Passmedicine - Pharmacology Questions 101 to 150

Passmedicine online course 2012 Pharmacology (Q101-150)

Question 101 of 250

C.A Ethambut olia

A 57-year-old man with a history of ischaemic heart disease is keen to try sildenafil for erectile dysfunction. Which one of the following medications may contraindicate its use?ia

D.A Isoniazidia E.A Pyrazinamideia

A.A Nebivololia

Rifampicin is a P450 enzyme inducer and will therefore increase the metabolism of warfarin, therefore decreasing the INR.

B.A Losartania C.A Nicorandilia

P450 enzyme system

D.A Nifedipineia sqweqwesf erwrewfsdfs adasd dhe Induction usually requires prolonged ex posure to the inducing drug, as opposed to P450 inhibitors, where effects are often seen rapidly

E.A Ramiprilia

Viagra? - contraindicated by nitrates and nicorandil

Inducers of the P450 system include       

Nicorandil has a nitrate component as well as being a potassium channel activator Sildenafil sqweqwesf erwrewfsdfs adasd dhe Sildenafil is a phosphodiesterase type V inhibit or used in the treatment of impotence Cont raindications    

Inhibitors of the P450 system include

patients taking nitrates and relat ed drugs such as nicorandil hypotension recent stroke or myocardial infarction non-arteritic anterior ischaemic optic neuropathy

          

Side-effects     

antiepileptics: phenytoin, carbamazepine barbiturates: phenobarbitone rifampicin St John's Wort chronic alcohol intake griseofulvin smoking (affects CYP1A2, reason why smokers require more aminophylline)

visual disturbances e.g. blue discolouration, non-arteritic anterior ischaemic neuropathy nasal congestion flushing gastroint estinal side-effects headache

antibiotics: ciprofloxacin, erythromycin isoniazid cimetidine, omeprazole amiodarone allopurinol imidazoles: ketoconazole, fluconaz ole SSRIs: fluoxetine, sertraline ritonavir sodium valproat e acute alcohol intake quinupristin

Question 103 of 250 Which one of the following is least recognised as an adverse effect of taking bendroflumethiazide?ia

Question 102 of 250

A.A Photosensitivity rashia The INR of a patient who has recently started treatment for tuberculosis drops from 2.6 to 1.3. Which one of the following medications is most likely to be responsible?ia

B.A Agranulocytosisia C.A Hypokalaemiaia

A.A Rifampicinia D.A Pancreatitisia B.A Streptomycinia

E.A Hirsuitismia 1

 Bendroflumethiazide sqweqwesf erwrewfsdfs adasd dhe Bendroflumethiazide (bendrofluazide) is a thiazide diuretic which works by inhibiting sodium absorption at the beginning of the distal convoluted tubule (DCT). Potassium is lost as a result of more sodium reaching the collecting ducts. Bendroflumethiazide has a role in the treatment of mild heart failure although loop diuretics are better for reducing overload. The main use of bendroflumethiazide currently is in hypertension (part of the effect is due to vasodilation)





Common adverse effects      

dehydration postural hypotension hyponatraemia, hypokalaemia, hypercalcaemia gout impaired glucose tolerance impotenc e





Rare adverse effects    

patients should be offered nicotine replacement therapy (NRT), varenicline or bupropion - NICE state that clinicians should not favour one medication over another NRT, varenicline or bupropion should normally be prescribed as part of a commitment to stop smoking on or before a particular date (target stop date) prescription of NRT, varenicline or bupropion should be sufficient to last only until 2 weeks after the target stop date. Normally, this will be after 2 weeks of NRT therapy, and 3 -4 weeks for varenicline and bupropion, to allow for the different met hods of administration and mode of action. Further prescriptions should be given only to people who have demonstrated that their quit attempt is continuing if unsuccessful using NRT, varenicline or bupropion, do not offer a repeat prescription within 6 months unless special circumstances have intervened do not offer NRT, varenicline or bupropion in any combination

Nicotine replacement therapy 

thrombocytopenia agranulocytosis photosensitivity rash pancreatitis



(An eagle eyed user noticed that this entry is very similar to the Wikipedia one. I can assure you that the material has been cut-and-pasted from passmedicine to Wikipedia, and not vice-versa! Note the English spellings of hyponatraemia etc. Check the Wikipedia 'history' page for more details.)

adverse effects include nausea & vomiting, headaches and flu-like symptoms NICE rec ommend offering a combination of nicotine patches and another form of NRT (such as gum, inhalator, lozenge or nasal spray) to peopl e who show a high level of dependence on nicotine or who have found single forms of NRT inadequat e in the past

Varenicline  

Question 104 of 250  A 45-year-old man is prescribed bupropion to help him quit smoking. What is the mechanism of action of bupropion?ia



A.A Nicotinic recept or partial agonistia 

B.A Selective serotonin reuptake inhibitoria C.A Norepinephrine and dopamine reuptake inhibitor, and nicotinic antagonistia



D.A Dopamine agonistia E.A Dopamine antagonistia



a nicotinic recept or partial agonist should be started 1 week before the patients target date to stop the recommended course of treatment is 12 weeks (but patients should be monitored regularly and treatment only continued if not smoking) has been shown in studies to be more effective than bupropion nausea is the most common adverse effect. Other common problems include headache, insomnia, abnormal dreams varenicline should be us ed with caution in patients with a history of depression or selfharm. There are ongoing studies looking at the risk of suicidal behaviour in patients taking varenicline contraindicated in pregnancy and breast feeding

Smoking cessa tion Bupropion

sqweqwesf erwrewfsdfs adasd dhe NICE released guidance in 2008 on the management of smoking cessation. General points include:



2

a norepinephrine and dopamine reuptake inhibitor, and nicotinic antagonist

  

Erythromycin may potentially interact with amiodarone, warfarin and simvastatin. Levofloxacin reacts to a lesser extent with both amiodarone and warfarin.

should be started 1 to 2 weeks before the patients target date to stop small risk of seizures (1 in 1,000) contraindicated in epilepsy, pregnancy and breast feeding. Having an eating disorder is a relative contraindication

Macrolides sqweqwesf erwrewfsdfs adasd dhe Erythromycin was the first macrolide used clinically. Newer examples include clarithromycin and azithromycin.

Question 105 of 250 Which one of the following drugs is most likely to cause impaired glucose tolerance?ia

B.A Azathioprineia

Macrolides act by inhibiting bacterial protein synthesis. If pushed to give an answer they are bacteriostatic in nature, but in reality this depends on the dose and type of organism being treated.

C.A Leflunomideia

Adverse effects of erythromycin

A.A Sulfasalazineia

D.A Methotrexateia

 

E.A Tacrolimusia



gastroint estinal side-effects are common cholestatic jaundice: risk may be reduc ed if erythromycin stearate is used P450 inhibitor

Question 107 of 250 Drug-induced impaired glucose tolerance Which one of the following drugs cannot be cleared by haemodialysis?ia

sqweqwesf erwrewfsdfs adasd dhe Drugs which are known to cause impaired glucose tolerance include:      

A.A Aspirinia B.A Tricyclicsia

thiazides, furosemide (less common) steroids tacrolimus, ciclosporin interferon-alpha nicotinic acid atypical antipsychotics e.g. olanzapine

C.A Lithiumia D.A Barbituratesia E.A Aminophyllineia

Beta-blockers cause a slight impairment of glucose tolerance. They should also be used with caution in diabetics as they can interfere with the metabolic and autonomic responses to hypoglycaemia

Haemodialysi s in overdose sqweqwesf erwrewfsdfs adasd dhe Drugs that can be cleared with haemodialysis mnemonic: BLAST

Question 106 of 250

    

A 67-year-old man with a history of atrial fibrillation and ischaemic heart disease presents with symptoms consistent with a chest infection. His current medication includes amiodarone, warfarin and simvastatin. Which one of the following antibiotics is it most important to avoid if possible?ia

Barbiturate Lithium Alcohol (inc methanol, ethylene glycol) Salicylates Theophyllines (charcoal haemoperfusion is preferable)

A.A Trimethoprimia Drugs which cannot be cleared wit h haemodialysis include

B.A Co-amoxiclavia C.A Cefacloria

    

D.A Levofloxacinia E.A Erythromycinia

3

tricyclics benzodiazepines dextropropoxyphene (Co-proxamol) digoxin beta-blockers

years do not need to be given a statin. We suggest reviewing the NICE T2DM guidelines for further information

Question 108 of 250 Which one of the following patients should not automatically be prescribed a statin in the absence of any contraindication?ia

Statins should be taken at night as this is when the majority of cholesterol synthesis takes place. This is especially true for simvastatin which has a shorter halflife than other statins

A.A A 51-year-old man who had a myocardial infarction 4 years ago and is now asymptomaticia

Current guidelines for lipid lowering* B.A A 57-year-old female smoker with a 10-year cardiovascular risk of 23%ia

Total cholesterol (mmol/l)

LDL cholesterol

Joint British Societies

< 4.0

< 2.0

National Service Framework for CHD

< 5.0

< 3.0

SIGN 2007

< 5.0

< 3.0

C.A A 53-year-old man with intermittent claudicationia D.A A 62-year-old man who had a transient ischaemic attack 10 months agoia E.A A 37-year-old man with well controlled diabetes mellitus type 2ia

*current NICE guidelines do not rec ommend a target cholesterol in primary prevention

Statins sqweqwesf erwrewfsdfs adasd dhe Statins inhibit the action of HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis

Question 109 of 250 Which one of the following may be associated with an increased risk of venous thromboembolism?ia

Adverse effects 



A.A Fluoxetineia

myopathy: includes myalgia, myositis, rhabdomyolysis and asymptomatic raised creatine kinase. Risks factors for myopathy include advanced age, female sex, low body mass index and pres ence of multisystem disease such as diabetes mellitus. Myopathy is more common in lipophilic statins (simvastatin, atorvastatin) than relatively hydrophilic statins (rosuvastatin, pravastatin, fluvastatin) liver impairment: the 2008 NICE guidelines recommend checking LFTs at baseline, 3 months and 12 months. Treatment should be discontinued if serum transaminase concentrations rise to and persist at 3 times the upper limit of the reference range

B.A Selegilineia C.A Diazepamia D.A Amitriptylineia E.A Olanzapineia

Venous thromboembolism : ri sk factors sqweqwesf erwrewfsdfs adasd dhe Common predisposing factors include malignancy, pregnancy and the period following an operation. The comprehensive list below is partly based on the 2010 SIGN venous thromboembolism (V TE ) guidelines:

Who should receive a statin?   

all people wit h established cardiovascular disease (stroke, TIA, ischaemic heart disease, peripheral arterial disease) NICE rec ommend anyone with a 10-year cardiovascular risk >= 20% the management of blood lipids in type 2 diabetes mellitus (T2DM) has changed slightly. Previously all patients with T2DM > 40-yearsold were prescribed statins. Now patients > 40years-old who have no obvious cardiovascular risk (e.g. Non-smoker, not obes e, normotensive etc) and have a cardiovascular risk < 20%/10

General         4

increased risk with advancing age obesity family history of VTE pregnancy (especially puerperium) immobility hospitalisation anaesthesia central venous catheter: femoral >> subclavian

Adrenaline

Underlying conditions           

sqweqwesf erwrewfsdfs adasd dhe Adrenaline is a sympathomimetic amine with both alpha and beta adrenergic stimulating properties

malignancy thrombophilia: e.g. Activated protein C resistance, prot ein C and S deficiency heart failure antiphospholipid syndrome Behcet's polycythaemia nephrotic syndrome sickle cell disease paroxysmal nocturnal haemoglobinuria hyperviscosity syndrome homocystinuria

Indications  

Recommend Adult Life Support (ALS) adrenaline doses  

Medication    

combined oral contraceptive pill: 3rd generation more than 2nd generation hormone replacement therapy raloxifene and tamoxifen antipsychotics (especially olanz apine) have recently been shown to be a risk factor

anaphylaxis: 0.5ml 1:1,000 IM cardiac arrest: 10ml 1:10,000 IV or 1ml of 1:1000 IV

Management of accident al injection 

local infiltration of phent olamine

Question 111 of 250 Which one of the following adverse effects is most likely to be seen in patients taking ciclosporin?ia

SIGN also state that the following are risk factors for recurrent VTE:    

anaphylaxis cardiac arrest

A.A Hypertensionia

previous unprovoked V TE male sex obesity thrombophilias

B.A Hypokalaemiaia C.A Alopeciaia D.A Dehy drationia

Question 110 of 250

E.A Atrophy of the gumsia

A 14-year-old boy is brought to the Emergency Department. Whilst in school he injected his friends EpiPen into the palm of his left hand. Shortly afterwards the left middle finger became cold and pale. The capillary refill time was around 5-6 seconds. What is the most appropriate management?ia

Ciclosporin side-effects: everything is increased - fluid, + BP, K , hair, gums, glucose

A.A Inhalation of Nitrox (mixture of nitrogen + oxygen)ia

Ciclosporin

B.A Intravenous nitrate infusionia sqweqwesf erwrewfsdfs adasd dhe Ciclosporin is an immunosuppressant whic h decreases clonal proliferation of T cells by reducing IL-2 release. It acts by binding to cyclophilin forming a complex which inhibits calcineurin, a phosphotase that activat es various transcription factors in T cells

C.A Local infiltration of histamineia D.A Intravenous prostacyclin infusionia E.A Local infiltration of phentolamineia

Adverse effects of ciclosporin (not e how everything is + increased - fluid, BP, K , hair, gums, glucose)

Adrenaline induced ischaemia - phentolamine

    

Phentolamine, a short acting alpha blocker, may be used in this situation. It is normally used mainly to control blood pressure during surgical resection of phaeochromocytoma 5

nephrotoxicity hepatotoxicity fluid retention hypertension hyperkalaemia

   

prophylatically in bipolar dis order but also as an adjunct in refractory depression. It has a very narrow therapeutic range (0. 4-1. 0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys. Lithium toxicity generally occurs following conc entrations > 1.5 mmol/L.

hypert richosis hyperplasia of gum tremor impaired glucose tolerance

Indications   

Toxicity may be precipitated by dehydration, renal failure, diuretics (especially bendroflumethiazide) or ACE inhibitors

following organ trans plantation rheumatoid arthritis psoriasis (has a direct effect on keratinocytes as well as modulating T cell function) ulcerative colitis pure red cell aplasia

 

Features of toxicity    

Question 112 of 250 A 43-year-old man with a history of bipolar disorder is admitted with acute confusion. Whilst being transferred to hospital he had generalised seizure whic h terminated spontaneously after around 30 seconds. On arrival in the Emergency Department his GCS is 14/15 and he is noted to have a coarse tremor. A diagnosis of lithium toxicity is suspected. Intravenous access is obtained, bloods are taken and a saline infusion is started. Blood results reveal the following:

coarse tremor (a fine tremor is seen in therapeutic levels) acute confusion seizure coma

Management   

Lithium level 4.2 mmol/l

mild-moderate toxicity may respond to volume resuscitation with normal saline haemodialysis may be needed in severe toxicity sodium bicarbonate is sometimes used but there is limited evidence to support this. By increasing the alkalinity of the urine it promotes lithium excretion

136 mmol/l

Question 113 of 250

+

4.6 mmol/l

What is the most appropriat e time to take blood samples for therapeutic monitoring of ciclosporin levels ?ia

Urea

8.1 mmol/l

Creatinine

99 µmol/l

+

Na K

A.A 6 hours after last doseia B.A Immediately before next doseia C.A At any timeia

Bicarbonate 18 mmol/l D.A 12 hours after last doseia What is the most appropriat e management ?ia

E.A 4 hours after last doseia

A.A Arrange haemodialysisia B.A Intravenous magnesiumia Therapeutic drug monitoring

C.A Intravenous bicarbonateia

sqweqwesf erwrewfsdfs adasd dhe Lithium

D.A Intravenous hypertonic salineia E.A Arrange plasma exchangeia

 

The high lithium level and reduced GCS are an indication for haemodialysis in this patient

range = 0.4 - 1.0 mmol/l take 12 hrs post-dose

Ciclosporin

Lithium toxicity



sqweqwesf erwrewfsdfs adasd dhe Lithium is mood stabilising drug used most commonly 6

trough levels immediately before dose

Conversion between opioids Digoxin 

To

Oral codeine

Oral morphine Divide by 10

Oral tramadol Oral morphine Divide by 5

Phenytoin 

From at least 6 hrs post-dose

trough levels immediately before dose

From

To

Oral morphine Oral oxycodone

The BNF states that oral morphine sulphate 80-90mg over 24 hours is approximately equivalent to one '25 mcg/hour' fent anyl patch, therefore product literature should be consulted.

Question 114 of 250 A 72-year-old man with met astatic colon cancer is reviewed. He currently takes co-codamol 30/500 2 tablets qds for pain relief. Unfortunately this is not controlling his pain. What is the most appropriate change to his medication?ia A.A Switch to MST 15mg bd + paracetamol 1g qdsia B.A Switch to MST 35mg bd + paracetamol 1g qdsia C.A Add tramadol 50-100mg 1-2 qdsia

From

To

Oral morphine

Subcutaneous diamorphine

Divide by 3

Oral oxycodone

Subcutaneous diamorphine

Divide by 1.5

Question 115 of 250

D.A Switch to MST 25mg bdia

Which one of the following drugs used in the management of diabetes mellitus is most likely to cause cholestasis?ia

E.A Switch to MST 15mg bdia

A.A Metforminia

His total codeine dose is 30 * 2 * 4 = 240 mg/day. Converting this to oral morphine = 24 mg/day. It is therefore reasonable to start MST 15mg bd as his pain is not currently controlled. Paracetamol should be continued as it has been shown to give benefits even to patients on large doses of morphine

B.A Gliclazideia C.A Acarboseia D.A Rosiglitazoneia E.A Insulinia

Palliative care prescribing: pain sqweqwesf erwrewfsdfs adasd dhe SIGN issued guidance on the control of pain in adults with cancer in 2008. Selected points    

Divide by 2

Drug-induced liver disease sqweqwesf erwrewfsdfs adasd dhe Drug-induced liver disease is generally divided into hepatocellular, cholestatic or mixed. There is however considerable overlap, with some drugs causing a range of changes to the liver

the breakthrough dose of morphine is one-sixth the daily dose of morphine all patients who receive opioids should be prescribed a lax ative opioids should be used with caution in patients with chronic kidney disease. Alfentanil, buprenorphine and fentanyl are preferred metastatic bone pain may respond to NSA IDs, bisphosphonates or radiotherapy

The following drugs tend to cause a hepatocellular picture:     

When increasing the dose of opioids the next dose should be increased by 30-50%.

    7

paracetamol sodium valproat e, phenytoin MAOIs halothane anti-tuberculosis: isoniazid, rifampicin, pyrazinamide statins alcohol amiodarone methyldopa

an analogue or inhibiting its breakdown, is therefore the target of two recent classes of drug

The following drugs tend to cause cholestasis (+/hepatitis):       

Glucagon-like peptide-1 (GLP-1) mimetics (e.g. exenatide)

oral cont raceptive pill antibiotics: flucloxacillin, co-amoxiclav, erythromycin*, nitrofurantoin anabolic steroids, testosterones phenothiazines: chlorpromazine, prochlorperazine sulphonylureas fibrates rare reported causes: nifedipine

     

Liver cirrhosis   

methotrexate methyldopa amiodarone

increase insulin secretion and inhibit glucagon secretion licensed for use in T2DM must be given by subcutaneous injection within 60 minut es before the morning and evening meals. It should not be given after a meal may be combined with metformin, a sulfonylurea or a thiazolidinedione typically results in weight loss major advers e effect is nausea and vomiting

NICE guidelines on the use of exenatide 

*risk may be reduced with erythromycin stearate 

Question 116 of 250

should be used only when insulin would otherwise be started, obesity is a problem (BMI > 35 kg/m^2) and the need for high dose insulin is likely continue only if beneficial response occurs and is maintained (> 1.0 percentage point HbA1c reduction and weight loss > 3% in 6 months)

What is the mechanism of action of exenatide?ia A.A Glucagon inhibitoria

The Medicines and Healthcare products Regulatory Agency has issued specific warnings on the use of exenatide:

B.A Dipeptidyl peptidase-4 (DPP-4) inhibitoria C.A Glucagon-like peptide-1 (GLP-1) mimeticia

 

D.A Incretin inhibitoria

increased risk of severe pancreatitis increased risk of renal impairment

E.A Alpha-glucosidase inhibitoria Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin) Exenatide = Glucagon-like peptide-1 (GLP -1) mimetic

  

Diabetes mellitus: GLP -1 and the new drugs sqweqwesf erwrewfsdfs adasd dhe A number of new drugs to treat diabet es mellitus have become available in rec ent years. Much research has focused around the role of glucagon-like peptide-1 (GLP -1), a hormone released by the small intestine in response to an oral glucose load

oral preparation trials to date show that the drugs are relatively well tolerated with no increased incidence of hypoglycaemia do not cause weight gain

NICE guidelines on DPP-4 inhibitors  

Whilst it is well known that insulin resistance and insufficient B-cell compensation occur other effects are also seen in type 2 diabetes mellitus (T2DM). In normal physiology an oral glucose load results in a greater release of insulin than if the same load is given intravenously - this known as the incretin effect. This effect is largely mediated by GLP-1 and is known to be decreased in T2DM. Increasing GLP-1 levels, either by the administration of 8

continue DPP-4 inhibitor only if there is a reduction of > 0.5 perc entage points in HBA1c in 6 months NICE suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight gain would cause significant problems, a thiazolidinedione is contraindicated or the person has had a poor response to a thiazolidinedione

Question 117 of 250

Question 118 of 250

A 37-year-old who is 38 weeks pregnancy is an inpatient on the obstetric ward for the management of pre-eclampsia. Blood pressure is 172/114 mmHg and urine dipstick shows proteinuria +++. A decision has been made to start magnesium sulphate therapy as she is deemed at risk of eclampsia. Of the following options, which are the most important parameters to monitor whilst the patient is receiving magnesium?ia

What is the main mechanism of action of ondansetron?ia A.A Dopamine receptor agonistia B.A 5-HT2 receptor antagonistia C.A Dopamine receptor antagonistia

A.A Blood sugar + pulse rateia

D.A 5-HT2 receptor agonistia

B.A Reflexes + respiratory rateia

E.A 5-HT3 receptor antagonistia

C.A Blood sugar + respiratory rateia D.A Reflexes + pulse rateia Drugs which act on serotonin receptors E.A Glasgow coma scale + pulse rateia sqweqwesf erwrewfsdfs adasd dhe Below is a summary of drugs which are known to act via modulation of the serotonin (5-HT) system. It should be not ed that 5-HT receptor agonists are used in the acute treatment of migraine whilst 5-HT receptor antagonists are used in prophylaxis

Magnesium sulphate - monitor reflexes + respiratory rate

Agonists Eclampsia



sqweqwesf erwrewfsdfs adasd dhe Eclampsia may be defined as the development of seizures in association pre-eclampsia. To recap, preeclampsia is defined as:



  

Antagonists

condition seen after 20 weeks gestation pregnancy-induced hypertension proteinuria



Magnesium sulphate is used to bot h prevent seizures in patients with severe pre-eclampsia and treat seizures once they develop. Guidelines on its use suggest the following:    

sumatriptan is a 5-HT1D receptor agonist which is used in the acute treatment of migraine ergotamine is a partial agonist of 5-HT1 receptors

 

should be given once a decision to deliver has been made in eclampsia an IV bolus of 4g over 5-10 minutes should be given followed by an infusion of 1g / hour urine output, reflexes, respiratory rate and oxygen saturations should be monitored during treatment treatment should continue for 24 hours after last seizure or delivery (around 40% of seizures occur post-partum)

pizotifen is a 5-HT2 rec eptor antagonist used in the prophylaxis of migraine attacks. Methysergide is anot her antagonist of the 5HT2 receptor but is rarely used due to the risk of retroperitoneal fibrosis cyproheptadine is a 5-HT2 receptor antagonist which is used to control diarrhoea in patients with carcinoid syndrome ondansetron is a 5-HT3 recept or antagonist and is used as an antiemetic

Question 119 of 250 Which one of the following side-effects is least recognised in patients taking isotretinoin?ia A.A Hypertensionia B.A Terat ogenicityia C.A Nose bleedsia D.A Depressionia

Other import ant aspects of treating severe pre eclampsia/eclampsia include fluid restriction to avoid the potentially serious consequences of fluid overload

E.A Raised triglyceridesia

9

Oesophageal varices

Isotretinoin adverse effects      

sqweqwesf erwrewfsdfs adasd dhe Acute treatment of variceal haemorrhage

teratogenicity - females MUS T be taking contraception low mood dry eyes and lips raised triglycerides hair thinning nose bleeds

  

Hypertension is not listed in the British National Formulary as a side-effect  Isotretinoin 

sqweqwesf erwrewfsdfs adasd dhe Isotretinoin is an oral retinoid used in the treatment of severe acne. Two-thirds of patients have a long term remission or cure following a course of oral isotretinoin

 

Adverse effects       

teratogenicity: females should ideally be using two forms of contrac eption (e.g. Combined oral contraceptive pill and condoms ) dry skin, eyes and lips: the most common sideeffect of isotretinoin low mood raised triglycerides hair thinning nose bleeds (caused by dry ness of the nasal mucosa) benign intracranial hypertension: isotretinoin treatment should not be combined with tetracyclines for this reason

ABC: patients should ideally be resuscitated prior to endoscopy correct clotting: FFP, vit amin K vasoactive agents: terlipressin is currently the only licensed vasoactive agent. It has been shown to be of benefit in initial haemostasis and preventing rebleeding. Octreotide may also be used although there is some evidence that terlipressin has a greater effect on reducing mortality prophylactic antibiotics have been shown in multiple meta-analyses to reduce mort ality in patients with liver cirrhosis endoscopy: endoscopic variceal band ligation is superior to endoscopic sclerotherapy Sengstaken-Blakemore tube if uncontrolled haemorrhage Transjugular Intrahepatic Portosystemic Shunt (TIPSS) if above measures fail

Prophylaxis of variceal haemorrhage  

propranolol: reduced rebl eeding and mortality compared to placebo endoscopic variceal band ligation (EVL) is superior to endoscopic sclerotherapy. It should be performed at two-weekly intervals until all varices have been eradicated. Prot on pump inhibitor cover is given to prevent EVL-induced ulceration

Question 121 of 250

Question 120 of 250

Low molecular weight heparin has the greatest inhibitory effect on which one of the following proteins involved in the coagulation cascade?ia

A 41-year-old alcoholic is admitted with a suspected variceal haemorrhage. Terlipressin is given. What is the main mechanism of action of terlipressin?ia

A.A Factor IXaia B.A Factor XIaia

A.A Portal system vasodilationia

C.A Factor Xaia

B.A Antifibrinolyticia C.A Constriction of hepatic venulesia

D.A Thrombinia

D.A Endothelin-1 ant agonistia

E.A Factor XIIaia

E.A Constriction of the splanchnic vesselsia Heparin Terlipressin - method of action = constriction of the splanchnic vessels

sqweqwesf erwrewfsdfs adasd dhe There are two main types of heparin - unfractionat ed, 'standard' heparin or low molecular weight heparin (LMWH). Heparins generally act by activating antithrombin III. Unfractionated heparin forms a complex which inhibits thrombin, factors Xa, IXa, XIa 10

and XIIa. LMWH however only increases the action of antithrombin III on factor Xa

Question 122 of 250

The table below shows the differences bet ween standard heparin and LMW H:

A 23-year-old female is commenced on varenicline to help her stop smoking. Which one of the following adverse effects is most likely to occur?ia

Standard heparin

Administration

Intravenous

Subcutaneous

Duration of action

Short

Long

Mechanism of action

Acti vates antithrombin III. Forms a complex that inhibits thrombin, factors Xa, IXa, Xia and XIIa

Acti vates antithrombin III. Forms a complex that inhibits factor Xa

Bleeding Heparin-induced thrombocytopaenia (HIT) Osteoporosis

Bleeding

Acti vated partial thromboplastin time (APTT)

Anti-Factor Xa (although routine monitoring is not required)

Useful in situations where there is a high risk of bleeding as anticoagulation can be terminated rapidly

Now standard in the management of venous thromboembolism treatment and prophylaxis and acute coronary syndromes

Side-effects

Monitoring

Notes

A.A Vivid dreamsia

Low molecular weight heparin (LMWH)

B.A Naus eaia C.A Constipationia D.A Insomniaia E.A Drug-induced lupusia Whilst all of the above adverse effects may occur nausea is the most common Smoking cessa tion

Lower risk of HIT and osteoporosis with LMWH

sqweqwesf erwrewfsdfs adasd dhe NICE released guidance in 2008 on the management of smoking cessation. General points include: 





Heparin-induced thrombocytopaenia (HIT)     

immune mediat ed - antibodies form which cause the activation of platelets usually does not develop until after 5-10 days of treatment despite being associated with low platelets HIT is actually a prothrombotic condition features include a greater than 50% reduction in platelets, thrombosis and skin allergy treatment options include alternative anticoagulants such as lepirudin and danaparoid





patients should be offered nicotine replacement therapy (NRT), varenicline or bupropion - NICE state that clinicians should not favour one medication over another NRT, varenicline or bupropion should normally be prescribed as part of a commitment to stop smoking on or before a particular date (target stop date) prescription of NRT, varenicline or bupropion should be sufficient to last only until 2 weeks after the target stop date. Normally, this will be after 2 weeks of NRT therapy, and 3 -4 weeks for varenicline and bupropion, to allow for the different met hods of administration and mode of action. Further prescriptions should be given only to people who have demonstrated that their quit attempt is continuing if unsuccessful using NRT, varenicline or bupropion, do not offer a repeat prescription within 6 months unless special circumstances have intervened do not offer NRT, varenicline or bupropion in any combination

Nicotine replacement therapy 

Both unfractionated and low-molecular weight heparin can cause hyperkalaemia. This is thought to be caused by inhibition of aldosterone secretion.



Heparin overdose may be reversed by protamine sulphate, although this only partially revers es the effect of LMW H.

11

adverse effects include nausea & vomiting, headaches and flu-like symptoms NICE rec ommend offering a combination of nicotine patches and another form of NRT (such as gum, inhalator, lozenge or nasal spray) to people who show a high level of dependence on nicotine or who have found single forms of NRT inadequat e in the past

Varenicline   

  



Tricyclic overdose

a nicotinic recept or partial agonist should be started 1 week before the patients target date to stop the recommended course of treatment is 12 weeks (but patients should be monitored regularly and treatment only continued if not smoking) has been shown in studies to be more effective than bupropion nausea is the most common adverse effect. Other common problems include headache, insomnia, abnormal dreams varenicline should be us ed with caution in patients with a history of depression or selfharm. There are ongoing studies looking at the risk of suicidal behaviour in patients taking varenicline contraindicated in pregnancy and breast feeding

sqweqwesf erwrewfsdfs adasd dhe Overdose of tricyclic antidepressants is a common presentation to emergency departments. Amitriptyline and dosulepin (dothiepin) are particularly dangerous in overdose. Early features relate to anticholinergic properties: dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision. Features of severe poisoning include:    

ECG changes include:   

Bupropion    

arrhythmias seizures metabolic acidosis coma

a norepinephrine and dopamine reuptake inhibitor, and nicotinic antagonist should be started 1 to 2 weeks before the patients target date to stop small risk of seizures (1 in 1,000) contraindicated in epilepsy, pregnancy and breast feeding. Having an eating disorder is a relative contraindication

sinus tachycardia widening of QRS prolongation of QT interval

Widening of QRS > 100ms is associated with an increased risk of seizures whilst QRS > 160ms is associated with vent ricular arrhythmias Management 

Question 123 of 250

 A 55-year-old female is admitted following an overdose of amitriptyline. On examination she has dilated pupils and is tachycardic at 160 bpm, with a blood pressure of 96/54 mmHg. ECG reveals a broad complex tachycardia. What is the most appropriate management?ia A.A IV amiodaroneia 

B.A IV bicarbonateia

IV bicarbonate may reduce the risk of seizures and arrhythmias in severe toxicity arrhythmias: class 1a (e.g. Quinidine) and class Ic antiarrhythmics (e.g. Flecainide) are contraindicated as they prolong depolarisation. Class III drugs such as amiodarone should also be avoided as they prolong the QT interval. Response to lignocaine is variable and it should be emphasized that correction of acidosis is the first line in management of tricyclic induced arrhythmias dialysis is ineffective in removing tricyclics

C.A IV magnesiumia

Question 124 of 250

D.A DC cardioversionia

Which one of the following drugs is least likely to cause gynaecomastia?ia

E.A Glucagonia

A.A Spironolactoneia B.A Sodium valproateia

Tricyclic overdose - give IV bicarbonate

C.A Digoxinia Arrhythmias following tricyclic overdose are difficult to treat as many commonly used anti -arrhythmics are contraindicated. The use of sodium bicarbonate has been shown to be effective, even in patients who are not acidotic

D.A Cimetidineia E.A Anabolic steroidsia

12

Whilst sodium valproat e may rarely causes gynaecomastia it is much more common after taking the other listed drugs.

Aspirin is a common cause of urticaria

Gynaecomastia Although all medications can potentially cause urticaria it is commonly seen secondary to aspirin

sqweqwesf erwrewfsdfs adasd dhe Gynaecomastia describes an abnormal amount of breast tissue in males and is usually caused by an increased oestrogen:androgen ratio. It is important to differentiate the causes of galactorrhoea (due to the actions of prolactin on breast tissue) from those of gynaecomastia

Drug cause s of urticaria sqweqwesf erwrewfsdfs adasd dhe The following drugs commonly cause urticaria:    

Caus es of gynaecomastia         

physiological: normal in puberty syndromes with androgen deficiency: Kallman's, Klinefelter's testicular failure: e.g. mumps liver disease testicular cancer e.g. seminoma secreting h CG ectopic tumour secretion hyperthy roidism haemodialysis drugs: see below

aspirin penicillins NSAIDs opiates

Question 126 of 250 Which one of the following statements regarding raloxifene in the management of osteoporosis is incorrect?ia A.A Has been shown to prevent bone loss and to reduce the risk of vertebral fracturesia

Drug causes of gynaecomastia B.A Is a selective oestrogen receptor modulatoria       

spironolactone (most common drug cause) cimetidine digoxin cannabis finasteride gonadorelin analogues e.g. Gos erelin, buserelin oestrogens, anabolic steroids

C.A May worsen menopausal symptomsia D.A Increases risk of thromboembolic eventsia E.A Increases the risk of breast canceria Raloxifene may actually dec rease the risk of breast cancer

Very rare drug caus es of gynaecomastia Osteoporosi s: secondary prevention      

tricyclics isoniazid calcium channel blockers heroin busulfan methyldopa

sqweqwesf erwrewfsdfs adasd dhe NICE guidelines were updated in 2008 on the secondary prevention of osteoporotic fractures in postmenopausal women. Key points include

Question 125 of 250



A patient presents to the Emergency Department following the development of an urticarial skin rash following the introduction of a new drug. Which one of the following is most likely to be responsible?ia A.A Omeprazoleia



B.A Sodium valproateia C.A Aspirinia

 

D.A Paracetamolia E.A Simvastatinia 13

treatment is indicated following osteoporotic fragility fractures in postmenopaus al women who are confirmed to have osteoporosis (a Tscore of – 2.5 SD or below). In women aged 75 years or older, a DE XA scan may not be required 'if the responsible clinician considers it to be clinically inappropriat e or unfeasible' vitamin D and calcium supplement ation should be offered to all women unless the clinician is confident they have adequate calcium intake and are vitamin D replete alendronate is first-line around 25% of patients cannot tolerate alendronate, usually due to upper gastroint estinal problems. These patients



should be offered risedronat e or etidronate (see treatment criteria below) strontium ranelate and raloxifene are recommended if patients cannot tolerate bisphosphonates (see treatment criteria below)



superior to etidronate in preventing hip fractures ibandronate is a onc e-monthly oral bisphosphonate

Vitamin D and calcium Treatment criteria for patients not taking alendronate



Unfortunately, a number of complicated treatment cutoff tables have been produced in the latest guidelines for patients who do not tolerate alendronate Risk factors (for use in the tables below)   

Raloxifene - selective oestrogen receptor modulator (SERM)

parental history of hip fracture alcohol intak e of 4 or more units per day rheumatoid arthritis





T-scores (S D) at (or below) which risedronate or etidronate is recommended when alendronate cannot be taken Age (years)

No ri sk factors

1 risk factor

2 risk factors

50–54

Not indicated

– 3.0

– 2.5

55–59

– 3.0

– 3.0

– 2.5

60–64

– 3.0

– 3.0

– 2.5

65–69

– 3.0

– 2.5

– 2.5

70 or older

– 2.5

– 2.5

– 2.5

  

No ri sk factors

1 risk factor

2 risk factors

50–54

Not indicated

– 3.5

– 3.5

55–59

– 4.0

– 3.5

– 3.5

60–64

– 4.0

– 3.5

– 3.5

65–69

– 4.0

– 3.5

– 3.0

70–74

– 3.0

– 3.0

– 2.5

75 or older

– 3.0

– 2.5

– 2.5

  

 

recombinant form of parathyroid hormone very effective at increasing bone mineral density but role in the management of osteoporosis yet to be clearly defined

Hormone replacement therapy  

Bisphosphonates



'dual action bone agent' - increases deposition of new bone by osteoblasts and reduces the resorption of bone by osteoclasts strong evidence base, may be second-line treatment in near future increased risk of thromboembolic events

Teriparatide

Supplementary notes on treatment



has been shown to prevent bone loss and to reduce the risk of vertebral fractures, but has not yet been shown to reduce the risk of nonvertebral fractures has been shown to increase bone density in the spine and proximal femur may worsen menopausal symptoms increased risk of thromboembolic events may decrease risk of breast cancer

Strontium ranelate

T-scores (S D) at (or below) which strontium ranelate or raloxifene is recommended when alendronate and either risedronate or etidronate cannot be taken Age (years)

poor evidence base to suggest reduced fracture rates in the general population at risk of osteoporotic fractures - may reduce rates in frail, housebound patients

alendronate, risedronat e and etidronat e are all licensed for the prevention and treatment of post-menopausal and glucocorticoid-induced osteoporosis all three have been shown to reduce the risk of both vertebral and non-vert ebral fractures although alendronate, risedronat e may be

has been shown to reduce the incidence of vertebral fracture and non-vertebral fractures due to concerns about increased rates of cardiovascular disease and breast cancer it is no longer recommended for primary or secondary prevention of osteoporosis unless the woman is suffering from vasomotor symptoms

Hip protectors   14

evidence to suggest significantly reduce hip fractures in nursing home patients compliance is a problem

old were prescribed statins. Now patients > 40years-old who have no obvious cardiovascular risk (e.g. Non-smoker, not obes e, normotensive etc) and have a cardiovascular risk < 20%/10 years do not need to be given a statin. We suggest reviewing the NICE T2DM guidelines for further information

Falls risk assessment  

no evidence to suggest reduced fracture rates however, do reduce rate of falls and should be considered in management of high risk patients

Question 127 of 250 Statins should be taken at night as this is when the majority of cholesterol synthesis takes place. This is especially true for simvastatin which has a shorter halflife than other statins

A 61-year-old man with peripheral arterial disease is prescribed simvastatin. What is the most appropriate blood test monitoring?ia A.A LFTs + creatinine kinase at baseline, 1-3 months and at intervals of 6 months for 1 yearia

Current guidelines for lipid lowering* Total cholesterol (mmol/l)

LDL cholesterol

Joint British Societies

< 4.0

< 2.0

National Service Framework for CHD

< 5.0

< 3.0

SIGN 2007

< 5.0

< 3.0

B.A LFTs at baseline and every 3 months for first yearia C.A Routine blood tests not recommendedia D.A LFTs at baseline and annuallyia E.A LFTs at baseline, 3 months and 12 monthsia A fasting lipid profile may also be checked during monitoring to assess response to treatment.

*current NICE guidelines do not rec ommend a target cholesterol in primary prevention

Statins sqweqwesf erwrewfsdfs adasd dhe Statins inhibit the action of HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis

Question 128 of 250 A 54-year-old man with a history of ischaemic heart disease is currently taking atorvastatin 40mg at night. A repeat lipid profile is ordered:

Adverse effects 



myopathy: includes myalgia, myositis, rhabdomyolysis and asymptomatic raised creatine kinase. Risks factors for myopathy include advanced age, female sex, low body mass index and pres ence of multisystem disease such as diabetes mellitus. Myopathy is more common in lipophilic statins (simvastatin, atorvastatin) than relatively hydrophilic statins (rosuvastatin, pravastatin, fluvastatin) liver impairment: the 2008 NICE guidelines recommend checking LFTs at baseline, 3 months and 12 months. Treatment should be discontinued if serum transaminase concentrations rise to and persist at 3 times the upper limit of the reference range

Total cholesterol 3.9 mmol/l HDL

0.7 mmol/l

LDL

2.6 mmol/l

Triglycerides

1.2 mmol/l

What would be the most effective way of increasing HDL levels?ia A.A Add nicotinic acidia B.A Add ezetimibeia

Who should receive a statin?   

C.A Switch atorvastatin to pravastatinia all people wit h established cardiovascular disease (stroke, TIA, ischaemic heart disease, peripheral arterial disease) NICE rec ommend anyone with a 10-year cardiovascular risk >= 20% the management of blood lipids in type 2 diabetes mellitus (T2DM) has changed slightly. Previously all patients with T2DM > 40-years-

D.A Add bezafibrateia E.A Add colestyramineia

15

Nicotinic acid increases HDL levels

Who should receive a statin?  

Nicotinic acid



sqweqwesf erwrewfsdfs adasd dhe Nicotinic acid is used in the treatment of patients with hyperlipidaemia, although its use is limited by sideeffects. As well as lowering cholesterol and triglyceride concentrations it also raises HDL levels Adverse effects   

flushing impaired glucose tolerance myositis

all people wit h established cardio vascular disease (stroke, TIA, ischaemic heart disease, peripheral arterial disease) NICE rec ommend anyone with a 10-year cardiovascular risk >= 20% the management of blood lipids in type 2 diabetes mellitus (T2DM) has changed slightly. Previously all patients with T2DM > 40-yearsold were prescribed statins. Now patients > 40years-old who have no obvious cardiovascular risk (e.g. Non-smoker, not obes e, normotensive etc) and have a cardiovascular risk < 20%/10 years do not need to be given a statin. We suggest reviewing the NICE T2DM guidelines for further information

Statins should be taken at night as this is when the majority of cholesterol synthesis takes place. This is especially true for simvastatin which has a shorter halflife than other statins

Question 129 of 250 A 67-year-old female is prescribed simvastatin for hyperlipidaemia. Which one of the following is most likely to interact with her medication?ia

Current guidelines for lipid lowering*

A.A Orange juiceia

Total cholesterol (mmol/l)

LDL cholesterol

Joint British Societies

< 4.0

< 2.0

National Service Framework for CHD

< 5.0

< 3.0

SIGN 2007

< 5.0

< 3.0

B.A Apple juiceia C.A Grapefruit juiceia D.A Cranberry juiceia E.A Carrot juiceia Grapefruit juice is a potent inhibitor of the cytochrome P450 enzyme CYP3A4 Statins

*current NICE guidelines do not rec ommend a target cholesterol in primary prevention

sqweqwesf erwrewfsdfs adasd dhe Statins inhibit the action of HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis

Question 130 of 250 Which one of the following drugs is contra-indicated whilst breast feeding?ia

Adverse effects 



A.A Aminophyllineia

myopathy: includes myalgia, myositis, rhabdomyolysis and asymptomatic raised creatine kinase. Risks factors for myopathy include advanced age, female sex, low body mass index and pres ence of multisystem disease such as diabetes mellitus. Myopathy is more common in lipophilic statins (simvastatin, atorvastatin) than relatively hydrophilic statins (rosuvastatin, pravastatin, fluvastatin) liver impairment: the 2008 NICE guidelines recommend checking LFTs at baseline, 3 months and 12 months. Treatment should be discontinued if serum transaminase concentrations rise to and persist at 3 times the upper limit of the reference range

B.A Carbamazepineia C.A Sodium valproateia D.A Methyldopaia E.A Amiodaroneia

16

Breast feeding: contraindications Hyper-, not hypocalcaemia may be a precipitating factor in digoxin toxicity

sqweqwesf erwrewfsdfs adasd dhe The major breast feeding contraindications tested in exams relate to drugs (see below). Other contraindications of not e include:  

Digoxin and digoxin toxicity sqweqwesf erwrewfsdfs adasd dhe Digoxin is a cardiac glycoside now mainly used for rate control in the management of atrial fibrillation. As it has positive inotropic properties it is sometimes used for improving symptoms (but not mortality) in patients with heart failure.

galactosaemia viral infections - this is controversial with respect to HIV in the developing world. This is because there is such an increased infant mortality and morbidity associated with bottle feeding that some doctors think the benefits outweigh the risk of HIV transmission

Mechanism of action

Drug contraindications



The following drugs can be given to mothers who are breast feeding:



       

antibiotics: penicillins, cephalosporins, trimethoprim endocrine: glucocorticoids (avoid high doses), levot hyroxine* epilepsy: sodium valproate, carbamazepine asthma: salbutamol, theophyllines psychiatric drugs: tricyclic antidepressants, antipsychotics** hypertension: beta-blockers, hydralazine, methyldopa anticoagulants: warfarin, heparin digoxin

Digoxin toxicity Plasma concentration alone does not determine whet her a patient has developed digoxin toxicity. The BNF advises that the likelihood of toxicity increases progressively from 1.5 to 3 mcg/l. Features  

The following drugs should be avoided:       

decreases conduction through the atriovent ricular node which slows the ventricular rate in at rial fibrillation and flutter increases the force of cardiac muscle contraction due to inhibition of the + + Na /K A TPase pump

antibiotics: ciprofloxacin, tetracycline, chloramphenicol, sulphonamides psychiatric drugs: lithium, benzodiazepines aspirin carbimaz ole sulphonylureas cytotoxic drugs amiodarone

generally unwell, lethargy, nausea & vomiting, anorexia, confusion, yellow-green vision arrhythmias (e.g. AV block, bradycardia)

Precipitating factors         

*the BNF advises that the amount is too small to affect neonatal hypothyroidism screening **clozapine should be avoided Question 131 of 250 Which of the following is least likely to be a precipitating factor in digoxin toxicity?ia

classically: hypokalaemia* increasing age renal failure myocardial ischaemia hypomagnesaemia, hyperc alcaemia, hypernatraemia, acidosis hypoalbuminaemia hypothermia hypothyroidism drugs: amiodarone, quinidine, verapamil, spironolactone (compete for secretion in distal convoluted tubule therefore reduce excretion)

Management

A.A Hypernat raemiaia

  

B.A Hypocalcaemiaia

Digibind correct arrhythmias monitor potassium

C.A Hypokalaemiaia D.A Hypothermiaia

*hyperkalaemia may also worsen digoxin toxicity, although this is very small print

E.A Hypomagnesaemiaia 17

Question 132 of 250

Alpha-1 antagonists e.g. tamsulosin, alfuzosin

A 76-year-old man presents with lower urinary tract symptoms. Following a digital rectal examination and prostate specific antigen test a diagnosis of benign prostatic hyperplasia is made and finasteride is started. What is the mechanism of action of this drug?ia

  

A.A Alpha-1 antagonistia

decrease smooth muscle tone (prostate and bladder) considered first-line, improve symptoms in around 70% of men adverse effects: dizziness, postural hypotension, dry mouth, depression

B.A 5-alpha receptor antagonistia 5 alpha-reductase inhibitors e.g. finasteride

C.A Testosterone rec eptor antagonistia D.A Alpha-1 agonistsia



E.A Inhibits conversion of testosterone to dihydrotestosteroneia



Finasteride: 5 alpha-reductase inhibitor - inhibits conversion of testosterone to dihydrotestosterone 

block the conversion of testosterone to dihydrotestosterone (DHT), which is known to induce BPH unlike alpha-1 antagonists causes a reduction in prostate volume and hence may slow disease progression. This however takes time and symptoms may not improve for 6 months. They may also decrease PSA concent rations by up to 50% adverse effects: erectile dysfunction, reduced libido, ejaculation problems, gynaecomastia

Question 133 of 250

Benign prostatic hyperplasia

Which one of the following statements regarding drug metabolism is incorrect?ia

sqweqwesf erwrewfsdfs adasd dhe Benign prostatic hyperplasia (BPH) is a common condition seen in older men.

A.A Reduction is an example of a phase I reactionia

Risk factors 



B.A The majority of both phase I and phase II reactions take place in the liveria

age: around 50% of 50-y ear-old men will have evidence of BPH and 30% will have symptoms. Around 80% of 80-year-old men have evidence of BPH ethnicity: black > white > Asian

C.A Aspirin undergoes extensive first-pass metabolismia D.A Products of phas e I reactions are typically more lipid solubleia

BPH typically presents with lower urinary tract symptoms (LUTS), which may be categorised into:    

E.A Products of phas e II reactions are typically inactive and excreted in urine or bileia

voiding symptoms (obstructive): weak or intermittent urinary flow, straining, hesitancy, terminal dribbling and incomplete emptying storage symptoms (irritative) urgency, frequency, urgency incontinence and nocturia post-micturition: dribbling complications: urinary tract infection, retention, obstructive uropathy

Usually both phase I and II reactions decrease lipid solubility Pharmacokinetics: metabolism sqweqwesf erwrewfsdfs adasd dhe Drug metabolism usually involves two types of biochemical reactions - phase I and phase II reactions 

Management options  



watchful waiting medication: alpha-1 antagonists, 5 alphareductase inhibit ors. The use of combination therapy was support ed by the Medical Therapy Of Prostatic Symptoms (MTOPS) trial surgery: transurethral resection of prostate (TURP)



18

phase I reactions: oxidation, reduction, hydrolysis. Mainly performed by the P450 enzymes but some drugs are metabolised by specific enzymes, for example alcohol dehydrogenase and xanthine oxidase. Products of phase I reactions are typically more active and potentially toxic phase II reactions: conjugation. Products are typically inactive and excreted in urine or bile.

Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved

Which one of the following drugs should be discontinued?ia A.A Gliclazideia

The majority of phase I and phase II reactions take place in the liver

B.A Paroxetineia C.A Atenololia

First-pa ss metaboli sm

D.A Metforminia

This is a phenomenon where the concentration of a drug is greatly reduced before it reaches the systemic circulation due to hepatic metabolism. As a consequence much larger doses are need orally than if given by other routes. This effect is seen in many drugs, including:      

E.A Finasterideia As the patient has developed acute renal failure metformin should be stopped due to the risk of lactic acidosis. In the long term paroxetine may also need to be stopped as SSRIs can contribute to urinary retention.

aspirin isosorbide dinitrate glyceryl trinitrate lignocaine propranolol verapamil

Metformin sqweqwesf erwrewfsdfs adasd dhe Metformin is a biguanide us ed mainly in the treatment of type 2 diabetes mellitus. It has a number of actions which improves gluc ose tolerance (see below). Unlike sulphonylureas it does not cause hy poglycaemia and weight gain and is therefore first-line, particularly if the patient is overweight. Metformin is also used in polycystic ovarian syndrome and non -alcoholic fatty liver disease

Questions concerning zero-order kinetics and acetylator status are also common in the exam Zero-order kinetics Zero-order kinetics describes metabolism which is independent of the concentration of the reactant. This is due to metabolic pat hways becoming saturated resulting in a constant amount of drug being eliminated per unit time. This explains why people may fail a breathalyser test in the morning if they have been drinking the night before

Mechanism of action   

Drugs exhibiting zero-order kinetics    

phenytoin salicylates heparin ethanol

increases insulin sensitivity decreases hepatic gluconeogenesis may also reduce gastrointestinal absorption of carbohydrates

Adverse effects   

Acetylator status

gastroint estinal upsets are common (nausea, anorexia, diarrhoea), intolerable in 20% reduced vitamin B12 absorption - rarely a clinical problem lactic acidosis* with severe liver diseas e or renal failure

50% of the UK population are deficient in hepatic Nacetyltransferas e Cont raindications**

Drugs affected by acetylator status     



isoniazid procainamide hydralazine dapsone sulfasalazine

  

Question 134 of 250  A 59-year-old man with a history of type 2 diabetes mellitus and benign prostatic hypertrophy develops urinary retention associated with ac ute renal failure. 19

chronic kidney disease: NICE recommend reviewing metformin if the creatinine is > 130 µmol/l and stopping met formin if > 150 µmol/l do not use during suspected episodes of tissue hypoxia (e.g. Recent MI, sepsis) alcohol abuse is a relative contraindication stop 2 days before general anaesthetic, restart when renal function normal stop prior to IV contrast e.g. Angiography, restart when renal function normal

 *it is now increasingly recognised that lactic acidosis secondary to metformin is rare, although it remains important in the context of exams



**metformin is now sometimes used in pregnancy, for example in women with polycystic ovarian syndrome

reduced vitamin B12 absorption - rarely a clinical problem lactic acidosis* with severe liver diseas e or renal failure

Cont raindications** 

Question 135 of 250 A 65-year-old man with a history of ischaemic heart disease is admitted with chest pain. The 12-hour troponin T is negative. During admission his medications were altered to reduce the risk of cardiovascular disease and to treat previously undiagnosed type 2 diabetes mellitus. Shortly after discharge he presents to his GP complaining of diarrhoea. Which one of the following medications is most likely to be responsible?ia

   

chronic kidney disease: NICE recommend reviewing metformin if the creatinine is > 130 µmol/l and stopping met formin if > 150 µmol/l do not use during suspected episodes of tissue hypoxia (e.g. Recent MI, sepsis) alcohol abuse is a relative contraindication stop 2 days before general anaesthetic, restart when renal function normal stop prior to IV contrast e.g. Angiography, restart when renal function normal

*it is now increasingly recognised that lactic acidosis secondary to metformin is rare, although it remains important in the context of exams

A.A Gliclazideia B.A Clopidogrelia C.A Rosiglitazoneia D.A Metforminia

**metformin is now sometimes used in pregnancy, for example in women with polycystic ovarian syndrome

E.A Atorvastatinia

Question 136 of 250 A 26-year-old female is commenced on carbamazepine for complex partial seizures. She has no previous medical history of note and consumes a moderate amount of alc ohol. Three months later she is admitted due to series of seizures and carbamazepine levels are noted to be subtherapeutic. A pill-count reveals the patient is fully compliant. What is the most likely explanation?ia

Gastroint estinal problems are a common side-effect of many medications but are frequently seen in patients taking metformin If this patient had a raised troponin T then met formin may not be suitable as it is contraindicated following recent episodes of tissue hypoxia. Metformin

A.A Auto-inhibition of liver enzymesia

sqweqwesf erwrewfsdfs adasd dhe Metformin is a biguanide us ed mainly in the treatment of type 2 diabetes mellitus. It has a number of actions which improves gluc ose tolerance (see below). Unlike sulphonylureas it does not cause hy poglycaemia and weight gain and is therefore first-line, particularly if the patient is overweight. Metformin is also used in polycystic ovarian syndrome and non -alcoholic fatty liver disease

B.A Prescription of omeprazoleia C.A Prescription of fluox etineia D.A Auto-induction of liver enzymesia E.A Alcohol bingeia Carbamazepine is an inducer of the P450 system. This in turn increases the metabolism of carbamaz epine itself - auto-induction

Mechanism of action   

increases insulin sensitivity decreases hepatic gluconeogenesis may also reduce gastrointestinal absorption of carbohydrates

P450 enzyme system sqweqwesf erwrewfsdfs adasd dhe Induction usually requires prolonged ex posure to the inducing drug, as opposed to P450 inhibitors, where effects are often seen rapidly

Adverse effects 

Inducers of the P450 system include

gastroint estinal upsets are common (nausea, anorexia, diarrhoea), intolerable in 20%

  20

antiepileptics: phenytoin, carbamazepine barbiturates: phenobarbitone

    

Thoracic Society oxygen therapy guidelines advis e not giving oxygen unless the patient is hypoxic.

rifampicin St John's Wort chronic alcohol intake griseofulvin smoking (affects CYP1A2, reason why smokers require more aminophylline)

Antithrombin treatment. Fondaparinux should be offered to patients who are not at a high risk of bleeding and who are not having angiography within the next 24 hours. If angiography is likely within 24 hours or a patients creatinine is > 265 µmol/l unfractionated heparin should be given.

Inhibitors of the P450 system include           

antibiotics: ciprofloxacin, erythromycin isoniazid cimetidine, omeprazole amiodarone allopurinol imidazoles: ketoconazole, fluconaz ole SSRIs: fluoxetine, sertraline ritonavir sodium valproat e acute alcohol intake quinupristin

Clopidogrel 300mg should be given to patients with a predicted 6 month mortality of more than 1.5% or patients who may undergo percutaneous coronary intervention wit hin 24 hours of admission to hospit al. Clopidogrel should be continued for 12 months. Intravenous glycoprotein IIb/IIIa receptor antagonists (eptifibatide or tirofiban) should be given to patients who have an intermediat e or higher risk of advers e cardiovascular events (predicted 6-month mortality above 3.0% ), and who are scheduled to undergo angiography within 96 hours of hospital admission.

Question 137 of 250 

A patient is admitted with central chest pain and a diagnosis of non-S T elevation myocardial infarction is made. Aspirin and fondaparinux are given. What is the mechanism of action of fondaparinux ?ia

Coronary angiography should be considered within 96 hours of first admission to hospital to patients who have a predicted 6month mortality above 3.0%. It should also be performed as soon as possible in patients who are clinically unstable.

A.A Reversible direct thrombin inhibitoria B.A Glycoprot ein IIb/ IIIa receptor antagonistia

The table below summaries the mechanism of action of drugs commonly used in the management of acute coronary syndrome:

C.A Inhibits antithrombin IIIia D.A Inhibits ADP binding to its platelet receptoria

Aspirin

Antiplatelet - inhibits the production of thromboxane A2

Clopidogrel

Antiplatelet - inhibits ADP binding to its platelet receptor

Enoxaparin

Activates antithrombin III, which in turn potentiat es the inhibition of coagulation factors Xa

E.A Activates antithrombin IIIia 

Fondaparinux works in a similar way to lowmolecular weight heparin.

Acute coronary syndrome: management 

Fondaparinux Activates antithrombin III, which in turn potentiat es the inhibition of coagulation factors Xa

sqweqwesf erwrewfsdfs adasd dhe NICE produced guidelines in 2010 on the management of unstable angina and non-S T elevation myocardial infarction (NS TEMI). They advocate managing patients based on the early risk assessment using a recognised scoring system such as GRACE (Global Registry of Acute Cardiac E vents) to calculate a predicted 6 month mortality.

Bivalirudin

Reversible direct thrombin inhibitor

Question 138 of 250 All patients should receive - aspirin 300mg - nitrates or morphine to relieve chest pain if required

A 47-year-old female is reviewed in the neurology clinic. She was diagnosed with epilepsy whilst a teenager and her seizures are well controlled. She is however concerned about increasing numbness of her fingers and soles of her feet. Which one of the following medications is most likely to be responsible?ia

Whilst it is common that non-hypoxic patients receive oxygen therapy there is little evidence to support this approach. The 2008 British 21

Question 139 of 250

A.A Phenytoinia

Which of the following drugs is least likely to be affected by a patients acetylator status?ia

B.A Lamot rigineia C.A Sodium valproateia

A.A Hydralazineia

D.A Ethosuximideia

B.A Isoniazidia

E.A Levetirac etamia

C.A Rifampicinia D.A Procainamideia

Peripheral neuropat hy is a known adverse effect of phenytoin

E.A Sulphonamidesia

Phenytoin: side-effects sqweqwesf erwrewfsdfs adasd dhe Phenytoin is associated wit h a large number of adverse effects. These may be divided into acute, chronic, idiosyncratic and teratogenic

Pharmacokinetics: metabolism sqweqwesf erwrewfsdfs adasd dhe Drug metabolism usually involves two types of biochemical reactions - phase I and phase II reactions

Acute  

initially: vertigo, diplopia, nystagmus, slurred speech, ataxia later: confusion, seizures



common: gingival hyperplasia, hirsutism, coarsening of facial features megaloblastic anaemia (secondary to altered folate metabolism) peripheral neuropathy enhanced vitamin D metabolism causing osteomalacia lymphadenopathy dyskinesia



Chronic      

phase I reactions: oxidation, reduction, hydrolysis. Mainly performed by the P450 enzymes but some drugs are metabolised by specific enzymes, for example alcohol dehydrogenase and xanthine oxidase. Products of phase I reactions are typically more active and potentially toxic phase II reactions: conjugation. Products are typically inactive and excreted in urine or bile. Glucuronyl, acetyl, methyl, sulphate and other groups are typically involved

The majority of phase I and phase II reactions take place in the liver First-pa ss metaboli sm This is a phenomenon where the concentration of a drug is greatly reduced before it reaches the systemic circulation due to hepatic metabolism. As a consequence much larger doses are need orally than if given by other routes. This effect is seen in many drugs, including:

Idiosyncratic      

fever rashes, including severe reactions such as toxic epidermal necrolysis hepatitis Dupuytren's contracture* aplastic anaemia drug-induced lupus

     

Terat ogenic 

associated with cleft palate and congenital heart disease

aspirin isosorbide dinitrate glyceryl trinitrate lignocaine propranolol verapamil

Questions concerning zero-order kinetics and acetylator status are also common in the exam

*although not listed in the BNF

Zero-order kinetics Zero-order kinetics describes metabolism which is independent of the concentration of the reactant. This is due to metabolic pat hways becoming saturated 22

resulting in a constant amount of drug being eliminated per unit time. This explains why people may fail a breathalyser test in the morning if they have been drinking the night before

Mechanism of action   

Drugs exhibiting zero-order kinetics    

phenytoin salicylates heparin ethanol

increases insulin sensitivity decreases hepatic gluconeogenesis may also reduce gastrointestinal absorption of carbohydrates

Adverse effects 

Acetylator status



50% of the UK population are deficient in hepatic Nacetyltransferas e



gastroint estinal upsets are common (nausea, anorexia, diarrhoea), intolerable in 20% reduced vitamin B12 absorption - rarely a clinical problem lactic acidosis* with severe liver diseas e or renal failure

Drugs affected by acetylator status     

Cont raindications**

isoniazid procainamide hydralazine dapsone sulfasalazine

   

Question 140 of 250 A 62-year-old man presents four weeks after initiating metformin for type 2 diabetes mellitus. His body mass index is 27.5 kg/m^2. Despite slowly titrating the dose up to 500mg tds he has experienced significant diarrhoea. He has tried reducing the dose back down to 500mg bd but his symptoms persisted. What is the most appropriate action?ia



chronic kidney disease: NICE recommend reviewing metformin if the creatinine is > 130 µmol/l and stopping met formin if > 150 µmol/l do not use during suspected episodes of tissue hypoxia (e.g. Recent MI, sepsis) alcohol abuse is a relative contraindication stop 2 days before general anaesthetic, restart when renal function normal stop prior to IV contrast e.g. Angiography, restart when renal function normal

*it is now increasingly recognised that lactic acidosis secondary to metformin is rare, although it remains important in the context of exams

A.A Switch to pioglitazone 15mg odia B.A Switch to gliclazide 40mg odia

**metformin is now sometimes used in pregnancy, for example in women with polycystic ovarian syndrome

C.A Start modified release metformin 500mg od with evening mealia

Question 141 of 250

D.A Add loperamide as requiredia A 46-year-old man is admitted to hospital with chest pain. An ECG shows an anterior ST elevation myocardial infarction and he receives thrombolysis. His past medical history includes hypertension and he drinks around 70 units of alcohol per week. Three days following admission he becomes confused. What treatment is most likely to help?ia

E.A Arrange colonoscopyia If a patient is intolerant to standard metformin then modified-release preparations should be tried. There is some evidence that these produce fewer gastroint estinal side-effects in patients intolerant of standard-release met formin.

A.A Benzodiazepinesia B.A Thiamineia

Metformin

C.A Frusemideia

sqweqwesf erwrewfsdfs adasd dhe Metformin is a biguanide us ed mainly in the treatment of type 2 diabetes mellitus. It has a number of actions which improves gluc ose tolerance (see below). Unlike sulphonylureas it does not cause hy poglycaemia and weight gain and is therefore first-line, particularly if the patient is overweight. Metformin is also used in polycystic ovarian syndrome and non -alcoholic fatty liver disease

D.A Renal angioplastyia E.A Neurosurgical referralia The most likely cause for confusion in this man is alcohol withdrawal which should be treated with benzodiazepines in the acute phase. Wernicke's 23

encephalopat hy can cause confusion, but questions would normally hint at more classical feat ures such as ataxia, ophthalmoplegia or nystagmus. Also, if there were focal signs or failure to improve with benzodiazepines then a CT scan should be performed to exclude a subdural, given that he has a history of alcohol excess and has been thrombolysed

G6PD deficiency sqweqwesf erwrewfsdfs adasd dhe Glucose-6-phos phat e dehydrogenase (G6P D) deficiency is the commonest red blood cell enzyme defect. It is more common in people from the Mediterranean and Africa and is inherit ed in a X-linked recessive fashion. Many drugs can precipit ate a crisis as well as infections and broad (fava) beans

Alcohol withdrawal

Features

sqweqwesf erwrewfsdfs adasd dhe Mechanism 



  

chronic alcohol consumption enhances GABA mediated inhibition in the CNS (similar to benzodiazepines ) and inhibits NMDA-type glutamat e receptors alcohol withdrawal is thought to be lead to the opposite (dec reased inhibitory GABA and increased NMDA glutamate transmission)

Diagnosis is made by using a G6P D enzyme assay Some drugs causing haemolysis   

Features   

symptoms start at 6-12 hours peak incidence of seizures at 36 hours peak incidence of delirium tremens is at 72 hours



anti-malarials: primaquine ciprofloxacin sulphonamides

Some drugs thought to be safe     

Management  

neonatal jaundice is often seen intravascular haemolysis Heinz bodies on blood films

benzodiazepines carbamazepine also effective in treatment of alcohol withdrawal phenytoin is said not to be as effective in the treatment of alcohol wit hdrawal seizures

penicillins cephalosporins macrolides tetracyclines trimethoprim

Question 143 of 250 A 19-year-old female is brought to the Emergency Department by her friends following a night out. Her friends state she has taken an unknown drug whilst out clubbing. Which one of the following features would most point towards the use of ecstasy?ia

Question 142 of 250 A 34-year-old man who is known to have gluc ose-6phosphate dehydrogenase deficiency presents with symptoms of a urinary tract infection. He is prescribed an antibiotic. A few days later he becomes unwell and is noticed by his partner to be pale and jaundic ed. What drug is mostly likely to have been prescribed?ia

A.A Temperat ure of 39.5ºCia B.A Respiratory depressionia C.A Hypernat raemiaia

A.A Co-amoxiclavia D.A Miosisia B.A Trimethoprimia E.A Urinary incontinenceia C.A Ciprofloxacinia D.A Cefalexinia E.A Erythromycinia

Ecsta sy poi soning sqweqwesf erwrewfsdfs adasd dhe Ecstasy (MDMA, 3,4Methylenedioxymethamphetamine) use became popular in the 1990's during the emergence of dance music culture

The sulfamet hoxazole in co-trimox azole causes haemolysis in G6PD, not the trimet hoprim

Clinical features 24

    

neurological: agitation, anxiety, confusion, ataxia cardiovascular: tachycardia, hypert ension hyponatraemia hyperthermia rhabdomyolysis

Indications     

following organ trans plantation rheumatoid arthritis psoriasis (has a direct effect on keratinocytes as well as modulating T cell function) ulcerative colitis pure red cell aplasia

Management  

Question 145 of 250 supportive dantrolene may be used for hypert hermia if simple measures fail

A 31-year-old female with a history of epilepsy consults you following an unevent ful pregnancy. Which one of the following drugs would it be safe to continue during breast feeding?ia A.A Phenytoinia

Question 144 of 250

B.A Carbamazepineia What is the mechanism of action of ciclosporin?ia C.A Lamot rigineia

A.A Monoclonal antibody against IL-2 receptoria

D.A Sodium valproateia

B.A Interferes with purine synthesisia

E.A All of the aboveia

C.A Inhibits inosine monophosphate dehydrogenaseia D.A Decreases IL-2 release by inhibiting calcineurinia

Breast feeding is acceptable with nearly all antiepileptic drugs

E.A Mercapt opurine antagonistia The BNF states 'breast-feeding is acceptable with all antiepileptic drugs, taken in normal doses, with the possible exception of barbiturates'

Ciclosporin - decreases IL-2 releas e by inhibiting calcineurin

Epilepsy: pregnancy and breast feeding sqweqwesf erwrewfsdfs adasd dhe The risks of unc ontrolled epilepsy durin g pregnancy generally outweigh the risks of medication to the fetus. All women thinking about becoming pregnant should be advis ed to take folic acid 5mg per day well before pregnancy to minimise the risk of neural tube defects. Around 1-2% of newborns born to non-epileptic mothers have congenital defects. This rises to 3-4% if the mother takes antiepileptic medication.

Ciclosporin sqweqwesf erwrewfsdfs adasd dhe Ciclosporin is an immunosuppressant whic h decreases clonal proliferation of T cells by reducing IL-2 release. It acts by binding to cyclophilin forming a complex which inhibits calcineurin, a phosphotase that activat es various transcription factors in T cells

Other points

Adverse effects of ciclosporin (not e how everything is + increased - fluid, BP, K , hair, gums, glucose)         

 

nephrotoxicity hepatotoxicity fluid retention hypertension hyperkalaemia hypert richosis hyperplasia of gum tremor impaired glucose tolerance

   

25

aim for monotherapy there is no indication to monitor antiepileptic drug levels sodium valproat e: associated with neural tube defects carbamazepine: often considered the least teratogenic of the older antiepileptics phenytoin: associated with cleft palate lamotrigine: studies to date suggest the rate of congenital malformations may be low. The dose of lamot rigine may need to be inc reas ed in pregnancy

 Breast feeding is generally considered safe for mothers taking antiepileptics with the possible exception of the barbiturates

lithium blood level should ‘normally’ be checked every 3 mont hs. Levels should be taken 12 hours post-dose thyroid and renal function should be checked every 6 mont hs patients should be issued with an information booklet, alert card and record book

 

It is advised that pregnant women taking phenytoin are given vitamin K in the last month of pregnancy to prevent clotting disorders in the newborn

Question 147 of 250

Question 146 of 250

Which one of the following is least associated with cocaine toxicity?ia

Which one of the following features is least recognised in long-term lithium use?ia

A.A Metabolic alkalosisia

A.A Alopeciaia

B.A Hyperthermiaia

B.A Weight gainia

C.A Psychosisia

C.A Fine tremoria

D.A Rhabdomyolysisia

D.A Goitreia

E.A Seizuresia

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

Cocaine sqweqwesf erwrewfsdfs adasd dhe Cocaine use may cause a wide variety of adverse effects

Lithium sqweqwesf erwrewfsdfs adasd dhe Lithium is mood stabilising drug used most commonly prophylatically in bipolar dis order but also as an adjunct in refractory depression. It has a very narrow therapeutic range (0. 4-1. 0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys.

Cardiovascular effects     

Mechanism of action - not fully understood, two theories:  

interferes with inositol triphosphate formation interferes with cAMP formation

Neurological effects   

Adverse effects      

nausea/ vomiting, diarrhoea fine tremor polyuria thyroid enlargement, may lead to hypothyroidism ECG: T wave flattening/inversion weight gain

seizures hypertonia hyperreflexia

Psychiatric effects   

agitation psychosis hallucinations

Others

Monitoring of patients on lithium therapy 

myocardial infarction both tachycardia and bradycardia may occur hypertension QRS widening and QT prolongation aortic dissection

  

inadequate monitoring of patients taking lithium is common - NICE and the National Patient Safety Agency (NPSA) have issued guidance to try and address this. As a result it is often an exam hot topic

26

hyperthermia metabolic acidosis rhabdomyolysis

1-5% of patients who are treated with met hotrexate. Pulmonary fibrosis should be part of the differential diagnosis

Question 148 of 250 

A 47-year-old lorry driver presents following the development of a wides pread urticarial rash. This is associated with pruritus. What is the most appropriate medication to help relieve the itch?ia

Rheumatoid arthritis: re spiratory manifestations sqweqwesf erwrewfsdfs adasd dhe A variety of respiratory problems may be seen in patients with rheumatoid arthritis:

A.A Cetirizineia B.A Loratadineia

    

C.A Chlorphenamineia D.A Ranitidineia E.A Alimemazineia 

 

The obvious concern in a lorry driver is drowsiness. Of the non-sedating antihistamines there is some evidence that cetirizine causes more drowsiness than lorat adine



Question 150 of 250

Antihi stamines 

pulmonary fibrosis pleural effusion pulmonary nodules bronchiolitis obliterans complications of drug therapy e.g. methotrexate pneumonitis pleurisy Caplan's syndrome - massive fibrotic nodules with occupational coal dust exposure infection (possibly atypical) secondary to immunos uppression

Which one of the following symptom is least associated with salicylate overdose?ia

sqweqwesf erwrewfsdfs adasd dhe Antihistamines are of value in the treatment of allergic rhinitis and urticaria. Of the non sedating antihistamines there is some evidence that cetirizine may cause more drowsiness than other drugs in the class

A.A Tremoria B.A Tinnitusia C.A Hyperventilationia

Question 149 of 250

D.A Seizuresia

A 61-year-old female is reviewed in the rheumatology clinic with increasing shortness of breath. She has been on long-term drug therapy to control her rheumatoid arthritis and has a 40 pack-year history os smoking . Her oxygen saturations on room air are on 89%. Investigations reveal the following:

E.A Naus eaia

FEV1%

Salicylate overdose sqweqwesf erwrewfsdfs adasd dhe A key concept for the ex am is to understand that salicylate overdose leads to a mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis. In children met abolic acidosis tends to predominate

80%

Trans fer factor coefficient 41% (TLCO)

What is the most likely cause for her symptoms?ia A.A Pulmonary nodulesia

Features

B.A Methotrexate pneumonitisia



C.A Pulmonary haemorrhageia

      

D.A Bronchiolitis obliteransia E.A Chronic obstructive pulmonary diseaseia A FEV1% of 80% would not support a diagnosis of COP D or bronchiolitis obliterans. Methotrexate pneumonitis is potentially life-threatening and occurs in 27

hyperventilation (centrally stimulates respiration) tinnitus lethargy sweating, pyrexia* nausea/ vomiting hyperglycaemia and hypoglycaemia seizures coma

Treatment  



Indications for haemodialysis in salicylate overdos e      

general (ABC, charc oal) urinary alkalinization is now rarely used - it is contraindicated in cerebral and pulmonary oedema with most units now proceeding straight to haemodialysis in cases of severe poisoning haemodialysis

serum concentration > 700mg/L metabolic acidosis resistant to treatment acute renal failure pulmonary oedema seizures coma

*salicylates cause the uncoupling of oxidative phosphorylation leading to decreased adenosine triphosphate production, increased oxygen consumption and increased carbon dioxide and heat production

28