Therapeutics Mbchb4


Case 1 - Endocarditis

43 F
PC – fever, night sweats, chills 10/7
PMhx – mitral/aortic valve regurg due to rheum fever
O/E – conjunctival and nail hemorrhages
• echo shows vegetations on mitral valve
• blood cultures grow s.aureus (penicillin resistant, sens to fluclox, erythromycin, cotrimox, vancomycin) – from 3x cultures over 6 hrs

1. Dx
a. Bacterial endocarditis
b. Key features
i. Fever, night sweats, chills
ii. Splinter hemorrhages (micro-emboli in capillary)
iii. Valve vegetations on echo (dukes major)
iv. 3x positive blood cultures (dukes major) – typically viridans streptococci (s.mitis, mutans, sanguis) or s.aureus
2. Initial Tx
a. First choice - Fluclox IV
i. Dose - 2 g q6h (max) – only 0.5-1 g for children/renal impairment
ii. Duration – 4 weeks (small numbers of bacteria are buried in vegetations – difficult to eradicate)
iii. Ø oral – due to lower blood concentrations and that endocarditis traditionally been treated IV
iv. W/o appropriate tx – always fatal
b. Add Gentamicin (double antibiotic therapy) if pt is moderately-severely sick
i. Fluclox + Gent = synergistic effect (gent does not kill the bacteria, but somehow helps the fluclox kill more effectively)
c. Other antibiotic considerations
i. Vancomycin
1. Less effective killer than penicillins/cephalosporins (higher relapse rate)
2. Only used for MRSA endocarditis (when penicillins and cephalosporins rendered limp)
3. 4 weeks duration
ii. Erythromycin - bacteristatic (ie relies on immune sys to kill bacteria) → inappropriate for endocarditis
3. If penicillin allergy?
a. Red rash ~10% (low risk of anaphylaxis)
i. ∆ fluclox to 1st gen cephalosporin (eg cefazolin) – 1st gen has stronger G+ve killing power
1. Cefazolin + Gent double therapy also applicable
ii. ? co prescribe histamines and continue with penicillin
b. Anaphylaxis (facial edema + stridor) - rare

Case 2 – Meningitis

17 F
PC – headache, photophobia, fever 6/24
• protein 3.5 (0.15-0.45) ↑
• glucose 0.8 (2.8-4.4) ↓
• rbc 50x10(9)
• wbc 3.5x10(9) – 80% polymorphs
• Ø organisms seen in CSF

1. Dx – Bacterial meningitis
2. CSF analysis indicating a bacterial cause
a. ↑ protein – due to leaky capillaries
b. ↓ glucose – white cell have incr metabolism (ie chemotaxis, metabolic ingestion/destruction etc)
c. rbcs – Ø normally present
d. wbcs – high and mostly polymorphs (neutrophils)
3. Organisms implicated in bacterial meningitis
a. Strep.pneumoniae (most common, assoc w greater mortality)
b. N.meningitidis
c. H.influenzae
4. CSF Cultures
a. G+ve cocci in chains = S.pneumoniae
b. Consider S.pneumoniae in cases where meningitis concomitant with pneumonia or sinusitis
5. Suscep of S.pneumoniae to penicillin
a. Most organisms acutely sensitive to penicillin → 4 mU q4h iv (1 mU = 0.6 mg)
b. Small minority witll be resistant to penicillin at standard dose (10-20%)
c. While awaiting MIC (minimum inhibitory conc) from lab → add vancomycin to cover these resistant strains
d. Ie – if clinical picture suggests s.pneumoniae meningitis or G+ve cocci seen on CSF microscopy – you should use penicillin + vancomycin until lab reports on sensitivity of s.pneumoniae to penicillin

Case 3 – UTI/Cystitis

32 F
PC – urinary freq + dysuria 5/7
HxPC – presented first 3/7 ago, urine dipstick test given but Ø microscopy or culture (prescribed trimethoprim)
Sxs have persisted unchanged, Ø loin pain, Ø fever
MSU – wbcs 160 x 10(6) + large numbers of bacteria

1. Dx – cystitis (wbcs >10(6) highly suggestive of infection)
2. Was MSU at first presentation reqd?
a. Urine dipsticks
i. Test for -
1. Protein (proteinuria)
2. Rbcs (hematuria)
3. Glucose and ketones
4. pH
5. Nitrites (bacteriuria)
6. Leucocytes/Leucocyte esterase
ii. High false negative rate
b. MSU → culture, microscopy (reqd if pt is pregnant or serious/complicated)
i. Negative culture – consider Chlamydia or gonorrhea
ii. High bacterial load but Ø leucocytes → contamination
c. No testing probably reqd here as pt not pregnant and not complicated dis
3. 6 x most likely pathogens
a. E.coli G-
b. Proteus G-
c. Klebsiella G-
d. Pseudomonas auerginosa G-
e. Staph.saprophyticus G+
f. Enterococcus faecalis G+
4. Commonly prescribed drugs
a. Trimethoprim
b. Norfloxacin
c. Augmentin
d. Nitrofurantoin - only used for UTIs due to poor conc in blood/tissue
e. Gentamicin IV – hospital mgt
f. Cef IV
5. Resistance
a. 20% E.coli resistant to trimethoprim
b. If possible – avoid using drug with broadest spectrum of activity as initial tx due to risk of resistance and adverse effects (eg gastroenteritis due to to suppression of normal flora)


Case 1 – Isolated BP elevation

58 F
Sitting BP 150/100 single measurement
Smoking hx 20 pack yrs, BMI 32
Random LDL 3.9, serum creat 80, msu NAD, ECG Ø LVH

1. What non-pharm advice would you give her about lowering her BP?
a. Weight loss – 1 kg loss = ~1 mmHg ↓
b. Exercise
c. Diet – sodium <100 mmol/day (<6 g/day) – nearly impossible in developed countries
2. How often and over what time would you check her BP before starting anti-hypertensive meds?
a. Single measurement (unless severe) does not warrant meds
b. 3x measurements over a few months reqd
3. Starting medication
a. Start tx when sys >160 or dias >100
b. In addition, consider cardiovascular risk tables
i. If 10 yr CV risk >20% → anti-HTN med reqd regardless of baseline level (based on linear r/ship betw BP + CVA risk)
c. Deficiencies of tables
i. Framingham – wealthy caucasian, eastern USA popn
ii. No TGs, CRP or f.hx considered
iii. Only 10 yr risk – Ø lifetime risk (inadequate risk assessment in young people)
4. Choosing medications
a. AB CD Rule
i. B-blockers – no longer regarded as 1st choice as less effective at stroke prevention → A CD Rule
ii. ACEIs – more effective if pt young (<50 y) – incr renin underlying BP in younger pts
iii. Diuretics – more effective if pt older (>50 y) – normal or ↓ renin levels in older people
b. Bendrofluazide 2.5 mg od max dose
c. Add ACEI if diuretic ineffective – cilazapril
5. Target BP
a. 140/85
b. 130/80 – if DM, MI etc
c. 120/75 – if proteinuria, RF etc

Case 2 – Post-Ischemic Stroke / TIA

75 M
Current tx – metoprolol 95 mg od
• HTN, angina on exertion (Ø angina since starting metoprolol 2 yrs ago)
• CVA 3/12 ago – weakness R arm/leg, Ø other neuro deficit, lucanar infarct on CT → weakness resolved but has had recent TIA (5 mins – numbness of R arm and face)
• Since CVA – 3x BP checked, never less than 150/100
• Resting PR 60/min, LDL 3.0, smoking hx 40 pack yrs, stopped 3 yrs ago
• Current meds – aspirin 150 mg od

What should be done with his meds?
1. Do not ∆ metoprolol – PR of 60 indicates sufficiently b-blocked, withdrawal may cause angina to return
2. More anti-hypertensive effect required → AB CD Rule
a. Add bendrofluazide
b. CCB ie felodipine also appropriate
c. Co-morbidities may influence choice here – eg alpha blocker if prostatism
3. Target BP – 130/80
4. Other medications
a. Simvastatin 40 mg od
i. SPARKL study – atorvastatin 80mg vs placebo → small ↓ in TIAs in atorvastatin grp
ii. This is the only study post stroke for statins, many people dropped out due to side effects
b. Continue aspirin
c. ?dipyridamole → ↓ recurrent TIAs, no effect on mortality

Case 3

72 M
• 20 yr hx T2DM
• Received HTN tx for 15 yrs (currents meds – felodipine 10 mg od, bendrofluazide 5 mg od, glipizide 2.5 mg od)
• Ave BP over past yr 170/95
• C/o ankle swelling, chest discomfort on exertion, Ø SOB
• BMI 29.5, creat 130, BG 9.6, HbA1c 8.4%. LDL 5, HDL 1

1. Possible causes of his peripheral edema
a. Side effect of felodipine (vasodilator)
b. HF 2ndry to macrovascular complications of T2DM
c. Hypoalbuminaemia (nephrotic syndr causing gross proteinuria and pedal edema)
2. What changes would you make to his medications?
a. Ø Felodipine – assoc w ankle swelling
b. Bendrofluazide - ↓ dose to 2.5 mg od (maximum recommended dose)
c. Add Cilazapril (starting dose 0.5 mg, increasing to 2.5 mg then to max 5 mg – potential for high first dose hypotension)
d. If Bendrofluazide + Cilazapril ineffective → add metoprolol 95 mg
3. Other medication changes
a. Add metformin (provided Creatinine <160 or GFR >30) – alternatively incr glipizide dose to 5 mg od
b. Add simvastatin 40 mg od
c. Add Aspirin 150 mg od

Case 4

36 F
Life long asthma, uses salbutamol inhaler freq
At age 32 – presented with headaches + persistent BP ~170/110 (treated with enalapirl 20 mg)
O/E – BP 160/105, never been better than this despite therapy
Creatinine 0.9 mg/L (0.7-1.2 correlates to 60-110 umol/l), Serum K 4.0

1. Would you do further ixs?
a. Consider 2ndry causes of HTN in a pt this young
i. Phaechromocytoma – palpitations, headache, sweating attacks → 24 catecholamine test
ii. Drugs – OCP, cocaine, NSAIDs
iii. Fibromuscular dysplasia or renal arteries leading to renal artery stenosis → renal bruit o/e, renal US (renal Doppler, ?polycystic kidney)
iv. Conn’s syndrome – unlikely here as Na retention would cause K loss (serum K normal) → serum aldosterone/renin
2. How would you control her BP?
a. Tx of any underlying cause
b. add diuretic
c. ∆ enalapril to a cilazapril (longer acting)
3. Pregnancy issues
a. ACEI/ARBs → Contra in pregnancy due to congenital abnormalities of fetal kidneys (ie Ang 11 critical in normal kidney devt throughout entire preg)
b. Safe drugs
i. lobetalol (mixed a/b antagonist – Contra in asthma
ii. CCBs – nifedipine LA
iii. Diuretics
iv. Methyldopa


Case 1 – Sotalol and Torsades de pointes
60 M
CRF (serum Creatinine 400 umol/l) adm to hosp, found to be in rapid AF, reverts to sinus rhythm spontaneously
Echo – moderate m.stenosis, normal LV func
Recommendation is made for tx w Sotalol160 mg day
One week later → collapses, ECG shows torsades de pointes
1. Torsades de pointes (twisted ribbon) – caused by QT prolongation
2. QT prolongation can be caused by –
a. Sotalol
b. Amiodarone
c. ↓ mg
d. ↓ k
3. Sotalol
a. Non-selective b-blocker AND class 3 anti-arrhythmic activity
i. Prolongs phase 3 of AP (slows delayed k rectifier efflux/current)
ii. Assoc w QT prolongation (dose dependent) and torsades de pointes
b. ½ life 12 hrs, renal excretion (low lipid solubility, not protein bound)
4. Management of torsades de pointes
a. Eliminate potential causes – eg mg, k
b. Overdrive pacing wire – allows for faster rate than torsades de pointes
c. Note that DC is ineffective (is effective in some forms of VT)

Case 2 – Phenytoin toxicity
25 M
Epilepsy well controlled on phenytoin 300 mg per day
He develops nephrotic syndr, serum albumin 20 g/l
Phenytoin level is 20 umol/l (therapeutic range 40-80 umol/l)
Phenytoin dose incr to 360 mg /day → he develops drowsiness and ataxia
1. Phenytoin toxicity
a. Cerebellar syndrome – eg ataxia, clumsiness, nystagmus (DASHING) etc
b. Drowsiness
2. Two reasons for phenytoin toxicity
a. Saturation kinetics (most drugs have linear kinetics) – small dose ↑ can cause significant problems
b. Disproportionate ↑ in fraction of unbound (active) drug due to decr protein binding (hypoalbuminemia) – ie phenytoin is albumin bound in plasma, only the free drug is active
3. Nephrotic syndrome features
a. Proteinurea
b. Hypoalbuminaemia
c. Edema
4. Impt non-linear kinetic drugs – phenytoin, alcohol, heparin (unfractionaed infusion)

Case 3 - Digoxin
70 F
Has HF, tx w enalapril 20 mg daily, frusemide 80 mg morning and midday
Is in sinus rhythm
HF is not adequately controlled, so you start tx w digoxin
Weight = 50 kg, serum Creatinine 300 umol/l
1. Features of digoxin
a. Concentration dependent on renal function
b. Narrow t.index
c. Adv effects incl arrhythmia, n/v
d. Indications – rate control in AF (slows AF down thus improving CO)
e. Poor evidence for use of digoxin in HF when in sinus rhythm → may improve sxs, Ø effect on mortality, drug of last choice
2. Would you give a loading dose?
a. LD only reqd if therapeutic drug levels urgently reqd – not required here
b. If were giving a LD – this pt would require ↓ LD due to impaired renal function (↑ conc due to impaired renal function)
c. 3-4 ½ lives to reach steady state (1/2 life ~1 day) → hence 3-4 days normally reqd to reach steady state conc
d. Drugs with a long ½ life are therefore given initially with a LD
e. Normal loading doses (less reqd for this pt)
i. Rapid oral loading – 750-1500 mcg as single dose (or 2 divided doses 6 hrs apart if less urgent/toxicity concern)
ii. Slow oral loading – 250-750 mcg daily for 1 week followed by appropriate maintenance dose (expect clinical response within one week)
3. What maintenance dose?
a. In practice, most pts w HF are maintained on 125-250 mg daily
b. A dose of 62.5 mcg may be more applicable in a pt with renal failure
4. Do you need to check her digoxin levels?
a. Yes – concern over toxic effects
b. Normal range is however only a guide (you can still get toxic effects below the normal range)
5. When would you check digoxin levels?
a. After 4-5 ½ lives (4-5 days)
6. If digoxin levels are 2.8 nmol/l, would you adjust the dose?
a. Would depend on clinical situation
b. If sxs improve and no adv effects → leave alone
c. Ensure levels were measured before a dose (ie trough conc)
7. Digoxin toxicity
a. Appetite loss
b. Nausea
c. Vomiting
d. Diarrhea
e. Blurred vision / Visual disturbance (yellow-green halos)
f. Confusion, drowsiness, dizziness

Case 4 – Lithium toxicity
60 F
BPAD – treated with maintenance Lithium CR 400 mg bd
3 years ago, lithium level was 1 mmol/l (target conc 0.5-0.8)
2/52 ago, started on bendrofluazide 5 mg daily
Serum Creatinine checked at same time and was 180 umol/L
PC – anorexia, vomiting, unsteadiness
1. Most likely explanation
a. Lithium toxicity → features incl anorexia, vomiting, unsteadiness
b. Lithium is renally excreted
c. Causes for lithium toxicity
i. Bendrofluazide blocks lithium excretion – due to compensatory ↑ of prox tubule resorption of Na+ and lithium
ii. Renal impairment (Creatinine 180) when started bendrofluazide (added renal impairment from diuretic dehydration?)
2. Management
a. Ø Bendrofluazide
b. Ø Lithium – wait for levels to return to normal range
c. Re-hydration

Case 5 – Hyperkalaemia and Diuretics
75 F
HTN, tx w amizide (hydrochlorothiazide + amiloride)
Serum Creatinine 180 umol/l
Serum K 4.5 mmol/l
BP remains elev at 170/105 – started on enalapril 40 mg /day
2/52 later, serum k is 6.0 mmol/l
1. Why is k elevated
a. Disproportionate retention of K
b. ACEI adv effect → hyperkalemia (decr aldosterone and limited k excr via this pway)
c. Amiloride = K sparing → hyperkalemia (inhibits Na absorption in DCT by blocking Na channels causing ↓ K excretion)
d. Hydrochlorothiazide → hypokalemia (thiazides inhibit Na/Cl absorption in prox segment distal tubule, incr Na levels in the lumen then exchange w K + H causing hypokalemia)
2. Management of hyperkalemia in this case
a. Ø enalapril and amizide
b. ECG – look for features of hyperkalemia
i. peaked t waves (first sign)
ii. wide QRS
iii. then sinusoidal ECGs (‘pulling string tight’)
iv. then asystole
c. If ECG changes are present
i. <5.5 → Salbutamol (shifts K into cells)
ii. 5.5-6.5 → Salbutamol + Calcium gluconate (stabilises conducting pathways in cardiac muscle)
iii. >6.5 → Add Insulin/50% dextrose (shifts K into cells)
iv. +/- Calcium binding salts (Resonium) - calcium x∆ for K in gut (co-prescribed w senna/laxulose to prev constip)
v. +/- Frusemide IV
vi. Continue ECG monitoring

Case 6 – Hypovolaemia and NSAIDs
40 M
Pre-op serum Creatinine 140 umol/l
Post-op – receives paracetamol, tenoxicam, morphine for pain relief
Now c/o n/v
O/E – abdo soft, non-tender, bowel sounds normal, JVP -2cm (normal = +2-4 cm), serum Creatinine 750 umol/l
1. Why has he developed RF?
a. Low JVP suggests volume depletion
i. Surgical fluid losses
ii. N/V → fluid loss
b. Pre-renal failure also caused by tenoxicam (NSAID) inhibiting PG synthesis (PGs impt for renal vasodilation)
2. What were the risk factors for developing this problem?
a. Pre-operative renal impairment (normal 60-110)
b. Vomiting – due to analgesic use (anti-emetic useful)
c. Poor reserves – needed normal saline prior to surgery to prevent fluid depletion
3. Avoid NSAIDs + Hypovolaemia (surgical fluid loss, vomiting fluid loss)

Case 7 – Allopurinol and Renal Impairment
56 F
Asx hyperuricaemia, serum urate 0.60 mmol/l
Serum Creatinine 200 umol/l
Commenced on tx w allopurinol 300 mg /day
4/52 later, presents w fever, itchy maculopapular rash, nausea, deranged LFTs, eosinophil count 2.10(9)/L
1. High eosinophil count differential dx
a. Drug reactions
b. Parasites
c. Some lymphomas
2. Likely dx
a. Allergic reaction (hypersensitivity) to allopurinol
b. Allopurinol toxicity → skin reaction (macular rash)
c. Not features of anaphylaxis which would usu be immediate (hrs) rather than weeks
3. Steps that could have prevented this occurring
a. Low dose allopurinol reqd if renal impairment
b. Asx hyperuricaemia – is allopurionol actually needed?


Case 1 - Phenytoin

70 F
Epilepsy tx for 5 yrs w phenyotin 300 mg nocte
She tolerates the phenytoin well w/o side effects, but continues to have 1 or 2 generalised seizures a year
Phenytoin conc is 29 umol/l (therapeutic range 40-80 umol/l)

1. Would you change her tx?
a. Yes – seizures are not well controlled, issues around driving, social inconvenient and risk of injury
b. Options - ↑ phenytoin dose, add 2nd drug or change from phenytoin to another drug
c. Preference for monotherapy due to ↑ compliance and ↓ risk of side effects
d. She is already on phenytoin and she tolerates it well – best choice is to ↑ her dose
e. Although not first choice, many pts have been successfully on phenytoin for a long time
f. Side effects
i. Type A (augmented, ie dose related)
1. cerebellar sxs – eg nystagmus (vertical)
2. sedation
ii. Type B (bizarre, ie not dose related)
1. Hirsuitism (worse problem for girls)
2. Coarsening of facial feats
3. Gum hypertrophy
2. If so, how?
a. ↑ phenytoin dose in increments of 30 mg (saturation kinetics)
b. TDM monitoring reqd – may be beneficial as seizures are very infrequent and you wont know success of tx for some time – drug levels remaining below the therapeutic range may be an indication for incr her dose further to 360 mg
i. Wait ~2 wks before measuring
c. Note – any dose reduction should be done gradually as a sudden dose ↓ can cause onset of seizures
3. Status epilepticus
a. Protracted seizures or intermittent seizures w/o recovering consciousness

Case 2 – First Generalised Seizure

52 M
Presents following generalised seizure witnessed by wife giving clear a/c of tonic clonic seizures
Ø previous seizure
PMhx unremarkable
Neuro exam normal

1. Ixs
a. Metabolic screen – Ca2+, Na, urea, drugs
b. If no clear precipitant, look for a focus
c. CT – cheaper, more readily available, shows blood better than MR
d. MRI – more detail, greater chance of identifying problems, esp hippocampal sclerosis
i. Etiology
1. Previous head injury (post-traumatic epilepsy common)
2. Cerebrovascular dis (common cause)
3. Abscess
4. Metabolic eg hypercalcemia
5. LF
6. RF
ii. Scan if >30-35 (unclear age margin but scanning adolescents is not required unless they have a 2nd seizure)
e. EEG – useful if unclear if person has had seizure (ie non-witnessed); epileptic activity suggests seizure cause for collapse
2. Do you start tx after just one seizure?
a. No – provided no focal features and ixs are normal
b. 25% chance that seizure will recur in this situation → never label epilepsy at this stage
c. However, if a 2nd seizure occurs, then 60-70% chance of further recurrence
d. Tx usu started after this point
e. Risk factors for ↑ chance of seizure recurrence
i. Focal neurology
ii. Structural brain dis
iii. Partial to generalised seizure
iv. Brain tumor (v high chance of recurrence – start tx immediately)
3. Which anti-convulsant for generalised epilepsy?
a. Sodium valproate (Epilim)
i. Valproate is probably slightly more effective than carbamazepine, easier to use and less concern over a narrow t.index
ii. Side effects – weight gain, menstrual irregularity, GI upset, fatigue
iii. Starting dose 600 mg daily ↑ by 200 mg at 3 day intervals until control is achieved
iv. Typical dose 1000-2000 mg/day
v. TDM not reqd as poor r/ship betw drug conc and efficacy
4. Advice about driving
a. Ø driving for 1 year
b. 6 months on neurologist recommendation if they believe it is unlikely to occur while driving

Case 3 – Carbazamepine and OCP/Pregnancy

19 F
Treated with carbazamepine for epilepsy for 7 yrs
2 years ago, carbamazepine stopped, but restarted after she had a further seizure
She is now sexually active and wants to start the OCP

1. Prescribing carbazamepine
a. Titrate slowly – start at 100 mg
b. Measure conc level – there is a r/ship betw conc and efficacy
c. Adv effects – non-specific feeling of unwell
2. Carbamazepine and OCP
a. Carbaz causes ↑ metabolism of OCP (Carbam is metabolised by and induces CYP3A4 which also degrades the OCP)
3. How would this affect your prescribing?
a. Different anticonvulant - ?valproate
b. ↑ OCP dose to compensate
i. SD of E2 in OCP is 30 ug, incr to 50 or 100 ug
ii. Watch for breakthrough bleeding which indicates E2 ineffective
iii. Alternate forms of contraception
1. Barrier methods - ↑ failure rate
2. IUD - ↑ PID risk
4. Other medications that interact with carbamazempine
a. CYP3A4 – CCBs, Benzos, Statins, Cyclosporin, Phenytoin, Warfarin
b. Carbaz mostly an enzyme inducer of 3A4 drugs
c. Carbaz toxicity
i. Verapamil and Diltiazem → ↓ carbaz metabolism
ii. Erythromycin inhibits carbaz clearance
4 years later, she wishes to become pregnant
5. Effect of anti-convulsants on the fetus
a. Balance of risk favours tx despite anti-convulsant teratogenecity risk
b. W/o medication – risk of ischemia to fetus during seizure → hypoxia and miscarriage
c. Valproate and carbamazepine – incr risk of neural tube defects
d. Lamotrigine – incr risk of cleft palate
e. Phenytoin syndrome – incr risk of congenital defects (cranial facial, digits, heart)
f. If staying on carbamazepine, she should receive folic acid (5 mg folate) for several months before trying to get pregnant to reduce the risk of spina bifida

Case 4

24 M
Developed 2ndry generalised seizures 6 yrs ago following a head injury
Unable to tolerate carbamazepine or phenytoin
Valproate 1000 mg bd (max dose) reduced the freq of seizures from 1 wk to 1 every 4 wks
You decide to add an additional tx and prescribe lamotrigine

1. Initiating lamotrigine
a. Standard initial lamotrigine dose = 25 mg/day, titrate up to 400 mg /day
b. Valproate inhibits lamotrigine metabolism → Start lamotrigine on a lower dose eg 25 mg every alternate day titrating up to 200 mg/day max
2. Would this differ if he was also on carbamazepine?
a. Carbamazepine can induce metabolism of lamotrigine → Higher doses of lamotrigine reqd
3. If he were to present with a newly diagnosed 2ndry generalised epilepsy today (eg aura etc), which med would you choose?
a. Complex partial seizures usu due to TLE
b. So first line tx - Carbazamepine or lamotrigine
4. 8/52 after starting lamotrigine, he develops a generalised erythematous macular papular rash
a. Lamotrigine – up to 10% get rash
b. May progress to Stevens-Johnson Syndrome (SJS)
i. Severe and life-threatening
ii. Hypersensitivity complex affecting skin and mucous membranes
iii. Characterised by flu-like prodromal period of fever, sore throat, redness of eyes, sudden devt of mucocutaneous lesion that can cover majority of skin
iv. Milder form of Toxic epidermal necrolysis syndrome (TENS)
v. Causes – post viral infection, allergic drug reactions, malignancy, idiopathic
c. Ø Lamotrigine to avoid progression (esp if widespread and severe)
d. Lamotrigine + Valproate → ↑ risk of skin rash

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