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.

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.

All the above side-effects, with the exception of alopecia, may be seen in patients taking lithium.

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.

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.

The given clinical scenario is suggestive of myo-neuropathy and is most likely to be caused by colchicine toxicity. It gives rise to subacute proximal muscle weakness and on occasions can lead to an acute necrotizing myopathy. Creatine phosphokinase may be normal or may be elevated.Weakness resolves when the drug is discontinued but the neuropathic features remain.Death is usually a result of respiratory depression and cardiovascular collapse.Treatment is symptomatic and supportive, and the treatment for colchicine poisoning includes lavage and measures to prevent shock.

Statins are a selective, competitive inhibitor of hydroxymethylglutaryl-CoA (HMG-CoA) reductase, which is the enzyme responsible for the conversion of HMG-CoA to mevalonate in the cholesterol synthesis pathway.Statins are usually well tolerated with myopathy, rhabdomyolysis, hepatotoxicity, and diabetes mellitus being the most common adverse reactions. This is the rate-limiting step in cholesterol synthesis, that leads to increased hepatic low-density lipoprotein (LDL) receptors and reduced hepatic VLDL synthesis coupled with increased very-low-density lipoprotein (VLDL) clearance.

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.

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.

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.

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

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.

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.

Blue tinge of vision/cyanopsia is caused due to the intake of sildenafil citrate.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.Note: Xanthopsia (yellow-green vision) may occur secondary to treatment with digoxin.

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.

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.

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.

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.

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 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.

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.

Metabolic acidosis is associated with cocaine overdose. In overdose, cocaine leads to agitation, tachycardia, hypertension, sweating, hallucinations, and finally convulsions. Metabolic acidosis, hyperthermia, rhabdomyolysis, and ventricular arrhythmias also occur.Chronic use may be associated with premature coronary artery disease, dilated cardiomyopathy, and increased risk of cerebral haemorrhage.There are 3 stages for acute cocaine toxicity:Stage I: CNS symptoms of headache, vertigo, pseudo hallucinations, hyperthermia, hypertension. Stage II: increased deep tendon reflexes, tachypnoea, irregular breathing, hypertension.Stage III: Areflexia, coma, fixed and dilated pupils, hypotension, ventricular fibrillation, apnoea, and respiratory failure.Treatment:- Airway, breathing, and circulation to be secured. The patient’s fever should be managed, and one should rule out hypoglycaemia as a cause of the neuropsychiatric symptoms. – Cardiovascular toxicity and agitation are best-treated first-line with benzodiazepines to decrease CNS sympathetic outflow.- The mixed beta/alpha blocker labetalol is safe and effective for treating concomitant cocaine-induced hypertension and tachycardia.- Non-dihydropyridine calcium channels blockers such as diltiazem and verapamil have been shown to reduce hypertension reliably, but not tachycardia. – Dihydropyridine agents such as nifedipine should be avoided, as reflex tachycardia may occur. – The alpha-blocker phentolamine has been recommended but only treats alpha-mediated hypertension and not tachycardia.

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.

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.

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.

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.

The blood investigations in this patient reveal hyponatremia as well as hypokalaemia. Among the options provided, Bendroflumethiazide therapy can cause the above presentation with the electrolyte disturbances. Note:- Spironolactone is a potassium-sparing diuretic that is associated with hyperkalaemia.- Enalapril therapy can cause side effects of dizziness, hypotension, cough, and rarely a rash.- Felodipine therapy can cause side effects of dizziness, headache, cough, and palpitations.

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.