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

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 best treatment for the patient in question would be methylene blue.The most probable diagnosis in this patient is methemoglobinemia due to the ingestion of amyl nitrate.Amyl nitrate promotes the formation of methaemoglobin, which avidly conserves oxygen and leads to decreased tissue oxygen saturations. Treatment of choice includes methylene blue and vitamin C.Adverse effects:Benign side effects include green or blue discoloration of urine and patients should be forewarned. Significant side effects are based on methylene blue, itself, being an oxidizing agent and an inhibitor of monoamine oxidase A (MAO-A). As an oxidizing agent, methylene blue can actually precipitate methemoglobinemia or haemolysis in high doses or when ineffectively reduced. Methylene blue administration in a patient taking a serotonergic agents may predispose to serotonin syndrome.Note: Although methylene blue administration is controversial in the setting of G6PD-deficiency due to reduced levels of NADPH, it is not contraindicated and should be administered cautiously and judiciously.

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

Benign Prostatic Enlargement or Hyperplasia (BPE/BPH) is the most probable diagnosis of the patient in question. It is a histological diagnosis characterized by proliferation of the cellular elements of the prostate. The initial treatment modality of choice is selective alpha 1 antagonists (such as Prazosin, Alfuzosin and Indoramin, and long acting agents like, Terazosin, Doxazosin, etc.) as they provide immediate relief from the bothersome lower urinary tract symptoms (LUTS).Other treatment modalities include:• Non-selective alpha blockers: no longer used due to severe adverse effects and the availability of selective alpha 1 blockers.• 5 alpha reductase inhibitors: Finasteride and Dutasteride, they target the underlying disease process and reduce the overall prostate volume. Thus, reduce the urinary retention and the lower urinary tract symptoms. (They do not provide immediate relief from LUTS and thus are not preferred as first line drugs over alpha 1 antagonists)• PDE-5 Inhibitors: The long-acting tadalafil has proven to be useful.• Surgical Treatment modalities: TURP, Prostatectomy, etc.

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.

The use of nitrates and nicorandil concomitantly with sildenafil citrate is contraindicated.Sildenafil (Viagra) is a phosphodiesterase type V inhibitor used in the treatment of impotence.Contraindications- Patients taking nitrates and related drugs such as nicorandil- Hypotension- Recent stroke or myocardial infarction (NICE recommend waiting 6 months)Side-effects:Visual disturbances e.g. cyanopsia, non-arthritic anterior ischaemic NeuropathyNasal congestionFlushingGastrointestinal side-effectsHeadache

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

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.

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.

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

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.

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.

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

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.

Confusion and pink mucosae are typical features of CO poisoning.The patient often presents, most commonly with headaches, and other symptoms like malaise, nausea, and dizziness.Carbon monoxide (CO) poisoning, 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%.Features of carbon monoxide toxicity- Headache: 90% of cases- Nausea and vomiting: 50%- Vertigo: 50%- Confusion: 30%- Subjective weakness: 20%- Severe toxicity: ‘pink’ skin and mucosae, hyperpyrexia, arrhythmias, extrapyramidal features, coma, deathTreatment:Use of Hyperbaric oxygen therapy (HBOT) for treating 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)

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)

Tiotropium is a specific long-acting antimuscarinic agent indicated as maintenance therapy for patients with COPD (chronic obstructive pulmonary disease). It should be used cautiously in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder neck obstruction.The most frequently encountered adverse effects of tiotropium include pharyngitis, bronchitis, sinusitis, dry mouth, cough, and headaches. Paradoxical bronchospasm may also occur as a rare side-effect. Dry mouth occurs in up to 14% of patients taking tiotropium, in keeping with its anticholinergic profile. Rarer side-effects include tachycardia, blurred vision, urinary retention, and constipation.

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.

Desmopressin test (done to differentiate nephrogenic diabetes insipidus from central diabetes insipidus), and serum lithium levels can together confirm a diagnosis of lithium-induced nephrogenic diabetes insipidus.Bipolar disease is most often managed with mood stabilizers like lithium. This patient develops gastrointestinal symptoms followed by an acute confusional state associated with polyuria and polydipsia. These symptoms are suggestive of diabetes insipidus.In a case where these symptoms occur in a bipolar patient under treatment, lithium-induced nephrogenic diabetes insipidus should be considered as the most probable cause.Lithium intoxication can present with symptoms of nausea, vomiting, mental dullness, action tremor, weakness, ataxia, slurred speech, blurred vision, dizziness, especially vertical nystagmus and stupor or coma. Diffuse myoclonic twitching and nephrogenic diabetes insipidus can also occur. Such a clinical syndrome occurs above the serum level of lithium of 1.5–2.0 mEq/L.Management: – Correcting electrolyte abnormalities in patients with acute disease is critical and often life-saving.- Treatment should be initiated with parenteral fluids to replete hypovolemia (normal saline at 200-250 mL/h), followed by administration of hypotonic fluid (0.5% normal saline). – On the restoration of the volume status of the patient forced diuresis should be initiated by the administration of parenteral furosemide or bumetanide accompanied by continued intravenous hypotonic fluid administration to maintain volume status.- Polyuria is managed with hydrochlorothiazide combined with amiloride, acetazolamide.

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

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.

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 statement that fits the characteristics of doxapram is, epilepsy is a contraindication for doxapram use. Concurrent use with theophylline may increase agitation not relaxation.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.

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.

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

Blue tinge of vision/cyanopsia is caused due to the intake of sildenafil citrate.Sildenafil citrate (Viagra) is the first oral drug to be widely approved for the treatment of erectile dysfunction. It is a potent and selective inhibitor of type-V phosphodiesterase, the primary form of the enzyme found in human penile erectile tissue, thereby preventing the breakdown of cyclic guanosine monophosphate (cGMP), the intracellular second messenger of nitric oxide.Uses:It is used for the treatment of erectile dysfunction, idiopathic pulmonary hypertension, premature ejaculation, high altitude illness, penile rehabilitation after radical prostatectomy, angina pectoris, and lower urinary tract symptoms.Adverse effects:Mild headache, flushing, dyspepsia, cyanopsia, back pain, and myalgias – due to a high concentration of PDE11 enzyme in skeletal muscle, which shows significant cross-reactivity with the use of tadalafil.It can also cause hypotension, dizziness, and rhinitis.Note: Xanthopsia (yellow-green vision) may occur secondary to treatment with digoxin.

All the above side-effects, with the exception of alopecia, may be seen in patients taking lithium.Common lithium side effects may include:- dizziness, drowsiness;- tremors in your hands;- trouble walking;- dry mouth, increased thirst or urination;- nausea, vomiting, loss of appetite, stomach pain;- cold feeling or discoloration in your fingers or toes;- rash; or.- blurred vision.

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.

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.

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 principal mechanism by which strontium inhibits osteoclast activity is by enhancing the secretion of osteoprotegerin (OPG) and by reducing the expression of the receptor activator of nuclear factor κB ligand (RANKL) in osteoblasts.Osteoporosis is defined as low bone mineral density caused by altered bone microstructure ultimately predisposing patients to low-impact, fragility fractures.Management:Vitamin D and calcium supplementation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D repleteAlendronate is the first-line treatment. Around 25% of patients cannot tolerate alendronate, usually due to upper gastrointestinal problems. These patients should be offered risedronate or etidronate.Strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates.Other medications that are useful in the treatment of osteoporosis are denosumab, teriparatide, raloxifene, etc.

Digoxin works by inhibiting the Na+/K+ ATPase pump in cardiac myocytes. Here’s how it works:

1. Inhibition of Na+/K+ ATPase: Digoxin binds to and inhibits the Na+/K+ ATPase pump, which is responsible for pumping sodium out of the cell and potassium into the cell.
2. Increased intracellular sodium: Inhibition of this pump leads to an increase in intracellular sodium levels.
3. Decreased activity of the sodium-calcium exchanger: The increased intracellular sodium reduces the activity of the sodium-calcium exchanger, which normally pumps calcium out of the cell in exchange for sodium.
4. Increased intracellular calcium: As a result, intracellular calcium levels rise because less calcium is being extruded from the cell. The increased calcium is then stored in the sarcoplasmic reticulum.
5. Enhanced contractility: During each action potential, more calcium is released from the sarcoplasmic reticulum into the cytoplasm, which enhances the contractility of the heart muscle (positive inotropic effect).

By increasing the force of contraction, digoxin helps improve cardiac output in patients with heart failure. Additionally, digoxin has vagomimetic effects, which can help control the heart rate in atrial fibrillation by increasing vagal tone and thereby reducing the conduction velocity through the atrioventricular node.

The 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.

Memantine is an antagonist of the NMDA (N-Methyl-D-Aspartate)-receptor subtype of glutamate receptor. It is used to slow the neurotoxicity thought to be involved in Alzheimer’s disease and other neurodegenerative diseases.

Drug interactions:

• When given concomitantly with other NMDA-receptor antagonists (e.g., ketamine, amantadine) there is increased risk of psychosis.
• Dopamine agonists, L-dopa, and anticholinergics enhance effects of memantine.
• Antispasmodics (e.g., baclofen) enhance effects, as memantine has some antispasmodic effects.
• Drugs excreted by cationic transporters in the kidney (e.g. quinine, cimetidine, ranitidine) reduce excretion.
• Common adverse effects include dizziness, headache, confusion, diarrhoea, and constipation.

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.

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

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 most probable diagnosis for this patient is delirium tremens due to alcohol withdrawal, which should be treated as a medical emergency. Delirium tremens is a hyperadrenergic state and is often associated with tachycardia, hyperthermia, hypertension, tachypnoea, tremor, and mydriasis.Treatment:- The most common and validated treatment for alcohol withdrawal is benzodiazepine: first-line treatment includes oral lorazepam. – If the symptoms persist, or the medication is refused, parenteral lorazepam, haloperidol or olanzapine should be given.- Central-acting, alpha-2 agonists such as clonidine and dexmedetomidine should not be used alone for the treatment of alcohol withdrawal.- It is also recommended to avoid using alcohol, antipsychotics, anticonvulsants, beta-adrenergic receptor blockers, and baclofen for the treatment of alcohol withdrawal as there are not enough studies to support the safety of these.

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.

Carbon monoxide (CO) poisoning, 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%.Use of Hyperbaric oxygen therapy (HBOT) for treatment of 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)Principle of HBOT:Exposing patients to 100 percent oxygen under supra-atmospheric conditions results in a decrease in the half-life (t1/2) of COHb, from , 90 min in atmospheric air to , 30 minutes. The amount of oxygen dissolved in the blood also rises from , 0.3 to 6 mL/dL, increasing the delivery of non-haemoglobin-bound oxygen to the tissues.

Sildenafil (Viagra) is a phosphodiesterase type V inhibitor used in the treatment of impotence.Contraindications:- Patients taking nitrates and related drugs such as nicorandil- Hypotension- Recent stroke or myocardial infarction (NICE recommend waiting 6 months)Side-effects:Visual disturbances e.g. cyanopsia, non-arthritic anterior ischaemic NeuropathyNasal congestionFlushingGastrointestinal side-effectsHeadache

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.

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

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

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.

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.

Dilation of systemic veins is a beneficial effect of nitro-glycerine.Administration of nitro-glycerine results in the dilation of systemic veins and decrease of myocardial wall tension and oxygen demand. Dilatation of systemic veins can cause reduced systemic vascular resistance leading to reduced cardiac workload thus reducing anginal symptoms secondary to demand ischemia.This is accompanied by vasodilation of large and medium-sized coronary arteries with increased coronary blood flow to the sub endocardium.

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.