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Rectal Certain irritant and unpleasant drugs can be put into rectum as suppositories or retenti on enema for system ic e ffect menstrual migraine discount 100 mg lady era amex. T his ro ute can a lso be used when the pa tient is having recurrent vomiting or is unconscious menstruation quotes tumblr lady era 100 mg mastercard. However, it is rather inconvenient a nd e mbarrassing; absorption is slower, irregu lar a nd often unpredictab le, though di azepam so lution and paraceta mol suppository are rapidly and dependably absorbed from the rectum in children. D rug absorbed into external haemorrhoidal veins (about 50%) bypasses liver, but not tha t absorbed into internal hae morrhoida l veins. Diazepam, indomethacin, paracetamo l, e rgotam ine and few other drugs are some times given rectally. The drug can be incorporated in an ointment and applied over specified area of sk in. Absorption of the drug can be enhanced by rubbing the preparation, by using an oily base a nd by an occlusive dressing. This route shou ld be avo ided in shock patients who are vasoconstricted- absorptio n wi ll be delayed. Repos itory (depot) preparations that a re aq ueous s uspensions can be injected for prolonged action. Inhalation Volatile liquids and gases are given by inhalation for systemic action. When adm inistration is di scontinued the drug diffuses back and is rapidly elimi nated in exp ired air. Irritant vapours (ether) cause inflammation of respiratory tract and increase secretio n. Nasal the mucous membrane of the nose can readi ly absorb many drugs; digestive juices and liver are bypassed. This route is being tried for some other peptide d rugs like insulin, as well as to bypass the blood-brai n barrie r. Disadvantages of parenteral routes are- the preparation has to be sterilized and is costlier, the technique is invasive and painful, assistance of another person is mostly needed (tho ug h self injection is possible. The important pare nteral routes are: In this method needle is not used; a hig h velocity jet of drug solution is projected from a microfine orifice using a gun like implement. The solution passes through the superficial layers and gets deposited in the subcutaneous tiss ue. Slow and uniform leaching of the drug occurs over months providing constant blood levels. The no nbiodegradable implant has to be removed later on but not the biodegradable one. It is less painful, but self injection is often impracticable because deep penetration is needed. Intra muscular inj ections should be avoided in anticoagu la nt treated patients, because it can produce local haematoma. The d rug reaches directl y into the b lood stream a nd e ffects a re prod uced immediate ly (great value in eme rgency). T hese complications can be m inimized by di luting the drug or injecting it into a run ning i. O nly aqueous sol utions (not suspe nsions, because drug particles can cause embolism) are to be injected i. The dose of the drug requ ired is smallest (bioavailabi li ty is I00%) and even large volumes can be infused. One big advantage with th is route is- in case res po nse is accurately measurable. A 5-yea r-old ch ild is brought to the hospit al with the com plai nt of feve r, cough, breath lessness and chest pain. The paediatrician makes a provisional diagnosis of acute pneumonia and orders releva nt haematological as well as bacte riological investigations. The intensity of response is related to concentration of the drug at the site of action, wh ich in turn is dependent on its pharmacokinetic properties. Pharmacokinetic considerations, therefore, determine the route(s) of admi ni stration, do.

Mill ions of tiny remodeling units are working on the surface of bone trabcculac and Havcrsian canals to dig micropits by ostcoclastic activi1y and then repair by osteoblastic acti ity in which first collagen and other protein~ (osteoid) are deposited followed by mineralization; the full cycle taking 4-o months women's health blood in urine buy 100 mg lady era free shipping. Diet womens health raspberry ketones purchase discount lady era line, exercise, se, era I hormones and drugs regulate the number and efficiency of bone remodeling units at any given time. Remodeling deficits accumulate over hfc-t ime lo account for age related bone loss. Estrogen lack after menopause mainly causes loss of trabecular bone, particularly aflecting vertebrae, wrist bones and femora l neck. About 300 mg of endogenous calcium is excreted da ily: ha lf in urine and half in faece s. To mainta in calc ium ba lance, the same amount has to be absorbed in the sma ll intestine from the diet. Because norma lly only I/3rd of ingested calcium is absorbed, the dietary allowance for calc ium is 0. T hiazide diuretics impede calc iu m excretion by fac ilitat ing its tubular reabsorption. Calcium carbonate (400/u Ca): It is an insoluble, tasteless and nonirritating salt. It is the most common salt present in calcium supplements, but gastnc acid is required for com ening it into the absorbablc fonn. Absorption and excretion Calcium is absorbed by facilitated di ffusion fro m the entire small intestine. Phytates, phosphates, oxalates and tetracycl ines complex with Ca 2+ in an insoluble form in the intestines and interfere with its absorption. As dietary supplement especially in growing children, pregnant, lactating and menopausal women. Calcium + vit D3 have adjuvant role to these drugs in the prevention and treatment of osteoporosis. It does not appear to reduce fracture ris k in otherwise healthy subjects taking adeq uate diet. Certain subgroups of osteoporotic subjects may benefit from calcium supplements, but the benefit appears to be marginal and limited to cortical bone loss only. Thus, calcium supplements should be given only to subjects taking diet low in calcium. It also promotes phosphate excretion which tends to supplement the hypercalcacmic clTcct. However, grossly increased plasma calcium level occurring in hyperparathyroidism overrides the direct action on tubules and calcium excretion in urine is actually increased. Pro longed hypoca lcacmia causes hypertrophy and hyperplasia of parathyroids, whi le sustained hypcrcalcaemia has the opposite elTect. In addition, birth rate of bone remodeling units into which osteoclasts are recruited is enhanced. Formation of the remodeling pit is followed by os1eoblas1ic deposition of new bone into it. A bone resorption pit is dug out by secretion of acid and proteolytic acid hydrolases. After formation of the remodeling pit, preosteoblasts from bone marrow stem cells proliferate, migrate to the base of the pit, transform into mature osteoblasts and laydown new osteoid, which is later mineralized. Calcitonin directly inhibits osteoclast function and probably enhances osteoblastic new bone formation. Cinacalcet can also be used to lower plasma Ca2+ in inoperable cases of parathyroid cancer. Teriparatide is the only agent which stimulates new bone formation, whereas the other two only check bone resorption.

The active principle sti mulates the mycnteric plexus to increase peristalsis and decrease segmentation menopause 30 symptoms lady era 100mg cheap. All inorganic salts used as osmotic (saline) purgatives have similar action-<lifTer only in dose women's health center clarksville order 100mg lady era otc. Saline purgatives are infrequently used now for the treatment of constipation because they are inconvenient/unpleasant, produce watery stools and after-constipation. However, they may be employed when constipation is to be relieved urgentl y and for preparation of bowel before surgery, colonoscopy; in food/drug poisoning and as after-purge in the treatment of tapeworm infestation. It is a se misynth etic di saccharide of fructose and lactose which is neither digested nor absorbed in the small intestine, th erefore retai ns wate r. Lactulosc is broken down in the colon by bacteri a to osmotieally more active and weak ly acidic products. In a dose of I 0-30 g taken with plenty of water, it produces soft forrned stools in 8- 24 hours. Lactito l is neither absorbed nor digested in ile um, but gets fennented by colonic bacteria into osmotical ly active and weakl y acidic products. The laxative efficacy of lactitol is comparab le to that of lactu lose, but its palatabi li ty and patient acceptability is c la imed to be belier. Side effects are disten tio n, flatule nce, cramps, dyspepsia, nausea and vom iting. Functional constipation Constipation is infrequent production of hard stools req uiring straining to pass, or a sense of incomplete evacuation. Proper assessment of the causative factor in the patient and its correction by high fibre diet. The first choice laxative is paghula or any of the soluble fibres taken over weeks/ months. If these measures do not work, a bulk forming agent or osmotic laxatives like lactulose or mag. Stimulant laxatives like bisacodyl or senna should be used only in patients with unsatisfactory response or those with poor compliance to the above. Bedridden patients (myocardial infarction, stroke, fractures, postoperative): bowel movement may be sluggish and constipation can be anticipated. To treat constipation: Enema (soap-water/glycerine) is preferred; bisacody l or senna may be used orally. Methylnaltrexone It is an opioid anltlgonist (primarily p receptor) that does not penetrate blood-brain barrier, but acts on opioid receptors in the gut. Mcthy lnaltrcxonc has been used to counteract opioid analge;ic induced constipation in cancer/ palliative care patients without blocking the analges ic action. Preparation of bowel for surgery, colonoscopy, abdominal X-ray The bowel needs to be emptied of the contents including gas. Fixed dose combinations of an anthclmintic (other than pipcraz inc) with a purgative is banned in lndta, as arc laJati, es "ith en1ymc preparations. Food/drug poisoning the idea is to d ri ve o ut the unabsorbed irritant/poisonous material from the inte stines. Purgative abuse Purgat ives are often self prescribed an d taken wi thout consulting a physic ian. Others use a purgati ve casually, obtain thorough bowel evacuation, and by the time the colon fills up for a proper motion (2- 3 days) they get convinced that they are constipated and start tak ing the purgative regularly. Diarrhoeal di eases constitute a major cause of morbidity and mortality worldwide; especially in developing countries. The Ministry of Health has estimated that 13 children die of diarrhoea every hour in India, and that there were > I 00,000 under 5 yr deaths in 2015 due to diarrhoea.

It has been located in the cholinergic neurones of the brainstem and spinal cord as well as in kidney menstrual discomfort order 100 mg lady era with mastercard, heart and lungs menstruation 9 days long order lady era 100 mg on line. Kinins are also generated by trypsin, proteolytic en1ymcs in snake and wasp venoms and by kallikrein present in kidney, pancreas and other tissues. Bradykinin can also be generated from kallidin on the removal of lysine residue by an aminopeptidase. Thus, physiologically only small amounts of kinins arc generated in plasma and tissues. Another carboxypcptidase Ki11i11ase I removes on ly one amino acid (argin ine) producing selec tive B receptor agonistic metabolites (dcsA rg bradykinin and desArg kallidin) which arc fu rther degraded by other peptidase. The tw o important plasma kinins, Ka//idin (decapeptide) and Bradykinin (nonapcptide) were discovered around 1950 by two independent lines of inves tigation into the hypotensive activity of urine and certain snake venoms. These and some o ther biological nuids were fo und to act indirectly: they contained enzymes which generated vasodilator substances in the plasma. Kinins are generated by proteolytic reactions triggered by tissue injury, inflammation, allergic reaction, etc. Generation and metabolism Kininogcns arc a, globulins present in plasma "hich also contains inactie kininogcnasc prekal/1kre111. Plasmin faci litates contact activation of Hageman factor Actions Bradyki nin and kallidin have similar actions. Smooth muscle Kinins induce contraction of intestine whi ch is characteristica ll y slow (bradys-slow, kinein- to move). Neurones Kinins strongly stimulate nociceptive afferents and produce a burning sensation. Applied to blister base or injected intraperitoneally or in the brachia(artery, bradykinin produces intense, transient pain and has been used in analgesic testing. Injected directly in brain they produce a variety of efTects including enhanced sympathetic discharge. Kidney Kinins increase renal blood flow as well as faci litate salt and water excretion by action on tubules. The di uretic effect of furosemide is reduced by kinin 8 2 receptor antagonists, indicating participation of locally generated kinins in this response. The 8 1 kin in receptors arc minimally expressed in normal tissues, but arc indu ced by inflammation and colocalize with kininase I enzyme, so that the B, agon istic des-Arg k. Mediation of inflammation Kinins produce all the signs of inHammation-redness, exudation. Tissue injury can cause local kinin production which then sets in motion the above defensive and reparative processes. The B, antagonists block acute pain produced by bradykinin, b~t induced B, receptors appear to mediate pain of chronic inHammation. As a result plasma bradykinin levels rise manifesting as unpredictable episodes of swelling of lips, tongue, face, respiratory and g. Bradykinin antagonists After characterization of 8 1 and 8 2 kinin receptors, and in view of prominent pathophysiological roles of kin ins, several peptide and nonpeptide kinin antagonists have been produced and tested for clinical use. It effectively reverses the swelling and other symptoms in hereditary angioedema, and is currently the best treatment option for this condition. By directly dilating ve ins, Ps lower central venous pressure and preload on the heart, which tends to reduce cardiac output in normal subjects, but may improve it in decompensated heart. T hey also decrease proxima l tu bular a+ reabsorption resulting in natriuresis a nd d iuresis.

Sulfasalazine has also been used as a disease modifying drug in rheumatoid a rthritis menopause night sweats treatment proven lady era 100mg. The absorbed sulfapyridine moiety appears to be responsible for the therapeutic effect (see p pregnancy videos buy 100 mg lady era amex. It may also be e mployed to treat mild-to-moderate exacerbations or as adjunct to corti costeroid in more severe active disease. Mesalazine (Mesalamine) Adverse effects Coated mesalazine is much better to lerated than sul fasa laz ine. Side effects noted are nausea, dia rrhoea, abdomina l pain a nd headache, but are mild and less frequent. Drug interactions Coated mesalazine may enhance the gastric toxicity of glucocorticoids and hypoglycaemic action ofsulfonylureas. Inte raction with coumarins, furosemide, spironolactone, methotrcxate and rifampicin are possi ble. However, it often aggravates diarrhoea initially by decreasing transit time for gut contents and increasing secretions. However, ri sks of chronic immunosuppression m ust be we ighed in each patient before instituting therapy with these drugs. Because of long latency of response, they are not suitable for acute flareups of the disease, but have good remission ma intaining and steroid-sparing property. In respons ive patients symptomatic relief usua lly starts within 3- 7 days and remission is induced in 2-3 weeks. In more severe di sease with extraintestinal man ifestations and for rapid relief therapy may be initiated with i. Corticosteroids a re generally used for short term; tapered over 8- 12 weeks a nd discontinued after remission is induced. Because of the high dosage requ irement even short term therapy with glucocorticoids is mostly attended by significa nt side effects, which should be managed symptomatically. T hiopurines have their own adverse effect potential, but the same is rated lower than that of prolonged steroid therapy. Thus, methotrexate has a role only in severe CrD and in patients not responsive to or not tolerati ng azath ioprine. Containing phthalylsulfathiazole, succinyls ulfathiazo le, sulfaguanidine, neomycin, streptomycin. The stools are relatively small volume, liquid but not watery, frothy and are preceded by griping pain in abdomen. The ir adve nt y changed the outl ook of the physician about the power drugs can have on diseases. T hey a re one of the few class of drugs which can cure, and not j ust pall iate disease. Their importance is magnified in the deve loping countries, where infective diseases predominate. Drugs in thi s class differ from all others in that they arc designed to inhibit/kill the infecting orga ni sm and to have no/ mini mal effect on the reci pient. Antibiotics these arc substances produced by microorganisms, which selectively suppress the growth of or ki ll other microorganisms at very low concen trations. Chemotherapeutic agent Initially this term was restricted to synthetic compounds, but si nce many antibiotics and their analogues have now been synthesized, th is cri teri on has become irrelevant; both synthetic and microbio logical ly produced drugs need to be included together. He developed the arsenicals-moxy/ for sleeping sickness, ar phe11a111ine in 1906 and neoarsphenamine in 1909 for syphilis. It was soon realized that the active moiety was paraamino benzene sul fonamide, and the dye pan was not essential. Fleming (1929) found that a diffusible substance was elaborated by Penicillium mould which could destroy Staphy/ococcus on the culnire plate.