By G. Chris. Emmanuel College. 2019.
In patients with benign prostatic hypertrophy proscar 5mg free shipping, opioids may cause acute urinary retention; repeated catheterization may be required buy proscar 5mg line. Drug Interactions The major interactions between morphine and other drugs are shown in Table 22 buy cheap proscar 5 mg on-line. Toxicity Clinical Manifestations Opioid overdose produces a classic triad of signs: coma safe 5 mg proscar, respiratory depression, and pinpoint pupils. Although the pupils are constricted initially, they may dilate as hypoxia sets in (secondary to respiratory depression). Treatment Treatment consists primarily of ventilatory support and giving an opioid antagonist. However, if the pellets are crushed, the naltrexone will be absorbed too, thereby blunting the effects of the morphine. As a result, potential abusers cannot get a quick high by crushing the pellets to release all of the morphine at once. As a result, the entire dose can be absorbed quickly—rather than over 24 hours—thereby causing a potentially fatal spike in morphine blood levels. Patients can swallow Embeda capsules whole, or they can open the capsules and sprinkle the pellets on applesauce, which must be ingested without chewing. High doses are required for patients with a low tolerance to pain or with extremely painful disorders. Patients with sharp, stabbing pain need higher doses than patients with dull pain. Neonates require relatively low doses because their blood-brain barrier is not fully developed. Outpatients should be warned not to increase dosage without consulting the prescriber. Routes and Dosages Oral Oral dosing is generally reserved for patients with chronic, severe pain, such as that associated with cancer. Because oral morphine undergoes extensive metabolism on its first pass through the liver, oral doses are usually higher than parenteral doses. However, oral dosing is highly individualized, and some patients may require 75 mg or more. Patients should be instructed to swallow these products intact, without crushing or chewing. Also, warn patients using Kadian or Embeda capsules not to drink alcohol, which can accelerate release of morphine from these products. Other Strong Opioid Agonists In an effort to produce a strong analgesic with a low potential for respiratory depression and abuse, pharmaceutical scientists have created many new opioid analgesics. However, none of the newer pure opioid agonists can be considered truly superior to morphine; these drugs are essentially equal to morphine with respect to analgesic action, abuse liability, and the ability to cause respiratory depression. Also, to varying degrees, they all cause sedation, euphoria, constipation, urinary retention, cough suppression, hypotension, and miosis. However, despite their similarities to morphine, the newer drugs do have unique qualities. Hence one agent may be more desirable than another in a particular clinical setting. With all of the newer pure opioid agonists, toxicity can be reversed with an opioid antagonist (e. Important differences between morphine and the newer strong opioid analgesics are discussed later. Fentanyl Fentanyl [Duragesic, Abstral, Actiq, Fentora, Onsolis, Lazanda, Subsys] is a strong opioid analgesic with a high milligram potency (about 100 times that of morphine). Eight formulations are available for administration by four different routes: parenteral, transdermal, transmucosal, and intranasal. Depending on the route, fentanyl may be used for surgical analgesia, chronic pain control, and control of breakthrough pain in patients taking other opioids. Fentanyl, regardless of route, has the same adverse effects as other opioids: respiratory depression, sedation, constipation, urinary retention, and nausea. Patients taking these inhibitors should be closely monitored for severe respiratory depression and other signs of toxicity. Transdermal System The fentanyl transdermal system [Duragesic] consists of a fentanyl-containing patch that is applied to the skin of the upper torso. The drug is slowly released from the patch and absorbed through the skin, reaching effective levels in 24 hours. Levels remain steady for another 48 hours, after which the patch should be replaced. If a new patch is not applied, effects will nonetheless persist for several hours, owing to continued absorption of residual fentanyl remaining in the skin. Transdermal fentanyl is indicated only for persistent severe pain in patients who are already opioid tolerant. The patch should not be used in children younger than 2 years or in anyone younger than 18 years who weighs less than 110 pounds. Also, the patch should not be used for postoperative pain, intermittent pain, or pain that responds to a less powerful analgesic. Like other strong opioids, fentanyl overdose poses a risk for fatal respiratory depression. If respiratory depression develops, it may persist for hours after patch removal, owing to continued absorption of fentanyl from the skin. Fentanyl patches are available in five strengths, which deliver fentanyl to the systemic circulation at rates of 12. If a dosage greater than 100 mcg/hour is required, a combination of patches can be applied. As with other long-acting opioids, if breakthrough pain occurs, supplemental dosing with a short-acting opioid is indicated. For most patients, patches can be replaced every 72 hours, although some may require a new patch in 48 hours. Used or damaged patches should be folded in half with the medication side touching and flushed down the toilet. Transmucosal Fentanyl for transmucosal administration is available in four formulations: lozenges on a stick [Actiq], buccal tablets [Fentora], sublingual spray [Subsys], and sublingual tablets [Abstral]. All five products are approved only for breakthrough cancer pain in patients at least 18 years old who are already taking opioids around-the-clock and have developed some degree of tolerance, defined as needing, for 1 week or longer, at least: 60 mg of oral morphine a day, or 30 mg of oral oxycodone a day, or 25 mg of oral oxymorphone a day, or 8 mg of oral hydromorphone a day, or 25 mcg of fentanyl per hour, or an equianalgesic dose of another opioid. Transmucosal fentanyl must not be used for acute pain, postoperative pain, headache, or athletic injuries. Furthermore, it is essential to appreciate that the dose of fentanyl in these formulations is sufficient to kill nontolerant individuals—especially children. Adverse effects of transmucosal fentanyl are like those of other opioid preparations. The most common are dizziness, anxiety, confusion, nausea, vomiting, constipation, dyspnea, weakness, and headache. Because of differences in bioavailability, transmucosal fentanyl products are not interchangeable on a microgram-for-microgram basis. For example, a 100- mcg buccal tablet produces about the same fentanyl blood level as does a 200- mcg lozenge. Accordingly, if a patient switches from one transmucosal product to another, dosage of the new product must be titrated to determine a strength that is safe and effective. To administer the unit, patients place it between the cheek and the lower gum and actively suck it. Analgesia begins in 10 to 15 minutes, peaks in 20 minutes, and persists 1 to 2 hours. If breakthrough pain persists, the patient can take another 200-mcg unit 15 minutes after finishing the first one (i. If the patient needs more than 4 units/day, it may be time to give a higher dose of his or her long-acting opioid. To promote safe and effective use of the Actiq system, the manufacturer provides an Actiq Welcome Kit as well as a Child Safety Kit with the initial drug supply. The kit contains educational materials and safe storage containers for unused, partially used, and completely used units.
B Laparoscopy and dye test should be ofered for women with comorbidities such as pelvic infammatory disease order proscar paypal, previous ectopic or endometriosis 5 mg proscar sale, so that tubal and pelvic pathology can be assessed at the same time buy proscar uk. J Semen analysis results show mild oligozoospermia with a sperm concentration of <15 million/ml and hence the test should be repeated 3 months afer the initial test to allow time for the cycle of spermatozoa formation to be completed order proscar 5 mg mastercard. However, if there is azoospermia or severe oligozoospermia a repeat test should be done as soon as possible. C In women with irregular prolonged menstrual cycles serum progesterone should be done later in the cycle – as, in this case, on day 28 of a 35 days cycle – and repeated weekly until the next menstrual cycle starts. H Urinary retention with overfow incontinence is a typical presentation in the postnatal period. Prolonged labour, regional anaesthesia, forceps delivery and perineal trauma predispose to urinary retention. Bladder scan to check post-void residual and ensure complete bladder emptying should be performed. J Urodynamic stress incontinence is the involuntary leakage of urine during increased intra-abdominal pressure in the absence of detrusor contractions and can only be diagnosed by urodynamic studies. Stress urinary incontinence is a 209 symptom/complaint of involuntary leakage of urine on efort or exertion, or on sneezing or coughing. F Overactive bladder is a chronic condition, defned as urgency with or without urge incontinence, usually with frequency or nocturia. Detrusor overactivity is probably the underlying condition, but the diagnosis can be confrmed on urodynamic testing. C In women with abdominal pains in early pregnancy and localized tenderness, the diagnosis of ectopic pregnancy should be considered until proven otherwise. F The history, symptoms and signs are suggestive of an acute infection of the lower genital tract: pelvic infammatory disease. B The likely diagnosis is ovarian cyst accident: torsion or rupture, given the clinical scenario of acute onset of pains in presence of an intrauterine pregnancy and an ovarian cyst. Subsequent spontaneous pregnancy rates in women who were previously sub-fertile are also improved with this treatment. A • Simple, unilateral, unilocular ovarian cysts, less than 5 cm in diameter, have a low risk of malignancy. It is unclear whether combined oral contraceptives should be taken conventionally, continuously or in a tricycle regimen (i. It is considered appropriate to try those therapies that have not been shown to be detrimental in view of poor understanding of the aetiology of premenstrual syndrome. It is caused by an overgrowth of anaerobes and most women present with vaginal discharge. Gardnerella vaginalis, also known as Haemophilus vaginalis, is a facultative anaerobic, non-fagellated, non-spore forming bacteria. It is recognized as one of the organisms responsible for causing bacterial vaginosis. The other organisms involved in this pathology include bacteriods, pepto-streptococcus, fuso- bacterium, mycoplasma hominis, mobilucus and veilonella. Women typically present with a thin grey homogenous vaginal discharge that has a characteristic fshy odour (alkalinity of semen may cause a release of volatile amines from the vaginal discharge – forms the basis for a whif test). Vulval itching, dysuria and dyspareunia are rare, unlike with Trichomonas vaginalis infection. It is also known to cause vault infection following hysterectomy and also pelvic infection afer abortion. In pregnant women it has been associated with premature rupture of membranes and preterm delivery. Wet- mount saline preparation with vaginal discharge shows ‘clue’ cells (vaginal epithelial cells have a stippled appearance due to adherence of cocobacilli) under low- and high-power microscopy. Topical clindamycin and metronidazole are also useful in bringing the vaginal fora to normal. Amsel’s criteria for the diagnosis of bacterial vaginosis are: • thin white homogenous discharge; • increase in vaginal pH (>4. It is an oestrogen- dependent condition and its prevalence decreases afer the menopause, as the oestrogen levels fall. The woman usually presents with menorrhagia and dysmenorrhoea (uterine tenderness may be present during periods). Submucous and intramural fbroids can cause both menorrhagia and dysmenorrhoea, especially if the endometrial lining is distorted. Causes of secondary amenorrhoea • Hypothalamic causes • Excessive weight loss (or sudden weight loss) • Excessive exercise • Eating disorders e. In most cases it is associated with another auto-immune disease such as Addison disease, thyroid disease and hypoparathyroidism. Menopausal status (use 3 for postmenopausal women and 1 for premenopausal women) 3. Ovarian conditions causing raised serum testosterone levels include theca cell tumours, arrhenoblastoma, gynandroblastoma, Leydig cell tumour (levels >5 nmol/l), ovarian hyperthecosis and polycystic ovarian syndrome (levels >3 nmol/l). Adrenal conditions causing raised serum testosterone levels include Cushing syndrome (levels >4 nmol/l) and adrenal tumours (if levels are >7 nmol/l suspect an androgen secreting tumour). Knowing the specifc tumour markers will aid in diagnosis, treatment (surgery or chemotherapy), to check response to treatment and follow up of patients. This explains the recurrence of the hair growth following stopping of anti-androgen therapy, unless the cause for hirsutism is removed. Cosmetic approaches • Permanent hair removal by using laser and electrolysis • Temporary hair removal by using chemical depilatories, bleaching, waxing, tweezing, mechanical epilators Further reading Collins S, Arulkumaran S, et al. Following menarche it generally takes more than a year to regulate ovulation and their periods. Acquired Von Willebrand disease is associated with hypothyroidism and is seen mainly in women. Investigations • Full blood count, platelet count, clotting profle • Blood flm to rule leukaemia • All the above clotting factors if indicated. It causes endometrial atrophy and decreases endometrial prostaglandins and fbrinolysis. Oral progestogens 5 mg three times daily from day 5 to 26 of the cycle cyclically can be given. It can also be used 221 back-to-back for 3 months to build up the haemoglobin levels. Tey are also used as second-line therapy for treatment of inherited bleeding disorder not responding to the other treatments or when these treatments are contraindicated. It is mainly efective in women with type 1 Von Willebrand disease and mild to moderate haemophilia. It is important to give a test dose prior to treatment in order to identify responders from non-responders. It is used as intranasal spray or administered by subcutaneous injection in women with Von Willebrand disease. It is defned as regular heavy menstrual bleeding without any postcoital or intermenstrual bleeding or any palpable pelvic pathology and should have a normal cervical smear result. However, if pipelle is not possible in the clinic a hysteroscopy and endometrial biopsy should be performed. It is also indicated if the ultrasound scan is suggestive of uterine polyps of submucous fbroids. Its use for the whole month may increase the risk of thromboembolism, about which the patient should be warned. Endometrial ablation • Mostly used in older women who have completed their family. Tese signs are seen in women with androgen-producing ovarian (Sertoli–Leydig cell tumours or arrhenoblastoma) or adrenal tumours (adrenal adenoma). Its use is limited to short-term therapy and long-term therapy would need add back therapy with oestrogens in view of its side efects (menopausal symptoms and osteoporosis). Terefore, its use should be limited to patients with severe forms of hyperandrogenemia (e. It antagonizes androgen receptor and has weak progestational and glucocorticoid activity. It suppresses actions of both testosterone and its metabolite dihydrotestosterone on tissues by blocking androgen receptors. The pharmacological actions of this drug are mainly attributed to the acetate form (cyproterone acetate has three times the anti-androgenic activity of cyproterone).
The pelvic musculature such as the levator muscles order genuine proscar on-line, obturators order generic proscar line, and peri- formis muscles sh ou ld be carefully palpat ed purchase 5mg proscar visa. T h e examin at ion sh ou ld begin wit h the nontender regions initially and then moving toward the more painful areas discount 5mg proscar visa. Tender nodules of the uterosacral ligaments or a fixed retroverted uterus may suggest endometriosis. A pelvic t ransvaginal ult rasound examinat ion is import ant t o assess for ut erine masses, adnexal masses, and perit oneal fluid. Co n s u l t a t i o n The patient should be referred to the appropriate consultant if the history, physi- cal, labor at or y, or imagin g su ggest s a n on gyn ecologic et iology. For in st an ce, if the patient has abdominal bloating, nausea, or diarrhea, then a gastrointestinal con- sult at ion is indicat ed. If t he pat ient has a hist ory of depression, sexual abuse, or trauma, then a psychiatric consultation is important. If a gyne- cologic etiology is suspected, then laparoscopy can be useful to est ablish a diagno- sis: principally endometriosis or pelvic adhesions. If after a 3- to 6- month trial of medications there is no relief, and careful search does not reveal nongynecologic con dit ion s, t h en a d iagn ost ic lapar oscopy is r eason able. In t h ese in st an ces, it is oft en h elpfu l t o h ave a mu lt idisciplin ar y team, such as a gynecologist, physical therapist, psychologist, sex therapist, pain specialist, and anest hesiologist. Excisional surgical procedures such as hysterectomy, oophorectomy, or salpingectomy should be used judiciously, since pelvic pain may persist or even worsen if there is no clear indication for these operat ions. Acupunct ure, ner ve blocks and t rig- ger p oin t in ject ion s can alleviat e p ain. O piate medications should be used with extreme caution since addiction is com- mon. Psychiatric evaluat ion should be obt ained when there is a reason, such as depression or a history of abuse. In cases of neuropat hic pain, t ricyclic ant idepressant t herapy can be help- ful. T his 16-year-old nulliparous female has primary dysmenorrhea, which is a condit ion wit h pain usually st art ing wit hin 6 mont hs of menarche. The mechanism is elevated prostaglandin F2 alpha levels, leading to intense uterine contractions, causing the pain with menses. Sh e d e n ie s b e in g t re a t e d fo r va g in it is o r se xu a lly t ra n sm it t e d d ise a se s. Sh e is in g o o d h e a lt h a n d t a ke s n o medications other than an oral contraceptive agent. Th e e x t e r n a l g e n i t a l i a a r e n o r m a l ; the s p e c u l u m e x a m i n a t i o n r e v e a l s a h o m o g e - neous, white vaginal discharge and a fishy odor. T h e sp ecu lu m exam in at ion r eveals a homogeneous, white vaginal discharge and a fishy odor. Best treatment for this condition: Metronidazole orally or vaginally; clindamy- cin is an alt er n at ive. Co n s i d e r a t i o n s This 18-year-old woman complains of a vaginal discharge that has a fishy odor, wh ich is the most common sympt om of bact erial vaginosis. The vaginal epit helium is not eryt hemat ous or inflamed, which also fit s wit h bact erial vaginosis. There- fore, ant ibiot ic t h erapy t arget ing anaerobes, su ch as met ron idazole or clin damycin, is appropriat e. Bact er ial vagin osis is n ot a t r u e in fect ion, b u t r at h er an over gr owt h of an aer obic bacteria, which replaces the normal lactobacilli of the vagina. The most common symptom is a fish y or “mu st y” od or, oft en exacer bat ed by m en ses or in t er cou r se. Sin ce bot h of these situations introduce an alkaline substance, the vaginal pH is elevated above normal. The addition of 10% potassium hydroxide solution leads to the release of amines, causing a fishy odor (whiff test ). T here is no inflammatory react ion; hence, the patient will not complain of swelling or irritation, and typically, the microscopic examinat ion does not usually reveal leukocyt es. Microscopy of t he discharge in normal saline (wet mount) typically shows clue cells (Figure 38– 1), which are coccoid bact er ia ad h er en t t o the ext er n al su r faces of epit h elial cells. Bact er ial vagin osis is associat ed wit h gen it al t r act in fect ion s su ch as en d om e- tritis, pelvic inflammatory disease, and pregnancy complications such as preterm delivery and preterm premature rupture of membranes. Patients should be instructed to avoid alcohol while tak- ing met ronidazole t o avoid a disulfiram react ion. Aside from cau sin g in fect ion of the vagin a, this or gan ism can also in h abit the u r et h r a or Skene’s glands. The most common symptom associated with trichomoniasis is a profuse “frot hy” yellow– green to gray vaginal discharge or vaginal irrit at ion. Intense inflammation of the vagina or cervix may be noted, with the classic punc- tate lesions of the cervix (strawberry cervix). If the wet mount is cold or there are excess leukocyt es present, t he movement of t he t richomonads may be inhibit ed. Optimal treatment consists of a fairly high dose of metronidazole (2 g orally) as a one-t ime dose, with the part ner t reated as well. A newer antiprotozoal agent, Tinidazole, has a similar dosing, side-effect profile, and cont raindicat ion for concurrent alcohol; due to its expense, it s main role is for met ronidazole-resistant cases. Treatment usually does not include vaginal metronidazole because of low therapeutic levels in the ure- thra or Skene’s glands where trichomonads may reside. Candidal vaginitis is usually caused by the fungus, Candida albicans, although other species may be causative. Diabetes mellitus, which suppresses immune function, may also predispose patients to these infections. The patient usually presents with intense vulvar or vaginal burning, irrit at ion, and swelling. The discharge usually appears curdy or like cottage cheese, in con- trast to the homogenous discharge of bacterial vaginosis. The microscopic diagnosis is confirmed by ident ification of the hyphae or pseudohyphae after the discharge is mixed with potassium hydroxide. Treatment includes oral fluconazole (D iflucan) or topical imidazoles, such as terconazole (Terazol), miconazole (Monistat), and clot r imazole ( Lot r im in ). Sh e complains of a 1-day h ist ory of it ch ing, burning, and a yellow- ish vaginal discharge. The speculum examination reveals an erythematous vagina and punctuations of the cervix. Frothy discharge, normal to acidic pH, and flagellated organ- isms are more t ypical of t richomoniasis. After antibiotic therapy, candidal organisms often proliferate and may induce an overt infect ion. T h e mechanism is likely t hat t he lact obacilli are eliminat ed by t he ant ibiot ic, allowing overgrowt h of yeast. Pat ient s sh ou ld be in st r u ct ed t o avoid alco- hol while taking metronidazole to avoid a disulfiram reaction. Erythromycin may be used in the treatment of syphilis in nonpregnant women allergic to penicillin. Clindamycin is typically used in conjunction with gentamicin in the t reatment of infections requiring broad-spect rum antibiot ics, necessit at - ing anaerobic coverage (ie, postpartum endomyomet rit is). Trichomonas vaginalis is a hardy organism and may be isolated from a wet surface up t o 6 hours aft er inoculat ion. T h e organism’s difficult y t o eradicat e is the reason t hat t herapy requires high t issue levels, met ronidazole 2 g orally all at once, to be able t o obt ain sufficient ly high t issue levels to be effect ive. Not uncommonly, a single course is not effective, and a 2- or 3-day course of metronidazole of high dose orally is needed. T h e pat ient t akes 2 g of m et r on idazole as a sin gle d ose t o at t ain sufficient tissue levels to eradicate the trichomonads. Erythematous vagina and punctuations of the cervix (strawberry cervix) are classic findings of the inflammatory effect s induced by t richomoniasis.
Rupture of these atherosclerotic plaques leads to platelet aggregation and thrombus formation generic proscar 5 mg without a prescription, which can cause total cheap proscar 5 mg fast delivery, transient buy generic proscar 5 mg online, or sub-total arterial occlusion and subsequent myocardial infarction buy proscar visa. If occurring shortly after the index infarct, acute mitral regurgitation due to papillary muscle rupture or ventricular septal rupture must be excluded. Decompensation of chronic heart failure The cause of this is commonly unclear, but includes sepsis, anaemia, poor compliance with medication, excess ﬂuid or sodium intake, or the devel- opment of arrhythmias. Non-ischaemic causes of cardiogenic pulmonary oedema Acute • Sepsis-induced myocardial dysfunction. It is thought to be predominantly due to the negative inotropic effects of pro-inﬂammatory cytokines on the myocardium. Non-cardiogenic causes of pulmonary oedema • Phaeochromocytoma—probably due to the vasoconstricting and direct toxic effects of chronically raised plasma catecholamine levels on the myocardium, which can result in a dilated cardiomyopathy. Thought to be due to reﬂex hyperactivation of the renin–angiotensin system and subsequent ﬂuid retention due to reduced renal perfusion. Pathophysiology The mechanism underpinning cardiogenic pulmonary oedema is increased intravascular pulmonary pressures with transudation of protein-de- pleted plasma down a pressure gradient into the pulmonary interstitium and alveoli. The pressure required to produce pulmonary oedema is reduced in the presence of capillary leak and hypoalbuminaemia. Diagnosis Clinical presentation The symptoms reﬂect hypoxia and reﬂex-increased sympathetic drive. Symptoms include: • Dyspnoea at rest • Orthopnoea • Paroxysmal nocturnal dyspnoea • Cough productive of frothy (occasionally blood stained) sputum. Clinical assessment Effective clinical examination and basic bedside investigations can conﬁrm the diagnosis of cardiogenic pulmonary oedema and the presence of coex- isting cardiogenic shock, and help ascertain the underlying cause. General signs The signs of cardiogenic and non-cardiogenic pulmonary oedema are very similar. Signs reﬂecting ﬂuid retention or cardiac pressure or volume over- load are more speciﬁc for a cardiogenic cause. A metabolic acidosis secondary to elevated lactate may also occur when tissue perfusion is markedly reduced. Trans-thoracic windows are often very poor in ventilated patients and trans-oesophageal echocardiography may be necessary. It must be remembered that this simply signiﬁes a disturbance of cardiomyocyte integrity, which has multiple causes, not just myocardial infarction due to atherosclerotic plaque rupture. These can largely be classiﬁed into conditions causing myocardial overload/stretch (e. The magnitude of the troponin release directly correlates with risk of subsequent mortality. Troponin levels may be elevated in renal failure in the absence of myocardial disease. No overall outcome beneﬁt from pulmonary artery catheterization has been demonstrated, and there is a worry that use of such invasive monitors may lead to overly aggressive therapy. Treatment modalities Diuretics and ﬂuid removal Intravenous furosemide 50–80mg has a venodilator as well as a diuretic action. Some patients may require ultraﬁltration if there is a poor response to diuretic due to poor renal perfusion and/or pre-existing chronic renal impairment. Opiates Patients with cardiogenic pulmonary oedema are often anxious and distressed, and opiates should be administered if possible. Pharmacological inotropic therapy Agents of choice differ between centres as no robust evidence base exists. Although myocardial oxygen consumption is increased by increased con- tractility, heart rate, or tachyarrhythmias, it will be lowered by reduced ventricular volumes and wall stress. Increased blood pressure and cardiac output may also improve myocardial oxygen delivery. Dobutamine This is a synthetic catecholamine that has an inodilating effect due to its actions on B1- and B2-adrenoreceptors. Adrenaline A naturally occurring catecholamine with effects on B- (lower dose) and A- (higher dose) adrenoreceptors. Adverse effects include tachydysrhythmias, vasoconstriction, hyperglycaemia, acidaemia hypokalaemia, and hyperlactataemia. Noradrenaline A naturally occurring catecholamine that is predominantly an agonist at A adrenoreceptors, with minor B activity. Phosphodiesterase inhibitors This group of drugs are inodilatory and includes amrinone, milrinone, and enoximone. They are associated with less tachycardia than catecholamines, and have the advantage of increasing the rate of diastolic relaxation (lusi- tropy). Calcium sensitisers There has been considerable interest in levosimendan, which is reported to increase contractility without increasing myocardial oxygen demand. Some studies have shown it to improve outcome in patients with acute decompensated heart failure without cardiogenic shock when compared to placebo or dobutamine. It is given as a loading dose of 24mcg/kg over 10min followed by an infusion of 0. In practice, the loading dose may cause hypotension and is sometimes incorporated in the 24h infusion. The aim of treatment is to: • Improve cardiac function by addressing preload, afterload, and contractility • Improve respiratory function and gas exchange • Address any underlying cause or precipitant. Systolic blood pressure >90mmHg with reduced peripheral perfusion (‘wet and cold’) These patients, although not meeting the criteria for cardiogenic shock, have a worse outcome than their well-perfused counterparts. Their cardiac output is low, their tissue perfusion compromised, and their blood pressure is only being maintained with peripheral vasoconstriction. Initial therapy should be closely monitored (with invasive monitoring if neces- sary) and unless there is a striking response they should be thought of and managed as cardiogenic shock. The mainstay of therapy is to improve cardiac and respiratory function and end organ perfusion whilst addressing the underlying cause. Right ventricular infarction This is usually a complication of inferior myocardial infarction and can also result in cardiogenic shock. The risk is often dose dependent, and the use of more than one immunosuppressive agent compounds this risk. Agents may increase the risk of infection through speciﬁc inhibition of leucocyte function, direct toxic effects on the bone marrow, and/or alteration of the usual host defence mechanisms. In some cases, speciﬁc prophylactic measures are recom- mended during routine therapy. Immunosuppressed patients are at risk of common infections, oppor- tunistic infections, or atypical infections at unusual sites. They may not display typical features of an infective illness nor an acute inﬂammatory response, therefore a high index of suspicion is essential to identify an unusual or subacute presentation, especially if there has already been a poor response to conventional broad-spectrum antibiotic therapy. Both agents suppress lymphocyte proliferation and interfere with antigen recognition, lymphocyte adhesion, and cell-mediated cytotoxicity. Immunosuppressant activity is prolonged by intracellular accumulation of active metabolites. Adverse effects Bone marrow suppression • Dose-related leucopenia can occur in up to 27% of patients. This defect is genetically determined, with partial deﬁciency being present in up to 10% of the general population. Infection risk • Infectious complications are reported in up to 9% of patients and can relate to either common pathogens or opportunistic infections. Corticosteroids Corticosteroids have dose-dependent anti-inﬂammatory and immun- osuppressive properties. Effects include: • Decreased production of pro-inﬂammatory cytokines • Reduction in circulating leucocyte levels, except neutrophils • Impaired bactericidal ability of neutrophils and monocytes. Adverse effects Corticosteroids are not associated with signiﬁcant bone marrow sup- pression. They have well-documented systemic side-effects, including cushingoid appearance, weight gain, hypertension, osteoporosis, diabetes mellitus, and myopathy. Demargination The apparent neutrophilia associated with steroid therapy is caused by reduced adherence of neutrophils to the endothelium of blood vessels.