Among the options provided, hypothermia is not a symptom of opioid withdrawal.Symptoms of opioid withdrawal include dysphoric mood, yawning, insomnia, muscle aches, lacrimation/rhinorrhoea, papillary dilatation, piloerection, fever, sweating, nausea/vomiting, diarrhoea.If the patient is having an opioid withdrawal reaction, then give 10 mg of methadone syrup and wait about 60 min to determine its effect.COWS (Clinical Opioid Withdrawal Scale) assessment for opioid withdrawal is commonly used to determine the severity of opioid withdrawal.

Vestibular damage is a neurological side effect of streptomycin.Streptomycin is an aminoglycoside bactericidal antibiotic. It is used in the treatment of tularaemia and resistant mycobacterial infections.The most common neurological side-effect is vestibular damage leading to vertigo and vomiting. Cochlear damage is less frequent and results in deafness. Other side-effects include rashes, angioneurotic oedema, and nephrotoxicity.

Lead can be absorbed through the skin and by inhalation. It is associated with iron deficiency and a microcytic anaemia. The most common gastrointestinal symptoms are abdominal colic and constipation.

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.

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 patient (known case of acromegaly) seems to have developed cholelithiasis (presenting with right upper quadrant pain) probably due to octreotide.It is a long-acting analogue of somatostatin which is released from D cells of the pancreas and inhibits the release of growth hormone, glucagon, and insulin.Uses- Acute treatment of variceal haemorrhage- Acromegaly- Carcinoid syndrome- Prevent complications following pancreatic surgery- VIPomas- Refractory diarrhoeaAdverse effectsGallstones (secondary to biliary stasis)Other options:- Bromocriptine – a dopamine agonist with side effects arising from its stimulation of the brain vomiting centre.- Desmopressin – predominantly used in patients with diabetes insipidus by increasing the presence of aquaporin channels in the distal collecting duct to increase water reabsorption from the kidneys. The main side effects include headache and facial flushing due to hypertension.- Metformin – mainly reduces hepatic gluconeogenesis in patients with type 2 diabetes, common side effects include diarrhoea, vomiting, and lactic acidosis- Levothyroxine – synthetic thyroxine used in patients with hypothyroidism, common side effects result from incorrect dosing and mimic the symptoms of hyperthyroidism.

Among the give options, reactivation of tuberculosis may occur in a patient under treatment with etanercept.Etanercept is a biological TNF inhibit commonly used to control ankylosing spondylitis, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, and rheumatoid arthritis.Etanercept is a soluble receptor that binds both TNF-alpha and TNF-beta to inhibit the inflammatory response in joints and skin that is characteristic of these autoimmune disorders.The most common adverse effects include infections (viral, bacterial, and fungal – mostly upper respiratory tract infections) and injection site reaction (erythema, itching, pain, swelling, bleeding, bruising).Rarely it can also cause, reactivation of hepatitis B and TB, pneumocystis pneumonia, congestive cardiac failure, Steven-Johnson syndrome, toxic epidermal necrolysis, etc.

1. Normal saline (N saline) should be started IV: Intravenous normal saline is recommended to enhance renal excretion of lithium. Adequate hydration is crucial because lithium is primarily excreted by the kidneys, and maintaining good urine output can help reduce lithium levels.
2. Dialysis: This is considered the most effective treatment for severe lithium toxicity, especially when serum levels are significantly elevated (typically >2.5 mmol/L) and the patient presents with severe symptoms such as seizures, altered mental status, or renal impairment. Given the patient’s lithium level of 3.2 mmol/L and her critical condition, dialysis is necessary to rapidly reduce lithium levels.

The other options are less appropriate or ineffective in this context:

• Gastric lavage should be considered: This is not typically recommended for lithium poisoning because lithium is rapidly absorbed and lavage is unlikely to be effective several hours post-ingestion.
• Activated charcoal is likely to be effective: Activated charcoal does not effectively bind lithium and is not recommended for lithium poisoning.
• 5% dextrose should be started IV: While maintaining hydration is important, normal saline is preferred over dextrose solutions in this context to promote renal excretion of lithium.
• Dialysis is not normally required unless levels are above 5 mmol/L: This statement is incorrect. Dialysis is often required at lower levels, particularly in cases of severe toxicity or if the patient is symptomatic, as seen in this case.

Finasteride inhibits the formation of dihydrotestosterone.Finasteride is a 5α-reductase inhibitor and thus, inhibits the conversion of testosterone to dihydrotestosterone (DHT). DHT is much more active than testosterone and binds more avidly to cytoplasmic receptors. DHT stimulates prostate growth and may be responsible for benign prostatic hyperplasia in the elderly. Thus, finasteride can cause a reduction in prostatic volume and help in managing a patient with benign prostatic hyperplasia.

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.

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

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.

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.

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.

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 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.

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.

1mg Prednisolone = 4mg hydrocortisone, so the actual equivalent daily dose is 7mg.

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

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.

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.

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%.Use of Hyperbaric oxygen therapy (HBOT) for treatment of 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)Principle of HBOT:Exposing patients to 100 percent oxygen under supra-atmospheric conditions results in a decrease in the half-life (t1/2) of COHb, from , 90 min in atmospheric air to , 30 minutes. The amount of oxygen dissolved in the blood also rises from , 0.3 to 6 mL/dL, increasing the delivery of non-haemoglobin-bound oxygen to the tissues.

Agitation, hypomania and suicidal intent within a few days after initiating corticosteroid therapy is highly suggestive of a diagnosis of corticosteroid-induced psychosis.In some patients corticosteroid related psychosis has been diagnosed up to 12 weeks or more after commencing therapy.Euphoria and hypomania are considered to be the most common psychiatric symptoms reported during short courses of steroids.During long-term treatment, depressive symptoms were the most common. Higher steroid doses appear to carry an increased risk for such adverse effects; however, there is no significant relationship between dose and time to onset, duration, and severity of symptoms. Management: Reduction or cessation of corticosteroids is the mainstay of treatment for steroid psychosis. For those patients who cannot tolerate this reduction/cessation of steroids, mood stabilizers may be of some benefit.

Clozapine can cause neutropenia or agranulocytosis.Clozapine is an atypical antipsychotic used in the treatment of schizophrenia, and in patients who are intolerant to, or unresponsive to other antipsychotics. It is a weak D2-receptor and D1-receptor blocking activity, with noradrenolytic, anticholinergic, and antihistaminic properties.Many antipsychotic drugs can occasionally cause bone marrow depression, but agranulocytosis is particularly associated with clozapine.Other side effects include:Hypotension, tachycardiaFever, sedation, seizures (with high doses)Appetite increaseConstipationHeartburnWeight gainExtrapyramidal symptomsAgranulocytosisNeuroleptic malignant syndrome

The use of nitrates and nicorandil concomitantly with sildenafil citrate is contraindicated.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

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.

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

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)

The best treatment for the patient in question would be methylene blue.The most probable diagnosis in this patient is methemoglobinemia due to the ingestion of amyl nitrate.Amyl nitrate promotes the formation of methaemoglobin, which avidly conserves oxygen and leads to decreased tissue oxygen saturations. Treatment of choice includes methylene blue and vitamin C.Adverse effects:Benign side effects include green or blue discoloration of urine and patients should be forewarned. Significant side effects are based on methylene blue, itself, being an oxidizing agent and an inhibitor of monoamine oxidase A (MAO-A). As an oxidizing agent, methylene blue can actually precipitate methemoglobinemia or haemolysis in high doses or when ineffectively reduced. Methylene blue administration in a patient taking a serotonergic agents may predispose to serotonin syndrome.Note: Although methylene blue administration is controversial in the setting of G6PD-deficiency due to reduced levels of NADPH, it is not contraindicated and should be administered cautiously and judiciously.

Spironolactone is an aldosterone antagonist which acts act in the distal convoluted tubule.