Cefalexin should be avoided in this patient.This patient is known to have a severe penicillin allergy. None of the above antibiotics are penicillin based. However, 0.5 – 6.5% of patients who are proven to have an IgE mediated penicillin allergy will also be allergic to cephalosporins, including cefalexin. Penicillin, cephalosporins, and carbapenems are all members of the beta-lactam group of antibiotics and share a common beta-lactam ring. There is, therefore, a small risk of allergy cross-over between all these antibiotics. The rates of allergy cross-over are lower with second and third-generation cephalosporins than first-generation cephalosporins such as cefalexin.It is important to question the patient carefully to ascertain what symptoms they had on exposure to penicillin. Symptoms such as an urticarial rash or itching make it more likely that they have an IgE mediated allergy.

Bradycardia and miosis should be anticipated following the administration of anticholinesterases.Anticholinesterase agents include the following medications:- Pyridostigmine, neostigmine, and edrophonium which play a significant role in the diagnosis and the management of myasthenia gravis.- Rivastigmine, galantamine and donepezil are cholinesterase inhibitors found to be significantly useful in the management of Alzheimer’s disease.Mechanism of action and pharmacological effects:Inhibition of cholinesterase increases the level and the duration of action of acetylcholine within the synaptic cleft. Thus, cholinergic effects such as a reduction in heart rate (bradycardia), miosis (pupillary constriction), increased secretions, increased gastrointestinal motility and reduction in BP may occur with anticholinesterases.Toxins such as organophosphates and carbamates also are primarily anticholinergic and cause the following typical SLUDGE symptoms:- Salivation- Lacrimation- Urination- Diaphoresis- Gastrointestinal upset- Emesis

Carbimazole is used to treat hyperthyroidism. Carbimazole is a pro-drug as after absorption it is converted to the active form, methimazole. Methimazole prevents thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, hence reducing the production of the thyroid hormones T3 and T4 (thyroxine).

Desmopressin test (done to differentiate nephrogenic diabetes insipidus from central diabetes insipidus), and serum lithium levels can together confirm a diagnosis of lithium-induced nephrogenic diabetes insipidus.Bipolar disease is most often managed with mood stabilizers like lithium. This patient develops gastrointestinal symptoms followed by an acute confusional state associated with polyuria and polydipsia. These symptoms are suggestive of diabetes insipidus.In a case where these symptoms occur in a bipolar patient under treatment, lithium-induced nephrogenic diabetes insipidus should be considered as the most probable cause.Lithium intoxication can present with symptoms of nausea, vomiting, mental dullness, action tremor, weakness, ataxia, slurred speech, blurred vision, dizziness, especially vertical nystagmus and stupor or coma. Diffuse myoclonic twitching and nephrogenic diabetes insipidus can also occur. Such a clinical syndrome occurs above the serum level of lithium of 1.5–2.0 mEq/L.Management: – Correcting electrolyte abnormalities in patients with acute disease is critical and often life-saving.- Treatment should be initiated with parenteral fluids to replete hypovolemia (normal saline at 200-250 mL/h), followed by administration of hypotonic fluid (0.5% normal saline). – On the restoration of the volume status of the patient forced diuresis should be initiated by the administration of parenteral furosemide or bumetanide accompanied by continued intravenous hypotonic fluid administration to maintain volume status.- Polyuria is managed with hydrochlorothiazide combined with amiloride, acetazolamide.

Ezetimibe is a cholesterol-lowering agent that acts to prevent cholesterol absorption by directly inhibiting cholesterol receptors on enterocytes.It does not affect the absorption of drugs (e.g. digoxin, thyroxine) or fat-soluble vitamins (A, D and K) as the anion-exchange resins do. It does not affect the cytochrome P450 enzyme system.The increased risk of myositis associated with the statins is not seen with ezetimibe.The most common adverse effects include headache, runny nose, and sore throat. Less common reactions include body aches, back pain, chest pain, diarrhoea, joint pain, fatigue, and weakness.

The total daily morphine dose is 30 x 2 = 60 mg. Therefore, the breakthrough dose should be one-sixth of this, 10 mg.

Tumour lysis syndrome (TLS) occurs most notably in patients with haematological malignancies including, Non-Hodgkin’s Lymphoma (NHL) and Acute Lymphocytic Leukaemia (ALL).Risk factors for TLS include:• Large tumour burden• Sensitivity of the tumour to chemotherapy• Rapid tumour growth rateTLS is characterized by:• Hyperuricemia• Hyperkalaemia• Hyperphosphatemia• HypocalcaemiaTreatment of TLS:• Allopurinol: It is a xanthine oxidase inhibitor, it reduces the conversion of nucleic acid by-products to uric acid. Thus, it prevents urate nephropathy and subsequent oliguric renal failure. Note: dose reduction is essential in renal failure or if given along with mercaptopurine or azathioprine.Alternatives to Allopurinol: Febuxostat; Rasburicase are useful in patients with hyperuricemia.• Hydration• Diuresis: Should be considered in well hydrated patients with insufficient urine output. Furosemide to be considered in normo-volemic patients with hyperkalaemia. Urine alkalization can be considered for promoting alkaline diuresis.• Treatment of electrolyte imbalances including hyperkalaemia, hyperphosphatemia, and hypocalcaemia.• Dialysis can be considered in refractory cases.

Activated charcoal is useful if given within one hour of the paracetamol overdose. Liver function tests, INR and prothrombin time will be normal, as liver damage may not manifest until 24 hours or more after ingestion.The antidote of choice is intravenous N-acetylcysteine, which provides complete protection against toxicity if given within 10 hours of the overdose.

Activated charcoal is useful if given within one hour of the paracetamol overdose. Liver function tests, INR and prothrombin time will be normal, as liver damage may not manifest until 24 hours or more after ingestion. The antidote of choice is intravenous N-acetylcysteine, which provides complete protection against toxicity if given within 10 hours of the overdose.

Acetazolamide is in the diuretic and carbonic anhydrase inhibitor families of medication. It works by decreasing the amount of hydrogen ions and bicarbonate in the body and can thus cause metabolic acidosis and electrolyte changes (hypokalaemia, hyponatremia).

The most appropriate treatment in this patient would be to stop warfarin therapy and keep the patient under observation.The drugs that lead to enhanced potency of warfarin include: disulfiram, trimethoprim-sulphamethoxazole, metronidazole, phenylbutazone, aspirin, heparin, and clofibrate. Liver disease, thrombocytopenia, hyperthyroidism also increase the oral anticoagulant potency.If the patient has minor bleeding and the international normalized ratio (INR) is >6.0, warfarin should be stopped; the INR should be rechecked daily and in addition to the stoppage of warfarin, vitamin K 2.5 mg oral or 0.5 mg intravenously should also be administered.In a patient with INR of 2.0 or 3.0, it takes two or three times longer for that individual’s blood to clot than someone who is not taking any anticoagulants. Most patients on warfarin have an INR goal of 2 to 3.If there is major bleeding then prothrombin complex concentrates 50 u/kg or fresh-frozen plasma 15 ml/kg may be considered.

Cyanide poisoning: Aetiology:Smoke inhalation, suicidal ingestion, and industrial exposure (specific industrial processes involving cyanide include metal cleaning, reclaiming, or hardening; fumigation; electroplating; and photo processing) are the most frequent sources of cyanide poisoning. Treatment with sodium nitroprusside or long-term consumption of cyanide-containing foods is a possible source.Cyanide exposure most often occurs via inhalation or ingestion, but liquid cyanide can be absorbed through the skin or eyes. Once absorbed, cyanide enters the blood stream and is distributed rapidly to all organs and tissues in the body. Pathophysiology:Inside cells, cyanide attaches itself to ubiquitous metalloenzymes, rendering them inactive. Its principal toxicity results from inactivation of cytochrome oxidase (at cytochrome a3), thus uncoupling mitochondrial oxidative phosphorylation and inhibiting cellular respiration, even in the presence of adequate oxygen stores.Presentation:• ‘Classical’ features: brick-red skin, smell of bitter almonds• Acute: hypoxia, hypotension, headache, confusion• Chronic: ataxia, peripheral neuropathy, dermatitisManagement:• Supportive measures: 100% oxygen, ventilatory assistance in the form of intubation if required.• Definitive: Hydroxocobalamin (iv) is considered the drug of choice and is approved by the FDA for treating known or suspected cyanide poisoning. • Coadministration of sodium thiosulfate (through a separate line or sequentially) has been suggested to have a synergistic effect on detoxification.Mechanism of action of hydroxocobalamin: • Hydroxocobalamin combines with cyanide to form cyanocobalamin (vitamin B-12), which is renally cleared.• Alternatively, cyanocobalamin may dissociate from cyanide at a slow enough rate to allow for cyanide detoxification by the mitochondrial enzyme rhodanese.

The blood gas analysis provided above is suggestive of a mixed respiratory alkalosis and metabolic acidosis characteristic of salicylate overdose.Pathophysiology:The direct stimulation of the cerebral medulla causes hyperventilation and respiratory alkalosis.As it is metabolized, it causes an uncoupling of oxidative phosphorylation in the mitochondria. Lactate levels then increase due to the increase in anaerobic metabolism. This, along with a slight contribution from the salicylate metabolites result in metabolic acidosis.Tinnitus is characteristic and salicylate ototoxicity may produce deafness. Other neurological sequelae include encephalopathy and agitation, seizures and CNS depression and coma. Cardiovascular complications include tachycardia, hypotension, and dysrhythmias (VT, VF, and asystole).

The cause for bone marrow suppression in this patient is most probably mercaptopurine toxicity.Azathioprine is metabolized to 6-mercaptopurine (6-MP), which itself is metabolized by xanthine oxidase. Xanthine oxidase inhibition by allopurinol leads to the accumulation of 6-MP which then precipitates bone marrow failure. This may be potentially fatal if unrecognized.Clinical presentation:Toxicity symptoms include gastrointestinal symptoms, bradycardia, hepatotoxicity, myelosuppression.

Here, the patient seems to be intolerant to standard metformin. In such cases, modified-release preparations is considered as the most appropriate next step. There is some evidence that these produce fewer gastrointestinal side-effects in patients intolerant of standard-release metformin.Metformin is a biguanide and reduces blood glucose levels by decreasing the production of glucose in the liver, decreasing intestinal absorption and increasing insulin sensitivity. Metformin decreases both the basal and postprandial blood glucose.Other uses: In Polycystic Ovarian Syndrome (PCOS), Metformin decreases insulin levels, which then decreases luteinizing hormone and androgen levels. Thus acting to normalize the menstruation cycle.Note:Metformin is contraindicated in patients with severe renal dysfunction, which is defined as a glomerular filtration rate (GFR) less than 30 ml/min/1.732m2. Metformin overdose has been associated with hypoglycaemia and lactic acidosis, for this reason, it has a black box warning for lactic acidosis.

Spironolactone is an aldosterone antagonist which acts in the distal convoluted tubule. It is a potassium-sparing diuretic that prevents the body from absorbing too much salt and keeps the potassium levels from getting too low. Spironolactone is used to treat heart failure, high blood pressure (hypertension), or hypokalaemia (low potassium levels in the blood).

Confusion and pink mucosae are typical features of CO poisoning.The patient often presents, most commonly with headaches, and other symptoms like malaise, nausea, and dizziness.Carbon monoxide (CO) poisoning, considered as the great imitator of other diseases as the patients present with a myriad of symptoms. The carbon monoxide diffuses rapidly across the pulmonary capillary membrane binding to the haem molecule with a very high affinity (240 times that of oxygen) forming carboxy-haemoglobin (COHb). Non-smokers have a baseline COHb of ,3% while smokers have a baseline COHb of 10-15%.Features of carbon monoxide toxicity- Headache: 90% of cases- Nausea and vomiting: 50%- Vertigo: 50%- Confusion: 30%- Subjective weakness: 20%- Severe toxicity: ‘pink’ skin and mucosae, hyperpyrexia, arrhythmias, extrapyramidal features, coma, deathTreatment:Use of Hyperbaric oxygen therapy (HBOT) for treating mild to moderate CO poisoning is not routine.The selection criteria for HBOT in cases of CO poisoning include:• COHb levels > 20-25%• COHb levels > 20% in pregnant patient • Loss of consciousness• Severe metabolic acidosis (pH <7.1)• Evidence of end-organ ischemia (e.g., ECG changes, chest pain, or altered mental status)

Anticholinergic syndrome occurs following overdose with drugs that have prominent anticholinergic activity including tricyclic antidepressants, antihistamines and atropine. Features include dry, warm, flushed skin, urinary retention, tachycardia, mydriasis (dilated pupils) and agitation.

Tacrolimus is a calcineurin inhibitor used as an immunosuppressive agent used for prophylaxis of organ rejection post-transplant.Pharmacology: Calcineurin inhibition leads to reduced T-lymphocyte signal transduction and IL-2 expression. It has a half-life of 12 hours (average).Other off-label indications for the use of tacrolimus include Crohn disease, graft-versus-host disease (GVHD), myasthenia gravis, rheumatoid arthritis.Adverse effects of tacrolimus includes: Cardiovascular: Angina pectoris, cardiac arrhythmias, hypertensionCentral nervous system: Abnormal dreams, headaches, insomnia, tremors.Dermatologic: Acne vulgaris, alopecia, pruritis, rashEndocrine and metabolic: Decreased serum bicarbonate, decreased serum iron, new-onset diabetes mellitus after transplant (NODAT), electrolyte disturbances.Gastrointestinal: Abdominal pain, nausea, vomiting, diarrhoeaGenitourinary: Urinary tract infectionHepatic: Abnormal hepatic function testsNeuromuscular and skeletal: Arthralgia, muscle crampsOphthalmic: Blurred vision, visual disturbanceOtic: Otalgia, otitis media, tinnitusRenal: Acute renal failureOther options:Sirolimus (a macrolide) is an mTOR inhibitor that blocks the response to IL-2 and has a half-life of 12–15 hours. Azathioprine inhibits purine synthesis, an essential step in the proliferation of white cells and has a half-life of around 5 hours.

Sodium cromoglycate principally acts by inhibiting the degranulation of mast cells triggered by the interaction of antigen and IgE. The inhibitory effect on mast cells appears to be cell-type specific since cromoglycate has little inhibitory effect on mediator release from human basophils.Thus, it inhibits the release of histamine, leukotrienes, and slow-reacting substance of anaphylaxis from mast cells by inhibiting degranulation following exposure to reactive antigens.Adverse effects include cough, flushing, palpitation, chest pain, nasal congestion, nausea, fatigue, migraine, etc.

The principal action of organophosphates is the inhibition of acetylcholinesterase’s, therefore leading to the accumulation of acetylcholine at muscarinic receptors (miosis, hypersalivation, sweating, diarrhoea, excessive bronchial secretions), nicotinic receptors (muscle fasciculations and tremor) and in the central nervous system (anxiety, loss of memory, headache, coma). Removal from the source of the organophosphate, adequate decontamination, supplemental oxygen and atropine are the initial treatment measures. Pralidoxime, an activator of cholinesterase, should be given to all symptomatic patients.

Sildenafil citrate (Viagra) is the first oral drug to be widely approved for the treatment of erectile dysfunction. It is a potent and selective inhibitor of type-V phosphodiesterase, the primary form of the enzyme found in human penile erectile tissue, thereby preventing the breakdown of cyclic guanosine monophosphate (cGMP), the intracellular second messenger of nitric oxide.Uses:It is used for the treatment of erectile dysfunction, idiopathic pulmonary hypertension, premature ejaculation, high altitude illness, penile rehabilitation after radical prostatectomy, angina pectoris, and lower urinary tract symptoms.Adverse effects:Mild headache, flushing, dyspepsia, cyanopsia, back pain, and myalgias – due to a high concentration of PDE11 enzyme in skeletal muscle, which shows significant cross-reactivity with the use of tadalafil.It can also cause hypotension, dizziness, and rhinitis.

Oxycodone is a safer opioid to use in patients with moderate to end-stage renal failure.Active metabolites of morphine accumulate in renal failure which means that long-term use is contraindicated in patients with moderate/severe renal failure. These toxic metabolites can accumulate causing toxicity and risk overdose. Oxycodone is mainly metabolised in the liver and thus safer to use in patients with moderate to end-stage renal failure with dose reductions.Adverse effects:Constipation is the most common overall side effect. Others include: asthenia, dizziness, dry mouth, headache, nausea, pruritus, etc. Medications in renal failure:Drugs to be avoided in patients with renal failureAntibiotics: tetracycline, nitrofurantoinNSAIDsLithiumMetforminDrugs that require dose adjustment:Most antibiotics including penicillin, cephalosporins, vancomycin, gentamicin, streptomycinDigoxin, atenololMethotrexateSulphonylureasFurosemideOpioidsRelatively safe drugs:Antibiotics: erythromycin, rifampicinDiazepamWarfarin

The most probable diagnosis in this patient is an oculogyric crisis, that is most appropriately managed with procyclidine or benztropine (antimuscarinic). An oculogyric crisis is a dystonic reaction to certain drugs or medical conditions.Features include:Restlessness, agitationInvoluntary upward deviation of the eyesCauses:PhenothiazinesHaloperidolMetoclopramidePostencephalitic Parkinson’s diseaseManagement:Intravenous antimuscarinic agents like benztropine or procyclidine, alternatively diphenhydramine or ethopropazine maybe used.

Moxonidine and alpha-methyl dopa are centrally acting antihypertensives and modify blood pressure through modifying sympathetic activity.Other options:Verapamil is a calcium antagonist.Minoxidil and hydralazine are both vasodilators.Phenoxybenzamine is an alpha-blocker.Adverse effects:Dry mouth and somnolence were the most frequently reported adverse events, followed by headache, dizziness, nausea and allergic skin reactions.

Anticholinergic syndrome results from the inhibition of muscarinic cholinergic neurotransmission. Clinical manifestations can be remembered by the mnemonic, red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, and full as a flask. The mnemonic refers to the symptoms of flushing, dry skin and mucous membranes, mydriasis (dilated pupil) with loss of accommodation, altered mental status, fever, and urinary retention, respectively.

The most likely cause for these results is delayed paracetamol nephrotoxicity.The blood investigations of this patient are highly suggestive of acute kidney injury. Paracetamol overdose is well known to cause hepatotoxicity, but not for its delayed nephrotoxicity, especially in significant overdose. Appropriate monitoring of a patient’s blood tests is important.Management:NAC (N-Acetyl cysteine) has a clear role in preventing acetaminophen-induced liver necrosis. Although NAC has not been proven to be harmful to the kidney, its role in patients without hepatoxicity and only isolated renal dysfunction is uncertain.Other options:-There are no features in the history that are suggestive of dehydration and pre-renal AKI presenting in this manner in a 25-year-old would be very unusual.- Minimal change nephropathy typically presents with a nephrotic picture of kidney injury.- Berger’s more commonly presents with isolated haematuria.

Amiodarone is a class III antiarrhythmic drug. Class III antiarrhythmics are potassium channel blockers, they prolong duration of action potential with resulting prolongation of effective refractory period.

Ethanol reduces the calcium-dependent secretion of anti-diuretic hormone (ADH) by blocking channels in the neurohypophyseal nerve terminal.Thus, ethanol’s inhibitory effect helps to explain the increased diuresis experienced during intoxicated states as well as increased free water loss; without appropriate ADH secretion, more water is excreted by the kidneys.Nausea associated with hangovers is mainly due to vagal stimulation to the vomiting centre. Following a particularly severe episode of alcohol excess, people may experience tremors due to increased glutamate production by neurons to compensate for the previous inhibition by ethanol.Management of alcoholism:Nutritional support: – Alcoholic patients should receive oral thiamine if their ‘diet may be deficient’.Pharmacological management:- Benzodiazepines for acute withdrawal- Disulfiram promotes abstinence – alcohol intake causes a severe reaction due to inhibition of acetaldehyde dehydrogenase. Patients should be aware that even small amounts of alcohol (e.g. In perfumes, foods, mouthwashes) can produce severe symptoms. Contraindications include ischaemic heart disease and psychosis.- Acamprosate reduces craving, known to be a weak antagonist of NMDA receptors, improves abstinence in placebo-controlled trials.

The symptoms of ataxia, slurred speech and blurred vision are all suggestive of phenytoin toxicity. Cimetidine increases the efficacy of phenytoin by reducing its hepatic metabolism.Phenytoin has a narrow therapeutic index (10-20 mg/L) and its levels are monitored by measuring the total phenytoin concentration.Cimetidine is an H2 receptor antagonist used in the treatment of peptic ulcers. It acts by decreasing gastric acid secretion.Cimetidine also has an inhibitory effect on several isoforms of the cytochrome enzyme system including the CYP450 enzymatic pathway. Phenytoin is metabolized by the same cytochrome P450 enzyme system in the liver. Thus, the simultaneous administration of both these medications leads to an inhibition of phenytoin metabolism and thus increases its circulating levels leading to phenytoin toxicity.