GERALD BLOOMFIELD, MD, MPH

• Department of Internal Medicine,The Johns Hopkins University
• School of Medicine, Baltimore

At about the age of 8-10 years pain medication for dogs tramadol cheap 10 mg elavil mastercard, the weak adrenal androgens cause a slight rise in the plasma testosterone level active pain treatment knoxville best elavil 75 mg, and terminal hair appear on the forearms and legs in both boys and girls (ambisexual hair) pain treatment center rochester general hospital order elavil 50 mg free shipping. At puberty blaustein pain treatment center hopkins buy cheap elavil 25mg, with the further rise in the plasma testosterone level into the adult female range pain treatment a historical overview elavil 10mg discount, terminal hair appear in the pubic and axillary regions; these hair are also ambisexual midwest pain treatment center llc buy 10mg elavil with visa. Boys with further advanced puberty and adult males develop terminal hair in other regions such as face and trunk (sexual hair). Further, it is responsible for the excessive loss of scalp hair in women with elevated plasma androgen levels. Hair growth is cyclic, with phases of growth (anagen), involution (catagen) and resting (telogen). In the scalp, about 80-88% of the hair are in anagen (for about 3 years), 1-2% are in catagen (for about 3 weeks) and the rest 10-20% are in telogen (for about 3 months), after which hair are shed. The growth of scalp hair is asynchronous, with hair in a given area in different phases; there is a balance among anagen, catagen and telogen hair in all regions of the scalp. A disruption of this balance causes many more hair to enter the telogen phase, and about 3 months later they are shed in bulk causing alopecia; this is called telogen effluvium. Severe stress can cause telogen effluvium; but as sudden severe hair loss occurs three months after the stressful event, the latter is likely to be forgotten. Alopecia of the scalp can be: I Scarring which is associated with inflammation, fibrosis and destruction of the hair follicles due to primary skin disorders such as lichen planus or systemic diseases such as lupus erythematosus. The other causes of non-scarring alopecia are: crash dieting, physical trauma, iron deficiency hypothyroidism, chronic malnutrition, chronic illness, androgen excess and, androgenetic alopecia. They may have other manifestations of hyperandrogenism such as menstrual abnormalities, hirsutism, acne and infertility the treatment is that of hyperandrogenism. The miniaturised hair of various lengths and diameters are the hallmark of this condition. In men, the alopecia ranges from bitemporal recession to thinning of the hair in the frontal and vertex regions to complete baldness except in the occipital and temporal regions. In women, the thinning is less severe but is maximum in the frontal and parietal regions. Endocrine testing is not required if the above described characteristic pattern of hair loss is present, and there is no evidence of hyperandrogenism. Treatment: this comprises of topical minoxidil (see below) in both sexes and oral finasteride in men (Chapter 69). The response to finasteride is better in the frontal region of the scalp, which has higher levels of 5-alpha reductase, than in the occipital region (which has higher levels of aromatase). It must be remembered that androgens cause: (a) the vellus-hair follicles to be replaced by terminal hair follicles in the region of ambosexual and sexual hair; and (b) Miniaturisation of the terminal hair follicles of the scalp. As these changes are irreversible, complete reversal of hirsutism (Chapter 69) and of androgenic/androgenetic alopecia is not to be expected. Alopecia areata (which is non-scarring) causes patches of complete baldness, varying in size, in any region of the body including the scalp. The treatment comprises of topical minoxidil and a topically injected glucocorticoid. Minoxidil, an antihypertensive agent (see Chapter 30), when applied locally as a 2-5% solution twice a day over a prolonged period, may produce some hair growth in a few patients. The results are best in mild cases and good to excellent results are seldom seen in more than 30% of patients even after prolonged use. Minoxidil increases the dermal blood flow causes an elongation and normalisation of the hair follicles. Cosmetically acceptable hair growth is uncommon, and the beneficial effect ceases when the treatment is discontinued. Drugs Affecting Skin Pigmentation Drugs can be used: To decrease localised hyperpigmentation such as freckles and post-inflammatory pigmentation. It is commonly used in the form of a 2-4% cream or lotion in the treatment of freckles, post-inflammatory pigmentation, and melasma of pregnancy and that due to oral contraceptives. Its effect is reversed by sunlight and hence it is used in combination with an opaque sunscreen. The treatment is unsatisfactory the affected skin can be painted by artificial tanning. If the desired effect is not obtained after 90 min of exposure, the dose is increased gradually upto a maximum of 80 mg daily Re-pigmentation. It is contraindicated in patients with diseases associated with photosensitivity such as porphyria and systemic lupus erythematosus, and should not be given concurrently with other photosensitising drugs. There is an increased risk of severe sunburn, skin wrinkling, cataract and skin cancer following long term therapy. Acanthosis nigricans: this is hyperpigmented, velvety thickening of the skin occurring most commonly on the neck, in the axillae and in the groins. It is believed to be a manifestation of hyperinsulinemia due to insulin resistance. Commercial skin lightening creams may alter the chemical structure of the skin by inhibiting synthesis of melanin. The common basic ingredients in these creams are hydroquinone, mercury and highly potent fluorinated steroids along with chemicals of unknown safety Constant use of these agents can give rise to skin rashes, dirty grayish. In fact, what one needs is a cosmetic that would improve the appearance of the skin or enhance its attractiveness without altering the basic structure. Examples are aminobenzoates, benzophosphophenones-3 (oxybenzone), methoxycinnamate (octinoxate), a salicylate (octisalate), octocrylone and a dibenzylmethane (avobenzene) (Table 71. Barrier preparations: They are used as water repellents to protect the skin against nappy rash. It binds to stratum corneum and changes the skin colour from white to orange-brown which lasts for 5-7 days. Another substance which also acts as an adsorbent and a mild antiseptic, added to such powders, is zinc stearate, a light, impalpable, amorphous powder. However, starch is a better absorbent of moisture than the substances mentioned above. Addition of phenol, menthol and camphor exert a local antipruritic and cooling action. To these basic ingredients, various antiseptics like boric acid and salicylic acid may be added. A powder containing salicylic acid 5g, boric acid 5 g, camphor 5g, starch 30g and talc to 100g can be easily and economically prepared at home. The powder has absorbent, mild antiseptic, antipruritic and cooling properties; it may be applied to the axillae and the groins once or twice daily, with benefit. Application of such powders may cause blocking of the sweat gland pores and hence, after-cleansing is essential. Use of talc on surgical gloves is known to cause granulomatous reaction in wounds. Baby powder generally contains zinc stearate and talc in the proportion of 1 to 2. In general, it is better to avoid such medicated powders in babies as they tend to form cake in skin fold causing dermatitis and may also get into the lungs. There is no evidence to suggest that medicated cosmetic powders are any better than non-medicated ones for routine use in individuals with healthy skin. Tooth paste or gels contain abrasives (calcium salts, silica), fluoride, and detergents. Various antiseptics and deodorants like clove oil, peppermint oil and lemon oil are added to these basic ingredients. Evidence suggests that non-medicated tooth pastes are as effective as medicated ones and possess the additional advantage of being cheaper and more acceptable. No toothpaste or powder can, however, act as a substitute for simple and repeated cleansing of mouth immediately after eating. Shampoos are liquid soaps or detergents used to wash the hair and clean the scalp of scales or dandruff. Medicated shampoos usually contain various antimicrobial agents such as selenium sulphide, ketoconazole, povidone and cetrimide. Most of the commercial cold creams are modifications of a popular emollient preparation, rose water ointment, which contains spermaceti (a waxy substance obtained from the head of the sperm whale), bleached bees wax, almond or prussic oil, rose water and rose oil. Dermal fillers given by injection are used for soft tissue augmentation of facial wrinkles and folds to give an young look. Majority of them consist of hyaluronic acid derived from bacteria or human/bovine collagen. They are used to remove facial wrinkles and lipoatrophy Their effect lasts for 6-24 months. Anhidrotics and Deodorants Sweating is common in the tropics and no drug should be used to block this normal physiological response. The eccrine sweat glands, although anatomically innervated by sympathetic nerves, are physiologically cholinergic. None of the available systemic anhidrotics, however, has a sufficiently predictable action without adverse effects. Aluminium chlorhydrate acts by local astringent action and blocks the sweat ducts at the skin surface. Formalin acts by forming keratin plugs in the orifices of sweat ducts; its frequent use may cause allergic reactions. Glutaraldehyde is a tanning agent with antibacterial and deodorant activity Anticholinergic drugs like propantheline bromide and. Mild hyperhridrosis of the feet is easily managed by foot-baths with potassium permanganate, 1:10,000, and simple talcum powder. Individuals should be instructed to avoid nylon socks and rubber footwear and to use open sandals. Where an emotional factor is suspected, counselling and small doses of an anxiolytic agent may help. Undesirable body odour results from the action of bacteria on the organic substances in the apocrine sweat. Excess eccrine sweat promotes this process by increasing wetness, which encourages bacterial growth. Hexachlorophane, Tetrachlorosalicylanilide, Trichlo-carbon, Thiram and Bithionol; and Masking perfumes Some of these agents can cause irritation, allergy contact dermatitis and photosensitivity, reactions. Drug-Induced Skin Disorders Adverse skin reactions to drugs are frequent in clinical practice (Table 71. Other relatively rare reactions are erythema multiforme, Stevens Johnson syndrome, exfoliative dermatitis and toxic epidermal necrolysis. Urticaria can be produced by allergic mechanism by several drugs such as ampicillin and antisera; and by drugs which liberate autocoids such as histamine. Urticaria can be dangerous if accompanied by angioedema of the larynx (Chapter 23). Photosensitivity disorders of the skin can occur following topical as well as systemic administration of drugs. Exfoliative dermatitis, Stevens-Johnson syndrome, and allergic vasculitis are serious drug reactions and will need systemic glucocorticoid therapy. With the first occurrence of an allergic drug reaction, the patient should be informed that he/she is allergic to the particular drug, and its future administration should be avoided. The eye is readily accessible to observation, and the diagnosis of several eye diseases can be made easily the drug treatment of eye problems is largely concerned with. The human eyeball is composed of three concencornea tric layers from outwards in: (a) the and cornea and sclera; (b) the iris, ciliary body and choroid; and the lens; and (c) the retina. Drug absorption across the cornea involves penetration through its multiple layers. The sclera is the outermost, dense, imperfectly elastic, opaque, supporting coat of the eyeball; its forward continuation is the cornea. The conjunctiva is a modified mucous membrane that lines the outer surface of the anteriormost part of the sclera and the inner surface of the eyelids. The pupillary size is controlled by two types of muscle fibres: (1) radial, innervated by the sympathetic nerve fibres, causing dilatation of the pupil (mydriasis); and (2) circular, innervated by the parasympathetic nerve fibres, causing constriction of the pupil (miosis). The ciliary body is made up of unstriated muscle fibres (ciliary muscle) and epithelial cells; the latter secrete aqueous humour into the posterior chamber; that fluid passes through the pupil into the anterior chamber, and from there drains into the canal of Schlemm. When the ciliary muscle contracts, the zonules which suspend the lens relax, and the lens becomes more convex and is drawn slightly forward. Pharmacokinetics of topically administered ocular drugs: Most drugs in ophthalmic practice are administered topically in the form of eye drops or ointments. The time-course of drug delivery from eye drops into the eyeball follows first order kinetics (Chapter 1). For majority of drugs, 1% or less of an applied dose is absorbed across the cornea to reach the anterior chamber. The classical pharmacokinetic theory based on systemic drug administration (Chapter 1) does not apply fully to all ocular drugs. Topically administered drugs can be absorbed through the cornea, conjunctiva and sclera. Systemically administered drugs have to cross the blood-eye barrier, which resembles the blood-brain barrier (Chapter 1), to enter the eye. Hence, drugs with large molecular size such as penicillin, administered systemically penetrate the normal, uninflamed eye, poorly but do so better if the drug is highly lipid-soluble. Lipid soluble drugs pass readily through the corneal epithelium and endothelium, whereas the water soluble agents penetrate through the stroma. Therefore, drugs with polar as well non-polar properties penetrate the cornea more freely than the purely polar or purely non-polar compounds.

Carbamazepine induces praziquantel metabolism and lowers its blood level pain treatment in pancreatitis generic elavil 25mg mastercard, but not that of albendazole pain treatment medicine clifton springs ny discount elavil 25mg amex. Dexamethasone (which has to be given) also lowers praziquantel blood levels joint pain treatment at home proven 75mg elavil, but increases albendazole absorption knee pain treatment options order elavil 75mg with amex. This is essential to suppress the inflammatory reaction to the dying cysticerci killed by albendazole therapy pain medication for dogs human order elavil 50mg otc. 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 pain treatment and wellness center pittsburgh discount 10 mg elavil. There 1s pauciiy ofdaw about safety of majority of drugs during pregnancy: largely because prospective drug trials in pregnant women arc fraught with ethical. The list is not exhaustive and manufacturers literature/ package inserts or other authoritative texts should be consulted. Pnnc1plos of proscribing during prcgmmcy Where possible use nondrug therapy Prescribe drugs only when definitely needed. Avoid newer drugs, unless safety is clearty established Over-the-counter drugs cannot be assvmed to be safe. Use the lowest effective dose Use drugs for the shortest penod necessary If possable. Cold-cough remedies Xylometazoline Oxymetazoline Budesonide Chlorpheniramine Promethazine Nasal drops 7. Antimalarial Isoniazid, Rifampicin, Ethambutol Diloxanide furoate, Paromomycin Chloroquine, Mefloquine, Proguanil Quinine (only in 1st trimester), Pyrimethamine + Sulfadoxine (only single dose) Piperazine Niclosamide Praziquantel Clotrimazole Nystatin Tolnaftate 12. Anthelmintic Albendazole (X), Mebendazole (X) Ivermectin, Pyrantel pamoate, Diethylcarbamazine (X) Amphotericin B (X), Fluconazole Itraconazole (X), Ketoconazole (X) Griseofulvin (X), Terbinafine 13. Estrogens (in oral contraceptives) and bromocriptine (D2 agonist) decrease milk production. Toxic effects on the infant are largely dependent on entry of the drug in milk in pharmacologically significant amounts. Maternal medication or breastfeeding should not be interfered in case of such drugs. However, currently available data are insufficient to make specific recommendations in the case of many drugs and the list given below is not exhaustive. Drugs whose amount in milk is too small to be harmful to the infant, or those found to be safe in ordinary doses Insulins Ipratropium Br. Vitamins (maintenance dose) Warfarin Acetazolamide Albendazole Antacids Antifungal drugs (topical) Aspirin (low dose) Baclofen Beclomethasone (Inhaled) Benzyl benzoate (topical) Bupivacaine Buprenorphine Cephalosporins Cloxacillin Codeine Cromoglycate sod. Fenfluramine Dexfenfluramine Terfenadine Astemizole Phenformin Rofecoxib Valdecoxib Rimonabant Rosiglitazone Nimesulide formulations for children below 12 years age Cisapride Phenylpropanolamine* Sibutramine and R-Sibutramine Gatifloxacin Tegaserod Human placental extract formulations, except for: i. Halogenated hydroxyquinolines in liquid oral antidiarrhoeals or any other dosage form for pediatric use. Corticosteroids with any other drug for internal use, except for metered dose inhalers and dry powder inhalers. Crude ergot with any drug except preparations containing ergotamine, caffeine, analgesics, antihistamines for treatment of migraine, headache. H2 receptor antagonists with Antacids (except those combinations approved by Drugs Controller, India). Salbutamol (or any other bronchodilator) with centrally acting Antitussive and/or an Antihistamine. Centrally acting Antitussives with Antihistamines having atropine like activity in expectorants. Centrally acting Antitussive and/or Antihistamine in preparations for cough associated with asthma. Ethambutol with Isoniazid, except in the following daily doses: Isoniazid 200 mg + Ethambutol 600 mg or Isoniazid 300 mg + Ethambutol 800 mg. Pyrazinamide with other antitubercular drugs, except that which provide the following daily doses: Rifampicin 450 to 600 mg Isoniazid 300 to 400 mg Pyrazinamide 1000 to 1500 mg 23. Essential oils with Alcohol having percentage higher than 20% proof (except preparations given in the I. Antidiarrhoeals containing adsorbants like kalolin, pectin, attapulgite, activated charcoal etc. Antidiarrhoeals containing phthalylsulfathiazole, succinyl sulfathiazole, sulfaguanidine, neomycin, streptomycin, dihydrostreptomycin. Antidiarrhoeal formulations for pediatric use containing diphenoxylate, loperamide, atropine, hyoscyamine. Pancreatine or pancrelipase containing amylase, protease and lipase with any other enzyme. Precooked rice equivalent to not less than 50 g and not more than 80 g as total replacement of dextrose. A drug, standards of which are prescribed in the 2nd schedule to Drugs and Cosmetics Act with an Ayurvedic, Siddha or Unani drug. Phenobarbitone with any antiasthmatic drug, or with hyoscine and/or hyoscyamine, or ergotamine and/or belladonna. Kala azar Treatment Policy (2011), Directorate of National Vector Borne Disease Control Programme. List of drugs banned for marketing in India; Drugs Control Organisation, Govt of India; http// Vandekerckhove P, Lilford R, et al: Withdrawn: Androgens versus placebo or no treatment for idiopathic oligo/asthenospermia. Dhillon S: Aripiprazole: a review of its use in the management of mania in adults with bipolar I disorder. Lee F, Cundiff D: Meperidine vs morphine in pancreatitis and cholecystitis; Arch Intern Med 158: 2399, 1998. Yusuf S, Sleight P, et al: Effects of an angiotensinconverting enzyme inhibitor ramipril, on cardiovascular events in high risk patients. Heart Protection Study collaborative group: Effects of cholesterol lowering with simvastatin on stroke and other major vascular events in 20,536 people with cerebrovascular disease or other high-risk conditions. Sazawal S et al: Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials: Lancet Infect Dis, 6; 374-382, 2006. Jefferson-MACROS-, Demicheli, V, et al: Antivirals for influenza in healthy adults: systematic review. Gargano N, et al: Therapeutic efficacy and safety of dihydroartemisinin-piperaquine versus artesunatemefloquine in uncomplicated Plasmodium falciparum malaria in India, Malaria Journal 11-233, 1-12, 2012. Treatment of kala-azar in Southern Sudan using a 17-day regimen of sodium stibogluconate combined with paromomycin: a retrospective comparison with 30-day sodium stibogluconate monotherapy. Patra P, et al: Efficacy of oral miltefosine in visceral leishmaniasis in rural West Bengal, India: Ind J Pharmacol 44: 500-503, 2012. See Peripheral vascular disease Bufotenin, 451 Bumetanide, 520, 579, 581 Bupivacaine, 362, 364, 365, 366, 367, 368, 369, 371 Buprenorphine, 479, 482 Bupropion, 122, 454, 458, 463 Buspirone, 171, 172, 465, 466-67, 468 Busulfan, 858, 859, 861, 873 Butamben, 360, 367, 368 Butenafine, 787, 797 Butorphanol, 479, 480, 482 Butyrocholinesterase (BuChE). See Pseudocholinesterase Capsicum, 888 Captopril, 500-02, 573 Captopril test, 505 Carbachol, 100, 104 Carbamazepine, 415-16, 421, 422, 423, 451, 598 Carbapenems, 731 Carbaryl, 105 Carbenicillin, 723, 762 Carbetocin, 331 Carbidopa, 425, 429, 430 Carbimazole, 246, 252, 253, 254 Carbocisteine, 218, 219 Carbolic acid. See Dicophane Decamethonium (C-10), 347, 348 Deep vein thrombosis, 622, 624, 626, 627 Deferiprone, 908 Deflazacort, 289 Dehydroemetine, 840, 843 Demeclocycline, 735, 736, 737 Demelanizing agents, 892 Dementia, 488 drugs for, 489-91 Demulcents, 886 Denosumab, 346 Depot preparations, 8, 9, 35 Deprenyl. See Selegiline Depression (of function), 37 mental, 435, 450, 454 Dequalinium chloride, 900 Dermatophytosis: drugs for, 790, 791, 792, 793, 795, 796, 797 Dermojet, 8 Desamino oxytocin, 331 Desensitization, 50, 52 Desferrioxamine, 604, 907-08 Desflurane, 375, 377, 380, 381 Desloratadine, 164, 166 Desmopressin, 596, 597, 616 Desogestrel, 316, 318, 321, 322 Dexamethasone, 288, 289, 670, 856, also See Corticosteroids sod. See Physostigmine Esmolol, 144, 149, 529, 533, 537, 573 Esomeprazole, 78, 649, 653, 657, also See Proton pump inhibitors Esophagitis. See Ethyl alcohol Ether, 372, 373, 377, 378 Ethical considerations in drug trials, 74, 79 Ethinyl estradiol, 306, 308, 321, 322 also See Oral contraceptives Ethinyl estranol. See Hormone replacement therapy Menotropins, 241 Menthol, 888 Mepacrine, 825 Meperidine. See Niacin, 913, 914 Nicotine, 100, 121-22 chewing gum, 122 transdermal, 122 Nicotinic acid (vit B3), 635, 636, 640, 913, 914 Nicotinic actions, 103 Nicotinic receptors, 102, 109, 348, 351 Nicotinyl xanthinate, 555 Nicoumalone. See Strongyloidosis Threatened abortion, 139, 319, 332-33 Thrombin, 616 Thrombolytics, 625-28. See Prostaglandins Thymol, 888 Thyroid disease: effect on drugs, 69 Thyroid hormones, 245-52 Thyroid inhibitors, 252-56 Thyroid storm: treatment of, 150, 255, 256, 293 Thyrotoxicosis, 252 drugs for, 150, 252-56 Thyrotropin, 243. See Acute necrotizing ulcerative gingivitis Tretinoin, 869, 894, 911 Triamcinolone, 288, 289 acetonide, 287, 895 Triamterene, 579, 589, 590 Triazolam, 398, 405 Triazole antifungals, 787, 791, 793-95 Trichloroacetic acid, 889 Trichomoniasis: drugs for, 763, 838, 839, 844 Tricyclic antidepressants, 180, 454, 455-60, 463-65 Trifluoperazine, 436, 439, 440 Trifluperidol, 436, 440, 441 Triflupromazine, 436, 439, 440 Trifluridine, 798 Trigeminal neuralgia, 413, 415, 470 Trihexyphenidyl, 113, 426, 433 Triiodothyronine (T3), 245, 246, 247, 248, 249-50, 251 Trimetazidine, 540, 553-54 Trimethaphan camforsulfonate, 123 Trimethoprim+ sulfamethoxazole, 706-08. See Cotrimoxazole Trimipramine, 454, 458, also See Tricyclic antidepressants Trioxsalen, 890 Tripotassium dicitrato-bismuthate, 656. Registered Office: 818, 8th Floor, Indraprakash Building, 21, Barakhamba Road, New Delhi 110001 Corporate Office: 14th Floor, Building No. Registered Office: 301, Mahalaxmi Chambers, 22, Bhulabhai Desai Road, Mumbai - 400 026 Pharmacology and Pharmacotherapeutics, 24e, R. Satoskar First Edition, 1969; Russian Edition, 1985; Twentieth Edition, 2007; Reprinted 2007, 2008, July 2008; Twenty-first Edition, 2009; Reprinted May 2010, December 2010; Twenty-second Edition, 2011; Reprinted July 2012; Twenty-third Edition, 2013; Reprinted September 2014; Twenty-fourth Edition 2015 All rights reserved. To the fullest extent of the law, neither the co-publishers nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a result of any actual or alleged libelous statements, infringement of intellectual property or privacy rights or matter of product liability negligence or otherwise, or from any use or, operation of any methods, products, instructions, or ideas contained in the material herein. Although all advertising material is expected to conform to ethical (medical) standards, inclusion in this publication does not constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer. Please consult full prescribing information before issuing prescription for any product mentioned in this publication. Dosage Note Pharmacology and drug therapy like medicine, is an everchanging science. The authors and publishers of this book have taken special care to provide drug information and dosage schedules, that are generally in accord with the accepted standards at the time of publication. However, it may be noted that in view of the possibility of human error or advances in medicinal sciences, such therapeutic approaches are liable to change. Neither the authors nor the publishers nor any other party who has been involved in the publication of this work warrants that the information contained herein is in every respect accurate and complete. Preface to the Twenty-fourth Edition the textbook of Pharmacology and Pharmacotherapeutics undergoes continuous update every 2 years to maintain its reputation as an authentic source of unbiased and reliable information about drugs and their uses in therapeutics. This revised 24th edition, apart from routine update has undergone some major changes. In addition, a section has been introduced on immunopharmacology which includes the basics of immunology, and the drugs and biologicals, which have prophylactic and therapeutic role in modulating immune status. This is a relevant change considering the recent advances in the field of immunotherapy. With the rapid advances in molecular biology and pathophysiology of diseases, several old concepts have undergone revision leading to changes in therapeutic approaches and this will continue in future. Further, observations on variations in dose response in various ethnic groups and even in individuals from the same group (Pharmacogenomics) have provided ample examples that point out the need for careful selection of available drug regimens. This is particularly important while treating chronic ailments such as asthma, diabetes mellitus, hypertension, mental illness and using drugs with narrow therapeutic index. Hence continuous updating of knowledge has become a necessity even more than before. It has become easier to retrieve drug information within no time with the advent of information technology but the application of this information in clinical practice is a real challenge. This book while giving the recent advances in drug therapy also discusses the various options available for managing the patient in a given situation. In this era of computerization and data analysis, there is a tendency to standardize the drug treatment and draw flowcharts and algorithms based on safety and efficacy profile of the drug in different population. In the last decade or so, we have seen many new drugs getting withdrawn from the market within a short period after their introduction due to recognition of adverse effects. Temptation of using multiple drugs with a hope of achieving quicker cure without rationale could be disastrous. Bhandarkar Preface to the First Edition Pharmacology has undergone phenomenal growth during the last twenty years and drug therapy now forms a major aspect of therapeutics. So far, pharmacology was traditionally associated with the study of drugs in dogs, cats and rats, while therapeutics or clinical application was regarded as an entirely independent and a mystical skill. This is becoming more and more important as the practising doctor is now confronted with so called "newer drugs" at such a great pace that even a full-time pharmacologist sometimes finds it difficult to keep abreast of their merits and demerits. It is highly desirable, therefore, that students of pharmacology should be educated to develop a critical outlook towards various drugs, as they are introduced. This means that book on pharmacology meant for medical students should not only give detailed account of various pharmacological actions but should also furnish a critical appraisal of their present day use in therapeutics. In addition, an outline of experimental evaluation of drugs in animals and man is also provided. While doing this, it was thought essential to give the relevant information from other disciplines like physiology pathology and clinical medicine. This, though a repetition to a certain extent, is no doubt useful to understand the basis of rational therapeutics. After all, pharmacology is in some respects a bridge between basic medical sciences on one hand and clinical medicine on the other. Most of the presently available text books, except a few classics written by many authors, fail to achieve this goal. It is a common experience of those who teach pharmacology in this country to find it difficult to recommend one single book to the undergraduate medical students. Many books which give excellent information about pharmacological actions treat the therapeutics very cursorily while others that give delightful therapeutics probably assume that students know most of the basic pharmacology It is not practicable to recommend. This book is written to fill up this gap between a big book and a concise, less informative work, so that students will get all the necessary information by reading one book. While doing this, obviously we have to restrict the size of the book, lest it would be unwieldy and defeat the very purpose for which it is written.

Mixed infections are likely to be present in chronic cases pain treatment hypnosis generic 75mg elavil, in diabetics sacroiliac pain treatment uk cheap 50mg elavil with amex, in those with obstructive uropathies and in those with indwelling bladder catheters midwest pain treatment center wausau cheap 10mg elavil fast delivery. Significance of bacteria in the urine: the normal urinary tract acute neck pain treatment guidelines buy cheap elavil 50mg, except for the distal urethra pain treatment consultants of wny order 25 mg elavil amex, is sterile dental pain treatment guidelines order elavil 25mg. A few bacteria may, however, be sometimes found even in properly collected urine of apparently healthy individuals. Colony counts equal to and above 105 per ml are designated as significant bacteriuria and are diagnostic of infection. However, some women with acute cystitis may have more than 104 but fewer than 105 bacteria per ml of urine. A few apparently healthy individuals with normal urinary tract and those on corticosteroid therapy excrete in their urine bacteria in excess of 105/ml of urine. On the other hand women with frequency of urination, dysuria and pyuria due to urethritis (acute urethral syndrome) may have fewer than 105 bacteria per ml of urine or even a sterile urine on routine cultures (symptomatic abacteriuria). However, the in vitro drug sensitivity of bacteria does not always correlate with the clinical response. The definition of significant bacteriuria applies to urine obtained by midstream technique. Catheterisation of the bladder for collection of urine is totally unjustified as it may lead to dangerous infection. Pre-treatment urine culture is not required in the first attack in young women with dysuria and pyuria, and without a known underlying abnormality of the urinary tract; such attacks can be treated straightaway as if they are due to E. In pregnant women incidence of bacteriuria is high and may cause growth retardation in fetus. General principles of therapy: In acute cases, an appropriate drug may be started as soon as the urine has been collected for bacteriological examination. When the results of drug sensitivity of the pathogen grown are available, another drug may be substituted for the first one, if necessary Although. This means that for successful treatment, the drug must achieve adequate concentration in the tissues as well as in the urine. Further, the effects of the antimicrobial agent on the vaginal flora are also important in the lasting eradication of bacteriuria. The concentration of trimethoprim and fluoroquinolones in the vaginal secretions is high enough to eradicate the E. The last dose should be given immediately before retiring, having emptied the bladder completely. This is important because the diminished urinary flow and frequency at night encourage bacterial growth. This is because these organisms produce urease, an enzyme which splits urea to form ammonia. In such cases, acidifying drugs are ineffective and can cause fatality due to uncompensated acidosis and hence should not be used. Hence, the initial choice of the drug depends upon the relative cost and the known adverse effects of the drugs. Classification of drugs: I Bacteriostatic agents such as Sulfonamides, Doxycycline and Nitrofurantoin. Urinary antiseptics are the drugs which act as antibacterial agents only in the urinary tract. In smaller doses (as low as one tablet twice a week) it has been claimed to be effective in eliminating chronic bacteriuria. As trimethoprim has been reported to be teratogenic in animals, cotrimoxazole should be avoided during pregnancy. Renal insufficiency leads to retention of trimethoprim and can alter the optimum 1:5 ratio of trimethoprim to sulfamethoxazole in urine. The fixed dose combination is, therefore, likely to be rendered less effective in renal insufficiency As. Pseudomonas is resistant to it and it is ineffective against beta lactamase producing strains of Staph. It produces good tissue levels and is excreted unchanged in the urine in high concentrations. Amoxicillin-clavulanic acid or Ampicillin-sulbactum may be used if resistance is suspected. They must, however, not be mixed in the same vial or syringe because carbenicillin inactivates gentamicin (Chapter 46). It is particularly useful in patients with renal impairment where aminoglycosides are to be avoided. They have to be given parenterally and can cause ototoxicity and renal toxicity the nephrotoxicity can be considerably reduced by giving the entire daily dose as a single. The high tissue and urine concentrations even in acid urine far exceed the bactericidal concentrations against most pathogens including Pseudomonas (Chapter 45). However their extensive misuse has resulted in fluoroquinolone resistant organisms. The third generation cephalosporins are particularly effective against multi-resistant enterobacteria and Pseudomonas resistant to other antibiotics. Most strains of Pseudomonas and some strains of Proteus are resistant (Chapter 45). As nitrofurantoin is mainly excreted by glomerular filtration and tubular secretion, it is not effective and more toxic in the presence of kidney damage. It is mainly useful in infections which are resistant to other, more commonly used drugs and in patients with mixed infections or infection accompanied by obstructive uropathy It is generally safe in. The drug is not effective against: (1) Upper urinary tract infections as it is washed down too rapidly for therapeutic amounts of formaldehyde to be generated; (2) Proteus and pseudomonas species; and (3) Acute infections. It should not be used along with sulfamethizole as the latter drug forms an insoluble precipitate with formaldehyde. Cotrimoxazole and fluoroquinolones should be avoided during pregnancy (Chapter 80). Fluoroquinolones are not recommended as first line empirical treatment of uncomplicated cystitis. Cotrimoxazole is perhaps the best initial choice for empirical therapy in a non-pregant woman. Extension of therapy to 7-14 days achieves both clinical and bacteriological cure. It is indicated in: Failure of the 3 day regimen Symptomatic men Recurrences in both men and women Elderly (age more than 65 years) Symptoms persisting more than 7 days Pregnant women Children and Patients with underlying renal disease, urinary tract obstruction/abnormalities and diabetes mellitus. In addition, a single dose antibiotic regimen fails to eradicate Gram negative bacteria from the rectum, the major reservoir for recruitment of ascending uropathogens. Single dose therapy with fosfomycin tromethamine (3 g) has been advocated for uncomplicated, first attack of infection in a pregnant woman. Follow-up urine culture is done 1 to 2 weeks after treatment and then monthly until delivery. In such patients, hidden source of infection or a urological abnormality should be looked for. The use of diaphragm, spermicides and vaginal tampons has been associated with recurrences in some patients. Recurrence should be documented by a culture at least once before starting therapy Such women should receive treatment for at. Other expensive alternatives are: amoxicillin + clavulanic acid; a third generation cephalosporin such as cefixime or cefpodoxime proxetil. In patients with suspected prostatic focus of infection, drugs like trimethoprim, erythromycin (for Gram positive bacteria), fluoroquinolones, doxycycline and aminoglycosides are recommended. Despite prolonged (6-12 weeks) therapy with these agents, failure rates in men with chronic bacterial prostatitis are usually 30-40%. It should be remembered that nonbacterial prostatitis is far commoner than proven bacterial prostatitis. The entity is diagnosed by evidence of prostatic inflammation with genitourinary symptoms but negative cultures of urine and prostatic fluid. Where bacteriuria cannot be eradicated, chronic suppressive therapy with 1 tablet of cotrimoxazole or 50-100 mg of nitrofurantoin once daily can suppress symptomatic infection. Trimethoprim alone should be avoided for suppression for fear of development of drug resistance. In such patients, only acute symptomatic infections should be treated with one of the 7-14 day regimens given above. Long term continued administration of antibacterial agents only leads to the emergence of drug resistant organisms. Attempt should be made to discontinue the catheter prior to starting antimicrobial therapy If indwelling urinary catheter cannot be discontinued. The available data do not support routinely treating all men with asymptomatic bacteriuria. Treatment is appropriate (i) before genitourinary instrumentation in patients with congenital or acquired abnormality of the genitourinary tract; (ii) in infection with microorganisms with special virulence such as urea-splitting bacteria; and (iii) in immunocompromised host. However, children and pregnant women with asymptomatic bacteriuria must be treated adequately to prevent chronic renal infection. Such a patient should be initially treated by a full course of a suitable antibacterial drug. This may be followed by a single dose of ampicillin 250 mg, nitrofurantoin 100 mg or a cotrimoxazole tablet after each coitus. Urine and blood cultures are mandatory before starting the therapy; the results are helpful in modifying the initial therapy which is started without waiting for the culture report. If fever and flank pain persist after 3 days of therapy urine culture should be repeated, and ultrasonography should be carried out to rule out a perinephric or intrarenal abscess, or an anatomical abnormality Follow up urine culture is recommended after 2 weeks of. The total duration of treatment is guided by urine culture and is usually longer than 21 days. The antibacterial drug treatment must be prolonged and the choice of the drug is governed by the identity of the organisms and their drug sensitivity and by the, extent of renal impairment (see below). It is important to detect drug failure early so that an ineffective drug is discontinued; its continuation can only help superinfection with resistant organisms. Nitrofurantoin and nalidixic acid do not achieve adequate urinary concentration in patients with renal failure. Follow up: Successful treatment of an acute attack with an antibacterial agent leads to disappearance of bacteriuria within 24 hours; but pyuria and symptoms take longer to disappear. Patients should be followed up for at least 6 months after treatment and urine cultures should be repeated at 1-2 month intervals. Cases with recurrent acute infection or with chronic infection need prolonged suppressive drug therapy (6-12 months) after the initial treatment. Unarrested or repeated kidney infection not only leads to chronic pyelonephritis but also prevents the kidney growth in children. Antibiotics maintain the urine sterile and prevent infections while awaiting spontaneous resolution of vesicoureteric reflux, which occurs over a time. Daily cotrimoxazole or trimethoprim or nitrofurantoin (1-2 mg/kg) given for a prolonged period, reduces the incidence of pyelonephritis and helps to resotre the kidney growth. Trimethoprim or cephalexin (10mg/kg) is probably better and safer for this purpose. Antimicrobial Prophylaxis this is indicated: Following instrumentation of the urinary tract. Cotrimoxazole, nitrofurantoin (50-100 mg tds) and ampicillin are the most commonly employed agents for this purpose. It must be remembered, however, that doses which are employed for long term suppressive therapy may not produce adequate tissue levels. Thus, although the urine may remain sterile, renal infection may continue to progress without being detected. Intermittent catheterisation carried out with aseptic precaution causes a lower incidence of bacteriuria than long-term indwelling catheterisation. During long term catheterisation, measures such as closed drainage are far more important than drugs. Permissiveness, homosexuality and changing sexual practices, particularly among the adolescents, are responsible for such increase in all societies, rich and poor. Clinically, syphilis manifests as: (a) Primary syphilis, characterised by genital or extra-genital, painless indurated ulcer (chancre), occurring within 3 weeks after the infection. This can be diagnosed easily by dark-field microscopy or direct fluorescent antibody test of the exudates. Reversal of positive serology to negative one is possible in early syphilis; it may not occur in late syphilis. Finally syphilis is considered a great imitator, and almost every organ in the body can be, affected. Principles of therapy: the spirochete is extremely sensitive to penicillin, plasma concentrations as low as 0. The concentration must be continuously maintained (time dependent killing) for about 10 days in cases with early syphilis and about 14-20 days in late syphilis. Dark-field microscopy of material from surface lesions is a must in the case of primary chancre and secondary syphilis. When surface lesions are absent, one has to rely on serological tests such as (1) Treponemal-specific tests such as-MACROS-. Further, some patients may distrust such a regime consisting of a single injection, whereas others may take the disease lightly, knowing that it can be cured by a single injection.

Its pharmacokinetics matches with piperacillin with which it has been combined for use in severe infections like peritonitis pain medication for dogs on prednisone order 75mg elavil visa, pelvic/urinary/respiratory infections caused by -lactamase producing bacilli pain treatment pregnancy generic elavil 25 mg amex. However best treatment for shingles nerve pain elavil 25 mg with visa, the combination is not active against piperacillin-resistant Pseudomonas pain medication for dying dogs cheap elavil 75mg mastercard, because tazobactam (like clavulanic acid and sulbactam) does not inhibit inducible chromosomal lactamase produced by Enterobacteriaceae pain diagnostics and treatment center dallas generic elavil 25 mg without prescription. It is also of no help against Pseudomonas that develop resistance by losing permeability to piperacillin treatment for lingering shingles pain generic 50mg elavil overnight delivery. All cephalosporins are bactericidal and have the same mechanism of action as penicillin, i. Acquired resistance to cephalosporins could have the same basis as for penicillins, i. It is the preferred parenteral first generation cephalosporin, especially for surgical prophylaxis. Fourth generation cephalosporins (c) elaboration of -lactamases which destroy specific cephalosporins (cephalosporinases); the most common mechanism. Though the incidence is low, resistance has been developed by some organisms, even against the third generation compounds. Individual cephalosporins differ in their: (a) Antibacterial spectrum and relative potency against specific organisms. Cefazolin It is the prototype first generation cephalosporin that is active against most PnG sensitive organisms, i. Streptococci (pyogenes as well as viridans), gonococci, meningococci, Cephalexin It is the most commonly used orally effective first generation cephalosporin, similar in spectrum to cefazolin, but less active against penicillinase producing staphylococci and H. It is excreted unchanged in urine; the dose needs to be reduced only if creatinine clearance is < 50 ml/min. The antibacterial activity of cefadroxil and indications are similar to those of cephalexin. Cefotaxime It is the prototype of the third generation cephalosporins; exerts potent action on aerobic gram-negative as well as some grampositive bacteria, but is not active on anaerobes (particularly Bact. It is an alternative to ceftriaxone for typhoid fever, and can be utilized for single dose therapy (1 g i. Cefotaxime is deacetylated in the body; the metabolite exerts weaker but synergistic action with the parent drug. Cefaclor It retains significant activity by the oral route and is more active than the first generation compounds against H. Cefprozil this 2nd generation cephalosporin has good oral absorption (>90%) with augmented activity against Strep. Ceftizoxime It is similar in antibacterial activity and indications to cefotaxime, but inhibits B. Ceftriaxone has shown high efficacy in a wide range of serious infections including bacterial meningitis (especially in children), multiresistant typhoid fever, complicated urinary tract infections, abdominal sepsis and septicaemias. Ceftazidime the most prominent feature of this third generation cephalosporin is its high activity against Pseudomonas aeruginosa, and the specific indications are-febrile neutropenic patients with haematological malignancies, burn, etc. Its activity against Enterobacteriaceae is similar to that of cefotaxime, but it is less active on Staph. Neutropenia, thrombocytopenia, rise in plasma transaminases and blood urea have been reported. Cefpodoxime proxetil It is the orally active ester prodrug of 3rd generation cephalosporin cefpodoxime. In addition to being highly active against Enterobacteriaceae and streptococci, it inhibits Staph. Cefdinir this orally active 3rd generation cephalosporin has good activity against many lactamase producing organisms. Cefoperazone Like ceftazidime, it differs from other third generation compounds in having stronger activity on Pseudomonas and weaker activity on other organisms. The indications are-severe urinary, biliary, respiratory, skin-soft tissue infections, typhoid, meningitis and septicaemias. Ceftibuten Another oral 3rd generation cephalosporin, active against gram-positive and few gram-negative bacteria, but not Staph. Ceftamet pivoxil this ester prodrug of ceftamet, a 3rd generation cephalosporin has high activity against gram-negative bacteria, especially Enterobacteriaceae and N. Cefepime Developed in 1990s, this 4th generation cephalosporin has antibacterial spectrum similar to that of 3rd generation compounds, but is highly resistant to -lactamases, hence active against many bacteria resistant to the earlier drugs. Due to high potency and extended spectrum, it is effective in many serious infections like hospital-acquired pneumonia, febrile neutropenia, bacteraemia, septicaemia. Diarrhoea due to alteration of gut ecology or irritative effect is more common with orally administered compounds like cephalexin, cefixime and parenteral cefoperazone, which is largely excreted in bile. Hypersensitivity reactions are the most important adverse effects of cephalosporins. Rashes are the most frequent manifestation, but anaphylaxis, angioedema, asthma and urticaria have also occurred. About 10% patients allergic to penicillin show cross reactivity with cephalosporins. Those with a history of immediate type of reactions to penicillin should better not be given a cephalosporin. Nephrotoxicity Some cephalosporins have low-grade nephrotoxicity which may be accentuated by preexisting renal disease, concurrent administration of an aminoglycoside or loop diuretic. Bleeding occurs with cephalosporins having a methylthiotetrazole or similar substitution at position 3 (cefoperazone, ceftriaxone). This is due to hypoprothrombinaemia caused by the same mechanism as warfarin and is more common in patients with cancer, intra-abdominal infection or renal failure. Neutropenia and thrombocytopenia are rare adverse effects reported with ceftazidime and some others. Its zwitterion character permits better penetration through porin channels of gram-negative bacteria. It is resistant to many -lactamases; inhibits type 1 -lactamase producing Enterobacteriaceae and it is more potent against grampositive and some gram-negative bacteria than the 3rd generation compounds. Adverse effects Cephalosporins are generally well tolerated, but are more toxic than penicillin. Respiratory, urinary and soft tissue infections caused by gram-negative organisms, especially Klebsiella, Proteus, Enterobacter, Serratia. Cephalosporins preferred for these infections are cefuroxime, cefotaxime, ceftriaxone. Septicaemias caused by gram-negative organisms: an aminoglycoside may be combined with a cephalosporin. Ceftazidime + gentamicin is the most effective therapy for Pseudomonas meningitis. Gonorrhoea caused by penicillinase producing organisms: ceftriaxone is a first choice drug for single dose therapy of gonorrhoea if the penicillinase producing status of the organism is not known. For chancroid also, a single dose is as effective as erythromycin given for 7 days. They are preferred over fluoroquinolones (especially in children) for empirical therapy, since many S. Mixed aerobic-anaerobic infections in cancer patients, those undergoing colorectal surgery, obstetric complications: cefuroxime, cefaclor or one of the third generation compounds is used. Hospital acquired infections, especially respiratory and other infections in intensive care units, resistant to commonly used antibiotics: cefotaxime, ceftizoxime or a fourth generation drug may work. Prophylaxis and treatment of infections in neutropenic patients: ceftazidime or another third generation compound, alone or in combination with an aminoglycoside. Thus, it is a -lactam antibiotic with a spectrum resembling aminoglycosides, and is resistant to gram-negative -lactamases. The main indications of aztreonam are hospitalacquired infections originating from urinary, biliary, gastrointestinal and female genital tracts. Lack of cross sensitivity with other -lactam antibiotics except ceftazidime (which has chemical similarity to aztreonam) is the most prominent feature of aztreonam: permiting its use in patients allergic to penicillins or cephalosporins. It is resistant to most -lactamases; inhibits penicillinase producing staphylococci. A limiting feature of imipenem is its rapid hydrolysis by the enzyme dehydropeptidase I located on the brush border of renal tubular cells. Imipenem has propensity to induce seizures at higher doses and in predisposed patients. Diarrhoea, vomiting, skin rashes and other hypersensitivity reactions are the side effects. Meropenem is a reserve drug for the treatment of serious nosocomial infections like septicaemia, febrile neutropenia, intraabdominal and pelvic infections, etc. The adverse effects of meropenem are similar to imipenem, but it is less likely to cause seizures. Meropenem this newer carbapenem is not hydrolysed by renal peptidase; does not need to be protected by cilastatin. Like imipenem, it is active against both gram-positive and gram- Doripenem Introduced recently, this carbapenem has antimicrobial activity similar to meropenem, but is more active against some resistant Pseudomonas. Other properties, including nonsusceptibility to renal peptidase, as well as clinical indications are also similar to meropenem. Adverse effects are nausea, diarrhoea, superinfections and phlebitis of the injected vein. The boy also complains of abdominal pain, bloating, loose motions, loss of appetite, occasional vomiting, weakness, malaise and cough. A local doctor had given some tablets for the past 3 days, but the condition has worsened. He looks ill, mildly dehydrated with coated tongue; pulse is 70/min, abdomen is distended and tender on pressing. The first to be introduced was chlortetracycline in 1948 under the name aureomycin (because of the golden yellow colour of S. Oxytetracycline soon followed; others were produced later, either from mutant strains or semisynthetically. All tetracyclines are slightly bitter solids which are slightly water soluble, but their hydrochlorides are more soluble. The subsequently developed members have high lipid solubility, greater potency and some other differences. The tetracyclines still available in India for clinical use are: Tetracycline Doxycycline Oxytetracycline Minocycline Demeclocycline Glycylcycline: Tigecycline Many others like Chlortetracycline, Methacycline, Rolitetracycline, Lymecycline are no longer commercially available. The sensitive organisms have an energy dependent active transport process which concentrates tetracyclines intracellularly. The more lipid-soluble members (doxycycline, minocycline) enter by passive diffusion also (this is partly responsible for their higher potency). The carrier involved in active transport of tetracyclines is absent in the host cells. Moreover, protein synthesizing apparatus of host cells is less susceptible to tetracyclines. These two factors are responsible for the selective toxicity of tetracyclines for the microbes. However, promiscous and often indiscriminate use has gradually narrowed the field of their usefulness. Cocci: All gram-positive and gram-negative cocci were originally sensitive, but now only few Strep. Clostridia and other anaerobes, Listeria, Corynebacteria, Propionibacterium acnes, B. The nacent peptide chain is attached to the peptidyl (P) site of the 50S ribosome. The nascent peptide chain is transferred to the newly attached amino acid by peptide bond formation. Finally the process is terminated by the termination complex and the protein is released. Notable bacilli that are not inhibited are Pseudomonas aeruginosa, Proteus, Klebsiella, Salmonella typhi and many Bact. Protozoa like Entamoeba histolytica and Plasmodia are inhibited at high concentrations. In such bacteria, usually the tetracycline concentrating mechanism becomes less efficient or the bacteria acquire capacity to pump it out. Due to widespread use, tetracycline resistance has become common among grampositive cocci, E. Incomplete cross resistance is seen among different members of the tetracycline group. Some organisms not responding to other tetracyclines may be inhibited by therapeutically attained concentrations of doxycycline and minocycline (the most potent agent). Partial cross resistance between tetracyclines and chloramphenicol has been noted. Pharmacokinetics the pharmacokinetic differences between individual tetracyclines are included in Table 52. Tetracyclines have chelating property-form insoluble and unabsorbable complexes with calcium and other metals. Milk, iron preparations, nonsystemic antacids and sucralfate reduce their absorption. Administration of these substances and tetracyclines should be staggered, if they cannot be avoided altogether.

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