Initiation of allopurinol treatment during an attack can exacerbate and prolong the episode. Thus treatment should be delayed until the attack resolves.

The most appropriate steps of initial management include iv glucagon and iv isoprenaline.The most likely diagnosis in the above scenario (decreased conscious level, profound hypertension, and bradycardia) is β-blocker toxicity/overdose. Bronchospasm rarely occurs in an overdose of β-blockers, except where there is a history of asthma.Immediate management is to give iv glucagons (50–150μg/kg) followed by infusion to treat hypotension and isoprenaline or atropine to treat bradycardia. Where patients fail to respond to these measures, temporary pacing may be required. If the patient is seen within the first 4 hours of the overdose, gastric lavage may be of value.

N-acetylcysteine depletes glutathione reserves by providing cysteine, which is an essential precursor in glutathione production.Glutathione within the liver can normally detoxify these minuscule quantities of NAPQI and prevent tissue damage.N-acetylcysteine (NAC) is the mainstay of therapy for acetaminophen toxicity.Paracetamol overdose:The liver normally conjugates paracetamol with glucuronic acid/sulphate. During an overdose, the conjugation system becomes saturated leading to oxidation by cytochrome P450 (predominately CYP2E1) mixed-function oxidases. This produces a toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI).Normally glutathione acts as a defence mechanism by conjugating with the toxin forming the non-toxic mercapturic acid. If glutathione stores run-out, the toxin forms covalent bonds with cell proteins, denaturing them and leading to cell death.Other uses: In COPD, cystic fibrosis, and other lung conditions, nebulized NAC has mucolytic, anti-inflammatory, and antioxidant properties.

All the above side-effects, with the exception of alopecia, may be seen in patients taking lithium.Common lithium side effects may include:- dizziness, drowsiness;- tremors in your hands;- trouble walking;- dry mouth, increased thirst or urination;- nausea, vomiting, loss of appetite, stomach pain;- cold feeling or discoloration in your fingers or toes;- rash; or.- blurred vision.

Carbon monoxide (CO) poisoning:It is 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%.Clinical features of carbon monoxide toxicity:Headache: 90% of cases (most common clinical feature)Nausea and vomiting: 50%Vertigo: 50%Confusion: 30%Subjective weakness: 20%Severe toxicity: ‘pink’ skin and mucosa, hyperpyrexia, arrhythmias, extrapyramidal features, coma, deathCherry red skin is a sign of severe toxicity and is usually a post-mortem finding.Management• 100% oxygen• Hyperbaric oxygen therapy (HBOT)The use of Hyperbaric oxygen therapy (HBOT) for treatment 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)

Digoxin works by inhibiting the Na+/K+ ATPase pump in cardiac myocytes. Here’s how it works:

1. Inhibition of Na+/K+ ATPase: Digoxin binds to and inhibits the Na+/K+ ATPase pump, which is responsible for pumping sodium out of the cell and potassium into the cell.
2. Increased intracellular sodium: Inhibition of this pump leads to an increase in intracellular sodium levels.
3. Decreased activity of the sodium-calcium exchanger: The increased intracellular sodium reduces the activity of the sodium-calcium exchanger, which normally pumps calcium out of the cell in exchange for sodium.
4. Increased intracellular calcium: As a result, intracellular calcium levels rise because less calcium is being extruded from the cell. The increased calcium is then stored in the sarcoplasmic reticulum.
5. Enhanced contractility: During each action potential, more calcium is released from the sarcoplasmic reticulum into the cytoplasm, which enhances the contractility of the heart muscle (positive inotropic effect).

By increasing the force of contraction, digoxin helps improve cardiac output in patients with heart failure. Additionally, digoxin has vagomimetic effects, which can help control the heart rate in atrial fibrillation by increasing vagal tone and thereby reducing the conduction velocity through the atrioventricular node.

Hyperthermia (Temperature 39.5 C) points towards the use of ecstasy.MDMA (3,4 – methylenedioxymethamphetamine), or more commonly known as Molly or Ecstasy, is a synthetic psychoactive substance.Patients who consumed MDMA may present in a tachycardic, hypertensive, hyperthermic, and agitated state. Adverse effects, even at minor recreational doses, include increased muscle activity (such as bruxism, restless legs, and jaw clenching), hyperactivity, insomnia, difficulty concentrating and feelings of restlessness.Treatment of MDMA overdose:Emphasis should be on maintaining the airway along with the stabilization of breathing and circulation.Patients may present obtunded due to hyponatremia requiring endotracheal intubation.For the hyperthermic patient, evaporative cooling along with ice packs to the groin and axilla are beneficial.Patients who present in severe toxicity within one hour of ingestion can receive activated charcoal PO or via an NG tube. Antipyretics, such as acetaminophen, should be avoided as they have no role and can worsen an already compromised liver.

Different Oral Hypoglycaemic Agents (OHAs) and their respective mechanism(s) of action include:• Sulfonylureas (such as, glipizide, gliclazide, glimepiride) – bind to ATP sensitive Potassium channels (K – ATP channels) in the 𝝱 cells of the islets of the pancreas. Inhibition of these channels lead to an altered resting membrane potential in these cells causing an influx of calcium which increases insulin secretion.• Meglitinides (like Repaglinide) through a different receptor, they similarly regulate K – ATP channels thereby causing an increase in insulin secretion.• Biguanides (e.g., Metformin) increase the hepatic AMP-activated protein kinase activity leading to reduced gluconeogenesis and lipogenesis and increased insulin-mediated uptake of glucose in muscles. (it doesn’t increase insulin secretion)• Thiazolidinediones (rosiglitazone, pioglitazone) bind to PPAR-𝝲 and increase peripheral uptake of glucose and decrease hepatic glucose production.• α-Glucosidase inhibitors (such as acarbose, miglitol, voglibose) competitively inhibit α-glucosidase enzymes in the intestine that digest the dietary starch thus, inhibiting the polysaccharide reabsorption as well as metabolism of sucrose to glucose and fructose.• DPP-4 inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin) prolong the action of glucagon-like peptide. This leads to inhibition of glucagon release, increase in insulin secretion and a decrease in gastric emptying leading to a decrease in blood glucose levels.• SGLT2 inhibitors (dapagliflozin and canagliflozin) inhibit glucose reabsorption in the proximal tubules of the renal glomeruli leading to glycosuria which in-turn reduces blood glucose levels.Note: Side effects of pioglitazone are weight gain, pedal oedema, bone loss and precipitation of congestive cardiac failure.

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.

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.

Drug metabolism can be broadly classified into:Phase I (functionalization) reactions: also termed non-synthetic reactions, they include oxidation, reduction, hydrolysis, cyclization and de-cyclization. The most common and vital reactions are oxidation reactions. (Of the given enzymes only Alcohol dehydrogenase is involved in phase I drug metabolism. Succinate dehydrogenase, is a vital enzyme involved in the Kreb’s cycle and the mitochondrial electron transport chain). They are mainly catalysed by Cytochrome P-450 enzyme.Phase II (conjugation) reactions: occur following phase I reactions, they include reactions: glucuronidation and sulphate conjugation, etc. They are mostly catalysed by UDP-glucuronosyltransferase enzyme. Other phase II enzymes include: sulfotransferases, N-acetyltransferases, glutathione S-transferases and methyltransferases.

The rationale behind the use of sodium bicarbonate is that it increases the alkalinity of the urine promoting lithium excretion. The preferred treatment in severe cases would be haemodialysis.Lithium is a mood-stabilizing drug used most commonly prophylactically in bipolar disorder but also as an adjunct in refractory depression. It has a very narrow therapeutic range (0.4-1.0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys. Lithium toxicity generally occurs following concentrations > 1.5 mmol/L.Toxicity may be precipitated by dehydration, renal failure, diuretics (especially Bendroflumethiazide), ACE inhibitors, NSAIDs and metronidazole.Features of toxicityCoarse tremor (a fine tremor is seen in therapeutic levels)HyperreflexiaAcute confusionSeizureComaManagementMild-moderate toxicity may respond to volume resuscitation with normal salineHaemodialysis may be needed in severe toxicitySodium bicarbonate is sometimes used but there is limited evidence to support this. By increasing the alkalinity of the urine it promotes lithium excretion.

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.

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.

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.

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.

The most probable diagnosis in this patient is serotonin syndrome.The serotonin syndrome is a cluster of symptoms and signs (range from barely perceptible tremor to life-threatening hyperthermia and shock). It may occur when SSRIs such as citalopram, escitalopram, fluoxetine, fluoxetine, paroxetine, and sertraline that impair the reuptake of serotonin from the synaptic cleft into the presynaptic neuron are taken in combination with monoamine oxidase inhibitors or tricyclic antidepressants. It has also been reported following an overdose of selective serotonin reuptake inhibitors (SSRIs) alone.Treatment:Most cases of serotonin syndrome are mild and will resolve with removal of the offending drug alone. After stopping all serotonergic drugs, management is largely supportive and aimed at preventing complications. Patients frequently require sedation, which is best facilitated with benzodiazepines.Antipsychotics should be avoided because of their anticholinergic properties, which may inhibit sweating and heat dissipation.

MDMA commonly known as ecstasy or molly, is a psychoactive drug primarily used as a recreational drug. The desired effects include altered sensations, increased energy, empathy, and pleasure. Features of MDMA abuse include hyponatraemia, tachycardia, hyperventilation, and hyperthermia.

The presence of tinnitus, fever and hyperventilation are clues for aspirin (salicylate) toxicity. Clinical Presentation of salicylate toxicity can include:• Pulmonary manifestations include: Hyperventilation, hyperpnea, severe dyspnoea due to noncardiogenic pulmonary oedema, fever and dyspnoea due to aspiration pneumonitis• Auditory symptoms caused by the ototoxicity of salicylate poisoning include: Hard of hearing and deafness, and tinnitus (commonly encountered when serum salicylate concentrations exceed 30 mg/dL).• Cardiovascular manifestations include: Tachycardia, hypotension, dysrhythmias – E.g., ventricular tachycardia, ventricular fibrillation, multiple premature ventricular contractions, asystole – with severe intoxication, Electrocardiogram (ECG) abnormalities – E.g., U waves, flattened T waves, QT prolongation may reflect hypokalaemia.• Neurologic manifestations include: CNS depression, with manifestations ranging from somnolence and lethargy to seizures and coma, tremors, blurring of vision, seizures, cerebral oedema – With severe intoxication, encephalopathy• GI manifestations include: Nausea and vomiting, which are very common with acute toxicity, epigastric pain, GI haemorrhage – More common with chronic intoxication, intestinal perforation, pancreatitis, hepatitis – Generally in chronic toxicity; rare in acute toxicity, Oesophageal strictures – Reported as a very rare delayed complication• Genitourinary manifestations include: Acute kidney injury (NSAID induced Nephropathy) is an uncommon complication of salicylate toxicity, renal failure may be secondary to multisystem organ failure.• Hematologic effects may include prolongation of the prothrombin and bleeding times and decreased platelet adhesiveness. Disseminated intravascular coagulation (DIC) may be noted with multisystem organ failure in association with chronic salicylate toxicity.• Electrolyte imbalances like: Dehydration, hypocalcaemia, acidaemia, Syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypokalaemiaManagement of these patients should be done in the following manner:• Secure Airway, Breathing, and Circulation• Supportive therapy• GI decontamination• Urinary excretion and alkalization• Haemodialysis

Among the given anti-epileptics the best drug that can be given in this patient is lamotrigine.Topiramate, carbamazepine, phenytoin, and phenobarbital are all hepatic enzyme inducers and are associated with decreased effectiveness of the oral contraceptive (OCP) due to acceleration of the metabolism of oestrogens and progestogens.If she is planning on pregnancy then registry studies suggest that lamotrigine would also be the best choice.Other hepatic enzyme inducers include rifampicin, spironolactone, griseofulvin, etc.

The most likely complaint of this patient would be hot flushes.

Alopecia and cataracts are listed as possible side-effects, however they are not as prevalent as hot flushes, which are very common in pre-menopausal women.

Tamoxifen is a Selective Oestrogen Receptor Modulator (SERM) which acts as an oestrogen receptor antagonist and partial agonist. It is used in the management of oestrogen receptor-positive breast cancer

Adverse effects:

• Menstrual disturbance: vaginal bleeding, amenorrhoea
• Hot flushes – 3% of patients stop taking tamoxifen due to climacteric side-effects.
• Venous thromboembolism.
• Endometrial cancer (although antagonistic with respects to breast tissue, tamoxifen may serve as an agonist at other sites. Therefore the risk of endometrial cancer is increased). Raloxifene is a pure oestrogen receptor antagonist and carries a lower risk of endometrial cancer.

Tamoxifen is typically used for 5 years following the removal of the tumour.

Tiotropium is a specific long-acting antimuscarinic agent indicated as maintenance therapy for patients with COPD (chronic obstructive pulmonary disease). It should be used cautiously in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction.The most frequently encountered adverse effects of tiotropium include pharyngitis, bronchitis, sinusitis, dry mouth, cough, and headaches. Paradoxical bronchospasm may also occur as a rare side-effect. Dry mouth occurs in up to 14% of patients taking tiotropium, in keeping with its anticholinergic profile. Rarer side-effects include tachycardia, blurred vision, urinary retention, and constipation.

The most probable diagnosis for this patient is delirium tremens due to alcohol withdrawal, which should be treated as a medical emergency. Delirium tremens is a hyperadrenergic state and is often associated with tachycardia, hyperthermia, hypertension, tachypnoea, tremor, and mydriasis.Treatment:- The most common and validated treatment for alcohol withdrawal is benzodiazepine: first-line treatment includes oral lorazepam. – If the symptoms persist, or the medication is refused, parenteral lorazepam, haloperidol or olanzapine should be given.- Central-acting, alpha-2 agonists such as clonidine and dexmedetomidine should not be used alone for the treatment of alcohol withdrawal.- It is also recommended to avoid using alcohol, antipsychotics, anticonvulsants, beta-adrenergic receptor blockers, and baclofen for the treatment of alcohol withdrawal as there are not enough studies to support the safety of these.

Temazepam is an orally available benzodiazepine used in the therapy of insomnia. The soporific activity of the benzodiazepines is mediated by their ability to enhance gamma-aminobutyric acid (GABA) mediated inhibition of synaptic transmission through binding to the GABA-A receptor.The recommended initial dose for insomnia is 7.5 mg before bedtime, increasing as needed to a maximum dose of 30 mg. The most common side effects of temazepam are dose-related and include daytime drowsiness, lethargy, ataxia, dysarthria, and dizziness.Tolerance develops to these side effects, but tolerance may also develop to the effects on insomnia.

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.

Tricyclic compounds can’t be cleared by haemodialysis.Drugs that can be cleared with haemodialysis include: (BLAST)- Barbiturate- Lithium- Alcohol (inc methanol, ethylene glycol)- Salicylates- Theophyllines (charcoal hemoperfusion is preferable)Drugs which cannot be cleared with haemodialysis include:- Tricyclics- Benzodiazepines- Dextropropoxyphene (Co-proxamol)- Digoxin- Beta-blockers

Metoclopramide causes extrapyramidal effects (especially in children and young adults), hyperprolactinaemia, and occasionally tardive dyskinesia on prolonged administration. Also reported are drowsiness, restlessness, diarrhoea, depression, neuroleptic malignant syndrome, rashes, pruritus, oedema.

Excessive sweating points towards a morphine overdose.Morphine is considered the classic opioid analgesic with which other painkillers are compared. Like other medications in this class, morphine has an affinity for delta, kappa, and mu-opioid receptors.Most commonly used in pain management, morphine provides major relief to patients afflicted with pain.Among the more common adverse effects of morphine use is constipation. Other side effects include nausea, vomiting, drowsiness, and confusion. Psychological and physical dependence may occur.Other side effects include bronchospasm, angioedema, urinary retention, ureteric or biliary spasm, dry mouth, sweating, rash, facial flushing, vertigo, tachycardia, bradycardia, palpitations, orthostatic hypotension, hypothermia, restlessness, mood change, hallucinations, seizures (adults and children) and miosis, headache and allergic reactions (including anaphylaxis) and decreased libido or potency.Raised intracranial pressure occurs in some patients. Muscle rigidity may occur with high doses. Elevated liver enzymes may occur due to biliary sphincter constriction. Large doses can lead to respiratory depression, circulatory failure, and coma.Treatment of opioid overdose:Initial treatment of overdose begins with supportive care.Naloxone is a pure competitive antagonist of opiate receptors and has no agonistic activity. The drug is relatively safe and can be administered intravenous, intramuscular, subcutaneous or via the endotracheal tube.Alternatively, nalmefene and naltrexone maybe considered.

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.

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.

Loss of vision after consumption of antifreeze is a characteristic presentation of methanol poisoning.

Pathophysiology of methanol toxicity: When ingested, methanol is absorbed rapidly via the gastrointestinal tract in less than 10 minutes. Methanol is not protein-bound and is absorbed directly into the total body water compartment. Metabolism occurs mainly in the liver through serial oxidation via alcohol dehydrogenase and aldehyde dehydrogenase but begins with alcohol dehydrogenase present in the gastric mucosa. Alcohol dehydrogenase oxidizes methanol to formaldehyde, and aldehyde dehydrogenase subsequently oxidizes formaldehyde to formic acid. Formic acid is the primary toxic metabolite that accounts for the associated anion gap metabolic acidosis and end-organ damage.

Clinical presentation: Patients who present within the first 12 to 24 hours following ingestion may appear normal, and this is described as the latent period. Nausea, vomiting, and abdominal pain subsequently ensue, followed by CNS depression and hyperventilation due to metabolic acidosis. Ocular symptoms associated with retinal toxicity are often evident in the form of blurry vision, decreased visual acuity, photophobia, and “halo vision.”

Treatment: Treatment options for methanol toxicity include supportive care, fomepizole (Antizole, 4-Methylpyrazole or 4MP), ethanol, dialysis, and folate.

The principal mechanism by which strontium inhibits osteoclast activity is by enhancing the secretion of osteoprotegerin (OPG) and by reducing the expression of the receptor activator of nuclear factor κB ligand (RANKL) in osteoblasts.Osteoporosis is defined as low bone mineral density caused by altered bone microstructure ultimately predisposing patients to low-impact, fragility fractures.Management:Vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D repleteAlendronate is the first-line treatment. Around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate.Strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates.Other medications that are useful in the treatment of osteoporosis are denosumab, teriparatide, raloxifene, etc.

Memantine is an antagonist of the NMDA (N-Methyl-D-Aspartate)-receptor subtype of glutamate receptor. It is used to slow the neurotoxicity thought to be involved in Alzheimer’s disease and other neurodegenerative diseases.

Drug interactions:

• When given concomitantly with other NMDA-receptor antagonists (e.g., ketamine, amantadine) there is increased risk of psychosis.
• Dopamine agonists, L-dopa, and anticholinergics enhance effects of memantine.
• Antispasmodics (e.g., baclofen) enhance effects, as memantine has some antispasmodic effects.
• Drugs excreted by cationic transporters in the kidney (e.g. quinine, cimetidine, ranitidine) reduce excretion.
• Common adverse effects include dizziness, headache, confusion, diarrhoea, and constipation.

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.

The cardiovascular effects of β-adrenoceptor block result from reduction of the sympathetic drive which includes reduced heart rate (automaticity) and reduced myocardial contractility (rate of rise of pressure in the ventricle). This will lead to reduced cardiac output and an overall fall in oxygen consumption.

Sildenafil (Viagra) is a phosphodiesterase type V inhibitor used in the treatment of impotence.Contraindications:- Patients taking nitrates and related drugs such as nicorandil- Hypotension- Recent stroke or myocardial infarction (NICE recommend waiting 6 months)Side-effects:Visual disturbances e.g. cyanopsia, non-arthritic anterior ischaemic NeuropathyNasal congestionFlushingGastrointestinal side-effectsHeadache

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.

In such a clinical scenario, NICE guidelines support initiating treatment with bisphosphonates without waiting for a DEXA scan.Osteoporosis is defined as low bone mineral density caused by altered bone microstructure ultimately predisposing patients to low-impact, fragility fractures.Management:Vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D repleteAlendronate is the first-line treatment. Around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate.Strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates.Other medications that are useful in the treatment of osteoporosis are denosumab, teriparatide, raloxifene, etc.

The presentation of the patient is typical of chronic lithium toxicity (due to the presence of mainly neurological manifestations). Additional to the blood investigations mentioned, urine analysis, electrolyte levels, and renal function should also be performed. A low urine Anion gap and a low urine specific gravity are highly suggestive of lithium toxicity.ECG obtained in this patient is likely to show: nonspecific, diffuse ST segment depression with T wave inversion.Acute lithium toxicity presents with more GI manifestations while, the clinical features of chronic lithium toxicity are mainly neurological and can include:Coarse tremors (fine tremors are seen in therapeutic levels), hyperreflexia, acute confusion, seizures, and coma.The management of lithium toxicity is as follows:Immediate GI decontamination with gastric lavage (in case of acute intoxication)Saline Administrations: the goal of saline administration is to restore GFR, normalize urine output and enhance lithium clearance.Haemodialysis remains the mainstay treatment for lithium toxicity as lithium is readily dialyzed because of water solubility, low volume of distribution, and lack of protein binding.The Extracorporeal Treatments in Poisoning Workgroup (EXTRIP Workgroup) recommendations for dialysis (extracorporeal treatment) in lithium toxicity include:• Impaired kidney function and lithium levels > 4.0 mEq/L• Decreased consciousness, seizures, or life-threatening dysrhythmias, regardless of lithium levels• Levels are > 5.0 mEq/L, significant confusion is noted, or the expected time to reduce levels to < 1.0 mEq/L is more than 36 hoursAs post-dialysis rebound elevations in lithium levels have been documented, continuous veno-venous hemofiltration (CVVH) has been advocated.

The most appropriate intervention in this patient is intravenous hydroxocobalamin.The clinical scenario provided is suggestive of acute cyanide toxicity secondary to burning plastics in the house fire. Cyanide ions inhibit mitochondrial cytochrome oxidase, preventing aerobic respiration. This manifests in normal oxygen saturations, a high pO2 and flushing (or ‘brick red’ skin) brought on by the excess oxygenation of venous blood. In the question above it is important to note that the blood gas sample given is venous rather than arterial. His blood gas also demonstrates an increased anion gap, consistent with his high lactate (generated by anaerobic respiration due to the inability to use available oxygen).The recommended treatment for moderate cyanide toxicity in the UK is one of three options: sodium thiosulfate, hydroxocobalamin or dicobalt edetate. Among the options given is hydroxocobalamin and this is, therefore, the correct answer. Hydroxocobalamin additionally has the best side-effect profile and speed of onset compared with other treatments for cyanide poisoning.Other options:- Intubation would be appropriate treatment in the context of airway burns but this patient has no evidence of these, although close monitoring would be advised. – High-flow oxygen is the treatment for carbon monoxide poisoning – a sensible differential, but this man’s very high lactate and high venous pO2 fit better with cyanide toxicity. Intravenous dexamethasone would be another treatment for airway oedema once an endotracheal tube had been placed. – Intravenous sodium nitroprusside is a treatment for high blood pressure that can cause cyanide poisoning, and would, therefore, be inappropriate.Note:Cyanide may be used in insecticides, photograph development and the production of certain metals. Toxicity results from reversible inhibition of cellular oxidizing enzymesClinical presentation:Classical features: brick-red skin, the smell of bitter almondsAcute: hypoxia, hypotension, headache, confusionChronic: ataxia, peripheral neuropathy, dermatitisManagement:Supportive measures: 100% oxygenDefinitive: hydroxocobalamin (intravenously), also a combination of amyl nitrite (inhaled), sodium nitrite (intravenously), and sodium thiosulfate (intravenously).

Dilation of systemic veins is a beneficial effect of nitro-glycerine.Administration of nitro-glycerine results in the dilation of systemic veins and decrease of myocardial wall tension and oxygen demand. Dilatation of systemic veins can cause reduced systemic vascular resistance leading to reduced cardiac workload thus reducing anginal symptoms secondary to demand ischemia.This is accompanied by vasodilation of large and medium-sized coronary arteries with increased coronary blood flow to the sub endocardium.

Among the given options the most appropriate management in this patient would be ethanol and haemodialysis.Ethanol competes with ethylene glycol for alcohol dehydrogenase and thus, helps manage a patient with ethylene glycol toxicity.Ethylene glycol is a type of alcohol used as a coolant or antifreezeFeatures of toxicity are divided into 3 stages:Stage 1: (30 min to 12 hours after exposure) Symptoms similar to alcohol intoxication: confusion, slurred speech, dizziness (CNS depression)Stage 2: (12 – 48 hours after exposure) Metabolic acidosis with a high anion gap and high osmolar gap. Also tachycardia, hypertensionStage 3: (24 – 72 hours after exposure) Acute renal failureManagement has changed in recent times:Fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol.Ethanol has been used for many years works by competing with ethylene glycol for the enzyme alcohol dehydrogenase this limits the formation of toxic metabolites (e.g. glycolaldehyde and glycolic acid) which are responsible for the hemodynamic/metabolic features of poisoning.Haemodialysis has a role in refractory cases.

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

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.

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.

Before the initiation of trastuzumab, an echocardiography is a must to rule out any pre-existing cardiac abnormalities as trastuzumab is cardiotoxic.Trastuzumab (Herceptin) is a monoclonal antibody directed against the HER2/neu receptor. It is used mainly in metastatic breast cancer although some patients with early disease are now also given trastuzumab.Adverse effects include:Flu-like symptoms and diarrhoea are common.Cardiotoxicity: – Risk increases when anthracyclines are used concomitantly. – Trastuzumab-induced cardiac dysfunctions are regarded as less severe and largely reversible because primary cardiomyocyte do not show ultrastructure changes unlike those associated with anthracycline-induced cardiotoxicity. – Primary myocyte injury does not occur in patients who were treated with trastuzumab.

The next step in managing this patient is to give 10 mg and continue administering in 10 mg increments each hour until symptoms are under control.Methadone alleviates opioid withdrawal symptoms and reduces cravings. Methadone is useful for detoxification from longer-acting opioids such as morphine or methadone itself.Methadone should be used with caution if the patient has:Respiratory deficiencyAcute alcohol dependenceHead injuryTreatment with monoamine oxidase inhibitors (MAOIs)Ulcerating colitis or Crohn’s diseaseSevere hepatic impairmentThe dose must be reviewed on a daily basis and adjusted based upon how well the symptoms are controlled and the presence of side effects. The greater the dose of opioids used by the patient, the greater the dose of methadone required to control withdrawal symptoms. To avoid the risk of overdose in the first days of treatment The recommended dosing of methadone is 30mg in two doses of 15mg morning and evening.It is important to note that a methadone dose equivalent to what the patient reports they are taking should never be given. It is rare to need more than 40 mg per 24 hours: beware of overdosing which can lead to respiratory arrest.

Although rare, ocular toxicity in the form of optic neuritis (most commonly retrobulbar neuritis) has been well documented as a side effect of ethambutol. It is renally excreted and not associated with hepatitis.

Triptans are specific 5-HT1 agonists used in the acute treatment of migraine. They are generally used as first-line therapy in combination with an NSAID or paracetamol.

Sumatriptan acts as an agonist on 5-HT1B/1D receptors by inducing vasoconstriction in the basilar artery and blood vessels within the dura mater. The drug reduces peripheral nociception either by selective cranial vasoconstriction or by affecting trigeminovascular nerves.

Antibiotics that should be avoided in pregnancy are included in the mnemonic: Countless SAFe Moms Take Really Good Care -Clarithromycin, Sulphonamides, Aminoglycosides, Fluoroquinolones, Metronidazole, Tetracyclines, Ribavirin, Griseofulvin, Chloramphenicol