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

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.

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.

Sarin acts by inhibiting acetylcholinesterase.Sarin gas is a highly toxic synthetic organophosphorus compound which causes inhibition of the enzyme acetylcholinesteraseSarin gas is a highly toxic synthetic organophosphorus compound which causes inhibition of the enzyme acetylcholinesterase. This results in high levels of acetylcholine (ACh).The effects of excessive ACh can be remembered by the mnemonic DUMBELLS:DiarrhoeaUrinationMiosis/muscle weaknessBronchorrhea/BradycardiaEmesisLacrimationSalivation/sweatingOrganophosphate insecticide poisoning:One of the effects of organophosphate poisoning is inhibition of acetylcholinesteraseFeatures can be predicted by the accumulation of acetylcholine (mnemonic = SLUD)SalivationLacrimationUrinationDefecation/diarrhoeacardiovascular: hypotension, bradycardiamiosis, muscle fasciculation.Organophosphate poisoning is treated with the anti-muscarinic atropine.

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

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.

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.

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

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.

Benign Prostatic Enlargement or Hyperplasia (BPE/BPH) is the most probable diagnosis of the patient in question. It is a histological diagnosis characterized by proliferation of the cellular elements of the prostate. The initial treatment modality of choice is selective alpha 1 antagonists (such as Prazosin, Alfuzosin and Indoramin, and long acting agents like, Terazosin, Doxazosin, etc.) as they provide immediate relief from the bothersome lower urinary tract symptoms (LUTS).Other treatment modalities include:• Non-selective alpha blockers: no longer used due to severe adverse effects and the availability of selective alpha 1 blockers.• 5 alpha reductase inhibitors: Finasteride and Dutasteride, they target the underlying disease process and reduce the overall prostate volume. Thus, reduce the urinary retention and the lower urinary tract symptoms. (They do not provide immediate relief from LUTS and thus are not preferred as first line drugs over alpha 1 antagonists)• PDE-5 Inhibitors: The long-acting tadalafil has proven to be useful.• Surgical Treatment modalities: TURP, Prostatectomy, etc.

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.

Bisphosphonates are analogues of pyrophosphate, a molecule which decreases demineralisation in bone. They inhibit osteoclasts by reducing recruitment and promoting apoptosis.

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 true statement among the given options is that she will still be protected against pregnancy if she takes amoxicillin for a lower respiratory tract infection while on the combined pill.Other than enzyme-inducing antibiotics such as rifampicin, antibiotics do not reduce the efficacy of the combined oral contraceptive pill.It was previously advised that barrier methods of contraception should be used if taking an antibiotic while using the contraceptive pill, due to concerns that antibiotics might reduce the absorption of the pill. This is now known to be untrue. However, if the absorptive ability of the gut is compromised for another reason, such as severe diarrhoea or vomiting, or bowel disease, this may affect the efficacy of the pill.The exception to the antibiotic rule is that hepatic enzyme-inducing antibiotics such as rifampicin and rifaximin do reduce the efficacy of the pill. Other enzyme-inducing drugs, such as phenytoin, phenobarbital, carbamazepine or St John’s Wort can also reduce the effectiveness of the pill.Other options:The combined pill is often prescribed for women with heavy periods as it can make them lighter and less painful. There is no evidence that women on the combined pill put on any significant weight, although they may experience bloating at certain times in the course. Women on the pill require monitoring of their blood pressure. There are multiple different types of combined pills.

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.

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.

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.

Renal elimination of a drug has no role in altering the bioavailability of a drug.The bioavailability of a drug is the proportion of the drug which reaches systemic circulation. Mathematically, bioavailability is the AUCoral/AUCiv x 100%, where AUC = area under the concentration-time curve following a single (oral or iv) dose. Other options are true:By definition, the bioavailability of a drug given intravenously is 100%.Drugs given orally that undergo high pre-systemic (first-pass) metabolism in the liver or gut wall have a low bioavailability e.g. lidocaine. Bioavailability is also affected by the degree of absorption from the gut and this can change depending on gut motility and administration of other drugs.

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.

The two statements that fit the characteristics of doxapram are, epilepsy is a contraindication for doxapram use and concurrent use with theophylline may increase agitation.Doxapram is a central respiratory stimulant. In clinical practice, doxapram is usually used for patients who have an acute exacerbation of chronic obstructive pulmonary disease (COPD) who are unsuitable for admission to the intensive therapy unit for ventilatory support. Doxapram infusion may buy an extra 24 h to allow for recovery.Contraindications include: ischaemic heart disease, epilepsy, cerebral oedema, acute stroke, asthma, hypertension, hyperthyroidism, and pheochromocytoma. The infusion may worsen agitation and dyspnoea and lead to hypertension, nausea, vomiting and urinary retention.Drug interactions:Concomitant administration of doxapram and aminophylline (theophylline) can cause increased skeletal muscle activity, agitation, and hyperactivity.

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.

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.

Hormone replacement therapy (HRT) involves the use of a small dose of oestrogen, combined with a progestogen (in women with a uterus), to help alleviate menopausal symptoms. The main indication is the control of vasomotor symptoms. The other indications, such as reversal of vaginal atrophy and prevention of osteoporosis, should be treated with other agents as first-line therapies.

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

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.

The statement that fits the characteristics of doxapram is, epilepsy is a contraindication for doxapram use. Concurrent use with theophylline may increase agitation not relaxation.Doxapram is a central respiratory stimulant. In clinical practice, doxapram is usually used for patients who have an acute exacerbation of chronic obstructive pulmonary disease (COPD) who are unsuitable for admission to the intensive therapy unit for ventilatory support. Doxapram infusion may buy an extra 24 h to allow for recovery.Contraindications include: ischaemic heart disease, epilepsy, cerebral oedema, acute stroke, asthma, hypertension, hyperthyroidism, and pheochromocytoma. The infusion may worsen agitation and dyspnoea and lead to hypertension, nausea, vomiting and urinary retention.Drug interactions:Concomitant administration of doxapram and aminophylline (theophylline) can cause increased skeletal muscle activity, agitation, and hyperactivity.

The patient’s symptoms and lab results are indicative of ethylene glycol poisoning, commonly found in engine coolant. Ethylene glycol is metabolized to toxic metabolites, including glycolic acid and oxalic acid, which can cause metabolic acidosis (evidenced by the low pH and low bicarbonate levels) and can bind calcium, leading to hypocalcemia.

Fomepizole is an antidote that inhibits alcohol dehydrogenase, the enzyme that converts ethylene glycol into its toxic metabolites. This prevents further formation of the harmful substances, allowing time for the ethylene glycol to be excreted unchanged in the urine.

While haemodialysis is also an important treatment for severe ethylene glycol poisoning, especially in cases of significant acidosis or renal failure, the immediate administration of fomepizole is the most urgent intervention to prevent further toxicity. Haemodialysis can be considered if the patient does not respond adequately to fomepizole or if there are signs of severe toxicity.

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.

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.