Similar macrofilaricidal effect has been reported in onchocerciasis, with doxycycline 100 mg/d for six months. However, it is not the drug of choice for treating filariasis, nor it is useful for mass treatment. Mass treatment of filariasis: In endemic areas, mass treatment is given with the objective of reducing microfilariae to subinfective levels. Mansonelliasis infection: Mansonella perstans, is usually asymptomatic and considered as minor filariasis. Long term doxycycline (200 mg daily for 6 weeks) has been claimed to be effective. Drug Therapy of Guinea Worm Dracunculus medinensis infestation is transmitted by drinking of water containing infected cyclops (water flea). The adult female usually remains in subcutaneous tissue and may come out through a small ulcer, usually on the foot. Mebendazole in the dose of 200 mg tid orally for 7-10 days is also claimed to be effective in helping easy expulsion. This is very simple as the intermediate host, cyclops, can easily be filtered out from the drinking water by using a piece of cloth. Drug Therapy of Tapeworms this infestation is transmitted by ingestion of infected beef or pork and can be prevented by avoiding the ingestion of suspected meat or by its thorough cooking. In a single dose of 10 mg/kg it is highly effective against intestinal taeniasis, T. The segments of the worm which are voided after its administration are partially digested by the action of the intestinal proteolytic enzymes; this makes identification of the scolex impossible. The criterion for cure with this drug, therefore, is absence of eggs and proglottids in the stools for 3 to 4 months after therapy. This makes it mandatory to use a purge within 1-2 hours after niclosamide is given, in order to prevent digestion of the segments. As niclosamide does not affect the ova, regurgitation of viable ova into the duodenum in case of Taenia solium exposes the patient to the risk of digestion of the ova, autoinfection with larvae and thus cysticercosis. After keeping the patient on a low residue diet on the day before and fasting overnight, 2 tablets of the drug (1 g) are given in the morning on an empty stomach. The tablets should be chewed in order to ensure a thorough mixing of the drug with the intestinal contents. A saline purge may be given 1 to 2 hours after the second dose but is not essential except in T. Drug Therapy of Schistosomiasis Schistosomiasis (bilharziasis) is caused by blood flukes (Schistosomes) that parasitise the venous channels of the definitive hosts. Unlike the other infestations, schistosomal infestations can be considered as systemic, as the parasites are localised in organs other than the gut. Man and domestic animals act as hosts for schistosomes, the ova of which contaminate water. Free living cercariae, emerging from the snail, penetrate the human skin and mature into the adult worms. The drug increases the permeability of cell membrane to calcium ions, leading to strong muscular contractions and tegumental damage causing the schistosomes to detach from the wall of the vein. Absorption, fate and excretion: Given orally praziquantel is rapidly absorbed, but, significant proportion of the drug is metabolised during the first pass. Adverse reactions: these are dose dependent and are usually mild such as headache, anorexia, drowsiness, lassitude, colic and allergic reactions. Katayama fever, a hypersensitivity reaction is mainly treated with a glucocorticoid along with praziquantel. Rarely it may cause hallucinations, excitement or psychotic symptoms, particularly in the, Japanese. Experimental evidence indicates that it has no mutagenic, carcinogenic, embryotoxic or teratogenic effect.
But it has to be taken 2-3 times a day Chlorpropamide controls hyperglycemia in a. Although doses larger than 500 mg per day are pharmacologically more effective, they may cause a disproportionate increase in adverse effects. Glibenclamide is effective in a single daily dose and may be effective in patients who are not controlled by maximum doses of chlorpropamide. In patients with renal impairment, tolbutamide or gliclazide is the preferred drug. If good glycemic control is not achieved with maximum doses of sulfonylureas, one should use combination oral drug therapy or change to insulin. Meglitinides (Glinides): these drugs, chemically unrelated to sulfonylureas, have the same mechanism of action. However, they do not stimulate further release of insulin in patients on maximum dose of a sulfonylurea. It controls postprandial hyperglycemia effectively Because of its short duration of action, it is. It must be taken any time 30 mins before each major meal to just at the start of a meal in the dose of 0. A free guanidine radical is thought to be essential for the hypoglycemic effect of biguanides. It does not stimulate insulin release from the pancreas and the presence of either exogenous or endogenous insulin is necessary for its action. Pharmacological actions: Metformin does not lower the blood sugar in normal subjects. Hence, diabetics on metformin may develop ketoacidosis with minimum hyperglycemia and glycosuria. In 20% of the patients, it produces bitter or metallic taste, anorexia, nausea, and abdominal discomfort. This can be minimised by starting with a small dose and giving it with, rather than before, meals. Lactic acidosis, though reported rarely during metformin therapy could be lethal during, an acute illness such as a severe infection. Before prescribing metformin to an elderly patient, serum creatinine should be measured to assess the renal function. Metformin should be omitted and insulin substituted the day before major surgery It may be resumed after. It is generally started in the dose of 250 mg 2-3 times a day with major meals, and the dose increased gradually upto 2000 mg per day. Fixed dose combinations with a sulfonylurea do not allow individualisation of the doses of the two drugs and should generally be avoided. In such patients, the anorectic action of metformin is of additional help in making the patients lose weight. Mechanism of action: It binds competitively to carbohydrate binding sites of alpha glucosidases enzymes in the brush border of the enterocytes in the jejunum. It thus inhibits the absorption of carbohydrates but not of glucose because it does not interact with the intestinal sodium dependent glucose transporter. Pharmacological actions: Given orally acarbose reduces postprandial hyperglycemia which, is claimed to activate coagulation cascade. It is administered in the dose of 25-50 mg, chewed and swallowed after eating the first few morsels during each meal. Adverse reactions: these include flatulence abdominal discomfort and loose stools due to undigested carbohydrates. Since their action is genetic regulation, their maximum effect is seen after weeks or months. They synergise with sulfonylureas and metformin, as well as insulin in their antidiabetic effects. Thus, they ameliorate hyperinsulinemia and thereby may protect the body from the damaging effects of chronic endogenous hyperinsulinemia.
It is important to be certain that the tumour is benign and the other ovary healthy by frozen-section biopsy. Because of the risk of spillage of cyst content in a dermoid cyst resulting in peritonitis and mucinous material spillage causing pseudomyxoma peritonei in a case of mucinous cyst, some prefer open surgery. In a laparoscopic surgery, retrieval of the tumour in a plastic bag reduces the risk of spillage of cyst contents. Laparoscopy carries a low morbidity and allows a quick recovery without a conventional abdominal scar. Laparoscopic ovarian cystectomy is performed by first aspirating the cyst fluid followed by dissection of the cyst wall or by ablation. Mere aspiration of fluid is not recommended on account of recurrence of the tumour. Aspirated material/cyst wall should be subjected to histopathology and cancer ruled out. Ablation of the cyst wall carried out with cautery or laser carries the risk of recurrence of the cyst. While dissection or peeling off of the cyst wall avoids recurrence, bleeding during dissection, adhesion formation and reduction in the ovarian reserve (due to destruction of a portion of the ovary) are the disadvantages. Ovarian Tumours Associated with Pregnancy the ovarian tumour discovered during pregnancy is an enlarged corpus luteal cyst, a benign as well as a malignant tumour. An asymptomatic tumour is discovered during routine ultrasound scanning in early pregnancy. The benign tumour should be removed in the second trimester between the 14th and 16th week. Earlier surgery may increase the risk of abortion, whereas laparotomy in the third trimester increases the surgical difficulty because of the growing uterus; preterm labour is also a possibility. The tumour discovered late in pregnancy should be removed in early puerperium to avoid torsion and infection. The malignant ovarian tumour requires laparotomy at the earliest, irrespective of the duration of pregnancy. Abdominal hysterectomy and bilateral salpingo-oophorectomy is recommended in a perimenopausal women, even if the tumour is benign and unilateral. The probability of discovering microscopic evidence of malignancy in histological specimens and thereby the need for second surgery can be avoided. Conservative surgery followed by chemotherapy is effective and has replaced the older treatment of hysterectomy with bilateral salpingo-oophorectomy and radiotherapy in young girls. Aspiration of the cyst is contraindicated because of low yield of malignant cells (false-negative) and possibility of spread of malignancy if the cyst proves malignant histologically. It is caused by ovarian adhesions to the vaginal vault, and causes cyclical abdominal pain and deep dyspareunia. Apart from these, it is also observed that many ovaries atrophy prematurely (within 4 years) following hysterectomy, if the ovarian vessels get kinked and obliterated during hysterectomy. The conservation of ovaries at hysterectomy for benign tumour therefore remains a debatable issue at present. Recent belief is to remove the ovaries at the time of hysterectomy and give hormone replacement therapy thereafter. Adnexal Mass the ovary and the fallopian tube form the adnexa along with a rare tumour in the broad ligament. It is important to differentiate between benign and malignant enlargements of the ovary to institute timely and effective treatment without undue delay. Benign ovarian tumour is surgically dealt with by ovarian cystectomy, ovariotomy, laparoscopic dissection of the cyst in a young woman and hysterectomy with bilateral removal of adnexa in an older woman. Write short notes on: n Brenner tumour n Mucinous epithelial tumour n Arrhenoblastoma n Theca cell tumour Key Points n n n n A wide variety of diverse ovarian tumours are known to arise from the ovary. The tumours are often asymptomatic to begin with, and are often far advanced by the time they are diagnosed. Sex cord tumours have a potential to secrete hormones which may manifest clinical symptoms like precocious puberty, menstrual disturbances and postmenopausal bleeding.
It is useful in some patients with stress-urge incontinence and nocturnal eneuresis (Chapter 14). Finally it should be remembered that the distal part of the female urethral epithelium, possesses estrogen receptors. The important agents belonging to this group are the alkaloids nicotine and lobeline. Although nicotine has no therapeutic utility it is the important constituent of tobacco. The actions of this compound, particularly its effects on autonomic ganglia, were studied by Langley and Dickinson in their classical experiments in 1889. Mechanism of action: Nicotine acts as an agonist at cholinergic receptors present in the brain, autonomic ganglia and neuromuscular junctions, which explains its multiple effects. Pharmacological actions: the amount of nicotine absorbed during smoking is sufficient to produce measurable pharmacological and psychopharmacological effects. In small doses, the effects are predominantly stimulant and may improve attention, learning, reaction time and problem solving. Smokers often report pleasure and relaxation, and reduction in anger, tension, depression and stress. Small doses reflexly stimulate respiration through aortic and carotid body chemoreceptors; while large doses directly stimulate the medullary respiratory centre. In sensitive individuals, this effect may become apparent after smoking 2 or 3 cigarettes. However, large doses of nicotine produce persistent depolarisation of these ganglionic cell bodies resulting in ganglionic blockade. Nicotine in large doses, therefore, paralyses the autonomic ganglia by a dual mechanism. The cardiovascular actions of nicotine in an intact animal usually vary according to preponderance of sympathetic or parasympathetic stimulation. The most consistent effects of smoking in humans are an increase in the heart rate and peripheral vasoconstriction. Blood pressure may rise and an increase in skeletal muscle and coronary blood flow may occur. These effects are due to increased release of catecholamines following stimulation of the sympathetic ganglia and adrenal medulla. Stimulation is usually followed by decrease in motility and tone, leading to constipation. Nicotine initially increases the salivary and bronchial secretions, followed by their inhibition. Salivation accompanying smoking, however, is due to irritant nature of the smoke rather than its nicotine content. In large doses, this stimulant effect is followed and often overshadowed by blockade of myoneural transmission. It must be pointed out, however, that nicotine has a much more prominent effect on the autonomic ganglia than on the myoneural junction. Inhalation of cigarette smoke enhances the metabolism of several drugs including nicotine in man. Excessive release of cortisol following nicotine could affect mood and may contribute to osteoporosis. This effect is attributed to cutaneous axon reflexes mediated by sympathetic nerves and serves as a basis for testing the integrity of the postganglionic sympathetic fibres. Tolerance and dependence: One third to one half of occasional smokers develop physical dependence. Most tobacco-dependent persons never achieve lasting abstinence and one half of all smokers die prematurely of tobacco-related diseases. A regular smoker is able to withstand large amounts of nicotine in contrast to a non-smoker. Withdrawal syndrome manifests as craving, depression, nervousness, restlessness, irritability anxiety impaired concentration, increased appetite and weight gain. Adverse reactions: Acute nicotine poisoning occurs in workers engaged in spraying nicotine as an insecticide.
Should this reveal the presence of a swelling separate from the uterus, then the presence of some adnexal pathology is confirmed. The ovary is not easily palpable; however, when palpated, it evinces a peculiar painful sensation that makes the patient to wince. The most common swelling is the loaded rectum, particularly if she is constipated. The nature of the tumour is determined on bimanual examination because the uterus can be identified apart from the abdominal tumour. In some cases the pedicle can be distinguished if the fingers in the vagina are placed high up in the posterior fornix. Introduction of a well-lubricated proctoscope to inspect the rectum and anal canal helps to complete the examination. Ultrasound today has reduced the importance of rectal examination except in cancer cervix and pelvic endometriosis. Investigations Detailed history and clinical examination often clinch the diagnosis or reduce the differential diagnosis to a few possibilities. Common disorders: Age related: Preoperative investigations are described in the chapter on preoperative and postoperative care. The fingers in the vagina are moved to one side of the cervix, and they feel the lower pole of the swelling. To recognize the uterus from the adnexal mass, push the cervix upwards, and if this is transmitted to the swelling it is the uterus. Instead a welllubricated finger inserted into the rectum can be used for a bimanual assessment of the pelvic structures. Today, practically all gynaecologists prefer ultrasonic scanning to rectal examination, which, apart from being unpleasant, is not that accurate. A rectal examination is a very useful additional examination whenever there is any palpable pathology in the pouch of Douglas. In parametritis and endometriosis, the uterosacral ligaments are often thickened, nodular and tender. It confirms the swelling to be anterior to the rectum, and if the rectum is adherent to that swelling. This is important in case of carcinoma of the cervix to determine the extent of its posterior spread. Special Tests Hanging Drop Preparation In women complaining of leucorrhoea, the discharge collected from the posterior fornix on the blade of the speculum should be suspended in saline and submitted to microscopic examination. A fresh suspension of the discharge may reveal the motile flagellated organisms known as Trichomonal vaginalis. Place a drop of the mixture on a slide, cover it with a cover slip, warm the slide and examine it under the low power of the microscope. Many cases of vaginitis are attributed to bacterial vaginosis (nonspecific vaginitis); also known as Gardnerella vaginalis. This test detects the presence of glycogen in the superficial cells of the vaginal epithelium. Unstained areas (negative test) are abnormal and require biopsy for histological examination. All women over the age of 35 years should undergo an annual check-up with the Pap test. Aside from premalignant and malignant changes, other local conditions can often be recognized by the cytologist. Positive test (abnormal cells) requires further investigations like colposcopy, cervical biopsy and fractional curettage. Reliability of the report depends upon the slide preparation and the skill of the cytologist.
Describe the clinical features of chronic inversion of the uterus and its management. Describe the clinical symptoms associated with uterine displacement in modern day practice. Key Points n n n the uterus is not a static organ; however, its usual position is that of anteversion and anteflexion. The uterus is retroverted in about 20% of women; mobile retroversion is often asymptomatic and requires no treatment. Fixed retroversion is often the aftermath of pelvic inflammatory disease or a result of endometriosis; these women may complain of chronic backache and deep dyspareunia which may contribute to infrequent coitus and infertility. Common dermatological disorders, allergies, infections, naevi, dystrophies, ulcers and new growths. Lipomas, fibromas, haemangiomas, varicosities, carcinomas, sarcomas and endometriosis. Despite the fact that vulvar diseases are not uncommon, and the vulva is easily accessible to clinical examination, there is often a delay in arriving at an early diagnosis due to a false sense of modesty which prevails and prevents the patient from seeking early advice. The symptoms most commonly produced by vulvar lesions are itching, swelling, ulceration or altered pigmentation which may be accompanied by itching, pain or bleeding. An accurate diagnosis can usually be made by inspection, palpation, smear and culture examination and biopsy. The above classification is obviously incomplete, but takes note of the commonly encountered disorders. Inflammatory Lesions Skin Infections Intertrigo and Folliculitis Intertrigo and folliculitis are commonly seen in obese women, using tight garments which prevent evaporation of the moisture from these parts leading to chaffing followed by bacterial and fungal infection. The treatment involves weight reduction, use of loose undergarments, advice regarding personal hygiene, use of bland soap and unmedicated protective dusting powder. Antimicrobial ointments may be useful initially to control secondary bacterial infection. Tinea Cruris Tinea cruris or ringworm of the thigh, vulva and groin is not infrequently encountered in the tropics. The characteristic erythematous circumscribed areas are found in the skin flexures of the thighs and outer aspect of the labia. A fine papular rash is usually seen sharply demarcated from the adjacent healthy skin. Treatment consists of meticulous hygiene, the use of frequently changed light underclothes, dusting with fungicidal powder or application of fungicidal ointment containing benzoic and salicylic acids. The silvery scale can be easily scraped off to reveal a red papular underlying surface. The aetiology is not known but the condition responds satisfactorily to treatment with local steroids. Threadworms Enterobius vermicularis may secondarily infect the vulva from the anorectal area, particularly in children. Filariasis this is caused by the worm Wuchereria bancrofti which is spread by mosquitoes. The parasite reproduces in the lymphatics and causes lymphatic oedema of the legs and elephantiasis of the legs and vulva. Vulvovaginitis Vulvovaginitis in children may be nonspecific due to a foreign body accidentally introduced in the vagina or threadworm infection. Bartholinitis is mostly gonococcal but other cocci may also be responsible, and present with a painful and tender swelling over the labia majora (Figure 27. Contact Vulvitis Contact vulvitis often represents a local reaction to undergarments made from synthetic materials, to soaps and detergents, to chemicals (deodorants) and occasionally to medicaments and industrial pollutants. Examination reveals oedema and reddening of the vulvar skin and vestibule without accompanying vaginitis. The acute symptoms can be controlled by administering oral antihistamines, application of local steroidal ointments or creams, using cotton underwear, advocating the use of bland soaps and scrupulously avoiding offending drugs. Note the extent of the lesion extending laterally to the inner thighs and posteriorly to involve the perianal skin and cleft.
Diseases
Octequitide is a peptide hormone secreted by hypothalamus which inhibits the growth hormone and insulin. The micronutrients include vitamin D, minerals, chromium, selenium, inositol and folic acid (ovacare, one tablet twice daily). Any form of treatment is likely to give temporary relief and may be required to be repeated and varied at various times during her reproductive years. The treatment will also ensure that in the long term, diabetes and endometrial cancer do not develop. Medical therapy fails Hyperstimulation occurs Infertile women Previous pregnancy losses Surgery comprises laparoscopic drilling or puncture of not more than four cysts in each ovary either by laser or by unipolar electrocautery (Figure 32. Advantages of surgery are as follows: n Key Points n n n n n n n n Tubal testing with chromotubation can be performed simultaneously. Disadvantages of surgery are as follows: Surgery involves anaesthesia and laparoscopy. Premature ovarian failure due to destruction of ovarian tissue if cautery is used. While avoiding laparoscopic surgery and postoperative adhesions, it occasionally causes skin burn; bowel burn is also reported. Complete cure should be ensured to avoid late sequel such as diabetes, hypertension, cardiovascular disease and hyperlipidaemia. A young 22-year-old nullipara presents with 6 weeks amenorrhoea, acute abdominal pain and slight vaginal bleeding. Suresh Kini: In: Polycystic ovary syndrome: diagnosis and management of related infertility practice points. Of all the malignant tumours, 90% are epithelial in origin, 80% are primary in the ovary and 20% secondary from breasts, gastrointestinal tract and colon. Mucinous cyst becomes malignant in 5% but papillary cyst adenoma becomes malignant in 50% if left untreated. Unfortunately, patients with ovarian tumours are often symptom-free for a long time, and the signs are often nonspecific. By the time ovarian malignancy is established, about two-thirds of these are already far advanced and the prognosis in such cases is unfavourable. An ovarian tumour in adolescent and post-menopausal women is more often malignant. Epithelial ovarian neoplasms arise from the mesoepithelial cells on the ovarian surface. Histologically, these tumours are intermediate between truly benign neoplasms and those with invasive characteristics. Tumour-likeconditions Characteristics of Borderline Ovarian Tumours n n n n n Patients have a high survival rate of 90%. Risk Factors Low parity infertility and failure to lactate increase the risk of developing these tumours. Oral combined pills do not provide any protection against development of a borderline ovarian tumour. The degree of cellular differentiation of the epithelial ovarian neoplasm expressed as histologic grade has an important prognostic significance as well as in identifying malignancy. The criteria of grading used include mitotic count, stratification, cellular pleomorphism, nuclear atypism and proportion of solid areas within the tumour. Pathology Borderline ovarian tumours are mainly serous (endosalpinx and endocervical type) and mucinous, the former being more common than the latter. The diagnosis is entirely dependent on several sections studied histologically; frozen section is necessary in young women.
Although these drugs are chemically related, their toxicity is relatively different. Thus, vinblastine is more toxic to the bone marrow while vincristine causes more neurotoxicity and alopecia. Vinorelbine, a semisynthetic derivative of vinblastine is used for non-small cell lung cancer, breast cancer and ovarian cancer. It binds to the beta subunit of tubulin and forms stable non-functioning microtubule bundle, thus interfering with mitosis. Docetaxel, an analogue of paclitaxel with similar properties but a longer half-life. Camptothecin analogues: these have been isolated from the Chinese tree Camptotheca acuminata and include irinotecan and topotecan. Hormones and Anti-Hormonal Drugs Hormones act differently from the cytotoxic drugs and hence can be usefully combined with them in certain malignancies. However, as they stimulate the granuloblasts, they are ineffective in acute myeloid leukemia. Hormones do not directly kill the susceptible malignant cells, do not cause hyperuricemia and are slower in their effect. The best results are obtained by combining estrogens with orchidectomy Synthetic estrogens which are as. Diethylstilbestrol is used in the dose of 5 mg tid for several days and then reduced to 1 mg tid. In males, these mainly include sexual impotence and gynecomastia: Aromatase inhibitors: these nonsteroidal drugs inhibit the enzyme aromatase responsible for the conversion of the adrenal androgen androstenedione to estrone (Chapter 67). The currently used non-steroidal aromatase inhibitors are anastrozole and letrozole. Such estrogen synthesis may be important in the pathogenesis of breast cancer growth in postmenopausal women. Aromatase inhibitors are selective in action (selective medical adrenalectomy) and do not inhibit synthesis of adrenal glucocorticoids. Adverse reactions are mild and include nausea, headache, fatigue, hot flushes and arthralgia. It acts by irreversibly inactivation of aromatase and has similar uses as other aromatase inhibitors. The metabolites of tamoxifen have a much stronger affinity for the receptors and are not easily displaced by circulating estradiol. It is extensively, metabolised in liver to active metabolites and undergoes enterohepatic circulation. With a standard dose of 10 mg twice a day a steady state serum concentration is achieved by 4, weeks of treatment. The approximate biological half-life of tamoxifen and its metabolite Ndesmethyltamoxifen are 7 and 14 days, respectively Hence, the drug can be detected in the. It may also give rise to vaginal bleeding and ocular toxicity Rarely it causes bone. Therapeutic uses: Tamoxifen is well tolerated, reasonably safe and of proven efficacy in patients with breast cancer. The dose is 10 mg orally twice daily the optimum duration of treatment is uncertain;. Fulvestrant: this selective estrogen receptor antagonist is an anti-cancer drug for metastatic breast cancer. Hydroxy-progesterone caproate and megestrol acetate have been used with success in metastatic endometrial carcinoma. It exerts substantial anti-tumor activity in patients with metastatic cancer of prostate. The drug does not inhibit either the production of gonadotropins or adrenocortical steroidogenesis. Its adverse effects are nausea, vomiting, loss of libido, sexual impotence, hot flushes and rarely serious hepatotoxicity. However, flutamide, used as a single drug in the dose of 250 mg tid is effective in the management of early prostatic cancer; it can also be used as the sole drug in orchidectomised patients, in whom it blocks the effects of the adrenal androgens.
Failure to block the vagus may precipitate hypotension and hiccough due to reflex stimulation during abdominal surgery Headache. Other complications include post-operative urinary retention and intestinal atony. It is the methylbenzoyl ester of ecgonine which is chemically closely related to atropine. Cocaine is not used as a local anaesthetic; but it is an important drug of abuse for its psychotropic effects. The concentration used to produce local anaesthesia is poisonous to many structures like leucocytes and tissue cells. It blocks the reuptake of dopamine and causes activation of the dopaminergic system, leading to sense of euphoria (mesolimbic and mesocortical pathways), strongly reinforcing the addicting property of the drug. Later, depletion of dopamine from the nerve endings gives rise to dysphoria so characteristic of cocaine withdrawal. This may account for the striking alteration of sleep-wake cycle and may enhance the central excitatory effect of dopamine. Since it is metabolised by plasma and liver cholinesterases, people with deficiency of these enzymes (liver disease), infants, pregnant women and old persons are at greater risk of cocaine toxicity Most. Drug dependence: Persons dependent on cocaine show paranoid and suicidal tendencies. It is nonirritant and as effective as cocaine as a local anaesthetic, but is much less toxic. Its disadvantages are that it is poorly absorbed from the mucous membranes and, therefore, has no topical use. Procaine is rapidly hydrolysed by esterases in the plasma and liver and is partly excreted in the urine, conjugated with glucuronic acid and glycine. Analgesia is complete within a few minutes and recovery occurs quickly within 2-3 hours, after spinal anaesthesia. The drug is recommended for topical use, nerve blocks, infiltration and epidural injection and for dental analgesia. It can be used in subjects allergic to procaine and other ester-type local anaesthetics. Lignocaine and prilocaine are solid bases but the combination of equal quantities (by weight) of the two agents results in an eutectic mixture. This means that the mixture has lower melting point than of either solid ingredient alone. The lignocaine/prilocaine mixture (either 2 or 7% of each) exists as oil with the melting point as 1800C. Applied topically under occlusive dressing 30- 60 mins prior to any procedure, it serves as an alternative to infiltration anaesthesia for procedures such as venipuncture, cannulation, skin graft harvesting or minor dermatological procedures. However, application to abraded skin and mucous membranes results in rapid absorption with systemic toxicity. Mepivacaine has N-methyl substituent in the place of the butyl group of bupivacaine. It is effective topically; its absorption from the vascular mucous membranes is very rapid and deaths have ocurred following its use in urethra and respiratory tract. Ropivacaine: this amide local anaesthetic agent, though less potent than bupivacaine, has been claimed to be less cardiotoxic. Benzocaine is poorly water soluble and is used topically as ointment, gel or liquid spray. Further, the drug has some inherent vasopressor activity and, therefore, does not require the addition of a vasopressor for infiltration anaesthesia. The concentrations in which various local anaesthetics are used are given in Table 16.
The capacity and calibre of the vagina is normal and it easily admits two fingers. Occasionally, the hymen is incompletely ruptured and the introitus inadequately dilated, but these findings are rare and their correction by plastic enlargement, though logical, does little to relieve the subsequent spasm since it is psychogenic rather than organic. There is some evidence that the mucous secretion contained in the cervical canal is extruded into the vagina during the orgasm. The seminal fluid is mainly deposited in the posterior fornix of the vagina, but it is possible that some of it is ejaculated directly into the cervical canal. It is also believed that the contractions of the uterus and the fallopian tubes during the female orgasm cause seminal fluid to be aspirated into the cavity of the uterus, and it is possible that this aspiration effect is responsible, in part at least, for the migration of spermatozoa upwards into the fallopian tubes. A more likely suggestion is that rhythmic contractions of the pelvic muscles direct the seminal ejaculate towards the cervix, where the propulsive power of the spermatozoa provides the forward momentum. The female orgasm is not essential for conception, and it is not uncommon to see women who have conceived without full consummation of the marriage and in whom the hymen is intact. In such cases the spermatozoa, having been deposited around the hymen, migrate through their own motility along the whole length of the vagina and uterus. Treatment the first essential of treatment is to win the confidence and cooperation of both husband and wife, interviewed separately. The interview demands great tact and experience, and is time-consuming, but if conducted correctly is most rewarding. Once the confidence of the couple is won over, the true cause of the trouble will usually be disclosed, and simple instruction in its rectification may often suffice. If the patient is obsessed with the idea that her genital tract is maldeveloped, she should be examined under an anaesthetic. The vagina is stretched to three fingers after which a large plastic dilator is inserted. When the patient recovers from the anaesthetic, this large dilator is removed and its visual presence demonstrates to her beyond argument that her vagina is of normal capacity. She is then instructed by demonstration to pass a slightly smaller dilator and is supplied with one to be introduced at will every day at home to gain enough confidence and overcome any unfounded fears. The regular passage of the dilator should convince her that there is no obstruction to coitus. A longitudinal incision is made in the midline through the lower third of the posterior vaginal wall and skin of the perineum. After undercutting the tissues on each side and dividing the superficial muscles of the perineum, the wound is closed by interrupted sutures so that the scar lies transversely. The incision should be made of a length such that the vaginal orifice subsequently admits three fingers. After this operation of plastic enlargement of the introitus, it is useful to pass a mediumsized plastic dilator daily, and the patient is supplied with one for use. Coitus should not be attempted until the perineotomy wound has healed soundly, usually in 3 or 4 weeks. Botulinum neurotoxin type A injection into levator ani muscle 4 weekly improves vaginismus. Vaginismus Vaginismus is regarded as hyperaesthesia which leads to spasm of the sphincter vagina and the levator ani muscles during attempted coitus or when an attempt is made to examine the patient vaginally. In primary vaginismus there is no organic lesion present, whereas in secondary vaginismus some obvious painful lesion in the region of the genital tract can be found on examination. In primary vaginismus, when the patient is being examined and an attempt is made to inspect the vulva by separating the labia, a muscle spasm is induced whereby the thighs are drawn together, the levator muscles become tonically contracted and the patient cries out and endeavours to push the medical attendant away from her. In secondary vaginismus, a minor degree of spasm is induced by painful local lesions such as small infected lacerations of the hymen, urethral caruncle, vulvitis, or a sequela of vaginal operations for the repair of prolapse when, as a result of the operation, the calibre of the introitus and the vagina is narrowed. The operation scar is naturally sensitive for some weeks after the repair, and premature attempts at coitus are painful. It is thus easy for organic dyspareunia to lead to a protective spasm in order to avoid the pain of coitus. The spasm is not unlike that seen in primary vaginismus, although it is never of the same degree.
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