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

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.

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

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 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.

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 farmer has most likely ingested an organophosphate insecticide.Organophosphorus compounds are used widely as:• Insecticides – Malathion, parathion, diazinon, dichlorvos• Nerve gases – Soman, sarin, tabun, VX• Ophthalmic agents – Echothiophate• Antihelmintics – Trichlorfon• Herbicides – merphos• Industrial chemical (plasticizer) – Tricresyl phosphateSigns and symptoms of Organophosphorus Poisoning (OPP) can be classified as:• Muscarinic effects:o Cardiovascular – Bradycardia, hypotensiono Respiratory – Rhinorrhoea, bronchorrhea, bronchospasm, cough, severe respiratory distresso Gastrointestinal – Hypersalivation, nausea and vomiting, abdominal pain, diarrhoea, faecal incontinenceo Genitourinary – Incontinenceo Ocular – Blurred vision, miosiso Glands – Increased lacrimation, diaphoresis• Nicotinic effects:o Muscle fasciculation, weakness, cramping, diaphragmatic failure, and autonomic side effects include: hypertension, tachycardia, and mydriasis.• Central nervous system (CNS) effects:o Anxiety, emotional lability, restlessness, confusion, ataxia, tremors, seizures, coma, apnoeaMainstay Treatment:• Decontamination• Securing Airway, Breathing and Circulation• Atropine• Pralidoxime• Benzodiazepines

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.

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.

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.

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

The cytochrome p450 3A4 enzyme system in the liver is affected by grapefruit juice. Patients taking antihistamines should be advised to avoid drinking grapefruit juice. This is because constituents of grapefruit juice such as naringin and bergamottin inhibit CYP3A4 in the liver, particularly at high doses, leading to decreased drug elimination via hepatic metabolism and can increase potential drug toxicities. Inhibition of this enzyme system leads to reduced metabolism of antihistamines leading to an increased incidence of side effects like excessive drowsiness and nausea as in this patient.

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 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.

Acute dystonic reactions (extrapyramidal symptoms) such as spasmodic torticollis, trismus, and oculogyric crises can occur following the administration of metoclopramide or stemetil and thus, neither is recommended for the treatment of nausea in young women.

Such reactions respond well to treatment with benztropine or procyclidine.

– Benztropine: It is an anticholinergic medication with significant CNS penetration. A single dose of benztropine 1 to 2 mg IV followed by 1 to 2 mg p.o twice a day for up to 7 days to prevent a recurrence. Subsequently, both the offending agent and those from the same group should be avoided.

– Alternatively, diphenhydramine can be used intravenously (up to a dose of 50mg) or intramuscularly followed by p.o therapy every 6 hours for 1 to 2 to prevent a recurrence.- Second-line therapy with IV benzodiazepines is reserved for those patients who do not respond to anticholinergics.

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.

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.

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.

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.

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.

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.

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.

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

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 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.

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.

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 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.

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