Opioid poisoning is classically associated with pinpoint pupils, reduced respiratory rate, bradycardia, drowsiness and coma. Hypothermia is a feature of barbiturate poisoning, while sweating and lacrimation are seen in cases of opiate withdrawal.

Ezetimibe is a cholesterol-lowering agent that acts to prevent cholesterol absorption by directly inhibiting cholesterol receptors on enterocytes.It does not affect the absorption of drugs (e.g. digoxin, thyroxine) or fat-soluble vitamins (A, D and K) as the anion-exchange resins do. It does not affect the cytochrome P450 enzyme system.The increased risk of myositis associated with the statins is not seen with ezetimibe.The most common adverse effects include headache, runny nose, and sore throat. Less common reactions include body aches, back pain, chest pain, diarrhoea, joint pain, fatigue, and weakness.

Tacrolimus is a calcineurin inhibitor used as an immunosuppressive agent used for prophylaxis of organ rejection post-transplant.Pharmacology: Calcineurin inhibition leads to reduced T-lymphocyte signal transduction and IL-2 expression. It has a half-life of 12 hours (average).Other off-label indications for the use of tacrolimus include Crohn disease, graft-versus-host disease (GVHD), myasthenia gravis, rheumatoid arthritis.Adverse effects of tacrolimus includes: Cardiovascular: Angina pectoris, cardiac arrhythmias, hypertensionCentral nervous system: Abnormal dreams, headaches, insomnia, tremors.Dermatologic: Acne vulgaris, alopecia, pruritis, rashEndocrine and metabolic: Decreased serum bicarbonate, decreased serum iron, new-onset diabetes mellitus after transplant (NODAT), electrolyte disturbances.Gastrointestinal: Abdominal pain, nausea, vomiting, diarrhoeaGenitourinary: Urinary tract infectionHepatic: Abnormal hepatic function testsNeuromuscular and skeletal: Arthralgia, muscle crampsOphthalmic: Blurred vision, visual disturbanceOtic: Otalgia, otitis media, tinnitusRenal: Acute renal failureOther options:Sirolimus (a macrolide) is an mTOR inhibitor that blocks the response to IL-2 and has a half-life of 12–15 hours. Azathioprine inhibits purine synthesis, an essential step in the proliferation of white cells and has a half-life of around 5 hours.

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.

Amiodarone is a class III antiarrhythmic drug. Class III antiarrhythmics are potassium channel blockers, they prolong duration of action potential with resulting prolongation of effective refractory period.

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.

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.

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.

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.

The principal action of organophosphates is the inhibition of acetylcholinesterase’s, therefore leading to the accumulation of acetylcholine at muscarinic receptors (miosis, hypersalivation, sweating, diarrhoea, excessive bronchial secretions), nicotinic receptors (muscle fasciculations and tremor) and in the central nervous system (anxiety, loss of memory, headache, coma). Removal from the source of the organophosphate, adequate decontamination, supplemental oxygen and atropine are the initial treatment measures. Pralidoxime, an activator of cholinesterase, should be given to all symptomatic patients.

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.

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.

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.

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.

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.

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.

Androgen deprivation therapy (ADT) for prostate cancer:Goserelin (Zoladex) is a synthetic gonadotropin-releasing hormone (GnRH) analogue; chronic stimulation of goserelin results in suppression of LH, FSH serum levels thereby preventing a rise in testosterone.Dosage form: 3.6 mg/10.8mg implants.Adverse effects include flushing, sweating, diarrhoea, erectile dysfunction, less commonly, rash, depression, hypersensitivity, etc.

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.

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

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.

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.

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.

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

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.

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.

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.

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

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.

Both fibrates and nicotinic acid have been associated with myositis, especially when combined with a statin. However, the Committee on Safety of Medicines has produced guidance which specifically warns about the concomitant prescription of fibrates with statins concerning muscle toxicity.Bezafibrate: It is a fibric acid derivative (fibrate) that has been used as a class of agents known to decrease triglyceride levels while substantially increasing HDL-C levels.Pharmacological effects:- Increases VLDL catabolism by increasing lipoprotein and hepatic triglyceride lipase.- Decreases triglyceride synthesis by inhibiting acetyl-CoA reductase.- Decreases cholesterol synthesis by inhibiting HMG-CoA reductase.Side effects:- Hypersensitivity- Primary biliary cirrhosis- Pre-existing gallbladder disease- Concurrent use with HMG-CoA inhibitors (statins) can produce myopathy- Hepatic/renal impairment in a patient warrants dose adjustment as this drug is primarily excreted via the renal mechanism.Contraindications: Concurrent use of MAO inhibitors, hypersensitivity, pre-existing cholestasis, and pregnancy.Use: It can be used to treat Barth syndrome (characterized by dilated cardiomyopathy, neutropenia (presenting with recurrent infections), skeletal myopathy and short stature)

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