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.

Agitation, hypomania and suicidal intent within a few days after initiating corticosteroid therapy is highly suggestive of a diagnosis of corticosteroid-induced psychosis.In some patients corticosteroid related psychosis has been diagnosed up to 12 weeks or more after commencing therapy.Euphoria and hypomania are considered to be the most common psychiatric symptoms reported during short courses of steroids.During long-term treatment, depressive symptoms were the most common. Higher steroid doses appear to carry an increased risk for such adverse effects; however, there is no significant relationship between dose and time to onset, duration, and severity of symptoms. Management: Reduction or cessation of corticosteroids is the mainstay of treatment for steroid psychosis. For those patients who cannot tolerate this reduction/cessation of steroids, mood stabilizers may be of some benefit.

Different Oral Hypoglycaemic Agents (OHAs) and their respective mechanism(s) of action include:• Sulfonylureas (such as, glipizide, gliclazide, glimepiride) – bind to ATP sensitive Potassium channels (K – ATP channels) in the 𝝱 cells of the islets of the pancreas. Inhibition of these channels lead to an altered resting membrane potential in these cells causing an influx of calcium which increases insulin secretion.• Meglitinides (like Repaglinide) through a different receptor, they similarly regulate K – ATP channels thereby causing an increase in insulin secretion.• Biguanides (e.g., Metformin) increase the hepatic AMP-activated protein kinase activity leading to reduced gluconeogenesis and lipogenesis and increased insulin-mediated uptake of glucose in muscles. (it doesn’t increase insulin secretion)• Thiazolidinediones (rosiglitazone, pioglitazone) bind to PPAR-𝝲 and increase peripheral uptake of glucose and decrease hepatic glucose production.• α-Glucosidase inhibitors (such as acarbose, miglitol, voglibose) competitively inhibit α-glucosidase enzymes in the intestine that digest the dietary starch thus, inhibiting the polysaccharide reabsorption as well as metabolism of sucrose to glucose and fructose.• DPP-4 inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin) prolong the action of glucagon-like peptide. This leads to inhibition of glucagon release, increase in insulin secretion and a decrease in gastric emptying leading to a decrease in blood glucose levels.• SGLT2 inhibitors (dapagliflozin and canagliflozin) inhibit glucose reabsorption in the proximal tubules of the renal glomeruli leading to glycosuria which in-turn reduces blood glucose levels.Note: Side effects of pioglitazone are weight gain, pedal oedema, bone loss and precipitation of congestive cardiac failure.

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

Tumour lysis syndrome (TLS) occurs most notably in patients with haematological malignancies including, Non-Hodgkin’s Lymphoma (NHL) and Acute Lymphocytic Leukaemia (ALL).Risk factors for TLS include:• Large tumour burden• Sensitivity of the tumour to chemotherapy• Rapid tumour growth rateTLS is characterized by:• Hyperuricemia• Hyperkalaemia• Hyperphosphatemia• HypocalcaemiaTreatment of TLS:• Allopurinol: It is a xanthine oxidase inhibitor, it reduces the conversion of nucleic acid by-products to uric acid. Thus, it prevents urate nephropathy and subsequent oliguric renal failure. Note: dose reduction is essential in renal failure or if given along with mercaptopurine or azathioprine.Alternatives to Allopurinol: Febuxostat; Rasburicase are useful in patients with hyperuricemia.• Hydration• Diuresis: Should be considered in well hydrated patients with insufficient urine output. Furosemide to be considered in normo-volemic patients with hyperkalaemia. Urine alkalization can be considered for promoting alkaline diuresis.• Treatment of electrolyte imbalances including hyperkalaemia, hyperphosphatemia, and hypocalcaemia.• Dialysis can be considered in refractory cases.

The 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

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.

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.

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

Metoclopramide causes extrapyramidal effects (especially in children and young adults), hyperprolactinaemia, and occasionally tardive dyskinesia on prolonged administration. Also reported are drowsiness, restlessness, diarrhoea, depression, neuroleptic malignant syndrome, rashes, pruritus, oedema.

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.

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

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

1mg Prednisolone = 4mg hydrocortisone, so the actual equivalent daily dose is 7mg.

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.

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.

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

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.

Sodium cromoglycate principally acts by inhibiting the degranulation of mast cells triggered by the interaction of antigen and IgE. The inhibitory effect on mast cells appears to be cell-type specific since cromoglycate has little inhibitory effect on mediator release from human basophils.Thus, it inhibits the release of histamine, leukotrienes, and slow-reacting substance of anaphylaxis from mast cells by inhibiting degranulation following exposure to reactive antigens.Adverse effects include cough, flushing, palpitation, chest pain, nasal congestion, nausea, fatigue, migraine, etc.

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.

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.

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

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.

Lidocaine is an example of class IB antiarrhythmics.The Vaughan-Williams classification of antiarrhythmicsI: Membrane stabilizing agentsIA: Quinidine, Procainamide, DisopyramideIB: Lidocaine, MexiletineIC: Propafenone, Flecainide II: β blockers – Propranolol, EsmololIII: Agents widening AP – Amiodarone, Dronedarone, Dofetilide, Ibutilide, SotalolIV: Calcium channel blockers – Verapamil, DiltiazemV: Miscellaneous – Digoxin, adenosine, magnesium

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.

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

1. Normal saline (N saline) should be started IV: Intravenous normal saline is recommended to enhance renal excretion of lithium. Adequate hydration is crucial because lithium is primarily excreted by the kidneys, and maintaining good urine output can help reduce lithium levels.
2. Dialysis: This is considered the most effective treatment for severe lithium toxicity, especially when serum levels are significantly elevated (typically >2.5 mmol/L) and the patient presents with severe symptoms such as seizures, altered mental status, or renal impairment. Given the patient’s lithium level of 3.2 mmol/L and her critical condition, dialysis is necessary to rapidly reduce lithium levels.

The other options are less appropriate or ineffective in this context:

• Gastric lavage should be considered: This is not typically recommended for lithium poisoning because lithium is rapidly absorbed and lavage is unlikely to be effective several hours post-ingestion.
• Activated charcoal is likely to be effective: Activated charcoal does not effectively bind lithium and is not recommended for lithium poisoning.
• 5% dextrose should be started IV: While maintaining hydration is important, normal saline is preferred over dextrose solutions in this context to promote renal excretion of lithium.
• Dialysis is not normally required unless levels are above 5 mmol/L: This statement is incorrect. Dialysis is often required at lower levels, particularly in cases of severe toxicity or if the patient is symptomatic, as seen in this case.

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.