at1sample examination paperdec2010 1

7/22/2019 At1sample Examination Paperdec2010 1

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SAMPLE EXAMINATION PAPER:

Campus Medway

School Pharmacy

Department

Programme

MPharm

COURSE TITLE AT1 - Applied Therapeutics

COURSE CODE PHAM1098

Stage Four

Date and Duration

(incl. reading time)

3 hours - Sample Paper

Paper Set by Dr B Apampa, Dr C Branch, Mr. Jerome Durodie, Dr S

Gammie, Mrs. E Worthing

INSTRUCTIONS TO CANDIDATES

Please use a separate answer sheet for each question and ensure that you have inserted

your University of Greenwich banner number only (not your name) in the space

provided on each answer sheet.

The paper is divided into TWO sections

Answer ALL questions in section A. You should spend no more than 60 minutes on this

section

Answer THREE questions in section B. You should spend no more than 120 minutes on

this section

The answer should be written as a well constructed essay NOT in bullet point form.


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S TION A:

Question 1

A randomised controlled trial of a new anticoagulant (Drug X) compared to warfarin has

recently been published.

In the trial 5,325 patients with first presentation of DVT (target INR 2.5) were randomised to

receive drug X (2,660 patients) or warfarin (2,665 patients). INR was measured over 3

months.

The trial was set up to measure a composite endpoint made up of number of: DVT

recurrences and pulmonary emboli (measured over 1 year), as well as the significant adverse

effect of major bleeding (measured over 3 months).

The results are shown below

Drug X Warfarin p value

Average INR 2.6 2.4 0.5

Composite

endpoint

4% 5% 0.064

Major bleeding 10% 5% >0.0001

a.

Calculate, where relevant, the relative and absolute risk reductions (or increases)

b. Calculate, where relevant, the NNT (or NNH)c. Comment on whether the results from this study should influence current clinical practice

[10 marks]


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Indicative Answer

Relative Risk

Reduction /

Increase

Absolute Risk

Reduction / Increase

NNT / NNH

Average INR Not statistically significantnot possible to do calculations

Composite

endpoint

Not statistically significantinappropriate to do calculations =

negative study

Major bleeding 100% 5% 20

a. Absolute Risk Reduction (ARR) = difference in events rates i.e. 10% - 5% = 5%Relative Risk Increase (RRI) = difference in event rates relative to the control group

(warfarin) i.e. 10 -5 x 100 = 100%

5

b. Number needed to harm (NNH) or treat (NNT)= 1/ARR or 100/ARR (%)In this case NNH is 100/5% = 20

c. Study shows a non-statistically significant difference in average INR and a non-statistically significant decrease in a broad composite endpoint.

This indicates that drug X may be of equivalent efficacy (as measured by average INR

and recurrence of DVT and PE)

Of concern is statistically significant increase in major bleeds.

Therefore, this study should not alter current clinical practice on basis of first do no harm.

Question 2

Mrs AB is a worried 25 year old whose 15 year old sister was recently diagnosed with type 1

diabetes mellitus (DM). A search on the internet revealed to her that diabetes runs in families.

She recently purchased a urine testing kit from the pharmacy. A positive test result has

convinced her that she is also diabetic. Her GP ran a random plasma glucose test which was

7.1mmol/L. Subsequent tests of her urine on 2 separate occasions were also positive for

glucose. Her GP runs an oral glucose tolerance test with the following results:

Fasting plasma glucose 5.2 mmol/L

OGTT 7.2 mmol/L

a. Should Mrs AB be concerned about developing diabetes?b. What are the factors that may have an influence on a positive urine test for glucose?c. Her sister is on an insulin replacement regimen; describe one way in which insulin

injections can be administered to mimic the physiological release of insulin from the

pancreas [10 marks]


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Indicative answera. Yes. There is an inherited predisposition to diabetes. In particular, type 2 DM may

develop when an excessive lifestyle in terms of excessive intake of calories, limited

exercise and obesity is superimposed on an inherited predisposition. Concordance in

identical twins is known to be nearly 100%. In type 1 DM concordance in identical twins

is less than 50%. It is believed that exposure to an environmental factor such as a virus ortoxin triggers off the autoimmune process in a susceptible individual.

b. The presence of glucose in urine is not necessarily diagnostic of diabetes, particularly ifnot accompanied by symptoms of diabetes such as polyuria and polydipsia. The presence

of glucose in urine depends on the individuals renal threshold and this varies from person

to person. It also increases with age and is affected by factors such as concentration of

urine and sometimes other drugs.

c. Basal-Bolus regimen involving 3 injections of meal time insulin e.g. insulin aspart plus 1-2 injections of basal insulin e.g. insulin isophane.

Question 3

Mrs ED, weight 50kg has received 9 litres of IV fluids over the past 3 days as she was made

NIL by MOUTH following her stroke. She now presents with pitting ankle oedema and a

raised JVP. Over these 3 days, her fluid balance chart also indicates a total urine output of 6

litres.

Useful Formulas

Estimated measurementsInsensible losses 10ml/kg/day

Sensible Losses 20ml/kg/day

Stool losses 50-100ml

a. Calculate the total fluid overload in this patient.b. What is the appropriate fluid management plan in this patient?

[10 marks]

Indicative Answer

a. Daily output Daily OutputIV fluid = 3000ml

Total daily input = 3000ml Insensible losses 500ml

Sensible Losses 2000ml

Stool losses 100ml

Total daily output 2600ml

Hence daily fluid overload is Total inputtotal output = 400ml per day or 1200ml over 3

days.

b. Stop all IV fluids, may want to give a diuretic- furosemide 20mg until homeostasis (fluidbalance) is achieved.


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Question 4Mrs EA is a 60 year old Caucasian woman with a history of recurrent early morning coughs

which are productive with thick mucus which is sometimes difficult to shift. Despite enjoying

generally good health, she occasionally suffers with chest infections up to two to three times

a year. She is a long term smoker (30 a day) having smoked cigarettes since she was 16 years

old. Her husband is also a heavy smoker. On questioning, she states that she is only short of

breath when walking up more than one flight of stairs. You decide to carry out a reversibility

test using spirometry.

Pre bronchodilator test Post bronchodilator test

FEV12.28L (81% of predicted) FEV12.44L (87% of predicted)

FVC 2.8L (85% of predicted) FVC 3.0L (90% of predicted)

a. Should Mrs EA be concerned about developing COPD?b. What factors indicate that she may be at risk of developing COPD?c. What interventions would you recommend for the initial management of Mrs EA?

[10 marks]

Indicative answera. Yes, she has chronic symptoms of early COPD with productive cough on awakening.

Review FEV1/FVC ratio- hallmark of obstructive airway disease re GOLD classification

and interpret findings. FEV1/FVC is about 81% which represents the previous stage 0 of

GOLD classification: patient at risk. COPD develops silently over several years anddyspnoea may be the only symptom present without accompanied changes in spirometry

or limitations to daily activities. Note that the dyspnoea of COPD is characterised by

cough, sputum production and recurrent respiratory infection.

b. Her significant smoking history- main causative factor for the development of COPD,exposure to passive cigarette smoke from her husband, early morning productive cough

which is characteristic of the early stages of COPD and recurrent chest infections.

c. Patient education on COPD and its causes. Smoking cessation is the 1 st step in themanagement of COPD and the only intervention that improves the natural history of thedisease.


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Question 5Mr AB is a resident in your local nursing home. You have just received a faxed prescription

for him, for 2 boxes of a hydrocolloid dressing 10cm x 10cm. This is a repeat of a

prescription you supplied 3 days ago. On speaking to the nurse manager at the home, you are

told that the dressings are being used to treat a pressure sore and are being changed daily

because of the heavy exudates being produced.

a. What are SIX properties of an ideal wound dressing?b. Comment on the use of a hydrocolloid dressing in this patient

[10 marks]

Indicative answer

a. Any SIX of: Create/Maintain a moist wound environment without maceration Allow gaseous exchange of oxygen, carbon dioxide and water vapour Remove excess exudates without allowing strike through to the surface of the dressing Provide thermal insulation Act as a barrier to micro-organisms Provide mechanical protection Be non-adherent and easily removed Be sterile Be non toxic, con-allergenic and non-sensitising Be easy to use Be cost effective Allow monitoring of the wound Be acceptable to the patient

b. Hydrocolloid dressings should not require changing more frequently than every 3 days More frequent changing may indicate that; dressing size is too small or it is not the

appropriate dressing for the wound - wound assessment required

Alternative dressings that may be considered include Alginate dressings. These are highlyabsorbent dressings that may be more appropriate for a highly exuding wound. They

absorb exudates to form a strong hydrophilic gel when applied to wounds.


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Indicative answer

a. Thiazide diuretics e.g. bedroflumethiazide Diuretic action by blockade of renal tubular sodium reabsorption, reduces peripheral

resistance by reducing circulating blood volume. In addition, and long term, vasodilatory

action reduces peripheral resistance. ALLHAT study provides evidence for first line use, recommended by NICE as 1st line

option for patients over 55 or blackflat dose response curve, therefore, dose must not be

higher than 2.5mg

Side-effectsmetabolic e.g. hypokalaemia, hyperglycaemia (though clinical significanceuncertain), gout, small increases in LDL-cholesterol and triglycerides. Erectile

dysfunction reported in men. Postural hypotension

Calcium- channel blockers, usually dihydropyridines e.g. amlodipine

Reduce peripheral resistance by blocking calcium channels in the peripheral arterioles ASCOT study provided evidence for use, recommended by NICE as 1st line option

for patients over 55 or black. Long acting, once daily preparations preferred to aid

adherence

Side-effects common and include oedema, flushing, constipation, posturalhypotension

ACE inhibitors, e.g. lisinopril, ramipril

Block the conversion of angiotensin I to angiotension II, which is a potentvasoconstrictor and stimulates release of aldosterone. Therefore, ACE inhibitors cause

vasodilation and reduction in salt and water retention thereby reducing peripheral

resistance.

ASCOT study provided evidence for use, recommended by NICE as 1st line optionfor patients under 55Can cause first dose hypotension so important to start with low

dose and then titrate dose

Side-effectshyperkalaemia, cough (thought to be linked to ACE inhibitors blockingkininase and preventing breakdown of bradykinin), renal impairment, postural

hypotension

b. Non-pharmacological approaches are important to reduce cardiovascular risk. Specificproblems identified for Mrs LV Smoking (24 cigarettes / day)needs advice and support to Stop Smoking BMI is 34 kg/m2 therefore Mrs LV is obese (obesity level 1) - recommend setting a

target weight and agreeing a weight reduction diet and exercise plan.

Alcohol intake (4 glasses of wine / day)should reduce to 2 units per dayGeneral advice

Promote healthy, cardioprotective diet reduced fat / 5 portions of fruit and

vegetables per day / 2 portions of fish per week

Minimise dietary salt intake to


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Indicative Answer

A good answer would demonstrate a knowledge and understanding of the clinical condition.

Identify any drug therapy problems the patient may have and in discussing your rationale forchoice of drug therapy, apply knowledge gained from a critical appraisal of the current

evidence base and/or guidelines. Describe any alternative choice of drug(s) or action, doses

of drug(s) recommended. A multi factorial approach is taken in the management of diabetes

therefore your answer should include a discussion of clinical outcomes such as HbA1c, lipid

profile, BP: What are the treatment targets and what monitoring would you recommend?

What patient education should be provided?

a.Subclass Mode of action/Effect Common side

effectsClinical Use

Biguanide e.g.

Metformin

Decreases hepatic and renal

gluconeogenesis

Slows intestinal glucose

absorption

Increased peripheral

utilisation of glucose

Decreased insulin resistance

GIT: abdominal

pain, nausea,

diarrhoea, anorexia

1st line in type 2

diabetes

Sulphonylureas

e.g. gliclazide

Stimulate pancreatic insulin

secretion by closure of

ATP-dependent potassium

channels in the pancreatic

beta cell membrane

membrane depolarisation

calcium entry into cell

insulin secretion

Hypoglycaemia,

weight gain

May be used when

further glycaemic

control desired in

addition to

Metformin use. 1st

line if intolerance or

contraindication to

Metformin use

GLP-1 agonists

e.g. Exenatide

Analogue of GLP-1 released

in intestinal epithelial cells

in response to food.

Bind to and stimulate the

GLP-1 receptor augmentinginsulin secretion in response

to a glucose load

Delay gastric emptying

Promote satiety

Inhibit glucagon secretion.

Promote weight loss

Nausea, vomiting,

diarrhoea,

abdominal pain

Less commonly

acute pancreatitis

May be used in

combination with

metformin,

sulphonylurea or

both (triple therapy)in people whose

blood glucose is not

adequately

controlled.

NICE specific

recommendation

about its use in

obese


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b. Blood pressure: His BP is not controlled by atenolol 50mg and bendroflumethiazide

2.5mg daily. He is therefore at increased risk of macrovascular complications of diabetes-

peripheral vascular disease, myocardial infarction and cerebrovascular disease. He should

be started on an ACEI and treated to target BP. ACEIs are recommended as 1st line

antihypertensive agents for diabetic patients because of their renoprotective effects which

slow the progression of kidney disease. The NICE target for BP in this patient would be


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Urinalysis for microalbuminuria

Check for adverse effects


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Question 8 [100%]

Patient presentation

Mrs. TE is a 52 year old lady with a history of mitral valve replacement. She presents in your

pharmacy with symptoms of urinary frequency and vaginal discharge.

Medication history: Well controlled warfarin.

[INR record taken from booklet is as follows:

3.63 days ago

3.5one month ago

3.62 months ago

3.431/2 months ago

3.65 months ago]

Other than her drug history of warfarin (which is well controlled at target) she otherwise

appears fit and well with no other expressed clinical signs or symptoms.

She is expecting a prescription for antibiotics (she is allergic to penicillins) for her infection.

a. What treatment would you offer this patient at this stage? Critically review Mrs. TEscase giving the rationale for your choices. [25%]

She returns to see you three days later with dysuria, and a greeny-yellow discharge.

Frequency has largely been replaced by a burning sensation on passing urine.Examination and results of initial investigations show:

Laboratory tests: Pathology

Test: DischargeCulture &

Sensitivity

Patient Test results

Culture Gramve diplococci

+++

Sensitivities (Antibiogram) Co-amoxiclavS

(Key: CiprofloxacinS/RS = sensitive ErythromycinR

R = resistant CefiximeS

S/R = borderline sensitivity) PenicillinR

TetracyclineR

SpectinomycinS


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Laboratory tests: Haematology

b. What is the INR target for this patient? Suggest a possible specific diagnosis for thispatient [10%]

c. What other actions need to be considered with respect to this patient given yourprovisional diagnosis. Explain what treatment options are available for the care of this

patient in the light of her symptoms. [35%]

d. Discuss any potential issues / problems that may need to be considered and how thesewould be dealt with. [30%]

Test Patient Test results Reference range

INR (today) 2.6 Target for mitral

valve replacement


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iii. Either antibiotic choice has potential of affecting (? increasing) INR resulting inbleed / haemorrhage. BUT: given as stat. doses; BUT also given at high

doses ..??

iv. Also consider that resolution of infection may of itself affect INR (drop in todaysINR may reflect infection itself + alteration in urinary frequency due to painful

symptoms).Therefore need to re-assess INR.

Check Yellow Book record for next due appointmentneed one for 7-10 days

time

+ patient needs to be reminded of signs and symptoms associated with side-effects

of warfarin eg. unexplained bleeding / bruising etc.

How to deal with Public Health issue ie. contact tracing: husband / partner(s).


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Question 9 [100%]


Mrs Browne is a 75-year-old woman admitted to hospital with a 1-week history of non-

radiating epigastric pain and discomfort. She stated that antacids and H2 histamine receptor

blockers appear to decrease pain severity. Five days ago she noticed that her stools were

black and tarry and complained of being thirsty and feeling weak. On the day of admission

she had an episode of haematemesis. On questioning, Mrs Browne denied having a history of

PUD or GI bleeding. She kept in good health with daily exercise and eats well. She was not

on any prescription medications but admitted to taking OTC ibuprofen regularly for the past

month for aches and pain in her knee.

Relevant laboratory tests are as follows:

Haemoglobin 9g/dl (11-15)

RBC 2.8 x 10 (3.84.8)

HCt 0.339 (0.36 -0.46)

MCV 75fl (80-100)

Scr 100umol/L (49-90)

Urea 10mmol/L (2.57.5)

On examination her BP was found to be 110/70 and her heart rate was recorded as 110bpm.

An OGD later performed revealed two small gastric ulcers and the presence of H.pylori. Mrs

Browne has no known drug allergies

.

a. Based on the patients signs and symptoms and clinical presentation, outline theappropriate management of Mrs Browne, starting first with her drug therapy problems.

[45%]

b. What counselling should be provided to Mrs Browne to ensure successful treatmentoutcomes with minimal adverse effects and enhanced compliance with therapy. [10%]

c. Six days into her hospital stay, the patient developed Clostridium difficile diarrhoea.Could any of Mrs Browne drug therapy be associated with her diarrhoea. Explain your

answer. [5%]

d. Proton pump inhibitors which are administered as inactive pro-drugs are referred to aspotent anti-secretory agents. Discuss the pharmacological and pharmacokinetic principles

that make them potent clinically useful agents. [40 %]


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Indicativeanswer:

a. Mrs Browne has presented with investigated dyspepsia because of her GI bleed(haematemesis and blood in her stools) which has been induced by the regular use ofibuprofen.

Risk factor to her NSAID induced GI bleed - she is elderly

As a result of her GI bleed she has developed iron deficient microcytic anaemia

confirmed by decreased haemoglobin, haematocrit, red blood cell count and mean cell

volume.

Her low blood pressure, dehydration (confirmed by her being thirsty, increased creatinine

and urea are evidence of her loss of blood and fluid volume. Dehydration versus renal

impairment (secondary to the NSAID) could be confirmed with rehydration fluid

challenge

Management Stop ibuprofen as her GI bleed is drug induced. Prescribe an alternative analgesic.

Restabilize patient

Start full dose daily PPIIV esomeprazole or omeprazole 40mg daily then switch tooral when no longer vomiting.

The OGD revealed two small gastric ulcers andH.pylori hence need to continue withfull dose PPI omeprazole 20mg daily for 2 months then start eradication therapy. Mrs

Browne does not have any drug allergies hence may be prescribed:

A 7-day treatment of PPI e.g. omeprazole 20mg po BD, amoxicillin 1gm po BD,

clarithromycin 500mg po BD

As patient was diagnosed with gastric ulcer, a repeat OGD should be done 6-8 weeks

following eradication therapy.

Start IV fluid therapy because of blood and fluid loss and low BPo Crystalloids1 L over 4 hours x 2 normal saline or Hartmans solution as patient

is dehydrated (loss of blood volume).

o Colloidse.g. gelofusin may need to be added to her drug therapy (especially ifblood pressure continues to fall) to expand plasma volume. Volume replacement

with colloids is necessary especially with her BP 110/70 as they remain in the

intravascular compartment longer than crystalloids.

o As her haemoglobin (Hb) is low, when oral intake is re-established, Mrs Browneneeds to be prescribed oral ferrous sulphate 200mg TDS until Hb is within normalrange and continue for a further 3 months to replenish stores

b. An optimal H.pylori treatment regimen would be one that has low minimal side effects,low risk of bacterial resistance and cost effective.

Need to stress the importance of compliance. Non-compliance is one of the two common

causes of treatment failure. Factors associated with non-compliance include:

o increase number of medicationso frequent dosingo long treatment durationo side effects of drugs


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It is very important that the patient be advised of the side effects of the drugs

If Mrs Browne is given a regimen containing metronidazole, she needs to be advised

about the metronidazole and alcohol interaction

c.

It may be due to her PPI therapy as she would not have yet started the triple eradicationtherapy with the broad spectrum antibiotic amoxicillin.

Clostridium difficile diarrhoea is the most serious type of hospital acquired infectious

diarrhoea and is associated with increased morbidity and mortality. Athough the use of

broad spectrum antibiotics is the most common cause, the use of the very potent anti-

secretory PPIs have also been associated with its cause.

Due to their potent inhibition of gastric acid production they may ease the passage of the

toxin in the intestines.

By changing the balance of the gut microflora, broad spectrum antibiotics such as

amoxicillin, co-amoxiclav, cephalosporins and clindamycin may cause the overgrowth of

the toxin.

Patients most at risk of developing this type of diarrhoea include the elderly or the

immuno-compromised and those who have recently been in hospital or live in a nursing

home

d. Proton pump inhibitors or PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazoleand rabeprazole) are referred to as potent anti-secretory agents because they block the

final pathway of acid secretion through the irreversible inactivation of the H +/ K+ -

exchanging ATPase (proton pump) in the gastric parietal cells. They therefore block bothfasting and meal stimulated acid secretion. It takes about 18 hours for new proton pump

to be synthesized. This is the reason why acid inhibition by these drugs last up to 24 hours

or longer despite them having an average half life of 1.5hours (range 0.52hours)

PPIs are inactive prodrugs and become activated near their site of action in the parietal

cells. To protect the acid labile prodrugs from rapid destruction within the acidic stomach

environment, they are formulated as acid resistant enteric coated capsules or tablets. The

enteric coating then dissolves in the alkaline intestinal lumen where the pro-drug is

absorbed. They then pass into and accumulate in the parietal cells and become activated

to form a covalent bond with H +/ K+ - exchanging ATPase hence irreversibly

inactivating the enzyme..

PPIs undergo rapid first-pass and systemic metabolism. All PPIs except rabepazole are

metabolised to varying degrees by the cytochrome P450 enzymes (CYP2C19 and CYP

3A4). Some PPIs except pantoprazole and rabepazole may also inhibit CYP2C19

enzymes hence may be involved with significant drug interactions e.g. clopidogrel.

Food decreases the bioavailability of the PPIs hence they should be given on an empty

stomach. They should preferably be administered in the morning about 1 hour before

breakfast so that their peak serum concentration coincides with the maximal activity of

the proton pump. If the PPIs have to be given twice a day the second dose should be

administered before the evening meal. PPIs are useful in the prevention and treatment of


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PUD, treatment of GORD and Barretts oesophagus, Zollinger Ellison syndrome and are

also included inHelicobacter eradication regimens.

Question 10 [100%]


Mrs CD is a 25 year old with a 15 year history of generalised seizures. These were forst noted

when she was 10 years old, occurring initially at regular intervals. They were tonic-clonic

seizures that would last for 20 seconds. She would be left feeling tired and barely responsive

for several hours afterwards. In the past 10 years Mrs CD has been seizure free, but she has

continued to take the following combination of anticonvulsants.

Sodium Valproate MR 500mg OM, 1000mg ON

Lamotrigine 100mg ON

Recently she has been feeling quite tired and lethargic along with feeling generally unwell.

She has been to see her GP who has performed the following blood tests.

Recent Blood Test Results

Sodium 135 133-149 mmol/L

Potassium 3.6 3.5-5.3 mmol/L

Urea 6.7 2.5-8.0 mmol/LCreatinine 56.8 62-133 mol/L

ALT 330 5-30 iu/L

ALP 195 20-100 iu/L

AST 180 5-40 iu/L

Hb 12.1 12-18 g/dl

WCC 16.5 4.0-11.0 x 10 /L

Neutrophil 12.4 1.8-8.0 x 10 /L

Platelets 325 100-450 x 10 /L

a. Outline the mechanism of action of both sodium valproate and lamotrigine[35%]

b. Identify any problems with her current treatment regimen and outline the treatmentregimen you would recommend. Provide a rationale for your choices.

[35%]

c. Mrs CD has been married for 2 years and has mentioned to the practice nurse about tryingfor a baby. The options open to Mrs CD would be either gradual withdrawal of theanticonvulsants or continued therapy with careful monitoring during pregnancy. What


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would be the risk and benefit for each option? How can Mrs CD be best supported in this

decision she has made? [30%]

Indicative Answer

NoteThis outline answer provides details as to the information that a good answer will

contain and the broad topics that will be covered. It should not be considered as a model

answer. Exam questions are required to be answered in a structured written format,

providing a logical progressive argument to the topics under consideration.

a. Sodium valproateThere are several mechanisms by which valproate may exert an anticonvulsant effect.

Precisely which mechanism is the key, or whether they all contribute equally, or whether

there is an as yet undefined mechanism of action, remains unclear. In outline the 3

mechanisms are:

i. Inhibition of voltage sensitive sodium channelsLeads to reduced sodium influx and subsequent glutamate excitatoryneurotransmission

ii. Boosting actions of gamma amino butyric acid (GABA) by either inhibition ofGABA reuptake, enhancing GABA release or inhibiting GABA metabolism

via GABA transaminase. This potentiate inhibitory effects of GABA on

neurotransmission

iii. Regulation of downstream signal transduction cascades. Leads to promotion ofneuroprotection and long term plasticity. This postsynaptic effect enhances

GABA transmission by an indirect means but it is not clear whether this leads

to an increase of inhibitory synaptic responses

LamotriginePrimary mechanism of action is thought to be due to inhibition of sodium channels and

thereby inhibiting the release of excitatory amino acids. Inhibition of voltage dependent

sodium channels reduce membrane excitability as they reduce the generation of an action

potential. Those neurones that are firing repetitively are possibly preferentially blocked as

the action of lamotrigine demonstrates the property of use dependence. The higher the

frequency of firing then the greater the block produced. This property may be of

particular importance in the prevention of seizure propagation. It should be noted that

lamotrigine shares the mechanism of action with other antiepileptic drugs such asphenytoin and carbamazepine. However lamotrigine demonstrates efficacy against a

wider range of seizure types. This might indicate a subtle difference in mechanism of

action from other antiepileptics

b. The lab results indicate possible deterioration of liver function. Liver enzymes are allraised, although not as much as sometimes seen in liver failure. On their own liver

enzymes are not a good predictor of liver function, but can be indicative of liver disease.

The vague symptoms of feeling tired, lethargic and generally unwell then this could

indicate liver disease, although these are non-specific symptoms. If it transpired that there

was impaired liver function then a concern would be the doses of sodium valproate andlamotrigine. Both of these are metabolised by the liver, so any impairment in liver


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