Selasa, 16 Desember 2008
DISORDERS OF MENSTRUATION
The first menstrual period usually occurs around 12 years of age but the range is between 9 and 16 years. The interval between normal menstrual cycles typically varies from 25 to 34 days. Cycles shorter than 3 weeks or longer than 40 days may indicate some abnormality in ovulation. The length of flow on the average is 5 + or – 2 days. A normal menstrual cycle correlates very highly with ovulation.
PRECOCIOUS PUBERTY
The appearance of sexual development before 8 years of age characterizes precocious
puberty (PP). Seventy to 80 percent of the cases of PP are due to an early “awakening” of the hypothalamic-pituitary axis – idiopathic PP. Any secondary sex characteristic appearing before the age of 8 years warrant a clinical evaluation that involves trying to exclude serious disease such as neoplasms of the brain, adrenal, or ovary, or some disorder of the thyroid. Besides the obvious body changes, PP also contributes to major phychosocial issues. The parents are often very distressed, and the child may experience problems relating to peers. If ovulation is present, no other studies need to be done. Ovulation does not occur
during any pathological or disease states associated wit precocious puberty. If the
problem is idiopathic, Gn-RH analog therapy is used for the curtailment of physical and behavioral symptoms.
PRIMARY AMENORRHEA
The absence of breast budding by age 14 and no menses by age 16, primary amenorrhea
(PA), constitutes reason for concern. Primary amenorrhea may be due to delayed
physiological menarche. Other possible reasons include a genetic cause impacting
ovarian or gonadal function, a congenital anomaly involving the vagina and/or uterus, or a central problem influencing hypothalamic function and Gn-RH pulsatile secretion. A clinical evaluation should be directed to different compartments: the utero-vaginal tract, ovary, pituitary, CNS-hypothalamus, and other systemic problems.
Congenital abnormalities associated with primary amenorrhea can be as minor as an
imperforate hymen or as major as the complete absence of the uterus and vagina. The
diagnosis of anatomic defects is readily evident on performing a careful physical exam.
A lack of sensitivity of androgen receptors, more commonly known as “testicular
feminization syndrome”, should be included in this category. These patients have 46XY
karyotype. These patients’ gonads should be removed because of the increase risk of
neoplasia. Other causes of anatomical abnormalities include Turner’s syndrome,45,XO;46XX and 46XY(Swyer’s syndrome). These abnormalities are associated with elevated FSH. Pituitary causes of primary amenorrhea are uncommon. Any patient with primary
amenorrhea should have a serum prolactin, elevation of which would indicate a tumor.
Kallmann’s syndrome is a Gn-RH deficiency associated with the inability to smell,
absence of secondary sexual characteristics and a low FSH level. Many psychosocial issues need to be addressed with these patients. Extensive counseling will be required.
SECONDARY AMENORRHEA
After a previously menstruating individual misses three consecutive periods or 6 months pass without a period, she had met the definition of secondary amenorrhea. When pregnancy has been excluded, clinical evaluation should be directed to different
compartments. CNS-hypothalamus, pituitary, ovary and the uterovaginal tract. The most
common problem resulting in secondary amenorrhea is hypothalamic dysfunction and
includes weight-change-related disorders, severe psychological stress, and exerciseinduced problems. Pituitary causes include neoplasms; the most common being a tumor that either directly or indirectly results in hyperprolactinemia. Premature ovarian failure, the cessation of periods before age 40, is another important cause, and is characterized by an elevated serum FSH of > 40mIU/ml. Intrauterine scarring can be sufficiently extensive to result in amenorrhea. These patients have usually had curettage after pregnancy or severe endometritis.
Anenorrhea associated with dramatic or sudden significant changes in weight (plus or
minus 15% from ideal body weigh) is often associated with hypothalamic amenorrhea.
Anorexia nervosa is the most extreme form of weight loss associated with amenorrhea.
At the other end of the spectrum is pseudocyesis, a strong desire for pregnancy, with mild to moderate weight gain.
A very common cause of secondary amenorrhea is polycystic ovarian syndrome (PCOS).
This is a hyperestrogenic and hyperandrogenic syndrome associated with anovulation.
The three cardinal symptoms of PCOS are menstrual disorders (aenorrhea,
oligomenorrhea, or dysfunctional uterine bleeding), which are present in about 90 % of the cases; hirsutism, which occurs in about 70% of the cases; and infertility, which is the presenting symptom in 75% of patients. The diagnosis is made by clinical features and by the presence of an elevated serum LH.
Another cause of amenorrhea or oligomenorrhea is congenital adrenal hyperplasia. It is a common genetic disorder. It is an enzyme failure in the production of cortisol. It results in increased ACTH, which results in increased androgens, causing hirsutism and oligomenorrhea.
PREMENSTRUAL SYNDROME
Symptoms associated with the menstrual cycle are common. When the number and
severity of the symptoms increase to the point where they interfere with daily existence, this is considered premenstrual syndrome (PMS). Predominant somatic symptoms can include the feeling of bloatedness, breast pain, headache, pelvic pain, and alterations in bowel function. The major psychological symptoms can include mood alterations such as irritability, aggressive tendencies, anxiety, depression, extreme lethargy, sleep disorders, crying spells, diminished libido, and loss of concentration. The incidence of PMS is reported to be between 5 and 95 %. Two to 3% of women have a severe form. There is no known cause for PMS. Patients should be encouraged to obtain a more healthy diet and to include a moderate amount of exercise. A multiple-feeding, highprotein diet and the elimination of caffeine and alcohol have been very effective for certain patients. The following table lists some medical therapies.
DYSMENORRHEA
Dysmenorrhea, lower abdominal-pelvic cramping pain with menses and usually with a
constellation of other symptoms, is classified as primary or secondary. It can be
incapacitating. Primary dysmenorrhea (PD) usually appears shortly after the menarche and is associated with ovulatory cycles. It is not caused by or associated with demonstratable pelvic pathology such as adhesions, infection or endometriosis. The pain is cramping in nature and may radiate to the back or thighs. Other symptoms, such as nauses, emesis, headache, fatique and diaphoresis have been associated with dysmenorrhea. The severity may be correlated with the amount and duration of menstrual flow. While the exact etiology of the pain is unknown, endogenous prostaglandin seem to be important. Over the counter pain medications usually provide adequate relief for the patients. Low-estrogen containing birthcontrol pills have also been helpful. Secondary dysmenorrhea (SD) usually occurs in women over the age of 20. The most likely cause is enodmetrosis, adenomyosis, and chronic pelvic infection. The treatment is the same. Occasionally, hysterectomy is needed to resolve the condition.
ABNOMAL UTERINE BLEEDING
Abnormal uterine bleeding (AUB) is a frequent complaint of patients. Making an
accurate diagnosis and ruling out serious etiologies are important. When a woman
complains of vaginal bleeding, it is important to rule out the possibility that the origin is actually form another site i.e. bowel, urinary tract, and vulva. For women above the age of 35, endometrial cancer must be ruled out. This is done by doing and endometrial biopsy.
PRECOCIOUS PUBERTY
The appearance of sexual development before 8 years of age characterizes precocious
puberty (PP). Seventy to 80 percent of the cases of PP are due to an early “awakening” of the hypothalamic-pituitary axis – idiopathic PP. Any secondary sex characteristic appearing before the age of 8 years warrant a clinical evaluation that involves trying to exclude serious disease such as neoplasms of the brain, adrenal, or ovary, or some disorder of the thyroid. Besides the obvious body changes, PP also contributes to major phychosocial issues. The parents are often very distressed, and the child may experience problems relating to peers. If ovulation is present, no other studies need to be done. Ovulation does not occur
during any pathological or disease states associated wit precocious puberty. If the
problem is idiopathic, Gn-RH analog therapy is used for the curtailment of physical and behavioral symptoms.
PRIMARY AMENORRHEA
The absence of breast budding by age 14 and no menses by age 16, primary amenorrhea
(PA), constitutes reason for concern. Primary amenorrhea may be due to delayed
physiological menarche. Other possible reasons include a genetic cause impacting
ovarian or gonadal function, a congenital anomaly involving the vagina and/or uterus, or a central problem influencing hypothalamic function and Gn-RH pulsatile secretion. A clinical evaluation should be directed to different compartments: the utero-vaginal tract, ovary, pituitary, CNS-hypothalamus, and other systemic problems.
Congenital abnormalities associated with primary amenorrhea can be as minor as an
imperforate hymen or as major as the complete absence of the uterus and vagina. The
diagnosis of anatomic defects is readily evident on performing a careful physical exam.
A lack of sensitivity of androgen receptors, more commonly known as “testicular
feminization syndrome”, should be included in this category. These patients have 46XY
karyotype. These patients’ gonads should be removed because of the increase risk of
neoplasia. Other causes of anatomical abnormalities include Turner’s syndrome,45,XO;46XX and 46XY(Swyer’s syndrome). These abnormalities are associated with elevated FSH. Pituitary causes of primary amenorrhea are uncommon. Any patient with primary
amenorrhea should have a serum prolactin, elevation of which would indicate a tumor.
Kallmann’s syndrome is a Gn-RH deficiency associated with the inability to smell,
absence of secondary sexual characteristics and a low FSH level. Many psychosocial issues need to be addressed with these patients. Extensive counseling will be required.
SECONDARY AMENORRHEA
After a previously menstruating individual misses three consecutive periods or 6 months pass without a period, she had met the definition of secondary amenorrhea. When pregnancy has been excluded, clinical evaluation should be directed to different
compartments. CNS-hypothalamus, pituitary, ovary and the uterovaginal tract. The most
common problem resulting in secondary amenorrhea is hypothalamic dysfunction and
includes weight-change-related disorders, severe psychological stress, and exerciseinduced problems. Pituitary causes include neoplasms; the most common being a tumor that either directly or indirectly results in hyperprolactinemia. Premature ovarian failure, the cessation of periods before age 40, is another important cause, and is characterized by an elevated serum FSH of > 40mIU/ml. Intrauterine scarring can be sufficiently extensive to result in amenorrhea. These patients have usually had curettage after pregnancy or severe endometritis.
Anenorrhea associated with dramatic or sudden significant changes in weight (plus or
minus 15% from ideal body weigh) is often associated with hypothalamic amenorrhea.
Anorexia nervosa is the most extreme form of weight loss associated with amenorrhea.
At the other end of the spectrum is pseudocyesis, a strong desire for pregnancy, with mild to moderate weight gain.
A very common cause of secondary amenorrhea is polycystic ovarian syndrome (PCOS).
This is a hyperestrogenic and hyperandrogenic syndrome associated with anovulation.
The three cardinal symptoms of PCOS are menstrual disorders (aenorrhea,
oligomenorrhea, or dysfunctional uterine bleeding), which are present in about 90 % of the cases; hirsutism, which occurs in about 70% of the cases; and infertility, which is the presenting symptom in 75% of patients. The diagnosis is made by clinical features and by the presence of an elevated serum LH.
Another cause of amenorrhea or oligomenorrhea is congenital adrenal hyperplasia. It is a common genetic disorder. It is an enzyme failure in the production of cortisol. It results in increased ACTH, which results in increased androgens, causing hirsutism and oligomenorrhea.
PREMENSTRUAL SYNDROME
Symptoms associated with the menstrual cycle are common. When the number and
severity of the symptoms increase to the point where they interfere with daily existence, this is considered premenstrual syndrome (PMS). Predominant somatic symptoms can include the feeling of bloatedness, breast pain, headache, pelvic pain, and alterations in bowel function. The major psychological symptoms can include mood alterations such as irritability, aggressive tendencies, anxiety, depression, extreme lethargy, sleep disorders, crying spells, diminished libido, and loss of concentration. The incidence of PMS is reported to be between 5 and 95 %. Two to 3% of women have a severe form. There is no known cause for PMS. Patients should be encouraged to obtain a more healthy diet and to include a moderate amount of exercise. A multiple-feeding, highprotein diet and the elimination of caffeine and alcohol have been very effective for certain patients. The following table lists some medical therapies.
DYSMENORRHEA
Dysmenorrhea, lower abdominal-pelvic cramping pain with menses and usually with a
constellation of other symptoms, is classified as primary or secondary. It can be
incapacitating. Primary dysmenorrhea (PD) usually appears shortly after the menarche and is associated with ovulatory cycles. It is not caused by or associated with demonstratable pelvic pathology such as adhesions, infection or endometriosis. The pain is cramping in nature and may radiate to the back or thighs. Other symptoms, such as nauses, emesis, headache, fatique and diaphoresis have been associated with dysmenorrhea. The severity may be correlated with the amount and duration of menstrual flow. While the exact etiology of the pain is unknown, endogenous prostaglandin seem to be important. Over the counter pain medications usually provide adequate relief for the patients. Low-estrogen containing birthcontrol pills have also been helpful. Secondary dysmenorrhea (SD) usually occurs in women over the age of 20. The most likely cause is enodmetrosis, adenomyosis, and chronic pelvic infection. The treatment is the same. Occasionally, hysterectomy is needed to resolve the condition.
ABNOMAL UTERINE BLEEDING
Abnormal uterine bleeding (AUB) is a frequent complaint of patients. Making an
accurate diagnosis and ruling out serious etiologies are important. When a woman
complains of vaginal bleeding, it is important to rule out the possibility that the origin is actually form another site i.e. bowel, urinary tract, and vulva. For women above the age of 35, endometrial cancer must be ruled out. This is done by doing and endometrial biopsy.
Investigation of the Solid State Properties of Amoxicillin Trihydrate and the Effect of Powder pH
Abstract
The purpose of this research was to investigate some physicochemical and solid-state properties of amoxicillin trihydrate (AMT) with different powder pH within the pharmacopoeia-specified range. AMT batches prepared using Dane salt method with the pH values from 4.39 to 4.97 were subjected to further characterization studies. Optical and scanning electron microscopy showed that different batches of AMT powders were similar in crystal habit, but the length of the crystals increased as the pH increased. Further solid-state investigations using powder x-ray diffraction (PXRD) demonstrated the same PXRD pattern, but the intensity of the peaks raised by the powder pH, indicated increased crystallinity. Differential scanning calorimetry (DSC) studies further confirmed that as the powder pH increased, the crystallinity and, hence, thermal stability of AMT powders increased. Searching for the possible cause of the variations in the solid state properties, HPLC analysis showed that despite possessing the requirements of the United States Pharmacopoeia (USP) for purity/impurity profile, there was a direct relationship between the increase of the powder pH and the purity of AMT, and also decrease in the impurity I (α-Hydroxyphenylglycine) concentration in AMT powder. Recrystallization studies confirmed that the powder pH could be controlled by adjusting the pH of the crystallization.
Keywords: Amoxicillin trihydrate, impurity profile, degree of crystallinity, DSC, PXRD, HPLC
The purpose of this research was to investigate some physicochemical and solid-state properties of amoxicillin trihydrate (AMT) with different powder pH within the pharmacopoeia-specified range. AMT batches prepared using Dane salt method with the pH values from 4.39 to 4.97 were subjected to further characterization studies. Optical and scanning electron microscopy showed that different batches of AMT powders were similar in crystal habit, but the length of the crystals increased as the pH increased. Further solid-state investigations using powder x-ray diffraction (PXRD) demonstrated the same PXRD pattern, but the intensity of the peaks raised by the powder pH, indicated increased crystallinity. Differential scanning calorimetry (DSC) studies further confirmed that as the powder pH increased, the crystallinity and, hence, thermal stability of AMT powders increased. Searching for the possible cause of the variations in the solid state properties, HPLC analysis showed that despite possessing the requirements of the United States Pharmacopoeia (USP) for purity/impurity profile, there was a direct relationship between the increase of the powder pH and the purity of AMT, and also decrease in the impurity I (α-Hydroxyphenylglycine) concentration in AMT powder. Recrystallization studies confirmed that the powder pH could be controlled by adjusting the pH of the crystallization.
Keywords: Amoxicillin trihydrate, impurity profile, degree of crystallinity, DSC, PXRD, HPLC
Prevalence and risk factors for menstrual disorders among systemic lupus erythematosus patients
ABSTRACT
Introduction: This study aims to determine the prevalence and the types of menstrual disorders among patients with systemic lupus erythematosus (SLE) and to identify factors that influence their development.
Methods: 61 patients with SLE were enrolled into a cross-sectional, observational study at the medical outpatient clinic, Hospital Universiti Sains Malaysia. A total of 120 healthy women were selected randomly to act as the control group. A
questionnaire was administered, vital signs were recorded, and blood was evaluated for routine investigations. A review of past medical records was also undertaken.
Results: The mean age and standard deviation for the study group was 33.23 +/- 10.96 years, the majority being ethnic Malays. 75 percent had a severe SLE disease activity index score on initial presentation, and 59 percent were on cyclophosphamide. 49 percent of the study population had menstrual irregularities, of
which 60 percent had sustained amenorrhoea. Nine patients with sustained amenorrhoea had hormonal assays, which confirmed the diagnosis of premature menopause.
Conclusion: This study showed that SLE patients had a higher risk of developing menstrual irregularities compared to the normal/healthy population. The risk was higher in the older age group (greater than 30 years old) and those on
cyclophosphamide therapy, especially those with a cumulative dose of more than 10 g. Sustained amenorrhoea was the commonest irregularity and a majority of them had confirmed premature menopause.
Keywords: amenorrhoea, menstrual disorders, premature menopause, systemic lupus erythematosus
Introduction: This study aims to determine the prevalence and the types of menstrual disorders among patients with systemic lupus erythematosus (SLE) and to identify factors that influence their development.
Methods: 61 patients with SLE were enrolled into a cross-sectional, observational study at the medical outpatient clinic, Hospital Universiti Sains Malaysia. A total of 120 healthy women were selected randomly to act as the control group. A
questionnaire was administered, vital signs were recorded, and blood was evaluated for routine investigations. A review of past medical records was also undertaken.
Results: The mean age and standard deviation for the study group was 33.23 +/- 10.96 years, the majority being ethnic Malays. 75 percent had a severe SLE disease activity index score on initial presentation, and 59 percent were on cyclophosphamide. 49 percent of the study population had menstrual irregularities, of
which 60 percent had sustained amenorrhoea. Nine patients with sustained amenorrhoea had hormonal assays, which confirmed the diagnosis of premature menopause.
Conclusion: This study showed that SLE patients had a higher risk of developing menstrual irregularities compared to the normal/healthy population. The risk was higher in the older age group (greater than 30 years old) and those on
cyclophosphamide therapy, especially those with a cumulative dose of more than 10 g. Sustained amenorrhoea was the commonest irregularity and a majority of them had confirmed premature menopause.
Keywords: amenorrhoea, menstrual disorders, premature menopause, systemic lupus erythematosus
Menstrual psychosis
Abstract :
This paper reviews the literature on menstrual psychosis and proposes a new classification, adapting that of v. Krafft-Ebing (1902) and Jolly (1914). The world literature consists mainly of case reports; they include a few with data good enough for a statistical demonstration of the link between onset and menses. These well-documented cases include examples of pre-menstrual, catamenial, paramenstrual and mid-cycle onsets, and continuous illnesses with phasic shifts rhythmic with the menstrual cycle. In sufferers, episodes seem to be concentrated around the menarche and after childbirth. The clinical picture resembles that of puerperal psychosis, and there are at least 20 women who have suffered both psychoses at different epochs in their lives. Both seem to fall within the manic depressive rubric, so that menstruation can be another trigger of a bipolar episode. Some work suggests an association with anovulatory cycles. Cases starting before the menarche suggest a diencephalic origin.
Keywords: Menstrual psychosis, menstruation, puerperal psychosis, manic depressive (bipolar) psychosis, menarche
This paper reviews the literature on menstrual psychosis and proposes a new classification, adapting that of v. Krafft-Ebing (1902) and Jolly (1914). The world literature consists mainly of case reports; they include a few with data good enough for a statistical demonstration of the link between onset and menses. These well-documented cases include examples of pre-menstrual, catamenial, paramenstrual and mid-cycle onsets, and continuous illnesses with phasic shifts rhythmic with the menstrual cycle. In sufferers, episodes seem to be concentrated around the menarche and after childbirth. The clinical picture resembles that of puerperal psychosis, and there are at least 20 women who have suffered both psychoses at different epochs in their lives. Both seem to fall within the manic depressive rubric, so that menstruation can be another trigger of a bipolar episode. Some work suggests an association with anovulatory cycles. Cases starting before the menarche suggest a diencephalic origin.
Keywords: Menstrual psychosis, menstruation, puerperal psychosis, manic depressive (bipolar) psychosis, menarche
Dalam pengobatan kasus otitis media supuratif kronis (OMSK) jinak aktif, prinsip
Dalam pengobatan kasus otitis media supuratif kronis (OMSK) jinak aktif, prinsip
terapi yang dianjurkan adalah pembersihan lokal kavum timpani dan liang telinga luar
disertai pemberian antibiotika lokal berupa tetes telinga yang rasional. Mikroorganisme
penyebab terbanyak adalah P. aeruginosa, P. mirabilis dan S. aureus, yang tidak
sensitif lagi dengan pemberian kloramfenikol dan gentamisin tetes telinga. Preparat
terbaru yang tersedia adalah antibiotika tetes telinga ofloksasin 0,3% yang kelihatan
efektif melawan mikroorganisme penyebab OMSK.
PENDAHULUAN
Infeksi kronis telinga tengah atau Otitis Media Supuratif Kronis (OMSK) adalah keluarnya sekret dari telinga tengah, menetap atau berulang dengan perforasi membrana timpani dan biasanya diikuti oleh penurunan pendengaran dalam beberapa tingkatan(1).
Infeksi kronis telinga tengah cenderung disertai sekret purulen. Proses infeksi ini sering disebabkan oleh campuran mikroorganisme aerobik dan anaerobik yang multiresisten terhadap standar yang ada saat ini. Kuman penyebab yang sering dijumpai pada OMSK ialah Pseudomonas aeruginosa sekitar 50%, Proteus sp. 20% dan Staphylococcus aureus 25%.(1,2)
Penyakit ini sangat mengganggu dan sering menyulitkan baik dokter maupun pasiennya sendiri. Perjalanan penyakit yang panjang, terputusnya terapi, terlambatnya pengobatan spesialis THT dan sosioekonomi yang rendah membuat penatalaksanaan penyakit ini tetap menjadi problem di bidang THT(3).
Antibiotika merupakan salah satu medikamentosa yang telah digunakan untuk pengobatan OMSK sejak dulu. Namun demikian sampai saat ini masih terdapat perbedaan persepsi mengenai manfaat antibiotika, baik yang diberikan secara topikal maupun sistemik(4).
Antibiotik topikal
Ada dua pertimbangan dasar pemilihan antibiotika pada penanganan otitis media kronis yaitu:
1.Dapat terdistribusi dengan baik pada jaringan yang terinfeksi; dalam hal ini telinga tengah.
2.Spektrum yang luas meliputi organisme yang ditemui pada infeksi telinga(2).
Paad OMSK jinak aktif prinsip terapi yang dianjurkan adalah pembersihan secara lokal kavum timpani dan liang telinga luar disertai pemberian obat lokal berupa antibiotik tetes telinga(5).
Pemberian antibiotika topikal jauh lebih baik dibanding pemberian secara oral karena dalam waktu singkat sudah ditemui dengan konsentrasi tinggi pada mukus dan debris di
telinga tengah(6). Keluarnya sekret menandakan adanya perforasi membrana timpani, oleh karena itu penggunaan antibiotik topikal menjadi praktis dan bermanfaat(7).
Ada beberapa pendapat mengenai penggunaan antibiotika topikal untuk OMSK.Riff menganjurkan irigasi dengan garam faal agar lingungan bersifat lebih asam dan merupakan media buruk untuk tumbuh kuman. Selain itu dikatakan bahwa tempat infeksi padaOMSK sulit dicapai oleh antibiotika topikal(4).
Djaafar dan Gitowirjono menggunakan antibiotika topikal sesudah irigasi sekret profus dengan hasil yang cukup memuaskan, kecuali kasus dengan jaringan patologis yang menetap pada telinga tengah dan mastoid(4).
Naser Aminifarshhidmehr (1996) dari Kuwait melaporkan irigasi asamasetat 2% menyebabkan keringnya sekret telinga pada 74 penderita OMSK (77%) dan pada 19 orang di antaranya (19%) perforasi membrana timpani menutup secara spontan(3).
Supaya didapatkan hasil yang efektif, larutan yang dipergunakan harus dilarutkan dalam cairan higroskopik; propylene glycol adalah yang terbaik untuk keperluan ini(7).
Mengingat pemberian obat topikal dimaksudkan agar masuk sampai ke telinga tengah, maka tidak dianjurkan menggunakan antibiotika yang ototoksik dan lamanya tidak lebih
dari satu minggu. Cara pemilihan antibiotika yang paling baik ialah berdasarkan kultur kuman penyebab dan uji resistensi(4).
Preparat antibiotika topikal untuk infeksi telinga tersedia dalam bentuk tetes telinga dan mengandung antibiotika tunggal atau antibiotika dalam kombinasi, jika perlu ditambahkan kortikosteroid untuk mengatasi manifestasi alergi lokal(4,7).
Antibiotika topikal yang sering digunakan untuk pengobatan OMSK adalah:
Ofloksasin
Merupakan derivat quinolon; sediaan yang terdapat dipasaran adalah berupa otic solution 0,3%. Pada penelitian secara in vitro ofloksasin mempunyai aktivitas yang kuat untuk bakteri Gram negatif dan Gram positif dan bekerja dengan cara
menghambat enzim DNA gyrase. DNA gyrase adalah suatu enzim yang berperan dalam mengontrol topologi DNA dan replikasi DNA sehingga sintesis DNA dari kuman akan terhambat(8).
Ofloksasin efektif terhadap kuman aerob Gram positif seperti Staphylococcus aureus dan Streptococcus pneumonia serta untuk kuman aerob Gram negatif seperti H. influenza, M.catarrhalis, P. mirabilis dan P. aeruginosa(8).
Konsentrasi ofloksasin ditemukan cukup tinggi di mukosa telinga tengah. Pada penderita OMSK dengan perforasi membrana timpani, konsentrasi tinggi ofloksasin telah ditemukan 30 menit setelah pemberian solusio ofloksasin 0,3%(8).
1) Kloramfenikol
Losin et. al (1983) melakukan penelitian pada 30 penderita OMSK jinak aktif mendapatkan bahwa sensitifitas kloramfenikol terhadap masing-masing kuman adalah sebagai berikut:
Bacteroides sp. (90%), Proteus sp. (73,33%), Bacillus sp.(62,23%), Staphylococcus sp. (60%), dan Pseudomonas sp.(14,23%). Amadasun (1991) melakukan penelitian pada penderita OMSK jinak aktif yang tidak sembuh mendapatkan bahwa kloramfenikol tidak efektif terhadap kuman Gram negatif terutama Pseudomonas sp. dan Proteus sp. Penelitian tersebut menunjukkan sensitifitas kedua kuman tersebut yang dominan
pada OMSK jinak aktif terhadap khloramfenikol sebesar 16% dibanding gentamisin sebesar 28%.
2) Polimiksin B atau Polimiksin E
Obat ini bersifat bekterisid terhadap kuman Gram negatif, Pseudomonas, E. coli, Klebsiella dan Enterobakter tetapi tidak efektif (resisten) terhadap kuman Gram positif seperti Proteus dan B. fragilis dan toksik terhadap ginjal dan susunan saraf(6).
3) Gentamisin
Gentamisin adalah antibiotika derivat aminoglikosida dengan spektrum yang luas dan aktif untuk melawan organisme Gram positif dan Gram negatif termasuk Pseudomonas sp.,
Proteus sp. dan Staphylococcus sp(6). Pemberian jangka pendek gentamisin 0,3% secara tunggal tanpa kombinasi di samping biayanya murah juga sangat efektif untuk melawan organisme berspektrum luas terutama Pseudomonas aeruginosa.(6)
Penam-
bahan steroid akan menyebabkan peningkatan biaya dua kali lipat. Penelitian Browning, Gatehouse and Calder (1988) mendapatkan bahwa penambahan steroid pada tetes telinga
gentamisin 0,3% tidak meningkatkan efektivitasnya, hasilnya tidak lebih baik dari plasebo(6).
Salah satu bahaya dari pemberian gentamisin tetes telinga adalah kemungkinan terjadinya kerusakan telinga dalam. Telah diketahui bahwa pemberian gentamisin secara sistemik akan menyebabkan efek ototoksik(4). Podoshin, Fradis dan Ben David (1989) pada penelitiannya menganjurkan untuk tidak memberikan gentamisin dan aminoglikosida tetes telinga lainnya untuk penanganan OMSK jangka panjang.
4) Ofloksasin
Merupakan derivat quinolon; sediaan yang terdapat dipasaran adalah berupa otic solution 0,3%. Pada penelitian secara in vitro ofloksasin mempunyai aktivitas yang kuat untuk bakteri Gram negatif dan Gram positif dan bekerja dengan cara
menghambat enzim DNA gyrase. DNA gyrase adalah suatu enzim yang berperan dalam mengontrol topologi DNA dan replikasi DNA sehingga sintesis DNA dari kuman akan ter-
hambat(8).
Ofloksasin efektif terhadap kuman aerob Gram positif seperti Staphylococcus aureus dan Streptococcus pneumonia serta untuk kuman aerob Gram negatif seperti H. influenza, M.catarrhalis, P. mirabilis dan P. aeruginosa(8).
Konsentrasi ofloksasin ditemukan cukup tinggi di mukosa telinga tengah. Pada penderita OMSK dengan perforasi membrana timpani, konsentrasi tinggi ofloksasin telah ditemukan 30 menit setelah pemberian solusio ofloksasin 0,3%.
Antibiotika topikal golongan kuinolon yang lain adalah siprofloksasin 0,3%, penelitian Utji (1999) mendapatkan bahwa pemakaian tetes 0,3% siprofloksasin pada penderita OMSK lebih berhasil guna dan lebih murah dibanding pemakaian tetes
telinga kloramfenikol, dan tidak dijumpai efek ototoksik (5).
Keuntungan lain pemakaian tetes telinga dari golongan kuinolon adalah dapat diberikan secara tunggal tanpa antibiotik oral dan dosis pemberian 2 kali sehari memungkinkan pasien merasa nyaman tanpa mengganggu aktifitas kerja maupun sekolah.
terapi yang dianjurkan adalah pembersihan lokal kavum timpani dan liang telinga luar
disertai pemberian antibiotika lokal berupa tetes telinga yang rasional. Mikroorganisme
penyebab terbanyak adalah P. aeruginosa, P. mirabilis dan S. aureus, yang tidak
sensitif lagi dengan pemberian kloramfenikol dan gentamisin tetes telinga. Preparat
terbaru yang tersedia adalah antibiotika tetes telinga ofloksasin 0,3% yang kelihatan
efektif melawan mikroorganisme penyebab OMSK.
PENDAHULUAN
Infeksi kronis telinga tengah atau Otitis Media Supuratif Kronis (OMSK) adalah keluarnya sekret dari telinga tengah, menetap atau berulang dengan perforasi membrana timpani dan biasanya diikuti oleh penurunan pendengaran dalam beberapa tingkatan(1).
Infeksi kronis telinga tengah cenderung disertai sekret purulen. Proses infeksi ini sering disebabkan oleh campuran mikroorganisme aerobik dan anaerobik yang multiresisten terhadap standar yang ada saat ini. Kuman penyebab yang sering dijumpai pada OMSK ialah Pseudomonas aeruginosa sekitar 50%, Proteus sp. 20% dan Staphylococcus aureus 25%.(1,2)
Penyakit ini sangat mengganggu dan sering menyulitkan baik dokter maupun pasiennya sendiri. Perjalanan penyakit yang panjang, terputusnya terapi, terlambatnya pengobatan spesialis THT dan sosioekonomi yang rendah membuat penatalaksanaan penyakit ini tetap menjadi problem di bidang THT(3).
Antibiotika merupakan salah satu medikamentosa yang telah digunakan untuk pengobatan OMSK sejak dulu. Namun demikian sampai saat ini masih terdapat perbedaan persepsi mengenai manfaat antibiotika, baik yang diberikan secara topikal maupun sistemik(4).
Antibiotik topikal
Ada dua pertimbangan dasar pemilihan antibiotika pada penanganan otitis media kronis yaitu:
1.Dapat terdistribusi dengan baik pada jaringan yang terinfeksi; dalam hal ini telinga tengah.
2.Spektrum yang luas meliputi organisme yang ditemui pada infeksi telinga(2).
Paad OMSK jinak aktif prinsip terapi yang dianjurkan adalah pembersihan secara lokal kavum timpani dan liang telinga luar disertai pemberian obat lokal berupa antibiotik tetes telinga(5).
Pemberian antibiotika topikal jauh lebih baik dibanding pemberian secara oral karena dalam waktu singkat sudah ditemui dengan konsentrasi tinggi pada mukus dan debris di
telinga tengah(6). Keluarnya sekret menandakan adanya perforasi membrana timpani, oleh karena itu penggunaan antibiotik topikal menjadi praktis dan bermanfaat(7).
Ada beberapa pendapat mengenai penggunaan antibiotika topikal untuk OMSK.Riff menganjurkan irigasi dengan garam faal agar lingungan bersifat lebih asam dan merupakan media buruk untuk tumbuh kuman. Selain itu dikatakan bahwa tempat infeksi padaOMSK sulit dicapai oleh antibiotika topikal(4).
Djaafar dan Gitowirjono menggunakan antibiotika topikal sesudah irigasi sekret profus dengan hasil yang cukup memuaskan, kecuali kasus dengan jaringan patologis yang menetap pada telinga tengah dan mastoid(4).
Naser Aminifarshhidmehr (1996) dari Kuwait melaporkan irigasi asamasetat 2% menyebabkan keringnya sekret telinga pada 74 penderita OMSK (77%) dan pada 19 orang di antaranya (19%) perforasi membrana timpani menutup secara spontan(3).
Supaya didapatkan hasil yang efektif, larutan yang dipergunakan harus dilarutkan dalam cairan higroskopik; propylene glycol adalah yang terbaik untuk keperluan ini(7).
Mengingat pemberian obat topikal dimaksudkan agar masuk sampai ke telinga tengah, maka tidak dianjurkan menggunakan antibiotika yang ototoksik dan lamanya tidak lebih
dari satu minggu. Cara pemilihan antibiotika yang paling baik ialah berdasarkan kultur kuman penyebab dan uji resistensi(4).
Preparat antibiotika topikal untuk infeksi telinga tersedia dalam bentuk tetes telinga dan mengandung antibiotika tunggal atau antibiotika dalam kombinasi, jika perlu ditambahkan kortikosteroid untuk mengatasi manifestasi alergi lokal(4,7).
Antibiotika topikal yang sering digunakan untuk pengobatan OMSK adalah:
Ofloksasin
Merupakan derivat quinolon; sediaan yang terdapat dipasaran adalah berupa otic solution 0,3%. Pada penelitian secara in vitro ofloksasin mempunyai aktivitas yang kuat untuk bakteri Gram negatif dan Gram positif dan bekerja dengan cara
menghambat enzim DNA gyrase. DNA gyrase adalah suatu enzim yang berperan dalam mengontrol topologi DNA dan replikasi DNA sehingga sintesis DNA dari kuman akan terhambat(8).
Ofloksasin efektif terhadap kuman aerob Gram positif seperti Staphylococcus aureus dan Streptococcus pneumonia serta untuk kuman aerob Gram negatif seperti H. influenza, M.catarrhalis, P. mirabilis dan P. aeruginosa(8).
Konsentrasi ofloksasin ditemukan cukup tinggi di mukosa telinga tengah. Pada penderita OMSK dengan perforasi membrana timpani, konsentrasi tinggi ofloksasin telah ditemukan 30 menit setelah pemberian solusio ofloksasin 0,3%(8).
1) Kloramfenikol
Losin et. al (1983) melakukan penelitian pada 30 penderita OMSK jinak aktif mendapatkan bahwa sensitifitas kloramfenikol terhadap masing-masing kuman adalah sebagai berikut:
Bacteroides sp. (90%), Proteus sp. (73,33%), Bacillus sp.(62,23%), Staphylococcus sp. (60%), dan Pseudomonas sp.(14,23%). Amadasun (1991) melakukan penelitian pada penderita OMSK jinak aktif yang tidak sembuh mendapatkan bahwa kloramfenikol tidak efektif terhadap kuman Gram negatif terutama Pseudomonas sp. dan Proteus sp. Penelitian tersebut menunjukkan sensitifitas kedua kuman tersebut yang dominan
pada OMSK jinak aktif terhadap khloramfenikol sebesar 16% dibanding gentamisin sebesar 28%.
2) Polimiksin B atau Polimiksin E
Obat ini bersifat bekterisid terhadap kuman Gram negatif, Pseudomonas, E. coli, Klebsiella dan Enterobakter tetapi tidak efektif (resisten) terhadap kuman Gram positif seperti Proteus dan B. fragilis dan toksik terhadap ginjal dan susunan saraf(6).
3) Gentamisin
Gentamisin adalah antibiotika derivat aminoglikosida dengan spektrum yang luas dan aktif untuk melawan organisme Gram positif dan Gram negatif termasuk Pseudomonas sp.,
Proteus sp. dan Staphylococcus sp(6). Pemberian jangka pendek gentamisin 0,3% secara tunggal tanpa kombinasi di samping biayanya murah juga sangat efektif untuk melawan organisme berspektrum luas terutama Pseudomonas aeruginosa.(6)
Penam-
bahan steroid akan menyebabkan peningkatan biaya dua kali lipat. Penelitian Browning, Gatehouse and Calder (1988) mendapatkan bahwa penambahan steroid pada tetes telinga
gentamisin 0,3% tidak meningkatkan efektivitasnya, hasilnya tidak lebih baik dari plasebo(6).
Salah satu bahaya dari pemberian gentamisin tetes telinga adalah kemungkinan terjadinya kerusakan telinga dalam. Telah diketahui bahwa pemberian gentamisin secara sistemik akan menyebabkan efek ototoksik(4). Podoshin, Fradis dan Ben David (1989) pada penelitiannya menganjurkan untuk tidak memberikan gentamisin dan aminoglikosida tetes telinga lainnya untuk penanganan OMSK jangka panjang.
4) Ofloksasin
Merupakan derivat quinolon; sediaan yang terdapat dipasaran adalah berupa otic solution 0,3%. Pada penelitian secara in vitro ofloksasin mempunyai aktivitas yang kuat untuk bakteri Gram negatif dan Gram positif dan bekerja dengan cara
menghambat enzim DNA gyrase. DNA gyrase adalah suatu enzim yang berperan dalam mengontrol topologi DNA dan replikasi DNA sehingga sintesis DNA dari kuman akan ter-
hambat(8).
Ofloksasin efektif terhadap kuman aerob Gram positif seperti Staphylococcus aureus dan Streptococcus pneumonia serta untuk kuman aerob Gram negatif seperti H. influenza, M.catarrhalis, P. mirabilis dan P. aeruginosa(8).
Konsentrasi ofloksasin ditemukan cukup tinggi di mukosa telinga tengah. Pada penderita OMSK dengan perforasi membrana timpani, konsentrasi tinggi ofloksasin telah ditemukan 30 menit setelah pemberian solusio ofloksasin 0,3%.
Antibiotika topikal golongan kuinolon yang lain adalah siprofloksasin 0,3%, penelitian Utji (1999) mendapatkan bahwa pemakaian tetes 0,3% siprofloksasin pada penderita OMSK lebih berhasil guna dan lebih murah dibanding pemakaian tetes
telinga kloramfenikol, dan tidak dijumpai efek ototoksik (5).
Keuntungan lain pemakaian tetes telinga dari golongan kuinolon adalah dapat diberikan secara tunggal tanpa antibiotik oral dan dosis pemberian 2 kali sehari memungkinkan pasien merasa nyaman tanpa mengganggu aktifitas kerja maupun sekolah.
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