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Rapid induction some- Uterine and skeletal muscle relaxation is similar times causes brief sympathetic stimulation and to halothane generic 200 mg viramune fast delivery treatment 5th finger fracture. Potentiation of neuromuscular tachycardia which may be risky in those with blockers is greater than that with halothane order viramune 200 mg visa medicine used during the civil war. Renal depression order 200mg viramune fast delivery medicine upset stomach, muscle relaxation, vasodilatation and and hepatic toxicity has not been encountered. It is a good desflurane can serve as a good alternative to maintenance anaesthetic, but not preferred for isoflurane for routine surgery as well, especially induction because of ether like odour which is prolonged operations. If closed circuit is used, not liked by conscious patients, especially soda lime should be fresh and well hydrated. It is an ultrashort acting thiobarbiturate, highly soluble in water yielding a very alkaline solution, which must be prepared freshly before injection. Its desflurane, it poses no problem in induction and undissociated form has high lipid solubility— is frequently selected for this purpose. However, as other less vascular motor functions are regained almost as quickly tissues (muscle, fat) gradually take up the drug, as with desflurane. Sevoflurane is suitable both blood concentration falls and it back diffuses for outpatient as well as inpatient surgery, from the brain: consciousness is regained in 6– induction as well as maintenance, but its high 10 min (t½ of distribution phase is 3 min). In India, are gradually filled up—lower doses produce only high-end hospitals are using it. Its ultimate Sevoflurane does not cause sympathetic disposal occurs mainly by hepatic metabolism stimulation and airway irritation even during rapid (elimination t½ is 8–12 hr), but this is irrelevant induction. The patient should not be allowed to leave precipitating propensity are similar to isoflurane. Painful bolized, but the amount of fluoride liberated is procedures should not be carried out under its safe for kidney and liver. However, it reacts with influence unless an opioid or N2O has been given; sodalime—not recommended for use in fully otherwise, the patient may struggle, shout and closed circuit. They are generally used Cardiovascular collapse may occur if hypovole- for induction because of rapidity of onset of mia, shock or sepsis are present. Anaesthesia is then usually maintained tachycardia occurs, but thiopentone does not by an inhalational agent. It is similar to thiopentone, 3 suffer, because there is greater decrease in times more potent, has a quicker and briefer (5–8 min) action. Propofol Currently, propofol has super- Thiopentone is a commonly used inducing seded thiopentone as an i. Unconscious- Adverse effects Laryngospasm occurs gene- ness after propofol injection occurs in 15–45 rally when respiratory secretions or other irri- sec and lasts 5–10 min. Propofol distributes tants are present, or when intubation is attempted rapidly (distribution t½ 2–4 min). This can be prevented t½ (100 min) is much shorter than that of by atropine premedication and administration of thiopentone due to rapid metabolism. Intermittent injection or continuous infusion Succinylcholine and thiopentone react chemi- of propofol is frequently used for total i. Shivering and delirium may occur during It lacks airway irritancy and is not likely to recovery. Postanaesthetic nausea and because residual impairment is less marked and vomiting are uncommon. Incidence of postoperative nausea It can precipitate acute intermittent porphyria and vomiting is low; patient acceptability is very in susceptible individuals, therefore contra- good. Baroreflex with psychiatric patients and for ‘narcoanalysis’ is suppressed; heart rate remains unchanged or of criminals; acts by knocking off guarding. They do not provoke depression which is more marked than with postoperative nausea or vomiting. It depression, but motor restlessness and rigidity is more distributes more gradually—awakening may be prominent as are pain on injection or nausea and vomiting on recovery. It is being preferred over supplementing anaesthesia as well as for diazepam for anaesthetic use: 1–2.

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Tetracyclines accumulate in tooth enamel and bone and are not recommended for use in children (or during pregnancy) because they cause discolouration of the teeth and stunt bone growth buy 200 mg viramune with amex medications used for migraines. Resistance to tetracyclines is common due to decreased accumulation in bacterial cells viramune 200mg on-line symptoms nicotine withdrawal. Because of this cheap viramune 200 mg free shipping symptoms non hodgkins lymphoma, broad-spectrum use of tetracyclines has declined and they are now used mainly to treat chlamydia infections, Lyme disease and acne. Adverse effects of tetracyclines include nausea, vomiting, diarrhoea and liver toxicity. People with myasthenia gravis or systemic lupus erythematosus (see Chapter 7) should not use tetracyclines because they can exacerbate these diseases. Erythromycin in particular is an alternative in individuals with penicillin hypersensitivity. Erythromycin has recently (November 2006) been added to the list of drugs that can be accessed and supplied by podiatrists registered with the Health Professions Council (see Chapter 14 for details of how the law applies to sale and supply of medicines by podiatrists). Resistance is a major problem with macrolides, due to reduced uptake into bacterial cells and alteration of macrolide binding proteins. Macrolides can cause drug interactions, through inactivation of liver enzymes, with antiarrhythmic drugs, anticoagulants, antipsychotic drugs, anxiolytics and antiepileptic drugs. Erythromycin in particular can increase the risk of myopathy if taken in combi- nation with lipid-lowering statins. Adverse effects of macrolides are nausea, vomiting, diarrhoea, deafness (with high doses but reversible) and jaundice. Because it is extremely toxic to bone marrow, its use is reserved for life-threatening infections where no other antibiotic is effective. Despite vaccination programmes in many parts of the world, tuberculosis remains the largest single cause of death by infectious disease, causing three million deaths 9. The problem is compounded by the emergence of resistant strains of the organism and the return of infection to parts of the world where the disease had been eradicated. Mycobacteria take a long time to duplicate themselves (18–24 hours compared with 30 minutes for Escherichia coli). This means it can take a long time to culture enough organisms for identification and there is a long period between infection and clinical manifestation of disease. Mycobacteria are unusual organisms in that the cell wall has several outer waxy lipid layers, which makes drug penetration very difficult. They do not take up the gram stain, but can be characterized by an acid-resistant stain. Mycobacteria are intracellular organ- isms and infect lung tissue mainly, but other tissues such as bones, joints and the brain can be infected. Treatment for tuberculosis is a long and difficult process, taking up to two years and requiring combinations of at least three different antibiotics. Drugs used to treat tuberculosis include isoniazid, rifampicin and pyrazinamide pri- marily with streptomycin and ethambutol as secondary drugs. Viruses are able to bind to cell membranes, penetrate and infect cells of other organisms. Viruses are intracellular parasites; they cannot replicate themselves without using the contents of the host cell to synthesize the cellular components necessary for their reproduction. This makes the development of effective antiviral drugs that do not damage healthy host cells very difficult. This was probably because the majority of viral infections are eliminated by the host’s immune system. As more is known about how viruses replicate inside cells and how they affect cell function, then no doubt more antiviral drugs will be developed. There may be reduced phosphorylation of the drug (for example with nucleoside analogues), alteration of viral enzyme targets (for example with reverse transcriptase inhibitors), or alteration of target channel protein (for example with amantadine). Use of the drug intravenously to treat systemic herpes can cause nausea and headache and possibly kidney damage. Adverse reactions can be severe so this drug is reserved for serious viral infections such as cytomegalovirus in immunocompromized patients. Zidovudine is a thymidine (a nucleoside) analogue and was the first drug introduced that inhibits reverse transcriptase.

It binds to β-tubulin and enhances Vincristine and vinblastine viramune 200 mg overnight delivery treatment 5th metacarpal fracture, though closely related its polymerization: a mechanism opposite to that chemically cheap 200 mg viramune amex medicine everyday therapy, have different spectrum of antitumour of vinca alkaloids viramune 200mg fast delivery symptoms 5 months pregnant. This Vincristine (oncovin) It is a rapidly acting stability results in inhibition of normal dynamic drug, very useful for inducing remission in child- reorganization of the microtubule network that hood acute lymphoblastic leukaemia, but is not is essential for interphase and mitotic functions. Other indications Abnormal arrays or ‘bundles’ of microtubules are are acute myeloid leukaemia, Hodgkin’s disease, produced throughout the cell cycle. Cytotoxic Wilms’ tumour, Ewing’s sarcoma, neuroblastoma action of paclitaxel emphasizes the importance and carcinoma lung. It also the approved indications of paclitaxel are causes ataxia, nerve palsies, autonomic dysfunction metastatic ovarian and breast carcinoma after (postural hypotension, paralytic ileus, urinary failure of first line chemotherapy and relapse retention) and seizures. Etoposide It is a semisynthetic derivative of Acute anaphylactoid reactions occur because of the cremophor podophyllotoxin, a plant glycoside. Pretreatment with dexamethasone, H1 and H2 mitotic inhibitor, but arrests cells in the G phase 2 antihistaminics is routinely used to suppress the reaction. Etoposide is used in testicular tumours, lung Docetaxel More potent congener of paclitaxel cancer, Hodgkin’s and other lymphomas, carci- with the same mechanism of action. Small cell cancer bioavailability is 50%; oral dose is double than lung, pancreatic, gastric and head/neck carcinomas i. Docetaxel is formulated in polysorbate medium Topotecan, Irinotecan are two semisynthetic which produces less acute hypersensitivity analogues of camptothecin, an antitumour reactions. Their a nitrogen mustard normustine, which has weak binding to this nuclear enzyme allows single strand estrogenic but no alkylating property. Combined with cisplatin, metabolism in liver into active as well as inactive it has been used in cervical cancer. Other adverse effects are pain normustine producing myelosuppression and abdomen, vomiting anorexia and diarrhoea. Dose limiting toxicity is Maximum action is exerted at S phase, but toxicity diarrhoea. Actinomycin D (Dactinomycin) It is a very potent antineoplastic drug, highly efficacious in Epirubicin this is a recently introduced Wilms’ tumour and childhood rhabdomyosarcoma. Epirubicin has resistant choriocarcinoma, Ewing’s sarcoma and been primarily used as a component of regimen metastatic testicular carcinoma. These are anthracycline antibiotics having anti- Mitoxantrone It is an anthracycline derivative tumour activity. However, utility of daunorubicin related to doxorubicin with lower cardiotoxicity, is limited to acute myeloid as well as lympho- probably because it does not produce quinone type blastic leukaemia (in which it is highly active), free radicals. Hydroxyurea It blocks the conversion of Though cardiomyopathy can occur, major toxicity ribonucleotides to deoxyribonucleotides by inhi- is marrow depression and mucosal inflammation. For induction in acute leukaemia 12 mg/ therapeutic value is in chronic myeloid leukaemia, m2/day for 5 days. It is also employed as a glycopeptide antibiotics having potent antitumour radiosensitizer before radiotherapy, and is a activity. It chelates copper or iron, produces first-line drug for sickle cell disease in adults. It is highly effective in testicular tumour and Myelosuppression is the major toxicity. Allergic and hypotensive reaction were found to be deficient in L-asparagine can occur after bleomycin injection. Further treatment may leukopenia, alopecia, or mucosal damage), but be given after a gap. Adverse effects of arsenic are nausea, it produces effects due to defective protein dizziness, malaise, fatigue, sensory disturbances, effusions, synthesis—hyperglycaemia, raised triglyceride breathlessness, hyperglycaemia, Q-T prolongation, A-V block. Tretinoin It is all trans-retinoic acid, a form of vit A acid Designing and development of drugs to attack (see Ch. Though, tretinoin alone can induce temporary remission available in India, are presented here.

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Thus purchase viramune 200mg without prescription symptoms 2 dpo, the balance between myocardial perfusion and oxygen de- mand (which is reduced with halothane) should be taken 40% N2O into account for patients with cardiac disease viramune 200mg free shipping symptoms xeroderma pigmentosum. In addition cheap viramune 200mg without a prescription treatment kennel cough, renal blood flow, filtration, and urine output decrease with the use of halothane. These changes also occur with other inhalational agents a b that reduce arterial blood pressure. The relaxation the effect of two concentrations of N2O on the alveolar is not adequate when muscle paralysis is a requirement tension of anesthetic with time. Occasionally frank tonic–clonic sei- metabolic factors, halothane and many of the halo- zures are observed. Consequently, other inhalational genated hydrocarbons undergo some biotransforma- agents are usually given to patients with preexisting tion. In the absence of oxygen, reductive Another concern associated with the use of enflu- intermediates of halothane metabolism may form and rane is its biotransformation, which leads to increased damage liver tissue. Following lengthy procedures in plicated in a controversial syndrome of halothane hep- healthy patients, fluoride may reach levels that result in atitis. This rare syndrome (1:35,000 anesthetics) is histo- a mild reduction in renal concentrating ability. The flurane should be used cautiously in patients with clini- likelihood of liver dysfunction increases with repeated cally significant renal disease. It has been suggested that Isoflurane (Forane) is a structural isomer of enflurane liver necrosis may be a hypersensitivity reaction, per- and produces similar pharmacological properties: some haps initiated by the reactive intermediates formed dur- analgesia, some neuromuscular blockade, and depressed ing halothane metabolism. In contrast, however, isoflurane is consid- use of halothane in patients with liver dysfunction that ered a particularly safe anesthetic in patients with isch- resulted from a previous exposure to the anesthetic. Also, blood pressure falls as a result of va- tional agent available, but its high solubility in tissues lim- sodilation, which preserves tissue blood flow. Its pharmacological causes transient and mild tachycardia by direct sympa- properties are similar to those of halothane with some thetic stimulation; this is particularly important in the notable exceptions. Furthermore, the metabolic tachycardia, so arterial blood pressure is better main- transformation of isoflurane is only one-tenth that of tained. Also, the oxidative metabolism of methoxyflurane enflurane, so fluoride production is quite low. Among results in the production of oxalic acid and fluoride con- the halogenated hydrocarbons, isoflurane is one of the centrations that approach the threshold of causing renal most popular, since it preserves cardiovascular stability tubular dysfunction. Desflurane Enflurane Desflurane (Suprane) shares most of the pharmacologi- Enflurane (Ethrane) depresses myocardial contractility cal properties of isoflurane. In contrast to and blood solubility compared with other halogenated halothane, it does not block sympathetic reflexes, and hydrocarbons, and its anesthetic partial pressure is thus therefore, its administration results in tachycardia. Recovery is similarly prompt However, the increased heart rate is not sufficient to op- when the patient is switched to room air or oxygen. In addition, enflurane from its rapid onset and prompt elimination from the sensitizes the myocardium to catecholamine-induced body by exhalation. A disadvantage is that desflurane ir- arrhythmias, although to a lesser extent than with ritates the respiratory tract; thus, it is not preferred for halothane. Enflurane depresses respiration through induction of anesthesia using an inhalational technique. Although Desflurane, like other halogenated hydrocarbon muscle relaxation is inadequate for many surgical proce- anesthetics, causes a decrease in blood pressure. The re- dures, the anesthetic enhances the action of neuromuscu- duced pressure occurs primarily as a consequence of lar blocking agents, thereby lowering the dose of the par- decreased vascular resistance, and since cardiac output alytic agent needed and minimizing side effects. N2O 25% pro- ity, which allows for rapid induction and emergence and duces the gas’s maximum analgesic effect. With this con- makes it useful for outpatient and ambulatory proce- centration, responses to painful surgical manipulations dures. It has the advantage of not being pungent, a char- are blocked as effectively as they would be with a thera- acteristic that permits a smooth inhalation induction, peutic dose of morphine. However, a concern for reflex-induced tachycar- the most common use of N2O is in combination with dia remains. It decreases the Sevoflurane undergoes hepatic biotransformation dosage requirement for the other anesthetics, thus lower- (about 3% of the inhaled dose), and it is somewhat de- ing their cardiovascular and respiratory toxicities.

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This dilutes the concentration of gases contraindication to its future use in that patient cheap viramune 200 mg mastercard treatment vitiligo. This effect is known as diffusion hypoxia discount 200 mg viramune with amex medicine 93 2264, and it is countered by the administration of 100% oxygen for 10 minutes discount 200 mg viramune treatment low blood pressure. There is evidence to suggest that prolonged exposure to Thus pressure can increase in the gut, lungs, middle ear and inhalational agents is hazardous to anaesthetists and other sinuses. There is a rapid increase in plasma concentration after admin- • Respiratory system – respiratory depression and a short istration of a bolus dose of an intravenous anaesthetic agent; this period of apnoea is common. Anaesthetic action depends on to laryngeal spasm if anaesthesia is light and there is the production of sufficient brain concentration of anaesthetic. The drug has to diffuse across the blood–brain barrier from arte- • Miscellaneous adverse effects – urticaria or anaphylactic shock rial blood, and this depends on a number of factors, including due to histamine release. Local tissue necrosis and protein binding of the agent, blood flow to the brain, degree of peripheral nerve injury can occur due to accidental ionization and lipid solubility of the drug, and the rate and vol- extravascular administration. Redistribution from blood to viscera is the main causes severe burning pain due to arterial constriction, and factor influencing recovery from anaesthesia following a single can lead to ischaemia and gangrene. Metabolism • Thiopental should be avoided or the dose reduced in is generally hepatic and elimination may take many hours. Recovery of consciousness occurs within five to Uses ten minutes after an intravenous bolus injection. The alkaline Propofol has superseded thiopental as an intravenous induc- solution is extremely irritant. The plasma t1/2β of the drug is tion agent in many centres, owing to its short duration of six hours, but the rapid course of action is explained by its action, anti-emetic effect and the rapid clear-headed recovery. It is rapidly metabolized in the liver and extra- lived anaesthesia results from the rapid fall (α phase) of the hepatic sites, and has no active metabolites. Its uses include: blood concentration (short t1/2α), which occurs due to the dis- tribution of drug into other tissues. When the blood concen- • Intravenous induction – propofol is the drug of choice for tration falls, the drug diffuses rapidly out of the brain. The insertion of a laryngeal mask, because it suppresses main early transfer is into the muscle. Relatively little of the drug enters fat initially because of its It is often used in conjunction with oxygen or oxygen- poor blood supply, but 30 minutes after injection the thiopen- enriched air, opioids and muscle relaxants. Maintainance recovery is slower than that following a single dose, of anaesthesia with thiopental is therefore unsafe, and its use accumulation is not a problem. The and in patients with raised intracranial pressure (in whom metabolites are excreted via the kidneys. Adverse effects Adverse effects • Cardiovascular system – propofol causes arterial • Central nervous system – many central functions are hypotension, mainly due to vasodilation although there is depressed, including respiratory and cardiovascular centres. It should be administered the sympathetic system is depressed to a greater extent particularly slowly and cautiously in patients with than the parasympathetic system, and this can result in hypovolaemia or cardiovascular compromise. Thiopental is not analgesic and at cause bradycardia, responsive to a muscarinic antagonist. If opioids are also administered, as with Intravenous induction agents other agents, the respiratory depression is more marked. Use and pharmacokinetics • Methohexitone – barbiturate similar to thiopental, less smooth induction, less irritant, may cause hiccup, tremor Ketamine is chemically related to phencyclidine (still used as and involuntary movements. It is a relatively safe anaesthetic from the • Ketamine – good analgesic, increases cardiac output viewpoint of acute cardiorespiratory effects since, unlike other and muscle tone. Due to unpleasant psychological effects intravenous anaesthetics, it is a respiratory and cardiac stimu- (e. It has been used for management of mass casualties or used intramuscularly, slow recovery, safer than other for anaesthesia of trapped patients to carry out amputations, agents in less experienced hands). It is used in shocked patients, because unlike other intra- venous anaesthetics it raises rather than lowers blood pressure. An intravenous dose produces anaesthesia within 30–60 seconds, which lasts for 10–15 minutes. There is a high incidence of hallucinations, nightmares and transient psychotic effects. Midazolam is a water-soluble benzodiazepine and useful Adverse effects intravenous sedative.

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