Mechanism of action of low molecular weight heparin (LMWH): It inhibits coagulation by activating antithrombin III. Antithrombin III binds to and inhibits factor Xa. In doing so it prevents activation of the final common path; Xa inactivation means that prothrombin is not activated to thrombin, thereby not converting fibrinogen into fibrin for the formation of a clot. LMHW is a small fragment of a larger mucopolysaccharide, heparin. Heparin works similarly, by binding antithrombin III and activating it. Heparin also has a binding site for thrombin, so thrombin can interact with antithrombin III and heparin, thus inhibiting coagulation. Heparin has a faster onset of anticoagulant action as it will inhibit not only Xa but also thrombin, while LMWH acts only on Xa inhibition.Compared to heparin, LMWHs have a longer half-life, so dosing is more predictable and can be less frequent, most commonly once per day.Dosage and uses:LMWH is administered via subcutaneous injection. This has long-term implications on the choice of anticoagulant for prophylaxis, for example, in orthopaedic patients recovering from joint replacement surgery, or in the treatment of DVT/PE.Adverse effects:The main risk of LMWH will be bleeding. The specific antidote for heparin-induced bleeding is protamine sulphate.Less commonly it can cause:Heparin-induced thrombocytopenia (HIT)Osteoporosis and spontaneous fracturesHypoaldosteronismHypersensitivity reactions

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 most likely complaint of this patient would be hot flushes.

Alopecia and cataracts are listed as possible side-effects, however they are not as prevalent as hot flushes, which are very common in pre-menopausal women.

Tamoxifen is a Selective Oestrogen Receptor Modulator (SERM) which acts as an oestrogen receptor antagonist and partial agonist. It is used in the management of oestrogen receptor-positive breast cancer

Adverse effects:

• Menstrual disturbance: vaginal bleeding, amenorrhoea
• Hot flushes – 3% of patients stop taking tamoxifen due to climacteric side-effects.
• Venous thromboembolism.
• Endometrial cancer (although antagonistic with respects to breast tissue, tamoxifen may serve as an agonist at other sites. Therefore the risk of endometrial cancer is increased). Raloxifene is a pure oestrogen receptor antagonist and carries a lower risk of endometrial cancer.

Tamoxifen is typically used for 5 years following the removal of the tumour.

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)

Although rare, ocular toxicity in the form of optic neuritis (most commonly retrobulbar neuritis) has been well documented as a side effect of ethambutol. It is renally excreted and not associated with hepatitis.

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

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.

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

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.

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.

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)

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.

Cefalexin should be avoided in this patient.This patient is known to have a severe penicillin allergy. None of the above antibiotics are penicillin based. However, 0.5 – 6.5% of patients who are proven to have an IgE mediated penicillin allergy will also be allergic to cephalosporins, including cefalexin. Penicillin, cephalosporins, and carbapenems are all members of the beta-lactam group of antibiotics and share a common beta-lactam ring. There is, therefore, a small risk of allergy cross-over between all these antibiotics. The rates of allergy cross-over are lower with second and third-generation cephalosporins than first-generation cephalosporins such as cefalexin.It is important to question the patient carefully to ascertain what symptoms they had on exposure to penicillin. Symptoms such as an urticarial rash or itching make it more likely that they have an IgE mediated allergy.

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.

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

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.

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.

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)

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.

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

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.

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

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

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.

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.

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.

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.

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.

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.