. Loose sense of taste because of respiratory infections or allergies may regain it when these conditions resolve . Proper oral hygiene is important to regaining and maintaining a well-functioning sense of taste.

42. THE END