PROZAC (FLUOXETIN), BAGAIMANA MEKANISME AKSI MOLEKULERNYA?

01/16/2009 by sarmoko in MOLECULAR PHARMACOLOGY

6 Votes

Prozac yang isinya fluoxetin bikinan Ely Lili merupakan satu dari 10 obat paling laris di dunia. Tahukah Anda obat apa ini? Kemarin, saya merasa penasaran dengan obat ini, cek di MIMS ternyata dia masuk kategori obat antidepresan. Bagaimanakah aksi kerjanya?Btw, di sini saya mau sharing tentang mekanisme aksi obat Fluoxetin, tentunya dalam ranah molekuler. Semoga ini bisa bermanfaat bagi Anda. Obat depresi berarti hubungannya dengan sistem saraf. Nah, kalau sudah ngomongin saraf, berarti tidak bisa lepas dari namanya neurotransmitter.

Sebelumnya, apa itu neurotransmitter? Secara sederhana, bisa dikatakan semacam hormon, dia yang bisa memberikan impuls dari saraf satu ke saraf yang lain. Bedanya dengan hormon, yang distribusinya lewat pembuluh darah, kalau neurotransmitter adalah dari sel saraf satu loncat ke saraf yang lain dan akhirnya sampailah ke reseptor. Ada berbagai macam neurotransmitter seperti serotonin, GABA, nor-epinefrin, nor-adrenalin, dll. Perlu diketahui, sedikit ada persamaan antara hormon dan neurotransmitter, begitu juga penamaannya. Kalau hormon tidak pakai kata NOR, misal adrenalin adalah suatu (hormon), noradrenalin adalah suatu (neurotransmitter). Ngomongin fluoxetin, neurotransmitter yang berperan adalah serotonin dan reseptornya tentunya reseptor serotonin.

Sebelum jauh membahas tentang reseptor ini, ada baiknya saya jelaskan dulu tentang pembagian target aksi obat. Jadi, ada beberapa tempat yang bisa menjadi target aksi obat yaitu kanal ion, transporter, atau

pada reseptor. Dari sekian banyak tadi, reseptor merupakan yang paling banyak sebagai target aksi obat. Reseptor yaitu suatu makromelekul seluler yang secara spesifik dan langsung berikatan dengan ligan, ligan disini bisa obat, homon, atau neurotransmitter.

Berdasarkan transduksi sinyalnya, maka reseptor dapat dikelompokkan menjadi 4 (empat) yaitu:

1. Ligand-gated ion chanel receptor (reseptor kanal ion) 2. G-protein coupled receptor (reseptor yang tergandeng dengan protein-G) 3. Tyrosine kinase-linked receptor (reseptor yang terkait dengan aktivitas kinase) 4. Nuclear receptor (reseptor inti). Kita bahas point 1, karena fuoxetin masuk dalam kelompok ini. Reseptor kanal ion disebut juga reseptor ionotropik. Golongan reseptor ini merupakan suatu reseptor membran yang langsung terhubung oleh suatu kanal ion dan memperantarai aksi sinaptik yang cepat, lebih cepat jika dibandingkan dengan transmisi sinaptik melalui reseptor yang tergandeng protein-G. Contohnya adalah reseptor asetilkolin nikotinik, reseptor GABA-A, reseptor glutamat, dan reseptor serotonin.

Nah, sekarang baru bahas reseptor serotonin. Reseptor serotonin nama lainnya adalah 5hydroxytriptamine (5-HT3). Sedangkan serotonin merupakan neurotransmitter monoamin yang terlibat dalam berbagai penyakit yang cukup luas cakupannya, meliputi penyakit psikiatrik: depresi, kecemasan, skizoprenia, dan gangguan obsesif konfulsif; sampai migraine. Serotonin dijumpai di jaringan kardiovaskuler, sistem saraf perifer, sel darah, dan SSP.

Serotonin disintesis dari prekursornya triptofan dengan bantuan enzim triptofan hidroksilase dan asam amino aromatik dekaroksilase. Serotonin yang terbentuk akan disimpan di dalam vesikel penyimpanan prasinaptik dengan bantuan transporter monoamine vesicular (VMAT = vesicular monoamine transporter). Selanjutnya, jika ada picuan maka serotonin akan dilepaskan menuju celah sinaptik.

Serotonin yang terlepas dapat mengalami beberapa peristiwa antara lain:

1. Berdifusi menjauh dari sinaps 2. Dimetabolisme oleh MAO (monoamine oksidase) 3. Mengaktivasi reseptor presinaptik (reseptor 5-HT1A dan 5-HT1D, suatu autoreseptor 4. Mengaktivasireseptor post-sinaptik 5. Mengalami re-uptake dengan bantuan transporter serotonin presinaptik (SERT = serotonin transporter). Pengambilan kembali serotonin ke dalam ujung pre-sinaptik oleh SERT (peristiwa re-uptake) merupakan mekanisme utama penghentian transmisi signal serotonin. Karena itu, obat yang dapat mengikat SERT dan menghambat re-uptake serotonin dapat memperpanjang aksi serotonin. Penyakit tertentu di mana kekurangan neurotransmitter serotonin, seperti depresi dapat diatasi dengan meningkatkan ketersediaan serotonin di tempat aksinya dengan cara menghambat re-uptake-nya.

Obat yang dimaksud tak lain adalah obat antidepresan golongan SSRI (selective serotonin re-uptake inhibitor). Fluoxetin masuk golongan obat ini, disamping fluvoksamin, paroksetin, dan sertralin. Ada juga sih obat anidepresan lain yang kerjanya hambat re-uptake serotonin, tapi kerjanya tidak selektif, dia juga

menghambat re-uptake nor-epinefrin. Contoh obatnya yaitu golongan TCA (tricyclic antidepresan: amitriptriptilin, imipramin, nortriptilin, dan despiramin).

Sudah paham? Itu kira-kira gambarannya. Kalo ada istilah-istilah medis yang belum jelas, bisa ditanyakan. Demikian posting untuk hari ini, next akan dibahas materi-materi menarik lainya.

Terima kasih. http://moko31.worpress.com

Referensi

Ikawati, Z., 2005, Pengantar Farmakologi Molekuler, Gadjah Mada University Press, Yogyakarta

Kata kunci: fluoxetin, serotonin, reseptor serotonin, neurotransmitter, transduksi signal, SSRI, antidepresan.

Struktur jaringan gigi terdiri dari jaringan keras gigi (enamel, dentin, sementum) clan jaringan lunak gigi (pulpa). Komponen enamel terdiri dari 96% bahan anorganik, sisanya adalah bahan organik dan air. Bahan anorganik pada enamel terdiri dari kalsium 36,7 %, fosfat 17,4%. Sedangkan dentin mengandung kalsium 25,1% dan fosfat 13,9% ( Smith, 1999 ). Enamel sebagian besar terdiri dari hidroksi apatit dan sebagian kecil fluor apatit ( Meurman, 1996 ). Erosi gigi adalah proses demineralisasi email oleh asam akibat proses kelarutan. Proses kelarutan email yang terjadi akibat proses kelarutan garam dalam larutan asam. Patogenese teIjadinya erosi gigi adalah akibat etching dari asam (Imfeld, 1996). Pada stadium awal erosi gigi hanya teIjadi pada permukaan enamel, selanjutnya lapisan enamel larut selapis demi selapis. Erosi gigi terjadi oleh karena demineralisasi pada pemukaan dengan penguraian prisma enamel perifer (Tuominen, 1992). Erosi gigi yang terjadi akibat industri kimia umumnya hanya terjadi pada permukaan labial gigi depan di rahang atas maupun di rahang bawah. Permukaan gigi yang mengalami erosi gigi terjadi pada sepertiga permukaan incisal sampai setengah permukaan labial gigi insicivus. Erosi pada gigi kaninus jarang terjadi. Tanda pertama erosi gigi akibat uap kimia adalah berupa adanya etching pada permukaan labio-incisal yang tampak seperti gelas yang terasah. Permukaan enamel menjadi licin, membulat dan berkilat. Pada proses yang lebih lanjut, dimana erosi gigi telah terjadi pada denting, dentin dapat mengalami pewarnaan, meskipun proses erosi di dentin tidak secepat di enamel. Selanjutnya dapat mengenai pulpa, selanjutnya dapat menyebabkan hipersensitif pada gigi terutama akibat rangsangan dingin. (Nunn, 1996). Klasifikasi erosi gigi : Cate (1961) mengestimasi tentang derajat erosi gigi:

1. Etching (Et) : Permukaan enamel gigi berkilat seperti kaca tanpa kehilangan kontur gigi 2. Derajat 1 Erosi (G 1) : Hilang lapisan enamel 3. Derajat 2 Erosi (G2) : Hilang lapisan enamel diikuti lapisan dentin 4. Derajat 3 Erosi (G3) : Hilang lapisan enamel, dentin dan sekunder dentin 5. Derajat 4 Erosi (G4) : Hilang lapisan enamel, dentin dan pulpa gigi.

Eccles, et al. (1982) mengklasifikasikan faktor penyebab erosi berupa faktor luar dan dalam. Salah satu faktor luar penyebab erosi gigi adalah faktor lingkungan industri. Faktor lingkungan industri dapat menyebabkan erosi gigi pada gigi depan akibat menghirup uap asam baik dalam bentuk aerosol ataupun kabut (fume). Mc Intyre J.M.(1992) membagi penyebab erosi : 1. Faktor ekstemal adalah karena :

1. 2. 3. 4.

Diet (jus buah, buah sitrun, karbonat yang berbahaya, asam cuka) Obat-obatan (asam klorida, asam askorbat, asam asetil salisilat, preparat besi) Pekerjaan (industri yang berhubungan dengan asam) Olahraga (berenang pada air yang mengandung klorit)

II. Faktor Internal:

1. Sendawa dari cairan lambung 2. Masalah psikologi misalnya anoreksia, pecandu alkohol yang berat, stres yang berat. 3. Efek samping dari obat sitostatika (obat untuk asma kronis, overdosis atau kelebihan obat yang dapat mengiritasi lambung).

What is tooth enamel erosion?

Dental erosion (tooth erosion) is the irreversible loss of tooth enamel due to chemical processes that do not involve bacterial action. Tooth enamel is a mineralized hard tissue that covers and protects the tooth. It is the hardest tissue of human body but it can be chemically dissolved in an acidic environment. The acids that cause dental erosion may come from intrinsic (e.g., gastroesophageal reflux, vomiting) or extrinsic sources (e.g., acidic beverages, citrus fruits). The tooth enamel loss caused by the acids produced by dental plaque bacteria (tooth decay) is not dental erosion. Other forms of tooth enamel loss caused by mechanical and not chemical factors tissues of are the tooth tooth caused by abrasion exposure to and acids for tooth long periods attrition. of time. Tooth erosion is a slow progressive process that leads to the loss of the protective hard

Modern life-style and dietary habits are responsible for a sharp increase in the prevalence of dental erosion, especially in the young population of developed countries. Teeth erosion is becoming increasingly common and can have long-term consequences for the patient's dental health. Dental erosion can cause mild tooth problems, such as tooth discoloration and mild sensitivity, to more severe dental problems, such as indentions in the teeth, severe tooth sensitivity, cracked teeth and tooth loss.

De & Re-mineralization of tooth enamel

If the tooth is exposed to acidic environment, the tooth enamel starts to loose minerals in a process called de-mineralization. Saliva slowly neutralises the acidity in the mouth and restores it to its natural balance. When the tooths environment becomes non-acidic the reverse process of remineralization begins. This natural tooth enamel restoration process repairs the enamel using minerals such as calcium from saliva and fluoride from toothpastes. If the two processes are balanced any damage to the tooth enamel is totally repaired. Unfortunately there are many factors that disturb this delicate balance in favor of the demineralization resulting in irreversible tooth enamel loss. In the case of dental erosion, the problem occurs from the fact that the increased intensity and frequency of acid attacks does not allow enough time to repair and restore tooth enamel through re-mineralization.

Causes of tooth erosion

Tooth erosion generally occurs as a result of the chemical action of acids on the tooth surfaces. These acids that can be either extrinsic or intrinsic dissolve gradually the tooth enamel from the surface of the tooth. outside the body):

Causes of tooth erosion due to extrinsic acids (from

Frequent consumption of acidic foods and drinks is the main cause of tooth enamel loss.
o Even though fruit juices and fresh fruits are considered as healthy foods, their overconsumption is not the best option for teeth because they are too acidic (very low pH). Most of the popular carbonated drinks, soft drinks, sports drinks and diet drinks are also very acidic. Even fizzy mineral water can be acidic. Common extrinsic dietary acids include citric acid, phosphoric acid, ascorbic acid, malic acid and carbonic acid. o The erosive potential of acidic drinks does not depend on pH alone. Also, factors such as frequency and method of intake of acidic beverages as well as proximity of tooth brushing after intake may influence susceptibility to teeth erosion. Drinking through a straw lessens the contact

time of the acids with the teeth. On the contrary, swishing the drink around the teeth increases their exposure to acids. Some medicines are acidic and, therefore, erosive. They can cause dental erosion on direct contact with the teeth when the medication is chewed or held in the mouth prior to swallowing.

Environmental factors such as the chlorine and other chemicals in swimming pools can cause
erosion over time. inside the body):

Causes of tooth erosion due to intrinsic acids (from

Gastroesophageal reflux disease (GERD) or acid reflux, in which stomach acids come up into the
oesophagus and mouth, can cause severe tooth erosion. Gastric acids are highly acidic with pH levels that by can the be less gastric than 1. acids.

Eating disorders that cause frequent vomiting are also responsible for tooth enamel loss caused Bulimia (anorexia nervosa) is another frequent cause of eroded teeth due to chronic excessive
vomiting. Besides vomiting, persons who suffer from bulimia tend to consume larger quantities of fresh fruits and also acidic cause beverages vomiting that related worsen loss of the tooth problem. enamel.

Alcoholism could

Low salivary flow rate is a significant risk factor for dental erosion due to reduced pH
buffering capacity (its ability to neutralize changes in mouths pH)

Signs and Symptoms of Tooth Erosion

Teeth erosion affects the whole surface of the teeth, unlike tooth abrasion and attrition where the symptoms are isolated in specific areas of the tooth. Most of the symptoms of dental erosion are caused by the decreased depth of the tooth enamel layer that covers the crown of the tooth.

Early Symptoms of Tooth Erosion

Teeth Discoloration - Since the dentin of the tooth is exposed during tooth erosion,
discoloration or yellowing of the teeth can occur. The more dentin that is exposed, the more yellow the teeth will become.

Tooth Sensitivity - Sensitive teeth are very common symptoms of teeth erosion because
the enamel that protects the teeth wears away, leaving exposed the dentin (the softer, sensitive part of the tooth).

Rounded/Shorter Teeth Teeth with dental erosion have usually a rounded look. If the
tooth enamel loss is extensive teeth might also look shorter.

Transparency - The tips of the front teeth might look transparent.

Advanced Symptoms of Tooth Erosion

Cracking - If tooth erosion continues, the edges of the teeth can start to crack and have
a rough feeling.

Pulp exposure in deciduous teeth Tooth decay teeth affected by dental erosion are more likely to suffer from tooth
decay. The cost involved with several dental treatments needed to restore tooth enamel loss is significant and you may not be able to afford it if you are not covered by your dental insurance. Learn how to choose a dental insurance plan that will help you provide the best dental treatment to yourself and your family.

Treatment of tooth erosion (restore tooth enamel)

Tooth erosion affects the whole surface of the tooth. If the problem is not identified and treated early enough, the damage to tooth structures may be so extensive that it requires expensive cosmetic dentistry to restore function and appearance. The treatment of dental erosion includes two separate steps. The first step is the identification and elimination of the reasons that have caused the tooth erosion and the second step is to treat the symptoms and to restore tooth enamel loss with restorative procedures by a cosmetic dentist.

A. Eliminate the causes of tooth erosion

Diet. If the cause of the dental erosion is the consumption of acidic foods or drinks, patient
education may solve the problem. The patient must make dietary modifications as those described in the next section about the prevention of tooth erosion.

Medical consultation. If the problem is caused by medical condition as GERD the patient
must consult a medical doctor for the appropriate treatment. In case of bulimia caused tooth erosion a psychologist may help to treat the condition.

B. Restore tooth enamel loss

Treatment of dental erosion depends on the severity of the damage. If the loss of tooth enamel is moderate without affecting the patients appearance, there is no need of restorative treatment. The dentist may recommend certain fluoride treatments and de-

sensitizing toothpastes to control the tooth sensitivity symptoms caused by teeth

erosion. Enhancing the re-mineralization process by providing minerals such as fluoride may be enough for natural tooth enamel restoration. The dentist may also apply a fluoride varnish on the affected teeth for further protection and repair of tooth enamel. Restorative cosmetic treatments become necessary if the tooth enamel damage is extensive. Depending on the degree of tooth wear, restorative treatment can range from placement of bonded composites (tooth bonding) in a few isolated areas of teeth erosion, to crowns, dental porcelain veneers, bridges or even full mouth reconstruction in the case of severe tooth enamel damage. A cosmetic dentist has to evaluate the situation and recommend the best cosmetic treatment to restore teeth function and appearance.

Regardless of the type of treatment required, the patient who has suffered dental erosion must follow a careful preventive plan to avoid further tooth enamel loss and the high expenses of the associated cosmetic treatments. Regular preventive dental visits are very important for the prevention of tooth erosion. During the dental exam, thedental hygienist can easily identify early signs of erosion before it causes significant damage to teeth. You should always check carefully before you choose a dental insurance if preventive dental visits and 'cosmetic' restorative procedures are covered.

Prevention of dental erosion and tooth enamel loss

Tooth erosion can do severe damage to your teeth, but it is preventable. There are several preventive measures that can be taken to control tooth enamel loss and prevent dental erosion: Decrease the consumption of acidic foods and/or drinks, both in quantity and frequency. Try to have them only at mealtimes. Replace carbonated drinks with water, milk or un-sweetened coffee and teeth tea, are especially exposed between to meals. acids). Drink acidic drinks quickly and do not swish them round the mouth (to reduce the time that the Use a straw when drinking carbonated beverages or fruit juices, which are very acidic (at least

to the

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teeth). neutralized.

After eating or drinking acidic foods or beverages, rinse your mouth with fresh water so that Because acids temporarily soften the tooth surface (de-mineralization), don't brush your teeth immediately after eating or drinking something acidic (or vomiting), as the softened enamel will be further damaged by the brushing and that will speed up the process of erosion. Wait at least an hour to allow calcium acids in saliva and to repair help tooth enamel teeth after to the acid exposure. Chewing sugar-free gum can help reduce dry mouth and increase the saliva flow, allowing it to neutralise remineralize. You should brush your teeth twice a day, with a soft toothbrush using fluoride toothpaste. Fluoride helps the remineralization of the tooth enamel and it is necessary for preventing tooth erosion. Follow your dentists instructions in order to prevent further tooth enamel loss. Your dentist may also recommend the periodic application of fluoride gel or varnish in the dental office to restore tooth enamel and prevent dental erosion.

The cost involved with several dental treatments needed to restore tooth enamel loss is significant and many patients can not afford it if they are not covered by their dental insurance. Learn how to choose a dental insurance

plan that will help you provide the best dental treatment to yourself and your
family.