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.

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.

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.

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

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.

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.

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.

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.

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

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.

Drug metabolism can be broadly classified into:Phase I (functionalization) reactions: also termed non-synthetic reactions, they include oxidation, reduction, hydrolysis, cyclization and de-cyclization. The most common and vital reactions are oxidation reactions. (Of the given enzymes only Alcohol dehydrogenase is involved in phase I drug metabolism. Succinate dehydrogenase, is a vital enzyme involved in the Kreb’s cycle and the mitochondrial electron transport chain). They are mainly catalysed by Cytochrome P-450 enzyme.Phase II (conjugation) reactions: occur following phase I reactions, they include reactions: glucuronidation and sulphate conjugation, etc. They are mostly catalysed by UDP-glucuronosyltransferase enzyme. Other phase II enzymes include: sulfotransferases, N-acetyltransferases, glutathione S-transferases and methyltransferases.

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

The most appropriate treatment in this patient would be to stop warfarin therapy and keep the patient under observation.The drugs that lead to enhanced potency of warfarin include: disulfiram, trimethoprim-sulphamethoxazole, metronidazole, phenylbutazone, aspirin, heparin, and clofibrate. Liver disease, thrombocytopenia, hyperthyroidism also increase the oral anticoagulant potency.If the patient has minor bleeding and the international normalized ratio (INR) is >6.0, warfarin should be stopped; the INR should be rechecked daily and in addition to the stoppage of warfarin, vitamin K 2.5 mg oral or 0.5 mg intravenously should also be administered.In a patient with INR of 2.0 or 3.0, it takes two or three times longer for that individual’s blood to clot than someone who is not taking any anticoagulants. Most patients on warfarin have an INR goal of 2 to 3.If there is major bleeding then prothrombin complex concentrates 50 u/kg or fresh-frozen plasma 15 ml/kg may be considered.

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.

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.

Among the following hypertensives, lisinopril (an ACE inhibitor) is contraindicated in patients who are planning for pregnancy.Per the NICE guidelines, when treating the woman in question, she should be treated as if she were pregnant given the absence of effective contraception. ACE inhibitors such as lisinopril are known teratogens and most be avoided.Drugs contraindicated in pregnancy:AntibioticsTetracyclinesAminoglycosidesSulphonamides and trimethoprimQuinolonesOther drugs:ACE inhibitors, angiotensin II receptor antagonistsStatinsWarfarinSulfonylureasRetinoids (including topical)Cytotoxic agentsThe majority of antiepileptics including valproate, carbamazepine, and phenytoin are known to be potentially harmful.

All patients require plasma-vancomycin measurement (after 3 or 4 doses if renal function normal, earlier if renal impairment). There is a risk of nephrotoxicity including renal failure, interstitial nephritis and ototoxicity.

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).

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.

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.

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.

Proton pump inhibitors can reduce gastric acid secretion by up to 99%. Acid production resumes following the normal renewal of gastric parietal cells.

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)

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.

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.

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 symptoms of ataxia, slurred speech and blurred vision are all suggestive of phenytoin toxicity. Cimetidine increases the efficacy of phenytoin by reducing its hepatic metabolism.Phenytoin has a narrow therapeutic index (10-20 mg/L) and its levels are monitored by measuring the total phenytoin concentration.Cimetidine is an H2 receptor antagonist used in the treatment of peptic ulcers. It acts by decreasing gastric acid secretion.Cimetidine also has an inhibitory effect on several isoforms of the cytochrome enzyme system including the CYP450 enzymatic pathway. Phenytoin is metabolized by the same cytochrome P450 enzyme system in the liver. Thus, the simultaneous administration of both these medications leads to an inhibition of phenytoin metabolism and thus increases its circulating levels leading to phenytoin toxicity.

The blood gas analysis provided above is suggestive of a mixed respiratory alkalosis and metabolic acidosis characteristic of salicylate overdose.Pathophysiology:The direct stimulation of the cerebral medulla causes hyperventilation and respiratory alkalosis.As it is metabolized, it causes an uncoupling of oxidative phosphorylation in the mitochondria. Lactate levels then increase due to the increase in anaerobic metabolism. This, along with a slight contribution from the salicylate metabolites result in metabolic acidosis.Tinnitus is characteristic and salicylate ototoxicity may produce deafness. Other neurological sequelae include encephalopathy and agitation, seizures and CNS depression and coma. Cardiovascular complications include tachycardia, hypotension, and dysrhythmias (VT, VF, and asystole).

Excessive sweating points towards a morphine overdose.Morphine is considered the classic opioid analgesic with which other painkillers are compared. Like other medications in this class, morphine has an affinity for delta, kappa, and mu-opioid receptors.Most commonly used in pain management, morphine provides major relief to patients afflicted with pain.Among the more common adverse effects of morphine use is constipation. Other side effects include nausea, vomiting, drowsiness, and confusion. Psychological and physical dependence may occur.Other side effects include bronchospasm, angioedema, urinary retention, ureteric or biliary spasm, dry mouth, sweating, rash, facial flushing, vertigo, tachycardia, bradycardia, palpitations, orthostatic hypotension, hypothermia, restlessness, mood change, hallucinations, seizures (adults and children) and miosis, headache and allergic reactions (including anaphylaxis) and decreased libido or potency.Raised intracranial pressure occurs in some patients. Muscle rigidity may occur with high doses. Elevated liver enzymes may occur due to biliary sphincter constriction. Large doses can lead to respiratory depression, circulatory failure, and coma.Treatment of opioid overdose:Initial treatment of overdose begins with supportive care.Naloxone is a pure competitive antagonist of opiate receptors and has no agonistic activity. The drug is relatively safe and can be administered intravenous, intramuscular, subcutaneous or via the endotracheal tube.Alternatively, nalmefene and naltrexone maybe considered.

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.