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By: Z. Hamid, M.B. B.CH., M.B.B.Ch., Ph.D.

Assistant Professor, College of Osteopathic Medicine of the Pacific, Northwest

The effects of oral erectile dysfunction youtube order viagra extra dosage 200mg with amex, transdermal (patch and gel) impotence and high blood pressure discount viagra extra dosage 150 mg mastercard, intranasal impotent rage definition discount viagra extra dosage 120 mg fast delivery, sublingual, buccal, vaginal, subcutaneous and intramuscular administration of estrogens, as well as of oral, vaginal, transdermal, intranasal, buccal, intramuscular and intrauterine application of progestogens are discussed. The various types of progestogens, their receptor interaction, hormonal pattern and the hormonal activity of certain metabolites are described in detail. The structural formulae, serum concentrations, binding affinities to steroid receptors and serum binding globulins, and the relative potencies of the available estrogens and progestins are presented. Differences in the tissue-specific effects of the various compounds and regimens and their potential implications with the risks and benefits of hormone replacement therapy are discussed. This casts compared to the rapid rise and fall after oral considerable doubts on the usefulness of regular administration. The good effectiveness and tolermeasurements of hormone levels for the predicability of intranasal estradiol therapy, which is tion or control of a therapeutic success. Another associated with extremely high peak levels occurclaim that turned out to be wrong was the story of ring within a few minutes after administration and a rapid fall thereafter, refuted this general opinion. There are many proteins (coactivators, corepressors) which the classical estrogenic hormones are C18 stermay interact with these complexes and regulate oids with a phenolic structure in ring A. The equine estrogens are involved in the control of the estrogen-induced characterized by one or two additional double biological response. The prerequisite of steroid-like Tamoxifen 7 6 actions of non-steroidal compounds is a stiff, 4-Hydroxy-tamoxifen 178 339 planar structure which is brought about by soClomiphene 25 12 called conjugate double bonds (single bond alterNafoxidine 44 16 nating with double bond) which couple the 5-androstenediol 6 17 aromatic systems of two rings. Diethylstilbestrol 3b-androstanediol 3 7 is a potent estrogen, because it is a stiff plane with Coumestrol 94 185 two hydroxy groups in a distance similar to that of Genistein 5 36 the estradiol molecule. Compounds with no Climacteric 5 Pharmacology of estrogens and progestogens Kuhl Estrone Estradiol-17β Estriol Equilin Dihydroequilin-17β Estradiol valerate ∆8-Estrone ∆8-Estradiol-17β Estradiol cypionate Equilenin Dihydroequilenin-17β Diethylstilbestrol 17α-Ethinylestradiol Mestranol Quinestrol Estradiol-17α Dihydroequilin-17α Dihydroequilenin-17α Figure 2 Structural formulae of estrogens phenolic hydroxy group. In the phytoestrogens differ largely in their contrast to esters and ethers, the introduction of estrogenic activity. Hormonal potency of estrogens Many attempts have been made to compare the potency of the various estrogens by means of a Interconversion between estradiol-17b and its simple bioassay. As every action of every estrogen metabolites is unique for every tissue, generalizing comparthe natural estrogens produced by the human are isons on the basis of a single parameter is highly estradiol, estrone, estriol, and their conjugates, i. The determination of a so-called the sulfuric acid esters (sulfates) and glucuronic ‘estrogenicity’ which reflects the effect of various acid esters (glucuronides). The equilin, equilenin, and D8-estrone which correlatter is dependent on the bioavailable (‘free’) spond structurally to estrone. Their conversion to fraction of the circulating steroid, the intracellular dihydroequilin-17b, dihydroequilenin-17b, and production and inactivation rate. Whereas the balance of the much more active than the natural estrogens, mutual interconversion between estradiol and its because the 17a-ethinyl group prevents the oxidametabolites is largely shifted to estrone and tion of the 17b-hydroxy group and is able – after estrone sulfate (Figure 3), that between dihydrothe oxidative formation of a very reactive interequilin-17b or dihydroequilenin-17b and the mediate – to inhibit irreversibly cytochrome P450 respective metabolites is nearly equal, resulting enzymes, which are involved in the metabolism of in a higher hormonal activity of the equine 15–17 steroids. In the Metabolism of estrogens endometrium, the latter is stimulated by progesterone and synthetic progestins, resulting in a Beyond these reversible conversion reactions at strong increase in the local inactivation rate of C17 of estradiol, further phase 1 metabolic 18 estradiol. There are Similar oxidative and reductive interconvertwo main pathways of oxidative metabolism; the sions occur between the equine estrogens and hydroxylation of ring A at C2 or C4 results in the their metabolites. Hyperthyroidism and thyroxine therapy reduce 16a-hydroxylation and enhance 2-hydroxylation, whereas hypothyroidPharmacokinetic properties ism has the opposite effect. Obesity stimulates the natural estrogens estradiol, estrone, estrone ring D metabolism and underweight causes a shift sulfate (sodium salt) and estriol are available in to the ring A metabolism. Estradiol and esEstriol is a weak, short-acting estrogen which trone are lipophilic, but show a sufficient water cannot be re-transformed to estradiol, but undersolubility, which is increased by binding to goes extensive conjugation. For oral treatment, estradiol is used in a C at C11b and C14a, in ring D at C15a, and at the microcrystalline form to increase compound sur18,19 angular C18 methyl group. The smaller the crystals, gates which are catalyzed by intestinal and the more rapid is the absorption and the higher is hepatic enzymes are important factors in the the bioavailability. The crystals contain some regulation of the pharmacokinetics and pharmawater (hemihydrate, two molecules estradiol are codynamics of estradiol. The conjugation of associated with one molecule water), which plays lipophilic steroids increases largely their water no role after resorption/dissolution. Therefore, during oral treatment with of the C17-hydroxy group of estradiol with estradiol or estrone sulfate, high amounts of valerianic acid results in estradiol valerate, which estrogen sulfates are circulating, while the prevents metabolism to estrone as long as hydroglucuronides are involved in the excretion of lysis has not taken place.

Additional information:

This may inhibit spread of seizure activity in epilepsy erectile dysfunction doctors in san fernando valley purchase 120 mg viagra extra dosage visa, control neuralgic pain by blocking synaptic transmission in the trigeminal nucleus and stabilise mood in bipolar disorder by reducing electrical ‘kindling’ in the temporal lobe and limbic system erectile dysfunction videos order 120mg viagra extra dosage otc. Important the most common dose-related adverse effects are gastrointestinal adverse effects upset erectile dysfunction cycling buy 200 mg viagra extra dosage free shipping. Carbamazepine hypersensitivity affects about 10% of people taking the drug and most commonly manifests as a mild maculopapular skin rash. Antiepileptic hypersensitivity syndrome affects about 1 in 5000 people taking carbamazepine or phenytoin, usually within 2 months of starting treatment. Stevens–Johnson syndrome, toxic epidermal necrolysis), fever and lymphadenopathy with systemic. Other common adverse effects include oedema and hyponatraemia due to an antidiuretic hormone-like effect. Warnings Carbamazepine exposure in utero is associated with neural tube defects, cardiac and urinary tract abnormalities and cleft palate. Women with epilepsy planning pregnancy should discuss treatment with a specialist and start taking high-dose folic acid supplements before conception. Prior antiepileptic hypersensitivity syndrome is a contraindication to both carbamazepine and phenytoin, due to potential cross-sensitivity. Carbamazepine should be prescribed with caution in patients with hepatic, renal or cardiac disease, due to increased risk of toxicity. Important Carbamazepine induces cytochrome P450 enzymes, reducing plasma interactions concentration and effcacy of drugs that are metabolised by P450 enzymes. Carbamazepine is itself metabolised by these enzymes, so its concentration and adverse effects are increased by cytochrome P450 inhibitors. Complex interactions occur with other antiepileptic drugs as most alter drug metabolism. The effcacy of antiepileptic drugs is reduced by drugs that lower the seizure threshold. As tolerance develops to adverse effects, the dose is increased gradually to a usual maximum of 1. Treatment should not be stopped suddenly, but should be withdrawn gradually under medical supervision, due to risk of seizure recurrence. Administration Oral carbamazepine is available as immediateor modifed-release tablets, chewable tablets and oral suspension. As carbamazepine bioavailability differs between formulations, switching between them is best avoided. Use of rectal suppositories should be limited to short periods when oral administration is not possible as rectal irritation may occur with prolonged use. Warn the patient to look out for signs of severe hypersensitivity, including skin rashes; bruising, bleeding, a high temperature or mouth ulcers (blood toxicity); reduced appetite or abdominal pain (liver toxicity). Advise patients that they must not drive unless they have been seizure-free for 12 months (or have at least a three-year pattern of seizures while asleep only). Monitoring Treatment effcacy is monitored by comparing seizure frequency before and after starting treatment or dose adjustment. The most useful way to monitor safety is by asking the patient to report any unusual symptoms immediately (as above). Routine measurement of full blood count and liver enzymes is unlikely to coincide with unpredictable hypersensitivity reactions. Plasma carbamazepine concentrations are not routinely measured, but may be useful in selected cases. Blood should be taken immediately before the next dose, when carbamazepine concentrations should be 4–12 mg/L. Time to steady-state plasma concentrations (and appropriate sampling for repeat measurements) is 2–4 weeks after starting treatment and 4–5 days after a dose change. There is no evidence that they are more effective than older drugs but they may be better tolerated.

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Pain the prediction of postconcussive symptoms: a after whiplash: a prospective controlled inception 3-month prospective study erectile dysfunction surgery cost discount viagra extra dosage amex. Incidence and traumatic headache: emphasis on chronic types folpredictors of chronic headache attributed to erectile dysfunction injections treatment order viagra extra dosage with paypal whiplowing mild closed head injury erectile dysfunction drugs uk buy viagra extra dosage 130mg without prescription. Post-traumatic headache: commentary: an head restraints – frequency of neck injury claims in overview. Scientific monograph of the Quebec Task Force Posttraumatic headache: biopsychosocial comparion Whiplash-Associated Disorders: redefining sons with multiple control groups. Post-craniotomy headache after acousCraniotomy site influences postoperative pain foltic neuroma surgery. This remains true when the new headartery disorder ache has the characteristics of any of the primary head6. This vical carotid or vertebral artery dissection rule applies similarly to new migraine-aura-like symp6. When a pre-existing headache with the characteristics artery dissection of a primary headache disorder becomes chronic,oris 6. The close temporal relationship betweentheheadacheandthese neuroDescription: New and usually acute-onset headache logical signs is therefore crucial to establishing causation. It is very rarely the orrhagic stroke, headache is overshadowed by focal signs presenting or a prominent feature of ischaemic stroke. In a number of other conditions that can Diagnostic criteria: induce both headache and stroke, such as dissections, cerebral venous thrombosis, giant cell arteritis and central nerA. Any new headache fulfilling criteria C and D vous system angiitis, headache is often an initial warning B. Evidence of causation demonstrated by either or ation of headache with thesedisorders in order todiagnose both of the following: correctly the underlying vascular disease and start appro1. A clue that points to an underlying vascular conlel with stabilization or improvement of other dition is the onset, usually sudden, of a new headache, symptoms or clinical or radiological signs of so far unknown to the patient. Whenever this occurs, ischaemic stroke vascular conditions should urgently be looked for. A cranial and/or cervical vascular disorder known to be able to cause headache has been demonstrated Note: C. It is usually of moderate intensity, parallel with improvement of the cranial and has no specific characteristics. It can be ipsilateral and/or cervical vascular disorder to the stroke or bilateral. Notes: Headache is, however, extremely common in acute arterial wall disorders that may lead to ischaemic 1. The ischaemic stroke has stabilized, spontaneously invariably, last less than one hour. It lasts less than 24 hours it may be isolated or associated with focal neurological deficits. Evidence of causation demonstrated by both of by non-traumatic intracerebral haemorrhage, associated the following: with focal neurological signs of the intracerebral haem1. Any new headache fulfilling criteria C and D and radiological features according to its various 1 B. Notes: the headache is usually overshadowed by focal deficits or coma, but it can be the prominent early feature 1. The three months should be counted from stabilizaof some intracerebral haemorrhages, notably cerebellar tion, spontaneously or through treatment, rather haemorrhage; this may require emergency surgical than onset of the subarachnoid haemorrhage decompression. Evidence of causation demonstrated by at least noid haemorrhage, older age, sensorimotor dysfunctwo of the following: tion, stereotyped aura-like spells and absence of 1. The most common reasons for misdiagnosis are failure to obtain appropriate neuroimaging, or Note: misinterpretation of it, or failure to perform lumbar puncture in cases where this is required. Isolated cases or small series have mostly been reported Description: Headache caused by non-traumatic acute by neurosurgeons. Headache is described in 25–100% subdural haemorrhage, typically severe and sudden, of cases depending on the series and the underlying peaking in seconds (thunderclap headache) or minutes.

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Renal Kala-azar Allopurinol inhibits Leishmania by altering its purine metabolism erectile dysfunction exercises treatment buy viagra extra dosage 200mg with visa. It was tried as adjuvant to erectile dysfunction drugs and medicare discount 120 mg viagra extra dosage overnight delivery sodium impairment increases the incidence of rashes and stibogluconate erectile dysfunction quad mix buy viagra extra dosage 150 mg mastercard, but abandoned due to poor efficacy. It is a recently introduced nonpurine xanthine Gastric irritation, headache, nausea and dizziness oxidase inhibitor, equally or more effective than are infrequent; do not need withdrawal. It is rapidly Precautions and contraindications Liberal absorbed orally, highly plasma protein bound, fluid intake is advocated during allopurinol oxidized as well as glucuronide conjugated in therapy. It is contraindicated in hypersensitive the liver and excreted by kidney; the plasma t½ patients, during pregnancy and lactation. It should be cautiously used in the elderly, children the most important adverse effect is liver and in patients with kidney or liver disease. Diarrhoea, nausea and Uses Allopurinol is the first choice drug in headache are the usual side effects. It can be used in both over producers xanthine oxidase, it has the potential to interact and under excretors of uric acid, particularly more with mercaptopurine, azathioprine and theophylsevere cases, with tophi or nephropathy. The two classes Febuxostat is an alternative drug for treating of drugs can also be used together when the body symptomatic gout only in patients intolerant to load of urate is large. It is not indicated in malignancy associated gradually disappear and nephropathy is halted, hyperuricaemia. Rasburicase It is a new recombinant xanthine oxidase enzyme that oxidizes uric acid to soluble and easily excreted To potentiate 6-mercaptopurine or azathioprine allantoin. It is indicated only for preventing chemotherapy in cancer chemotherapy and immunosuppressant associated hyperuricaemia when massive lysis of leukaemic therapy. Antitussives (Cough centre suppressants) (a) Opioids: Codeine, Ethylmorphine, Cough is a protective reflex, its purpose being Pholcodeine. Adjuvant antitussives airway, its suppression is not desirable, may even Bronchodilators: Salbutamol, Terbutalin. Apart from specific remedies Pharyngeal demulcents sooth the throat and reduce (antibiotics, etc. Expectorants (Mucokinetics) Sodium and potassium citrate are considered (a) Bronchial secretion enhancers: Sodium or to increase bronchial secretion by salt action. Potassium citrate, Potassium iodide, GuaiPotassium iodide is secreted by bronchial glands phenesin (Glyceryl guaiacolate), balsum of and can irritate the airway mucosa. Ammonium salts are nauseating—reflexly Acetylcysteine It opens disulfide bonds in mucoproteins increase respiratory secretions. A variety of expecpresent in sputum—makes it less viscid, but has to be torant formulations containing an assortment of administered directly into the respiratory tract. Bromhexine A derivative of the alkaloid vasiIt is available in combination with amoxicillin or cephalexin for treatment of bronchitis, bronchiectasis, sinusitis, etc. It is a common ingredient of many proprietary cough is blocked by naloxone indicating that it is exerted formulations (see antitussive combinations below). Abuse Chlophedianol It is a centrally acting antiliability is low, but present; constipation is the tussive with slow onset and longer duration of chief drawback. They afford relief in cough due to their Ethylmorphine It is closely related to codeine sedative and anticholinergic actions, but lack which is methylmorphine, and has antitussive, selectivity for the cough centre. They have no respiratory depressant properties like it, but is expectorant property, may even reduce secretions believed to be less constipating. They have been specially promoted for cough in respiratory allergic states, Pholcodeine It has practically no analgesic or addicting though their lack of efficacy in asthma is property, but is similar in efficacy as antitussive to codeine and is longer acting—acts for 12 hours; dose: 10–15 mg. It depresSecond generation antihistamines like fexofenases cough but has no narcotic, analgesic or dependine, loratadine, etc. It is nearly equipotent Peripherally acting antitussives antitussive as codeine, especially useful in spasmodic cough. Headache and nausea occur Prenoxdiazine In contrast to other antitussives, occasionally as side effect. It can release histamine it acts peripherally; desensitizes the pulmonary and produce bronchoconstriction in asthmatics. Though an old drug developed (N-methyl D-aspartate) receptor antagonist; the in Hungary, it has been introduced recently in d-isomer has antitussive action while l-isomer is India. Dextromethorphan does not depress mucociliary function of the airway mucosa and Bronchodilators Bronchospasm can induce or is practically devoid of constipating action. Stimulation of pulmonary Though considered nonaddicting, some drug receptors can trigger both cough and bronchoabusers indulge in it.