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For example allergy symptoms blisters generic flonase 50 mcg otc, sublingual nitroglycerin (see Chapter 27) is rapidly effective because it is nonionic, has high lipid solubility, and is not subject to the first-pass effect prior to reaching the heart and arterial system. Injection into a subcutaneous site can be done only with drugs that are not irritating to tissue; otherwise, severe pain, necrosis, and tissue sloughing may occur. The rate of absorption following subcutaneous injection of a drug often is sufficiently constant and slow to provide a sustained effect. Absorption of drugs implanted under the skin in a solid pellet form occurs slowly over a period of weeks or months; some hormones. Absorption of drugs in aqueous solution after intramuscular injection depends on the rate of blood flow to the injection site and can be relatively rapid. Absorption may be modulated to some extent by local heating, massage, or exercise. The rate is particularly slower for females after injection into the gluteus maximus, a feature attributed to the different distribution of subcutaneous fat in males and females and because fat is relatively poorly perfused. Slow, constant absorption from the intramuscular site results if the drug is injected in solution in oil or suspended in various other repository (depot) vehicles. In some instances, parenteral administration is essential for delivery of a drug in its active form, as in the case of monoclonal antibodies. Availability usually is more rapid, extensive, and predictable when a drug is given by injection; the effective dose can be delivered more accurately to a precise dose; this route is suitable for the loading dose of medications prior to initiation of oral maintenance dosing. The major routes of parenteral administration are intravenous, subcutaneous, and intramuscular. Absorption from subcutaneous and intramuscular sites occurs by simple diffusion along the gradient from drug depot to plasma. The rate is limited by the area of the absorbing capillary membranes and by the solubility of the substance in the interstitial fluid. Larger molecules, such as proteins, slowly gain access to the circulation by way of lymphatic channels. Drugs administered into the systemic circulation by any route, excluding the intra-arterial route, are subject to possible first-pass elimination in the lung prior to distribution to the rest of the body. Unfavorable reactions can occur because high concentrations of drug may be attained rapidly in plasma and tissues. There are therapeutic circumstances for which it is advisable to administer a drug by bolus injection. Gaseous and volatile drugs may be inhaled and absorbed through the pulmonary epithelium and mucous membranes of the respiratory tract. In addition, solutions of drugs can be atomized and the fine droplets in air (aerosol) inhaled. Advantages are the almost instantaneous absorption of a drug into the blood, avoidance of hepatic first-pass loss, and in the case of pulmonary disease, local application of the drug at the desired site of action (see Chapters 21 and 40), as in the use of inhaled nitric oxide for pulmonary hypertension in term and near-term infants and adults (see Chapter 31). Topically applied ophthalmic drugs are used primarily for their local effects (see Chapter 69). The use of drug-loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for direct delivery. Systemic absorption of drugs occurs much more readily through abraded, burned, or denuded skin. Toxic effects result from absorption through the skin of highly lipid-soluble substances. Absorption through the skin can be enhanced by suspending the drug in an oily vehicle and rubbing the resulting preparation into the skin. Hydration of the skin with an occlusive dressing may be used to facilitate absorption. For most drugs, the therapeutic range of plasma concentrations is limited; thus, the extent of binding and the unbound fraction are relatively constant. The extent of plasma protein binding also may be affected by disease-related factors. When changes in plasma protein binding occur in patients, unbound drug rapidly equilibrates throughout the body and only a transient significant change in unbound plasma concentration will occur. Thus, unbound plasma drug concentrations will exhibit significant changes only when either drug input or clearance of unbound drug occurs as a consequence of metabolism or active transport. Competition for plasma protein-binding sites may cause one drug to elevate the concentration of one bound less avidly. Binding of a drug to plasma proteins limits its concentration in tissues and at its site of action because only unbound drug is in equilibrium across membranes. Rectal Administration Approximately 50% of the drug that is absorbed from the rectum will bypass the liver, thereby reducing hepatic first-pass metabolism. However, rectal absorption can be irregular and incomplete, and certain drugs can cause irritation of the rectal mucosa. Recent advances in drug delivery include the use of biocompatible polymers and nanoparticles for drug delivery (Yohan and Chithrani, 2014). Two pharmaceutically equivalent drug products are considered to be bioequivalent when the rates and extents of bioavailability of the active ingredient in the two products are not significantly different under suitable and identical test conditions. Generic versus brand name prescribing is further discussed in connection with drug nomenclature and the choice of drug name in writing prescription orders (see Appendix I). Emergence from the anesthetic influence of this single dose of thiopental relies on redistribution, not on metabolism. Depletion of compartments will follow the same order as accumulation, as a function of their perfusion. Local destruction of the bone medulla also may result in reduced blood flow and prolongation of the reservoir effect as the toxic agent becomes sealed off from the circulation; this may further enhance the direct local damage to the bone. A vicious cycle results, whereby the greater the exposure to the toxic agent, the slower is its rate of elimination. The adsorption of drug onto the bone crystal surface and incorporation into the crystal lattice have therapeutic advantages for the treatment of osteoporosis. In obese persons, the fat content of the body may be as high as 50%, and even in lean individuals, fat constitutes 10% of body weight; hence, fat may serve as a reservoir for lipid-soluble drugs. Redistribution Bone the tetracycline antibiotics (and other divalent metal-ion chelating agents) and heavy metals may accumulate in bone by adsorption onto the bone crystal surface and eventual incorporation into the crystal lattice. Bone Termination of drug effect after withdrawal of a drug usually is by metabolism and excretion but also may result from redistribution of the drug from its site of action into other tissues or sites. Redistribution is a factor in terminating drug effect primarily when a highly lipid-soluble drug that acts on the brain or cardiovascular system is administered rapidly by intravenous injection or inhalation. Subsequently, the plasma and brain concentrations decrease as thiopental redistributes to other tissues, such as muscle and, finally, adipose tissue. The concentration of the drug in brain follows that of the plasma because there is little binding of the drug to brain constituents. Thus, both the onset and the termination of thiopental anesthesia are relatively rapid, and both are related directly to the concentration of drug in the brain. This approach can maximize the amount of the active species that reaches its site of action. For a number of therapeutic areas, clinical pharmacogenomics, the study of the impact of genetic variations or genotypes of individuals on their drug response or drug metabolism, allows for improved treatment of individuals or groups (Ramamoorthy et al. Excretory organs, the lung excluded, eliminate polar compounds more efficiently than substances with high lipid solubility. Thus, lipid-soluble drugs are not readily eliminated until they are metabolized to more polar compounds. Excretion of drugs in breast milk is important not because of the amounts eliminated (which are small) but because the excreted drugs may affect the nursing infant (also small, and with poorly developed capacity to metabolize xenobiotics). The metabolism of drugs and other xenobiotics into more hydrophilic metabolites is essential for their renal elimination from the body, as well as for termination of their biological and pharmacological activity. From the point of view of pharmacokinetics, the following are the three essential aspects of drug metabolism: First-order kinetics. Zero-order kinetics can also occur at high (toxic) concentrations as drug-metabolizing capacity becomes saturated.

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Many of these are multidrug resistant-not responsive to ampicillin and cotrimoxazole as well allergy testing las vegas buy cheap flonase online. However, few recent reports from certain parts of India indicate return of sensitivity to chloramphenicol. Being orally active and inexpensive, it may be used only if the local strain is known to be sensitive and responsive clinically. Bactericidal action is required to eradicate carrier state, because in this state, host defence mechanisms do not operate against these pathogenic bacteria; as if they were commensals. As second choice drug (a) to tetracyclines for brucellosis and rickettsial infections, especially in young children and pregnant women in whom tetracyclines are contraindicated. Because of risk of serious (though rare) bone marrow aplasia: (a) Never use chloramphenicol for minor infections or those of undefined etiology. Urinary tract infections Use of chloramphenicol is improper when safer drugs are available. It should be used only when kidney substance is involved and the organism is found to be sensitive only to this drug. Topical use on skin or other areas is not recommended because of risk of sensitization. She also suffers lower backache and feels deep pelvic pain during intercourse, which she has irregularly, because her husband works in the city and visits her off and on. Vaginal examination reveals mucopurulent discharge from the cervical canal and pelvic tenderness, but there is no pelvic mass or abscess. She expresses inability to get any investigations done, as she is poor and has to return to her village. A provisional diagnosis of chlamydial nonspecific endocervicitis is made, with possibility of gonococcal infection, concurrently or alone. Unlike penicillin, which was a chance discovery, aminoglycosides are products of deliberate search for drugs effective against gram-negative bacteria. Streptomycin was the first member discovered in 1944 by Waksman and his colleagues. All aminoglycosides are produced by soil actinomycetes and have many common properties (see box). Systemic aminoglycosides Streptomycin Amikacin Gentamicin Sisomicin Kanamycin Netilmicin Tobramycin Paromomycin Topical aminoglycosides Neomycin Framycetin Common properties of aminoglycoside antibiotics 1. All are used as sulfate salts, which are highly water soluble; solutions are stable for months. All are active primarily against aerobic gram-negative bacilli and do not inhibit anaerobes. They diffuse across the outer coat of gram-negative bacteria through porin channels. Entry from the periplasmic space across the cytoplasmic membrane is carrier mediated which is linked to the electron transport chain. These processes are inactivated under anaerobic conditions; anaerobes are not sensitive and facultative anaerobes are more resistant when O2 supply is deficient. Penetration is also favoured by high pH; aminoglycosides are ~20 times more active in alkaline than in acidic medium. Inhibitors of bacterial cell wall (-lactams, vancomycin) enhance entry of aminoglycosides and exhibit synergism. Once inside the bacterial cell, streptomycin binds to 30S ribosomes, but other aminoglycosides bind to additional sites on 50S subunit, as well as to 30S-50S interface. Different aminoglycosides cause misreading at different levels depending upon their selective affinity for specific ribosomal proteins. The cidal action of these drugs appears to be based on secondary changes in the integrity of bacterial cell membrane, because other antibiotics which inhibit protein synthesis (tetracyclines, chloramphenicol, erythromycin) are only static. After exposure to aminoglycosides, sensitive bacteria become more permeable; ions, amino acids and even proteins leak out followed by cell death. This probably results from incorporation of the defective proteins into the cell membrane. The conjugated aminoglycosides do not bind to the target ribosomes and are incapable of enhancing active transport like the unaltered drug. Nosocomial microbes have become rich in such plasmids, some of which encode for multidrug resistance. This is the most important mechanism of development of resistance to aminoglycosides. Thus, cross resistance was found between gentamicin and tobramycin or netilmicin, but not between these and streptomycin. Many nosocomial gram-negative bacilli resistant to gentamicin/tobramycin respond to amikacin. In some Pseudomonas which develop resistance, the antibiotic induced 2nd phase active transport has been found to be deficient. Ototoxicity this is the most important dose and duration of treatment related adverse effect. The vestibular or the cochlear part may be primarily affected by a particular aminoglycoside. These drugs are concentrated in the labyrinthine fluid and are slowly removed from it when the plasma concentration falls. Ototoxicity is greater when plasma concentration of the drug is persistently high and above a threshold value. For gentamicin this is estimated to be ~ 2 g/ml; if the trough level is above this value, vestibular damage becomes concentration dependent. It is recommended that dosing of gentamicin should be such that the measured trough plasma concentration is < 1 g/ml to avoid toxicity. The vestibular/cochlear sensory cells and hairs undergo concentration dependent destructive changes. Aminoglycoside ear drops can cause ototoxicity when instilled in patients with perforated eardrum; are contraindicated in them. Cochlear damage It starts from the base and spreads to the apex; hearing loss affects the high frequency sound first, then progressively encompasses the lower frequencies. No regeneration of the sensory cells occurs; auditory nerve fibres degenerate in a retrograde manner-deafness is permanent. Initially, the cochlear toxicity is asymptomatic and can be detected only by audiometry. Vestibular damage Headache is usually first to appear, followed by nausea, vomiting, dizziness, nystagmus, vertigo and ataxia. When the drug is stopped at this stage, it passes into a chronic phase lasting 6 to 10 weeks in which the patient is asymptomatic while in bed and has difficulty only during walking. Permanency of changes depends on the extent of initial damage and the age of the patient (elderly have poor recovery). Nephrotoxicity It manifests as tubular damage resulting in loss of urinary concentrating power, low g. Aminoglycosides attain high concentration in the renal cortex (proximal tubules) and toxicity is related to the total amount of the drug received by the patient. However, in patients with normal renal function, single daily dosing regimen appears to cause lesser nephrotoxicity than the conventional thrice daily dosing. Provided the drug is promptly discontinued renal damage caused by aminoglycosides is totally reversible. An important implication of aminoglycosideinduced nephrotoxicity is reduced clearance of the antibiotic resulting in higher and more persistent blood levels causing enhanced ototoxicity.

Diseases

• Leukomalacia
• Bacillus cereus infection
• Inborn renal aminoaciduria
• Heart aneurysm
• Thoracopelvic dysostosis
• Dysgerminoma
• Nance Horan syndrome
• Aase Smith syndrome

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Mumps virus vaccine live attenuated It is prepared from mumps virus grown in cell culture of chick embryo allergy treatment in homeopathy buy flonase 50mcg on line. Clinical disease may occur if the vaccine is given after exposure to natural mumps. Malnourished, chronically ill and tuberculous children must be protected to minimize the risk of serious complications of natural measles. It should be given with caution to children with history of febrile convulsions or parental history of epilepsy. It is used especially in girls from 1 yr age to puberty-for immunization against German measles; mostly as combined A single dose injected s. Mild fever, rash, enlargement of cervical/occipital lymph nodes and parotid glands and local induration may occur after ~5 days. It is absolutely contraindicated during pregnancy; adult female vaccinees should not conceive for at least 2 months. A single dose induces antibody response in > 98% children and affords protection for 10 years. Tetanus toxoid It is formaline treated exotoxin of tetanus bacilli; indicated for routine immunization in all children and adults. The adsorbed toxoid is superior-induces higher antibody titers and more prolonged immunity. In non-immunized or inadequately immunized individuals the toxoid should be given after any injury likely to introduce tetanus bacilli. Concomitant administration of chloramphenicol is avoided, as it may interfere with antibody response. Diphtheria toxoid adsorbed It is modified diphtheria exotoxin adsorbed onto aluminium hydroxide. It is used in children above 5 years and in younger children in place of triple antigen when pertussis vaccine is contraindicated. Pentavalent vaccine It contains toxoids of tetanus and diphtheria along with pertussis vaccine, hepatitis B vaccine and Haemophilus influenzae type b (Hib) vaccine. Used in place to triple antigen for primary immunization of infants, it affords protection against two additional common infections, and reduces the total number of injections that the infant receives for protection against these 5 infections. Pentavalent vaccine has been used in many countries, and now Government of India is introducing it in a phased manner in its universal immunization programme for infants and children. However, recently few infant deaths have been reported, though the relationship between these and the vaccine is not clear. At 10 years At 16 years It is the preparation of choice for primary active immunization against the 3 diseases in children below 5 years age. A positive test contraindicates administration but a negative test does not completely rule out systemic sensitivity. These may be nonspecific (normal) or specific (hyperimmune) against a particular antigen. However, large doses and repeated injections do increase risk; adrenaline should be available. It is especially valuable in agammaglobulinemia, premature infants and in patients of leukemia or those undergoing immunosuppression. It can augment the response to antibiotics in debilitated patients with bacterial infections. Tetanus (a) Tetanus immune globulin (human) It is indicated for prophylaxis in non-immunized persons receiving a contaminated wound who are at high risk of developing tetanus. If tetanus toxoid is given at the same time (but at a different site), development of primary immune response to the toxoid is not interfered with. It has also been used for the treatment of clinical tetanus, but the efficacy is variable. It is indicated promptly after suspected exposure and is given simultaneously with rabies vaccine to nonimmunized individuals. In case of viper bite some serum should also be infiltrated around the site to prevent venom induced gangrene. The antitoxin neutralizes the exotoxin released at the site of Allergic reactions, including anaphylactic shock, to the serum are possible. When time permits, sensitivity test should be done; otherwise adrenaline may be injected s. Chapter 69 Drug Interactions Drug interaction refers to modification of response to one drug by another when they are administered simultaneously or in quick succession. The possibility of drug interaction arises whenever a patient concurrently receives more than one drug, and the chances increase with the number of drugs taken. More commonly, multiple drugs are used to treat a patient who is suffering from two or more diseases at the same time. The chances of unintended/adverse drug interactions are greater in this later situation, because an assortment of different drugs may be administered to a patient depending on his/her diseases/symptoms. Several drug interactions are desirable and deliberately employed in therapeutics. These are well-recognized interactions and do not pose any undue risk to the patient. The focus of attention in this chapter are drug interactions which may interfere with the therapeutic outcome or be responsible for adverse effects, or may even be fatal (bleeding due to excessive anticoagulant action). More importantly, a large section of patients may be receiving one or several drugs for their chronic medical conditions like hypertension, diabetes, arthritis, etc. The physician may prescribe certain drugs which may interact with those already being taken by the patient and result in adverse consequences. It is, therefore, imperative for the doctor to elicit a detailed drug history of the patient and record all the medication that he/she is currently on. The list of potential adverse drug interactions is already quite long and constantly growing. It is practically impossible for anyone to know/remember all possible drug interactions. Fortunately, the clinically important and common drug interactions that may be encountered in routine practice are relatively few. More exhaustive Regular medication drugs (Likely to be involved in drug interactions) 1. Certain types of drugs (see box) can be identified that are most likely to be involved in clinically important drug interactions. The physician may take special care and pay attention to the possibility of drug interactions when the patient is receiving one or more of such medications, or when the doctor intends to prescribe any of such drugs. Types of drugs most likely to be involved in clinically important drug interactions Drugs with narrow safety margin. In certain cases, however, the mechanisms are complex and may not be well understood. Few interactions take place even outside the body when drug solutions are mixed before administration. Pharmacokinetic interactions these interactions alter the concentration of the object drug at its site of action (and consequently the intensity of response) by affecting its absorption, distribution, metabolism or excretion. Absorption Absorption of an orally administered drug can be affected by other concurrently ingested drugs. This is mostly due to formation of insoluble and poorly absorbed complexes in the gut lumen, as occurs between tetracyclines and calcium/iron salts, antacids or sucralfate.

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It has high lipidsolubility; distributes more in tissues than in blood after spinal/epidural injection allergy rhinitis treatment buy flonase 50mcg online. Therefore, it is less likely to reach the foetus (when used during labour) to produce neonatal depression. Ropivacaine A newer bupivacaine congener, equally long acting but less cardiotoxic. It blocks A and C fibres (involved in pain transmission) more completely than A fibres which control motor function. Though equieffective concentrations of ropivacaine are higher than those of bupivacaine, a greater degree of separation between sensory and motor block has been obtained with epidural ropivacaine. Continuous epidural ropivacaine is being used for relief of postoperative and labour pain. It is used as a surface anaesthetic on less delicate mucous membranes (anal canal). Use for spinal anaesthesia of long duration has declined after the availability of bupivacaine. They are used as lozenges for stomatitis, sore throat; as dusting powder/ointment on wounds/ulcerated surfaces and as suppository for anorectal lesions. Oxethazaine A potent topical anaesthetic, unique in ionizing to a very small extent even at low pH values. It is, therefore, effective in anaesthetising gastric mucosa despite acidity of the medium. Swallowed along with antacids it affords symptomatic relief in gastritis, drug induced gastric irritation, gastroesophageal reflux and heartburn of pregnancy. Surface anaesthesia It is produced by topical application of a surface anaesthetic to mucous membranes and abraded skin. Only the superficial layer is anaesthetised and there is no loss of motor function. Addition of Adr does not affect duration of topical anaesthesia, but phenylephrine can cause mucosal vasoconstriction and prolong topical anaesthesia. The sites and purposes for which surface anaesthesia is used are given in Table 26. Onset of action is almost immediate and duration is shorter than that after nerve block. The area of resulting anaesthesia is still larger compared to the amount of drug used. The latency of anaesthesia depends on the drug and the area to be covered by diffusion. Frequently performed nerve blocks are-lingual, intercostal, ulnar, sciatic, femoral, brachial plexus, trigeminal, facial, phrenic, etc. The primary purpose of nerve block anaesthesia is to abolish pain and other sensations. The accompanying motor paralysis may be advantageous by providing muscle relaxation during surgery, as well as disadvantageous if it interferes with breathing, ability to walk after the operation, or participation of the patient in labour or produces postural hypotension. The primary site of action is the nerve roots in the cauda equina rather than the spinal cord. The level of anaesthesia depends on the volume and speed of injection, specific gravity of drug solution and posture of the patient. The level of anaesthesia does not change with change of posture (becomes fixed) after 10 min. Since autonomic preganglionic fibres are more sensitive and somatic motor fibres less sensitive than somatic sensory fibres, the level of sympathetic block is about 2 segments higher and the level of motor paralysis about 2 segments lower than the level of cutaneous analgesia. The duration of spinal anaesthesia depends on the drug used and its concentration. Adr may be enhancing spinal anaesthesia by reducing spinal cord blood flow or by its own analgesic effect exerted through spinal 2 adrenoceptors (intrathecal clonidine, an 2 agonist, produces spinal analgesia by itself). Women during late pregnancy require less drug for spinal anaesthesia, because inferior vena cava compression leads to engorgement of the vertebral system and a decrease in the capacity of subarachnoid space. Spinal anaesthesia is used for operations on the lower limbs, pelvis, lower abdomen. Respiratory paralysis with proper care, this is rare; intercostal muscles may be paralysed, but diaphragm (supplied by phrenic nerve) maintains breathing. Hypotension and ischaemia of respiratory centre is more frequently the cause of respiratory failure than diffusion of the anaesthetic to higher centres. Due to paralysis of external abdominal and intercostal muscles, coughing and expectoration becomes less effective. Paralysis of skeletal muscles of lower limb is another factor reducing venous return. Sympathomimetics, especially those with prominent constrictor effect on veins (ephedrine, mephentermine) effectively prevent and counteract hypotension. Cauda equina syndrome is a rare neurological complication resulting in prolonged loss of control over bladder and bowel sphincters. It may be due to traumatic damage to nerve roots or chronic arachnoiditis caused by inadvertent introduction of the antiseptic or particulate matter in the subarachnoid space. Septic meningitis this may occur due to infection introduced during lumbar puncture. Nausea and vomiting after abdominal operations is due to reflexes triggered by traction on abdominal viscera. Epidural anaesthesia the spinal dural space is filled with semiliquid fat through which nerve roots travel. Epidural anaesthesia can be divided into 3 categories depending on the site of injection. The epidural space in this region is relatively narrow, smaller volume of drug is Contraindications to spinal anaesthesia Hypotension and hypovolemia. Onset is slower and duration of anaesthesia is longer with bupivacaine and action of both the drugs is prolonged by addition of adrenaline. Technically epidural anaesthesia is more difficult than spinal anaesthesia and relatively larger volumes of drug are needed. Cardiovascular complications are similar to that after spinal anaesthesia, but headache and neurological complications are less likely, because intrathecal space is not entered. This is especially valuable for obstetric purposes (mother can participate in labour without feeling pain) and for postoperative pain relief. The limb is first elevated to ensure venous drainage by gravity and then tightly wrapped in an elastic bandage for maximal exsanguination. Obstructing the blood supply of lower limb is more difficult and larger volume of anaesthetic is needed. There is no cephalopelvic disproportion or any other contraindication to normal vaginal delivery. If so, which type of regional anaesthesia with which drug would be most suitable for her The cardinal features of general anaesthesia are: Loss of all sensation, especially pain Sleep (unconsciousness) and amnesia Immobility and muscle relaxation Abolition of somatic and autonomic reflexes. In the modern practice of balanced anaesthesia, these modalities are achieved by using combination of inhaled and i. History Before the middle of 19th century a number of agents like alcohol, opium, cannabis, or even concussion and asphyxia were used to obtund surgical pain, but operations were horrible ordeals. Horace Wells, a dentist, picked up the idea of using nitrous oxide (N2O) from a demonstration of laughing gas in 1844. However, he often failed to relieve dental pain completely and the use of N2O had to wait till other advances were made. Morton, a dentist and medical student at Boston, after experimenting on animals, gave a demonstration of ether anaesthesia in 1846, and it soon became very popular. Chloroform was used by Simpson in Britain for obstetrical purpose in 1847, and despite its toxic potential, it became a very popular surgical anaesthetic. Cyclopropane was introduced in 1929, but the new generation of anaesthetics was heralded by halothane in 1956. Not only different anaesthetics appear to act by different molecular mechanisms, they also may exhibit stereospecific effects, and that various components of the anaesthetic state may involve action at discrete loci in the cerebrospinal axis.

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Maximum synergism is seen when the organism is sensitive to both the components allergy eye drops contacts purchase flonase 50mcg line, but even when it is moderately resistant to one component, the action of the other may be enhanced. This ratio is obtained in the plasma when the two are given in a dose ratio of 5: 1, because trimethoprim enters many tissues, has a larger volume of distribution than sulfamethoxazole and attains lower plasma concentration. Trimethoprim adequately crosses blood-brain barrier and placenta, while sulfamethoxazole has a poorer entry. Moreover, trimethoprim is more rapidly absorbed than sulfamethoxazole-concentration ratios may vary with time. Spectrum of action Antibacterial spectra of trimethoprim and sulfonamides overlap considerably. Additional organisms covered by the combination are-Salmonella typhi, Serratia, Klebsiella, Enterobacter, Yersinia enterocolitica, Pneumocystis jiroveci and many sulfonamide-resistant strains of Staph. Resistance to the combination has been slow to develop compared to either drug alone, but widespread use of the combination over a long period has resulted in reduced responsiveness of over 30% originally sensitive strains. Adverse effects All adverse effects seen with sulfonamides can be produced by cotrimoxazole. Cotrimoxazole is an alternative to penicillin for protecting agranulocytosis patients and for treating respiratory or other infections in them. Intensive parenteral cotrimoxazole therapy has been used successfully in septicaemias, but other drugs are more commonly employed now. Uses Though cotrimoxazole is still used, its popularity in the treatment of systemic infections has declined. Single dose therapy with 4 tablets of cotrimoxazole has been used successfully for acute cystitis. Cotrimoxazole is specially valuable for chronic or recurrent cases or in prostatitis, because trimethoprim is concentrated in prostate. Respiratory tract infections Both upper and lower respiratory tract infections, including chronic bronchitis and facio-maxillary infections, otitis media caused by gram positive cocci and H. Bacterial diarrhoeas and dysentery Cotrimoxazole may be used for severe and invasive infections by E. Though response rate is lower than previously, and fluoroquinolones are more commonly used, it is still a valuable alternative for empirical therapy of infective diarrhoea. Cotrimoxazole has prophylactic as well as therapeutic value, but high doses are needed. The first member Nalidixic acid introduced in mid-1960s had usefulness limited to urinary and g. A breakthrough was achieved in the early 1980s by fluorination of the quinolone structure at position 6 and introduction of a piperazine substitution at position 7 resulting in derivatives called fluoroquinolones with high potency, expanded spectrum, slow development of resistance, better tissue penetration and good tolerability. Nalidixic acid is absorbed orally, highly plasma protein bound and partly metabolized in liver: one of the metabolites is active. Most important toxicity is neurological-headache, drowsiness, vertigo, visual disturbances, occasionally seizures (especially in children). Nalidixic acid is primarily used as a urinary antiseptic, generally as a second line drug in recurrent cases or on the basis of sensitivity reports. This is necessary to prevent excessive positive supercoiling of the strands when they separate to permit replication or transcription. Mechanism of resistance Because of the unique mechanism of action, plasmid mediated transferable resistance is less likely. However, increasing resistance has been reported among Salmonella, Pseudomonas, staphylococci, gonococci and pneumococci. Pharmacokinetics Ciprofloxacin is rapidly absorbed orally, but food delays absorption, and first pass metabolism occurs. It is excreted primarily in urine, both by glomerular filtration and tubular secretion. Adverse effects Ciprofloxacin has good safety record: side effects occur in ~10% patients, but are generally mild; withdrawal is needed only in 1. Risk of tendon damage is higher in patients above 60 years of age and in those receiving corticosteroids. Notable resistant bacteria are: Bacteroides fragilis, Clostridia, anaerobic cocci. However, under pressing situations like Pseudomonas pneumonia in cystic fibrosis and multi-resistant typhoid, ciprofloxacin has been administered to millions of children in India and elsewhere. Though a few cases of joint pain and swelling have been reported, cartilage damage has not occurred. Urinary tract infections: High cure rates, even in complicated cases or those with indwelling catheters/prostatitis, have been achieved. Bacterial gastroenteritis: Currently, it is the most commonly used drug for empirical therapy of diarrhoea. Typhoid: Ciprofloxacin is one of the first choice drugs in typhoid fever since chloramphenicol, ampicillin and cotrimoxazole have become unreliable due to development of resistance. Because of wide-spectrum bactericidal activity, oral efficacy and good tolerability, it is being extensively employed for empirical therapy of any infection, but should not be used for minor cases or where grampositive organisms and/or anaerobes are primarily causative. This has been found to achieve 92% eradication rate compared to 50% by ampicillin. Bone, soft tissue, gynaecological and wound infections: caused by resistant Staph. Used along with clindamycin/ metronidazole (to cover anaerobes) it is a good drug for diabetic foot. Respiratory infections: Ciprofloxacin should not be used as the primary drug because pneumococci and streptococci have low and variable susceptibility. Cefoperazone and cefotaxime are the other third generation cephalosporins used in typhoid. It is seldom used, only in case the local strain is known to be sensitive and clinical experience supports its use. Gram-negative septicaemias: Parenteral ciprofloxacin may be combined with a third generation cephalosporin or an aminoglycoside. Tuberculosis It is a second line drug which can be used as a component of combination chemotherapy against multidrug resistant tuberculosis. It is also good for bacterial diarrhoeas, because high concentrations are present in the gut, and anaerobic flora of the gut is not disturbed. Dose of pefloxacin needs to be reduced in liver disease, but not in renal insufficiency. It is an alternative drug for nonspecific urethritis, cervicitis and atypical pneumonia caused by Chlamydia trachomatis. Ofloxacin is relatively lipid soluble; oral bioavailability is high, and higher plasma concentrations are attained. It is excreted largely unchanged in urine; dose needs to be reduced in renal failure. Ofloxacin is comparable to ciprofloxacin in the therapy of systemic and mixed infections. Good activity against Chlamydia and Mycoplasma has been Levofloxacin It is the active levo(s) isomer of ofloxacin having improved activity against Strep. It is mainly excreted unchanged, and a single daily dose is sufficient because of slower elimination and higher potency. Theophylline, warfarin, cyclosporine and zidovudine pharmacokinetics has been found to remain unchanged during levofloxacin treatment. The primary indication of levofloxacin is community acquired pneumonia and exacerbations of chronic bronchitis in which upto 90% cure rate has been obtained.

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Risk reduction is greatest in high risk subjects and protection is lost if > 3 drinks are consumed daily allergy medicine zoloft discount flonase 50 mcg with mastercard. However, it is considered inapproptiate to advise nondrinkers to start drinking on this account, since other adverse consequences may more than nullify this benefit. Megaloblastic anaemia occurring in chronic alcoholism is due to interference with folate metabolism. It does produce a sense of warmth due to cutaneous and gastric vasodilatation, but heat loss is actually increased in cold surroundings. They irritate buccal and pharyngeal mucosa which may transiently stimulate respiration reflexly. However, it is better not to depend on this, because the direct action of alcohol on respiratory centre is only a depressant one. Chronic alcoholism can produce impotence, testicular atrophy, gynaecomastia and infertility in both men and women. Endocrine effects Moderate amounts of alcohol increase Adr release which can cause hyperglycaemia and other sympathetic effects. However, acute intoxication is often associated with hypoglycaemia and depletion of hepatic glycogen, because gluconeogenesis is inhibited. Glucagon, thus fails to reverse it and glucose must be given to counteract hypoglycaemia. Absorption of alcohol from skin of adults is minimal but may be significant in infants given alcohol sponges. Excretion of alcohol occurs through kidney and lungs, but neither is quantitatively significant. The subject blows in a balloon and alcohol is measured by portable breath analyser. Individuals taking a sulfonylurea, cefoperazone, or metronidazole have experienced bizarre, somewhat disulfiram-like reactions when they consume alcohol. Metabolism of tolbutamide, phenytoin and some other drugs is similarly affected by acute and chronic alcohol intake. Hypoglycaemic action of insulin and sulfonylureas is enhanced by alcohol ingestion. However, it spares carbohydrates and fats as energy source, so that regular intake can contribute to obesity. Those who consume substantial part of their caloric intake as alcohol, often suffer from nutritional deficiencies. Unstable personalities: they are likely to abuse it and become excessive drinkers. Heavy drinking during pregnancy, in addition, increases the incidence of miscarriage, stillbirths and low birth-weight babies. Guidelines for safe drinking Physicians are often asked to advise on safe ways of drinking. Various official agencies, physician organizations and alcoholism experts have putforth guidelines in this regard, but they are not uniform. Side effects of moderate drinking Nausea, vomiting, flushing, hangover, traffic accidents. Acute alcoholic intoxication Unawareness, unresponsiveness, stupor, hypotension, gastritis, hypoglycaemia, respiratory depression, collapse, coma and death. Treatment: Gastric lavage is helpful only when the patient is brought soon after ingesting alcohol, which is rare. Since most patients are disoriented or comatose, the first priority is to maintain patent airway and prevent aspiration of vomitus. Tracheal intubation and positive pressure respiration may be needed if it is markedly depressed. Most patients will recover with supportive treatment, maintenance of fluid and electrolyte balance and correction of hypoglycaemia by glucose infusion till alcohol is metabolized. Chronic alcoholism On chronic intake, tolerance develops to subjective and behavioral effects of alcohol, but is generally of a low degree. It is both pharmacokinetic (reduced rate of absorption due to gastritis and faster metabolism due to enzyme induction) and cellular tolerance. It is manifested in alcohol-seeking behaviour, and the priority that the subject accords to obtaining and consuming alcohol over other needs, or the extent to which he will go for maintaining alcohol intake. Recent studies have confirmed that a genetic basis contributes to progression from social drinking to alcoholism in about 50% individuals. Diverse feelings and behaviours are provoked by alcohol in different individuals and in the same individual on different occasions. Alcohol can make people happy as well as sad, curtious as well as mean, talkative as well as silent, friendly as well as hostile. All this cannot be explained on the basis of pharmacological actions of alcohol alone. Attitudes, beliefs, peer groups, social setting and learned experiences all have a bearing. Alcohol is said to produce good mood, sense of wellbeing, self confidence, sociability, etc. In some societies, alcoholic beverages have become an acceptable form of extending courtesy and of entertainment. To the young, drinking may be a symbol of rebellion against the oppressive older generation and rejection of the values of the establishment. Incidence of oropharyngeal, esophageal and hepatic malignancy and respiratory infections is high; immune function is depressed. Withdrawal syndrome When a physically dependent subject stops drinking, withdrawal syndrome appears within a day. Its severity depends on the duration and quantity of alcohol consumed by the subject. It consists of anxiety, sweating, techycardia, tremor, impairment of sleep, confusion, hallucinations, delirium tremens, convulsions and collapse. Treatment Psychological and medical supportive measures are needed during withdrawal. Naltrexone: Several studies have demonstrated involvement of opioid system in the pleasurable reinforcing effects of alcohol through dopamine mediated reward function. The post-addict treated with the long-acting opioid antagonist naltrexone (see Ch. It reduced alcohol craving, number of drinking days and chances of resumed heavy drinking. Naltrexone is approved for use as adjuvant in comprehensive treatment programmes for alcohol dependent subjects and is being used in India at most deaddiction centres, after the individual has undergone withdrawal and is motivated. In conjunction with social and motivational therapy, it has been found to reduce relapse of the drinking behaviour. Heavy drinking is often associated with nutritional deficiencies, because food is neglected and malabsorption may occur. Astringent action of alcohol is utilized in antiperspirant and aftershave lotions. Alcohol in the form of whiskey or brandy may benefit by causing vasodilatation of blanched mucosae; but further exposure after taking alcohol may be deleterious because alcohol increases heat loss due to cutaneous vasodilatation. Aldehyde dehydrogenase inhibitor Disulfiram It inhibits the enzyme aldehyde dehydrogenase. When alcohol is ingested after taking disulfiram, the concentration of acetaldehyde in tissues and blood rises and a number of highly distressing symptoms (aldehyde syndrome) are produced promptly. These are-flushing, burning sensation, throbbing headache, perspiration, uneasiness, tightness in chest, dizziness, vomiting, visual disturbances, mental confusion, postural fainting and circulatory collapse. Because of risk of severe reaction, disulfiram is to be used with great caution, only in well-motivated subjects. Disulfiram aversion therapy is indicated in abstinent subjects who sincerely desire to leave the habit. After making sure that the subject has not taken alcohol in the past 12 hours, disufiram is given at a dose of 500 mg/day for one week followed by 250 mg daily.

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Moreover milk allergy symptoms in 3 year old generic 50mcg flonase, blood culture is not necessarily positive in all cases of typhoid fever. The most appropriate antibiotic is ceftriaxone (or a similar 3rd generation cephalosporin like cefoperazone, cefotaxime), becuase it produces the fastest and surest response. The daily dose for this boy would be (75 mg/kg x 25 kg) = 1875 mg or rounded off to 2. In case of typhoid fever, a single antibiotic is sufficient, since addition of another antibiotic has not been found to hasten or improve the response. The most appropriate drugs and regimens for treating chlamydial endocervicitis are: Azithromycin 1. Both these regimens are adequate to treat uncomplicated gonococcal infection as well as concurrent chlamydial and gonococcal infection. While azithromycin has the advantage of single dose treatment, doxycycline needs twice daily dosing for one week, but is cheaper. Other first choice antibiotics like amoxicillin and ceftriaxone for gonorrhoea are not effective against chlamydia. For a patient with creatinine clearance value of 50 ml/min, the dose has to be reduced to 50%, or 2 mg/kg/day. With renal impairment, this patient is not suitable for once daily dosing regimen, and he should be treated with the conventional 8 hourly regimen. As such, he may be injected with gentamicin 40 mg every 8 hours making it 120 mg/24 hours. This patient has renal impairment, half life of cefotaxime is likely to be prolonged. Since the patient has distressing urinary symptoms and is febrile, empirical antimicrobial treatment should be started after urine has been collected for bacteriological testing. The first line antimicrobials for this purpose are fluoroquinolones, cotrimoxazole, amoxicillinclavulanate, an oral 1st or 2nd generation cephalosporin, or nitrofurantoin. Nitrofurantoin is usually not preferred because it needs at least 7 days treatment, and often causes nausea and gastric pain. It relieves symptoms of bladder and uretheral irritation and can be given with the selected antimicrobial drug. Because this patient has suffered >3 episodes of cystitis within one year, she should be advised long term prophylactic therapy. The suitable prophylactic drug for her is cephalexin 250 mg once daily at bed time, because it is not contraindicated in pregnant women. Though this patient is not presently pregnant, she may conceive during use of the prophylactic drug. The other recommended prophylactic drugs, viz cotrimoxazole, nitrofurantoin and norfloxacin are all contraindicated during pregnancy. However, chemotherapy should be started immediately, because the culture and sensitivity tests take 6 weeks or more and defering treatment for such a long time may jeopardise outcome. This is a defaulted patient who has taken isoniazid and rifampin only for 3 months. For the initial 2 months, he should be given all 5 first line drugs, viz isoniazid 300 mg + rifampin 600 mg + pyrazinamide 1. Streptomycin should be stopped after that and the 4 oral drugs given for another 1 month. Pyrazinamide should be discontinued and 3 drugs rifampin, isoniazid and ethambutol should be continued for 5 more months. The regimen may be modified when the culture and sensitivity report becomes available. Since the patient had taken the standard multidrug therapy for the prescribed one year, and had responded clinically, the most likely cause of relapse is reactivation of dormant (persister) bacilli. As such, he should be treated with the same drugs, viz rifampin 600 mg + clofazimine 300 mg once a month alongwith dapsone 100 mg + clofazimine 50 mg daily for one year. The treatment of choice for Candida esophagitis is oral fluconazole 100 mg/day for 3 weeks, because it is highly effective and well tolerated. These may be treated with itraconazole 200/day or voriconazole 200 mg twice daily. Uncontrolled diabetes is an important predisposing factor in the causation of esophageal candidiasis, and appears to have played a role in this patient. Since the patient already had a complication of diabetes (Candida infection) it is desirable to shift her to insulin therapy (at least till the esophagitis is fully cured). The dose and frequency of insulin injections should be guided by repeated blood glucose monitoring. The intensity of action of glibenclamide (if continued in this case) is likely to be affected unpredictably. Thus, even if this drug is continued, close monitoring of blood glucose level and dose adjustment of the sulfonylurea is required. Therefore, it would be prudent to give prophylactic medication to further cut down chances of acquiring the infection. The dental surgeon should be advised to immediately start taking- Zidovudine 300 mg + Lamivudine 150 mg twice daily for 4 weeks. While majority of asexual schizonts are killed by chloroquine and the fever subsides, some survive and multiply to cause fever again. As broughtout above, recrudescence indicates chloroquine-resistance, which is particularly likely in this case, because the infection appears to be contacted from an area where chloroquineresistance among P. As such, she should be treated with an alternative drug effective against chloroquine-resistant P. Quinine 600 mg three times a day for 7 days along with doxycycline 100 mg once daily for 7 days. Artesunate 100 mg twice daily for 3 days, along with a single dose of sulfadoxine 1500 mg + pyrimethamine 75 mg. The primaquine therapy should be continued to complete the 14-day course, so as to totally eradicate the P. It was correctly changed to oral route once the patient improved, because oral bioavailability of metronidazole is nearly complete. Experience has shown that a single 10-day course of metronidazole is generally enough to kill all viable amoebae in the liver abscess, though the abscess cavity may persist for few weeks and heal spontaneously. Since the patient has improved clinically, visualization of persisting abscess cavity on ultrasound is not in itself an indication to extend/repeat metronidazole therapy. Since amoebic liver abscess is always secondary to colonization of colon by amoebae (which may be asymptomatic) and because metronidazole does not effectively eradicate cyst forming trophozoites from the colon (it is completely absorbed in the upper intestine, and very little reaches the colonic lumen), a luminal amoebicide should be given along with or after metronidazole. This patient of neurocysticercosis is suitable for treatment with anthelmintic drug, because there are multiple active parenchymal cysticerci in the cerebral cortex which in addition to seizures can cause other focal reactions in the brain. Planned killing of the cysticerci under corticosteroid cover may prevent future episodes of the reaction and may abolish the cause of seizures, so that long term antiseizure therapy can be avoided. The preferred drug is carbamazepine; start with 200 mg 3 times a day, increase by 200 mg/day if the seizures recur till they are fully suppressed or a maximum of 1200 mg/day dose is reached. To this patient, it should be given in a dose of 400 mg twice daily with milk or fat-rich food (to enhance absorption) for 15 days. Carbamazepine induces praziquantel metabolism and lowers its blood level, but not that of albendazole. Dexamethasone (which has to be given) also lowers praziquantel blood levels, but increases albendazole absorption. This is essential to suppress the inflammatory reaction to the dying cysticerci killed by albendazole therapy. Possible harm to the foetus by the administered drug ha~ to be weighed against hann to both mother and the baby due 10 untremed disease.

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Moreover allergy testing labcorp flonase 50mcg with mastercard, to be effective in metal poisoning, their distribution in the body should correspond to that of the metal to be chelated, and they should be water soluble. Efficacy of all chelating agents in promoting excretion of the toxic metal and in reversing toxic manifestations declines rapidly as the interval between entry of the metal in the body and the administration of the chelator increases. The complex of 2 molecules of dimercaprol with one metal ion is more stable than 1:1 complex. It is, therefore, desirable to maintain excess of dimercaprol in plasma to allow formation of 2: 1 complex. The dimercaprol-metal complex spontaneously dissociates releasing the metal at a slow rate; also dimercaprol is partly oxidized in the body: further emphasizing the necessity to have excess dimercaprol available. But due to dose dependent toxicity of dimercaprol, large amounts should not be given at a time. Because the dimercaprolmetal complex dissociates faster in acidic urine and the released metal can damage the kidney, urine is alkalinized during dimercaprol therapy. The urinary excretion of Pb is promptly increased, but declines quickly as the metal is removed from accessible sites (primarily bone). This is roughly dose-related and may be due to the toxic metal partly dissociating in the tubule. An acute febrile reaction with chills, bodyache, malaise, tiredness occurs in some individuals. Its calcium chelate has been used in metal poisonings (especially radioactive metals like uranium, plutonium) which It is contraindicated in iron and cadmium poisoning, because the dimercaprol-Fe and dimercaprol-Cd complex is itself toxic. Adverse effects these are frequent, dose related and distressing, but generally not damaging. Antihistaminics given 30 min before dimercaprol injection, reduce the intensity of adverse effects. Dimercaptosuccinic acid (Succimer) It is similar to dimercaprol in chelating properties, water soluble, less toxic and orally effective. When a slow infusion is given, tetany does not occur, because calcium is withdrawn from bones. However, because of its limited distribution in the body, results are not impressive. The d-isomer is used therapeutically, because the l-isomer and the recemate produce optic neuritis and are more toxic. It is adequately absorbed after oral administration, little metabolized in the body and excreted in urine and faeces. When given to patients with heavy metal toxicity, excretion of the metal is enhanced. It was used as a disease modifying drug in rheumatoid arthritis, but has been replaced now by safer drugs (see p. Adverse effects Short-term administration (as metal chelator) of penicillamine does not cause much problem. Dermatological, renal, haematological and collagen tissue toxicities are prominent. Desferrioxamine Ferrioxamine is a long chain iron containing complex obtained from an actinomycete. Chemical removal of iron from it yields desferrioxamine which has very high affinity for iron: 1g is capable of chelating 85 mg of elemental iron. The straight chain desferrioxamine molecule winds round ferric iron and forms a stable nontoxic complex which is excreted in urine. It removes loosely bound iron as well as that from haemosiderin and ferritin, but not from haemoglobin or cytochrome. Parenterally administered desferrioxamine is partly metabolized and rapidly excreted in urine. Transfusion siderosis: occurs in thalassemia patients who receive repeated blood transfusion. In its absence, plasma concentration of free Cu is high which gets deposited in liver, substantia nigra, basal ganglia of brain, and causes local degeneration. It is the drug of choice for Cu poisoning and alternative drug to dimercaprol/succimer for Hg poisoning. Other side effects are abdominal pain, loose motions, muscle cramps, fever and dysuria. Oral deferiprone is a somewhat less effective alternative to injected desferrioxamine. Deferiprone has also been indicated for acute iron poisoning (less effective than desferrioxamine) and for iron load in liver cirrhosis. Deferiprone It is an orally active iron chelator which has simplified the treatment of transfusion siderosis in thalassemia patients. Excessive haemolysis occurs in these patients, and they have to be given repeated blood transfusions. An iron chelator has Side effects are anorexia, vomiting, altered taste, joint pain, reversible neutropenia, rarely agranulocytosis. This definition excludes the inorganic essential trace minerals and essential amino acids and fatty acids which are required in much larger quantities. The different chemical forms and precursors of a vitamin can be called its Vitamers (analogy-isomers). The importance of vitamins as drugs is primarily in the prevention and treatment of deficiency diseases. Vitamin deficiencies occur due to inadequate intake, malabsorption, increased tissue needs, increased excretion, certain genetic abnormalities and drugvitamin interactions. Vitamins are traditionally divided into two groups: (a) Fat-soluble (A, D, E, K): these (except vit K) are stored in the body for prolonged periods and are liable to cause cumulative toxicity after regular ingestion of large amounts. Carotenoids are pigments found in green plants (carrot, turnip, spinach), Carotene is the most important carotenoid. Man on normal diet gets half of his vit A as retinol esters and half from carotenoids. Absorption and fate Retinyl palmitate, the chief retinyl ester in diet, is hydrolysed in intestines to retinol which is absorbed by carrier transport and reesterified. Absorption is normally complete, but not in steatorrhoea, bile deficiency and from protein poor diet. Small amount is conjugated with glucuronic acid, excreted in bile, undergoes enterohepatic circulation. It is split into two molecules of retinal in the intestinal wall; only half of this is reduced to retinol and utilized. A is stored in liver, deficiency symptoms appear only after long-term deprivation, but vit A deficiency is quite prevalent, especially among infants and children in developing countries. Interactions (i) Vit E promotes storage and utilization of retinol and decreases its toxicity. A in visual cycle Physiological role and actions (a) Visual cycle Retinal generated by reversible oxidation of retinol is a component of the light sensitive pigment Rhodopsin which is synthesized by rods during dark adaptation. This pigment gets bleached and split into its components by dim light and in the process generates a nerve impulse through a G-protein called Transducin. A similar pigment (Iodopsin) is synthesized in the cones-responsible for vision in bright light, colour vision and primary dark adaptation. A deficiency rods are affected more than cones; irreversible structural changes with permanent night blindness occur if the deprivation is longterm. A promotes differentiation and maintains structural integrity of epithelia all over the body. It also promotes mucus secretion, inhibits keratinization and improves resistance to infection. It appears to have the ability to retard development of malignancies of epithelial structures. Physiological amount of vit A appears to be required for proper antibody response, normal lymphocyte proliferation and killer cell function. Treatment consists of stopping further ingestion, supportive measures, and vit E which promotes storage of retinol in tissues and speeds recovery.

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Concurrent use of inhaled salmeterol with inhaled glucocorticoid produces effects equivalent to double dose of the corticoid alone allergy herbs purchase flonase 50mcg free shipping. They reduce breathlessness by preventing expiratory closure of peripheral airways and abolishing the reversible component of airway obstruction. The sources and average alkaloid contents of the beverages, as they are usually prepared are given below. Coffea arabica (Coffee seeds) Alkaloid content in beverage Caffeine Theophylline Caffeine 50 mg in an average 1 mg cup of tea 75 mg in an average cup of coffee 3. Theobroma cacao Theobromine 200 mg in an average (Cocoa, chocolate) Caffeine 4 mg cup of cocoa 4. Cola acuminata (Guru nuts) Caffeine 30 mg in 200 ml bottle of cola drink Formoterol Another long-acting selective 2 agonist which acts for 12 hrs when inhaled. It is used on a regular morning-evening schedule for round-the-clock bronchodilatation. All three alkaloids have qualitatively similar actions, but there are marked quantitative (Table 16. It is a constituent of older combination formulations and is used for mild to moderate chronic asthma. Theophylline is one of the three naturally occurring methylated xanthine alkaloids caffeine, theophylline and theobromine. These alkaloids also stimulate medullary vagal, respiratory and vasomotor centres. They tend to increase heart rate by cardiac action, but decrease it by causing vagal stimulation-net effect is variable. Tachycardia is more common with theophylline, but caffeine generally lowers heart rate. While consumption of > 9 cups of coffee per day has been found to be associated with increased incidence of arrhythmias, moderate ingestion of caffeine (upto 500 mg/day) does not increase frequency or severity of cardiac arrhythmias even in patients with ischaemic heart disease or preexisting ventricular extrasystoles. At high concentrations it increases release of Ca2+ from sarcoplasmic reticulum by direct action. At low doses, twitch response to nerve stimulation is augmented, while at toxic doses contracture is produced. Stomach Methylxanthines enhance secretion of acid and pepsin in stomach, even on parenteral injection. Release of endogenous catecholamines appears to be partly responsible for these effects. Mast cells and inflammatory cells Theophylline decreases release of histamine and other mediators from mast cells and activated inflammatory cells. Mechanism of action Three distinct cellular actions of methylxanthines have been defined- (a) Release of Ca2+ from sarcoplasmic reticulum, especially in skeletal and cardiac muscle. However, cranial vessels are constricted, especially by caffeine; this is one of the basis of its use in migraine. Smooth muscles All smooth muscles are relaxed, most prominent effect is exerted on bronchi, especially in asthmatics. Slow and sustained dose-related bronchodilatation is produced, but the effect is much less marked compared to inhaled 2 agonists. Biliary spasm is relieved, but effect on intestines and urinary tract is negligible. Action (b) and action (c) are exerted at concentrations in the therapeutic range and appear to contribute to bronchodilatation. Adenosine A1 receptor antagonism is considered responsible for cardiac arrhythmias and seizures occurring in theophylline toxicity. Recent evidence suggests that low concentations of theophylline ehnace histone deacetylation in airway inflammatory cells, suppressing proinflammatory gene transcription. Thus, even sub-bronchodilator doses of theophylline may exert some beneficial effect in asthma. Dose-dependent toxicity starts from the upper part of therapeutic concentration range. The depicted concentration ranges are approximate Theophylline Pharmacokinetics Theophylline is well absorbed orally; rectal absorption from suppositories is erratic. There are marked interindividual variations in plasma concentrations attained with the same dose. The irritant property of theophylline is reflected in gastric pain (with oral), rectal inflammation (with suppositories) and pain at site of i. Drugs which inhibit theophylline metabolism and increase its plasma level are-erythromycin, ciprofloxacin, cimetidine, oral contraceptives, allopurinol; dose should be reduced to 2/3. Theophylline enhances the effects of-furosemide, sympathomimetics, digitalis, oral anticoagulants, hypoglycaemics. Aminophylline injection should not be mixed in the same infusion bottle/syringe with-ascorbic acid, chlorpromazine, promethazine, morphine, pethidine, phenytoin, phenobarbitone, insulin, penicillin G, tetracyclines, erythromycin. Preparations and dose (i) Theophylline (Anhydrous) Poorly water soluble, cannot be injected. Because solubility of theophylline is low, a number of soluble complexes and salts have been prepared, particularly for parenteral use. Doxophylline A long-acting oral methylxanthine that is claimed not to interfere with sleep or stimulate gastric secretion. However, anhydrous theophylline is completely absorbed and gastric irritancy of the salts is the same in terms of theophylline content. However, because of narrow margin of safety and limited efficacy, its use has declined. Sustained release theophylline can be used in mild-tomoderately severe asthma, as a 3rd line or alternative/adjuvant drug, especially in patients with nocturnal asthma. Apnoea in premature infant: Theophylline reduces the frequency and duration of episodes of apnoea that occur in some preterm infants in the first few weeks of life. However, some recent evidence points to presence of M3 receptors on peripheral bronchiolar muscles as well, though they are not vagally innervated. Bronchodilatation, reduced sputum eosinophil count, suppression of bronchial inflammation, mucus and hyperreactivity are noted in asthma patients. Montelukast and zafirlukast are indicated for prophylactic therapy of mild-to-moderate asthma as alternatives to inhaled glucocorticoids. Though efficacy is low, they may obviate need for inhaled steroids, and may be more acceptable in children. In severe asthma, they have additive effect with inhaled steroids, may permit reduction in steroid dose and need for rescue 2 agonist inhalations, but the additive effect of long-acting 2 agonists is greater. Both montelukast and zafirlukast are very safe drugs; produce few side effects like headache and rashes. Few cases of Churg-Strauss syndrome (vasculitis with eosinophilia) have been reported. Salbutamol mainly relaxes bronchiolar smooth muscle; Ipratropium blocks bronchoconstriction mainly in the larger airways anticholinergics. Combination of inhaled ipratropium with 2 agonist produces more marked and longer lasting bronchodilatation; since their effects are additive. Long-term treatment decreases the cellular inflammatory response; bronchial hyperreactivity is reduced to variable extents. Bronchospasm induced by allergens, irritants, cold air and exercise may be attenuated. It is administered as an aerosol through metered dose inhaler delivering 1 mg per dose: 2 puffs 4 times a day.

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With respect to drug-drug interactions allergy symptoms lump in throat cheap flonase 50mcg without prescription, it is important to consider the effects of environmental exposures (smoking, nutraceuticals, grapefruit juice) and changes in these behaviors. Increased risk for cerebrovascular events and all-cause mortality is also seen in elderly patients with dementia (see Increased Mortality in Patients With Dementia). Use During Pregnancy and Lactation Human data from large database studies do not show increased rates of major congenital malformations after first trimester exposure (Huybrechts et al. The older, typical agents are widely used when a higher level of D2 antagonism is required. Nonetheless, there is recognition that patients who develop antidepressant-induced mania do have a bipolar diathesis even with no prior independent history of mania and should be followed carefully, especially if antidepressant treatment is again considered during periods of major depression. Mania is distinguished from its less-severe form, hypomania, by the fact that hypomania, by definition, does not result in functional impairment or hospitalization and is not associated with psychotic symptoms. Genetics studies of bipolar disorder have yielded several loci of interest associated with disease risk and predictors of treatment response, but the data are not yet at the phase of clinical application. Lithium carbonate was introduced fortuitously in 1949 for the treatment of mania and approved for this purpose in the U. Clozapine can be beneficial in patients with refractory mania as adjunctive therapy and as monotherapy (Geddes and Miklowitz, 2013). Certain antipsychotics have efficacy for adjunctive use (olanzapine) or as monotherapy (quetiapine, lurasidone) for bipolar depression, typically at much lower dosages than for acute mania. Therapeutic concentrations of Li+ have almost no discernible psychotropic effects in individuals without psychiatric symptoms. There are numerous molecular and cellular actions of Li+, some of which overlap with identified properties of other mood-stabilizing agents (particularly valproate) and are discussed next. An important characteristic of Li+ is that, unlike Na+ and K+, Li+ develops a relatively small gradient across biological membranes. Slow-release preparations of lithium carbonate minimize peak-to-trough ratios and permit once-daily dosing. Li+ initially distributes to the extracellular fluid, does not bind appreciably to plasma proteins, and gradually accumulates in tissues, with a volume of distribution of 0. The concentration gradient across plasma membranes is much smaller than those for Na+ and K+. The kinetics of Li+ can be monitored in human brain with magnetic resonance spectroscopy (Grandjean and Aubry, 2009b). When Li+ is stopped, there is a rapid phase of renal excretion followed by a slow 10- to 14-day phase. Li+ is secreted in saliva in concentrations about twice those in plasma, while its concentration in tears is about equal to that in plasma. Occasionally, patients with severe systemic illnesses are treated with Li+, provided that the indications are compelling, but the need for diuretics, nonsteroidal anti-inflammatory agents, or other medications that pose potential kinetic problems often precludes Li+ use in those with multiple medical problems. Li+ is the mood stabilizer with the most robust data on suicide reduction in bipolar patients; Li+ is also efficacious for augmentation in unipolar depressive patients who respond inadequately to antidepressant therapy (Grandjean and Aubry, 2009a). While Li+, valproate, and carbamazepine have efficacy in acute mania, in clinical practice these are usually combined with atypical antipsychotic drugs, even in manic patients without psychotic features, due to their complementary modes of action. Li+, carbamazepine, and valproic acid preparations are effective only with daily dosing that maintains adequate serum levels (requires monitoring of serum levels). Acutely manic patients may require higher dosages to achieve therapeutic serum levels, and downward adjustment may be necessary once the patient is euthymic. When adherence with oral capsules or tablets is an issue, the liquid Li+ citrate can be used. Divalproex is initiated at 30 mg/kg given as single or divided doses and titrated to effect based on the desired serum level. With immediate-release forms of valproic acid and divalproex sodium, 12-h troughs are used to guide treatment. An extended-release form of carbamazepine is effective as monotherapy with once-daily dosing. Nevertheless, certain individuals respond to carbamazepine after failing Li+ and valproate. Lamotrigine has no role in acute mania due to the slow, extended titration necessary to minimize risk of Stevens-Johnson syndrome and is used for bipolar maintenance (Rapoport et al. Overriding concerns guiding bipolar treatment are the high recurrence rate and the high risk of suicide. As with schizophrenia, lack of insight, poor psychosocial support, and substance abuse all interfere with treatment adherence. While the anticonvulsants lamotrigine, carbamazepine, and divalproex have data supporting their use in bipolar prophylaxis, only lithium has consistently been shown to reduce the risk of suicide compared to other treatments, specifically when compared to valproate acid derivatives (Goodwin et al. A recent large trial comparing Li+ and valproate found no significant differences in time to relapse between the two agents (Cipriani et al. Stopping mood stabilizer therapy can be considered in patients who have experienced only one lifetime manic episode, particularly when there may have been a pharmacological precipitant. Discontinuation of maintenance Li+ treatment in patients with bipolar I carries a high risk of early recurrence and of suicidal behavior over a period of several months, even if the treatment had been successful for several years. Recurrence is much more rapid than is predicted by the natural history of untreated bipolar disorder, in which cycle lengths average about 1 year. Based on its neuroprotective properties, Li+ treatment has been suggested for conditions associated with excitotoxic and apoptotic cell death, such as stroke and spinal cord injury, and in neurodegenerative disorders, including dementia of the Alzheimer type, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, progressive supranuclear palsy, and spinocerebellar ataxia type I (Chiu et al. The K+-sparing diuretics have more modest effects on the excretion of Li+, with concomitantly smaller increases in serum levels. Li+ discontinuation or a switch to single-daily dosing may reverse the impact on renal concentrating ability in patients with less than 5 years of Li+ exposure. The development of hypothyroidism is easily treated through exogenous replacement and is not a reason to discontinue Li+ therapy. Routine monitoring of serum Ca2+ should be included with measurements of electrolytes, thyroid indices, renal function, and serum Li+ levels (Shapiro and Davis, 2015). Severity and risk for tremor are dose dependent, with incidence ranging from 15% to 70%. The prolonged use of Li+ causes benign and reversible T-wave flattening in about 20% of patients. Allergic reactions such as dermatitis, folliculitis, and vasculitis can occur with Li+ administration. Li+ freely crosses the placenta, and fetal or neonatal Li+ toxicity may develop when maternal blood levels are within the therapeutic range (Grandjean and Aubry, 2009c). The resulting shorter t1/2 of Li+ demands dosing increases on a milligram/ kilogram basis, and multiple-daily dosing is often required. Use in children under 12 represents an off-label use for Li+, and caregivers should be alert to signs of toxicity. As with adults, ongoing monitoring of renal and thyroid function is important, along with clinical inquiry into extent of polyuria. Elderly patients frequently take numerous medications for other illnesses, and the potential for drug-drug interactions is substantial. Age-related reductions in total body water and creatinine clearance reduce the safety margin for Li+ treatment in older patients. Care must be taken to ensure that the patient is not Na+ and water depleted (Grandjean and Aubry, 2009c).