Revise Notes Pharma

Question 1

Drug-supported Withdrawal

Answer 1

Disulfiram
CVD: cardiac failure, CADm stroke, hypertension
Psychosis and suicide risk.
Acamprosate
Severe hepatic impairment, renal impairment (creatinine > 120 micromol/l)
Pregnancy

Bupropion

Mental health - eating disorders, bipolar disorder
Seizures
Pregnancy.
Bupropion causes Mental Seizures in Pregnancy!

Question 2

Pregnancy

Avoid the following in pregnancy:

Answer 2

Antibiotics:

Tetracyclines - teeth discolouration
Trimethoprim and sulphonamides (inc. co-trimoxazole) affect folate metabolism
Aminoglycosides (gentamicin)
Quinolones (ciprofloxacin)

ACEis/ARBs
Statins
Warfarin
Sulfonylureas
Retinoids (including topical use)

Caution with anti-epileptic drugs
Lamotrigine and levetiracetam are considered the safest
Valproate, topiramate, phenytoin, carbamazepine, phenobarbital all increase risk of teratogenesis

Question 3

Cautions & Contraindications
Renal Impairment

Avoid the following medications in renal failure if possible:

Answer 3

NSAIDs
Metformin (CI - if eGFR < 30)
Lithium - caution in mild-mod, avoid in severe renal impairment

Antibiotics
Tetracyclines - avoid unless benefits > risks (risk of accumulation)
Nitrofurantoin - avoid if eGFR < 45

Question 4

Heart failure

In patients with HF, avoid:

Answer 4

Thiazolidinediones (pioglitazone) – can cause fluid retention

Rate limiting CCBs (diltiazem/verapamil) – negative inotropic effects

NSAIDs & steroids – worsen fluid retention

Question 5

Complications of Chemotherapy
Commonly used chemotherapy drugs, and their complications include:

Vincristine

Peripheral neuropathy
Common uses: ALL, CML, lymphoma

Cisplatin

Electrolyte derangement - Hypomagnesemia, hypokalaemia, hypocalcaemia,

Peripheral neuropathy
Ototoxicity and nephrotoxicity

Answer 5

-Bleomycin

Lung fibrosis, pulmonary toxicity

-Doxorubicin

Acute cardiotoxicity (myopericarditis) - often presents within 2-3 days of administration with chest pain, palpitations, arrhythmias.
Cardiomyopathy

Other anthracyclines include: daunorubicin, epirubicin

A baseline echocardiogram should be performed before commencing anthracyclines

Cyclophosphamide

Haemorrhagic CYstitis
Mesna (sodium-2-mercaptoethanesulfonate) should be co-prescribed with cyclophosphamide - it combines with acrolein and detoxifies it reducing bladder toxicity

Decadron (Dexamethasone)

Water retention, resulting in facial and ankle swelling.
Hyperglycaemia

Question 6

Cytochrome P450 - Inducers & Inhibitors
The cytochrome P450 are a superfamily of enzymes which are important for the clearance of compounds, steroid synthesis, and drug metabolism (>75% of all drugs).

P450 Inducers

Inducers increase the activity of the P450 enzymes increasing drug metabolism and therefore reducing the effects of certain medications

Answer 6

PCBRASS

The inducers can be remembered by the mnemonic PCBRASS.

Phenytoin
Carbamazepine
Barbiturates
Rifampicin
Alcohol (chronic use)
Sulfonylureas
Smoking (particularly on CYP1A2)
St John’s wort
Clinical significance

P450 inducers increase the metabolism of warfarin and therefore reduce its anticoagulant effect

Therefore - if a patient who takes regular warfarin is commenced on an inducer, their INR may fall to subtherapeutic range, with resultant

complications

Patients on regular inducers may require higher doses of warfarin to achieve the desired anticoagulant effect

Question 7

P450 inhibitors

P450 inhibitors reduce drug metabolism which therefore increases drug action.

OAAK DEVICES

The inhibitors can be remembered with the mnemonic OAAK DEVICES.

Answer 7

Omeprazole
Amiodarone
Allopurinol
Ketoconazole

Disulfiram
Ethanol
Valproate
Isoniazid
Ciprofloxacin
Erythromycin, clarithromycin
Sulphonamides - e.g. sulfadiazine, sulfamethoxazole

Clinical significance

P450 inhibitors increase the anticoagulant effect of warfarin by decreasing its metabolism.
Therefore - if a patient who takes regular warfarin is commenced on an inhibitor, their INR may rise,

and result in complications such as haemorrhage.
Patients taking P450 inhibitors may require lower doses of warfarin to achieve their target INRs

Question 9

Trastuzumab

Answer 9

Trastuzumab (Herceptin)

Mechanism: Her2/neu receptor antagonist

Indications: Her-2 positive breast cancer

Adverse effects: cardiotoxic

Patients should undergo an echocardiogram before treatment

Question 10

Glitazones

Answer 10

Glitazones

Contraindications

HF
Bladder cancer or undiagnosed macroscopic haematuria

Hepatic impairment

Before initiation, measure:

LFTs - if ALT > 2.5x ULN/ evidence of liver disease - contraindicated
Following initiation, monitor:

LFTs ‘periodically’

Signs/symptoms of HF - such as peripheral oedema/weight gain

Warn of symptoms of bladder cancer - haematuria etc.

Question 11

Apixaban

Answer 11

Apixaban

Before initiation, measure:

FBC, UE, LFT, clotting screen
Monitoring:

FBC, UE and LFTs - yearly in most patients (consider 6 monthly if > 75 yrs age, or more frequently if renal impairment)

Question 12

Sodium valproate

Answer 12

Sodium valproate

Before initiation, measure:

FBC
LFTs
BMI

Monitoring:

After 6 months, check FBC, LFTs, BMI
Thereafter, check FBC/LFTs/BMI once every 12 months

Only check valproate level if suspected poor compliance/toxicity (not routinely!)

Question 13

Methotrexate

Answer 13

Methotrexate

Prescription

Once weekly (with folic acid 5mg once weekly, on a different day to the MTX)
Monitoring (the monitoring for azathioprine is the same)

FBC, UE, LFTs
Before treatment, then..

Every 2 weeks until dose has been stable for 6 weeks. Then..

Every 1 month for 3 months. Then..
At least once every 12 weeks

Increased monitoring is required with dose increases, or if at risk of toxicity

Question 15

Amiodarone

Before initiation, measure:

TFTs, LFTs, UEs
CXR
ECG
Monitoring:

Every 6 months check
TFTs
UEs
LFTs
Every 12 months - ECG

Answer 15

Complications:

Pulmonary toxicity - pneumonitis, pulmonary fibrosis

Thyroid dysfunction - hypo- or hyperthyroidism

Hepatobiliary disorders - cirrhosis, hepatitis, jaundice

Cardiac toxicity - conduction abnormalities

Visual disorders - corneal deposits
Blue-grey skin discolouration

Question 16

Levothyroxine

Answer 16

Levothyroxine

Monitoring

Consider measuring TSH every 3 months until stabilised (2 similar measurements)
Then yearly TSH

Question 17

ACE inhibitors

Before initiation, measure:

U&Es (renal fn, E-s), blood pressure
Titration

After every dose increase, after 1-2 weeks, recheck
UEs
Blood pressure
Titrate every 2 weeks until target achieved

Answer 17

Monitoring

Once stable, measure UEs every month for 3 months. Then..

Every 6 months and also if becomes acutely unwell

Creatinine/eGFR:
If Creatinine increases by 20% / eGFR falls by 15% - repeat UEs in 2 weeks

A total increase of creatinine < 30% is acceptable - no action required

If cr increases by > 30% reduce dose/withdraw and review clinically. Consider causes such as renal artery stenosis.
K+ - hyperkalaemia

A K+ level up to 5.5 is acceptable - if K+ > 5.5 - stop and seek specialist advice
Sick day rules

Diarrhoea & Vomiting - Stop ACEi for 1-2 days until recovered and maintain fluid intake. If persistent, get UEs checked.

Question 18

Statins

Mechanism

HMG-CoA reductase inhibitors
Adverse effects

Deranged LFTs, myositis
Monitoring

Before initiation, measure:

Full lipid profile, LFTs, HbA1c, renal function, TSH

CK is also required if: renal impairment, hypothyroid, unexplained muscle pain, history of liver disease

Answer 18

Targets:

Full lipid profile after 3 months of treatment

If a reduction in non-HDL cholesterol of 40% is not achieved, and compliance is good, consider increasing the dose

If still not achieved, despite max dose of statin, consider ezetimibe co-prescription

Ezetimibe reduces cholesterol reabsorption in the small bowel

Monitoring:

Lipid profile after 3 months, as above
Repeat LFTs within 3 months, and again at 12 months (if stable, no further monitoring unless indicated)

Check CK if muscle symptoms
Repeat HbA1C after 3 months if high risk of DM

Question 19

Azathioprine/mercaptopurine

Screening

Check TPMT levels - Approx. 1/300 patients have complete TPMT enzyme deficiecny - therefore at high risk of haematological toxicity

Answer 19

Allopurinol

Screening

Certain patients should be screened before commencing allopurinol as they are at high risk of dermatological complications (e.g. SJS/TENS).

High risk patient groups include those of Chinese, Thai and Korean origin
They should be sreened for the HLA-B5801 allele

Question 20

Gentamicin

Answer 20

Gentamicin

Complications

Ototoxic – CN8 damage
Neprotoxic – can cause acute tubular necrosis
Contraindications

Myasthenia Gravis
Other drugs that are contraindicated/must be used with caution in MG include:

Quinolones - cipro, levofloxacin, ofloxacin etc
Macrolides - can cause NM weakness

Question 21

Phosphodiesterase type V inhibitors

Mechanism of action

Increased cGMP – smooth muscle relaxation in BVs (vasodilation)
Contraindications

PDE5 inhibitors are contraindicated in patients on nitrate (e.g. nicorandil)
Recent stroke or MI (wait 6 months!)

Answer 21

Important side effects

Visual disturbance
Blue discolourtation
Tip: The blue pill (viagra) causes blue vision

Question 22

The Combined Oral Contraceptive Pill (COCP)

Advantages

Reduced risk of ovarian and endometrial cancer
Reduced risk of colorectal cancer

Disadvantages

Increased risk of breast + cervical cancer
Increased risk of clots – VTE, stroke, MI

Answer 22

Advice

If the COCP is started in the first 5 days of the cycle, the patient is protected

If it is started at any other point in the cycle, additional protection should be used for at least 7 days

Question 23

Contraindications - UKMEC4

Answer 23

Postpartum
Breastfeeding and < 6 weeks postpartum
<3 weeks postpartum with RFs for VTE

Past-medical history:
Uncontrolled HTN (>160/100)
Vascular disease
History of ischaemic heart disease, AF, heart failure or stroke/TIA

History of VTE
Major surgery with prolonged immobilisation
Migraine with aura

Genetics:
Breast cancer, or carrier of BRCA1/2 or known thrombogenic mutation

Smoking:
Age > 35 and smokes > 15/day

Question 24

Contraindications - UKMEC 3 – Risks > Benefits

Answer 24

> 35 yrs age and smoke (but < 15/day)
BMI > 35

Controlled hypertension
Family history of VTE
Immobility (e.g. wheelchair user)

BRCA 1 or 2 carrier
Gallbladder disease

Nb. A diagnosis of diabetes mellitus for longer than 20 years is also considered UKMEC 3 or 4 (depending on severity)

Question 25

Calcium channel blockers (CCB) Adverse effects & cautions

Answer 25

Heart failure - caution with RLCCBs diltiazem/verapamil (but amlodipine / nifedipine ok) Constipation Flushing Ankle swelling Headache Do NOT give rate limiting CCBs (diltiazem/verapamil) with beta blockers - can precipitate heart block

Question 26

Digoxin Mechanism Inhibition of Na+/K+ ATPase pump Increase myocardial contractility - positive inotropic effect Slowed conduction via the AVN - providing rate control

Answer 26

Digoxin toxicity Measure digoxin concentration 8-12 hours after the last dose Clinical features: Confusion, N&V Yellow-green vision Bradycardia or AVN block Precipitants: Hypokalaemia Digoxin and K+ compete for the same site on the Na+/K+ pump (so hypokalaemia = less competition for digoxin). Renal failure Other drugs: amiodarone, verapamil, diltiazem, spironolactone, thiazides. Management: Digibind Potassium replacement

Question 27

Adrenaline/Epinephrine Anaphylaxis 1:1000 adrenaline (repeat after 5 min if no better), given IM: Adult and children > 12 yrs - 500 mcg (0.5 mL) Child 6 -12 yrs - 300 mcg (0.3 mL) Child < 6 yrs - 150 mcg (0.15 mL)

Answer 27

Cardiac arrest 1mg every 3-5 minutes 10ml of 1:10,000 IV or 1ml of 1:1000 IV

Question 28

Antipsychotic Medications Antipsychotics can be categorised as typical and atypical. Typical antipsychotics were developed first, and are associated with a greater risk of extrapyramidal side effects.

Answer 28

Typical (first generation) Antipsychotics Examples Haloperidol, Chlorpromazine Mechanism of action Dopamine (D2) Receptor Antagonists Important side effects Hyperprolactinaemia - oligo-/amenorrhoea, loss of libido and erectile dysfunction, galactorrhoea Remember - dopamine inhibits prolactin release Extrapyramidal side effects - parkinsonism, dystonias, akathisia, tardive dyskinesia Antimuscarinic effects - dry mouth, blurred vision, urinary retention, constipation Impaired glucose tolerance Reduced seizure threshold - caution in patients with epilepsy

Question 29

Extrapyramidal side effects

Answer 29

Drug induced parkinsonism Classically of rapid onset and features are symmetrical. Unlike IPD - symptoms are of gradual onset, and typically asymmetrical Akathisia A feeling of severe restlessness Tardive Dyskinesia Involuntary, slow writhing movements Classical movements include chewing, grimacing, tongue protrusion, lip smacking. Dystonias Sustained muscle contractions - oculogyric crisis / torticolis Torticolis - also referred to as 'wry neck' - severe neck muscle spasm/contraction resulting in involuntary head tilting Oculogyric Crisis - involuntary, extreme upward deviation of gaze +/- the presence of torticolis, tongue protrusion, jaw spasm Management of acute dystonias: Procyclidine (anticholinergic) or Benzatropine

Question 30

Other complications of typical antipsychotics

Answer 30

Typical APs should be prescribed with caution in elderly patients, increasing the risk of stroke and DVT/PE. Neuroleptic Malignant Syndrome - see below Polymorphic VT/ Torsades de pointes - due to prolongation of the QTc (esp. with haloperidol)

Question 31

Atypical (second generation) Antipsychotics Atypical antipsychotics are first line in schizophrenia Mechanism of action Act on a wider variety of receptors (D2, D3, D4, 5-HT) Examples Olanzapine Risperidone Aripiprazole Quetiapine Clozapine Amisulpride

Answer 31

Advantages Lower risk of extrapyramidal side effects (EPSEs) vs typical APs Side effects Metabolic syndrome - weight gain, insulin resistance/diabetes, dyslipidemia - therefore associated with accelerated cardiovascular disease. Stroke and VTE (esp in elderly patients) EPSEs + hyperprolactinemia - less common

Question 32

Clozapine Clozapine is indicated in the management of schizophrenia, if symptoms are not adequately controlled despite the use of 2 or more antipsychotics for 6-8 weeks. This is due to its association with significant adverse effects, which include:

Answer 32

Agranulocytosis - FBC monitoring is essential Seizures Myocarditis - a baseline ECG is required before commencing treatment Constipation Clozapine induced Hypersalivation - a significant side effect, affecting approximately 1/3rd of patients. Hyoscine butylbromide can be prescribed to relieve hypersalivation

Question 33

Neuroleptic Malignant Syndrome (NMS) A known complication associated with the use of antipsychotics. NMS can also be triggered by missed doses of levodopa/parkinson’s meds.

Answer 33

Clinical features Pyrexia Muscle rigidity Agitation and delirium Autonomic lability - Hypertension and tachycardia Examination findings Reduced or absent reflexes Normal pupils Differential diagnosis - serotonin syndrome - characterised by dilated pupils, myoclonus and brisk reflexes. Complications Rhabdomyolysis and resultant AKI Management Stop antipsychotics IV fluids Dantrolene Bromocriptine/ dopamine agonists may be beneficial

Question 34

Antidepressants Selective Serotonin Reuptake Inhibitors (SSRIs) Mechanism of action Increase the extracellular levels of the neurotransmitter serotonin, by inhibiting its reuptake into the presynaptic cell. Examples Sertraline Fluoxetine Citalopram

Answer 34

Contraindications (NICE) Current mania Poorly controlled epilepsy Avoid citalopram/escitalopram if QT prolongation or in combination with other drugs which increase the QTc - risk of TDP Avoid sertraline in severe hepatic impairment SSRIs in cardiovascular disease Sertraline is safest Side effects of SSRIs Gastrointestinal side effects are the most common Consider PPI co-prescription (e.g. if on NSAIDs)

Question 35

SSRI

Answer 35

Interactions/contraindications Use with caution with aspirin or NSAIDs – increased risk of PUD/GI bleed Avoid with warfarin or heparin due to bleeding risk – give mirtazapine instead Avoid co-prescribing triptans or MAOIs – risk of serotonin syndrome Follow up Patients should be followed up shortly after commencing SSRIs due to the risk of increased anxiety and suicidal ideation If < 30 years of age, follow patients up in 1 week If > 30 years – follow up in 2 weeks Stopping SSRIs If patients show a good response, they should continue SSRIs for at least another 6 months before discontinuation, or there is a high risk of symptom relapse. Stopping SSRIs suddenly can result in high risk of discontinuation syndrome Clinical features: restlessness, anxiety and agitation, GI symptoms (diarrhoea etc.) Gradually reduce dose over 4 weeks before stopping to reduce this risk Paroxetine - highest risk of discontinuation syndrome

Question 36

Serotonin Syndrome Causes The following drugs are associated with serotonin syndrome, particularly if co-prescribed/ingested: SSRIs MAOIs Triptans Ecstasy/methamphetamines St Johns Wort

Answer 36

Clinical Features Neuromuscular excitation: Increased reflexes, myoclonus, rigidity Autonomic lability – tachycardia, hypertension, pyrexia Confusion, agitation, aggression Note: Myoclonus is a useful differentiating feature from neuroleptic malignant syndrome Management IV fluids Benzodiazepines – the mainstay of management In severe serotonin syndrome – cyproheptadine or chlorpromazine can be used (serotonin antagonists)

Question 37

SNRIs Mechanism of action Serotonin + noradrenaline reuptake inhibitors – increased levels of neurotransmitters at the synaptic cleft

Answer 37

Examples Venlafaxine Duloxetine

Question 38

Monoamine oxidase inhibitors (MAOIs) Mechanism of action Reduce metabolism of serotonin and noradrenaline in the presynaptic clefts)

Answer 38

Examples Phenelzine Side effects MAOIs are associated with hypertension particularly if used whilst tyramine containing foods are eaten (cheese, herring, broad beans)

Question 39

Tricyclic Antidepressants An old class of antidepressants which have a number of additional uses. For example, amitriptyline is used in the management of neuropathic pain & migraine prophylaxis. Adverse effects Antimuscarinic effects – dry mouth, constipation, urinary retention, blurred vision Drowsiness Prolongation of the QTc (risk of TDP)

Answer 39

TCAs in overdose TCAs are considered the most dangerous antidepressants in overdose (esp. Amitriptyline and dosulepin) Clinical features Drowsiness Dry mouth, blurred vision Pupils - dilated Arrhythmias Seizures Metabolic acidosis Coma ECG: Long QTc interval, widened QRS, tachycardia – broad complex tachyarrhythmia with long qt. Management IV Sodium Bicarbonate is the mainstay of management – indications include widened QRS > 100 or ventricular arrhythmia

Question 40

Benzodiazepines Mechanism of action Increase frequency of chloride channel transmission – increase effects of GABA

Answer 40

Discontinuation Withdraw benzodiazepines in steps of 1/8th at a time, every few weeks Clinical Features of BZD withdrawal Anxiety, tremor, irritability, tinnitus, sweating and seizures – last up to 3 weeks after last dose.

Question 41

Lithium Lithium is a mood stabiliser, commonly used in the management of bipolar affective disorder (BAD) Side effects/complications Nausea and vomiting Fine tremor (a coarse tremor suggests toxicity) Nephrogenic diabetes insipidus Hypothyroidism Weight gain IIH Hyperparathyroidism and hypercalcaemia

Answer 41

Monitoring Lithium levels - measure one week after starting treatment and one week after making any adjustments to dose. Once stable, check 3 monthly. 6 monthly - BMI, UE, Calcium, TFTs If urea/cr increases or eGFR decreases, measure lithium levels more frequently than 3 monthly as higher risk of toxicity

Question 42

Palliative Care Anticipatory medications

Answer 42

Pain 1st line: eGFR > 30 - Morphine sulfate eGFR < 30 - fentanyl or alfentanil Breathlessness 1st line: eGFR > 30 - Morphine sulfate eGFR < 30 - fentanyl or alfentanil Nausea and vomiting 1st Line: Levomepromazine SE: Sedation Alternatives: Cyclizine - effective for drug-induced, biochemical or obstructive causes of nausea Haloperidol - effective for drug-induced (e.g. opiate) or biochemical causes of nausea Metoclopramide - effective in cases of gastric stasis Hyoscine butylbromide 1st line in patients with obstructive bowel disorders who have N&V according to NICE If no improvement consider octreotide

Question 43

Palliative meds

Answer 43

Agitation and Anxiety 1st Line: Midazolam Alternatives Haloperidol, levomepromazine Respiratory secretion 1st Line: Hyoscine butylbromide Alternatives: Glycopyrronium bromide Atropine

Question 44

The Pain Ladder - Regular Analgesia Step 1: Non-opioid Paracetamol NSAIDs Step 2: Weak opioids Codeine Tramadol If regular doses of weak opioids do not relieve pain, move up to step 3 - do not change from one weak opioid to another. Step 3: Strong opioids Morphine is the drug of choice Starting with immediate release morphine is recommended as it allows for more flexibility in titration ( often start with 2.5 to 10mg four-hourly, lower in elderly patients/renal impairment). Examples include: sevredol, oramorph Titrate by up to 30-50% per day if pain remains poorly controlled Maintenance Once adequate pain relief has been achieved, the options include: Continuing immediate release preparations Change to 12 hourly modified release morphine (e.g. zomorph, MST) Each 12hrly dose totalling half of the total daily requirement

Answer 44

Breakthrough analgesia Should be PRN immediate release opioid - dose = 1/6th total daily opiate intake Side effects Constipation - regular stimulant laxatives (senna) should be co-prescribed when starting weak or strong opioids N&V - often occurs in first few days of treatment - haloperidol is effective for morphine induced N/V Strong opioids in renal failure No opioid drugs are free from risk in renal failure, but the following are recommended in patients with renal impairment Alfentanil, fentanyl Buprenorphine Oxycodone Morphine Use lower doses, PRN is safer if possible, immediate release preparations are safer than modified release preparations.

Question 45

Opioids An opiate regimen should consist of regular opiates (e.g. zomorph/MST) and breakthrough opiates (e.g. s/c morphine, oramorph) for periods of uncontrolled symptoms. Breakthrough: The recommended dose of breakthrough opiates is 1/6th TOTAL 24-HOUR OPIOID DOSE Opioid conversions may also crop us as questions..

Answer 45

Oral codeine/tramadol Oral morphine 60mg 6mg Oral codeine/tramadol are 1/10th the strength of oral morphine Oral oxycodone Oral morphine 5mg 7.5mg Oral oxycodone is 1.5x the strength of oral morphine Oral morphine Subcutaneous Morphine Subcutaneous Fentanyl 5mg 2.5mg (1/2 oral morphine) 25 micrograms

Question 46

Paracetamol Overdose Background Overdose may occur intentionally, or accidentally Doses of 75mg/kg in 24 hours or less can be potentially toxic. Patients are at high risk of hepatotoxicity with doses of more than 150 mg/kg in 24 hours. Terminology: Acute - Ingestion in < 1 hour Staggered - ingestion of doses over > 1 hour Therapeutic excess - POD in an attempt to treat pain/pyrexia etc.

Answer 46

Pathophysiology Normally, the liver conjugates paracetamol with glucuronic acid / sulphate In POD, this pathway becomes saturated. Therefore, paracetamol is oxidised by cytochrome P450 enzymes into a toxic metabolite called n-acetyl-b-benzoquinone (NAPQI) Normally glutathione binds NAPQI and protects the liver However - if glutathione reserves are depleted, NAPQI accumulates and causes hepatocyte necrosis N-Acetylcysteine (NAC - the mainstay of treatment) is a precursor to glutathione. This therefore boosts stores providing hepatocyte protection. Clinical features Patients are often asymptomatic May complain of nausea, vomiting If left untreated - features of acute liver (jaundice, encephalopathy, coagulopathy etc.), and renal failure (loin pain, haematuria, proteinuria after 24hrs)

Question 47

Acute pod

Answer 47

Investigations Patient’s weight Paracetamol level taken 4 hours after ingestion - for comparison with treatment graph Bloods inc. LFTs, INR, lactate/gas, OD screen if indicated (e.g. salicylates) Management of POD - NAC - N-Acetylcysteine Management depends on the timing/type of overdose Acute POD Acute POD attending < 8 hours post-ingestion Activated charcoal - if presenting within 1 hour and taken > 150 mg/kg - 50g activated charcoal NAC If presenting within 1-4 hours - check bloods 4 hours post ingestion If presenting 4-8 hours - check bloods immediately Commence NAC if PCM level > treatment line / liver injury (raised ALT)

Question 50

Acute pod 8 to 24 hrs

Answer 50

Acute POD attending between 8-24 hours post-ingestion Take bloods inc. paracetamol level ASAP If high-risk (>150mg/kg), commence NAC immediately and a/w bloods If < 150mg/kg - a/w bloods and commence NAC if PCM level > treatment level, or liver injury Acute POD attending > 24 hours post-ingestion Take bloods inc. paracetamol level ASAP There is no evidence that treating with NAC before the blood results confers any benefit Commence NAC if evidence of liver injury (INR > 1.3 or ALT > 2 x ULN) or if paracetamol detected. Staggered POD (doses taken over 1 hour) Send bloods and start NAC immediately in staggered OD Therapeutic excess Take bloods inc. paracetamol level Commence NAC if: Ingested > 150mg/kg in any 24hr period OR uncertainty re. Dose Jaundice, hepatic tenderness, deranged ALT/INR, detectable PCM > 24hr after last dose

Question 51

Adverse reactions to NAC

Answer 51

Clinical features Often within first 30 mins - N&V, flushing, urticarial rash Tachycardia, wheeze Management Stop infusion Give antihistamine (e.g. chlorphenamine), and other tx if required (e.g. Nebs/steroids) Restart infusion when symptoms of reaction have settled

Question 52

The Kings Criteria for Liver Transplant

Answer 52

The Kings Criteria can be used to identify patients in whom liver transplant is potentially indicated following POD-related liver failure. Indications: Arterial pH < 7.3 24 hours after ingestion or. All 3 of: PT > 100 seconds Creatinine > 300 Grade 3/4 encephalopathy

Question 53

Side Effects & Mnemonics Knowing the common side effects of various drugs is a very common subject in the MSRA. Pay attention to the following frequently tested medications/side effects to help you prepare.

Answer 53

Agranulocytosis Agranulocytosis: A severe reduction in granulocytes - often defined as an absolute neutrophil count of < 100 neutrophils per microlitre. Results in significantly increased risk of severe infection. The list of drugs which may precipitate agranulocytosis is extensive. Important examples include: Carbamazepine, valproate, phenytoin Carbimazole Co-trimoxazole, cephalosporins Clozapine Cytotoxics (e.g. methotrexate) Mnemonic: The 5 C’s of agranuloCytosis

Question 54

Steroids (e.g. prednisolone) Mnemonic: MY CUSHINGOID

Answer 54

MYopathy - insidious proximal upper/lower limb weakness Cataracts Ulcers Striae Hypertension Immunosuppression Necrosis of bone (avascular necrosis) Growth restriction Osteoporosis Increased intracranial pressure Diabetes mellitus

Question 55

Hypomagnasaemia

Answer 55

Mnemonic: Hypomagnasaeia causes: Aches, Cramps, Dizziness and PalPItations Aminoglycosides (gentamicin) Cisplatin Diuretics - furosemide, bumetainde PPIs - omeprazole, lansoprazole By decreasing intestinal absorption of magnesium

Question 56

Impaired Glucose Tolerance

Answer 56

Mnemonic: DiaBetic Nick’s Sugar InTolerance Drugs which cause impaired glucose tolerance include: Diuretics – furosemide, thiazides Beta Blockers Nicotinic acid Steroids – prednisolone, dexamethasone IFN-alpha Tacrolimus/ciclosporin

Question 57

Beta blockers

Answer 57

Side effects if beta-blockers include: OH BETA! Orthostatic Hypotension Bronchospasm/wheeze Erectile dysfunction Trouble sleeping & bad dreams AV block, arrhythmias

Question 58

Urinary retention

Answer 58

Drugs which increase the risk of urinary retention include: Tricyclic antidepressants - Amitriptyline etc. Disopyramide Anticholinergics – atropine NSAIDs Opiates Mnemonic: Terminate DAN’s (urine) Output

Question 59

Pulmonary Fibrosis

Answer 59

Drugs which can lead to pulmonary fibrosis include: Nitrofurantoin Ergot-derived dopamine R agonists (bromocriptine, cabergoline, pergolide) Sulfasalazine Cytotoxics (especially Bleomycin) Amiodarone Rheumatoid drugs – methotrexate Mnemonic: Remember to ask patients taking the above drugs if their lungs have NE SCARs (any scars..)

Question 60

Photosensitivity

Answer 60

Certain drugs can cause increased risk of dermatitis or sunburn. These include: Sulfonamides - sulfamethoxazole, sulfasalazine, co-trimoxazole etc. Thiazides and diuretics - hydrochlorothiazide, furosemide Tetracyclines (e.g. doxycycline, lymecycline) and quinolones (ciprofloxacin) Amiodarone NSAIDs - naproxen, piroxicam Mnemonic: STan’s TAN

Question 61

Thrombocytopaenia

Answer 61

Causes of drug-induced thrombocytopenia include: Quinine Quinidine Co-trimoxazole Vancomycin

Question 62

Drug-induced urticaria

Answer 62

Urticaria - very itchy weals (hives), with or without surrounding erythematous flares Weal - a superficial, skin-coloured skin swelling, typically surrounded by erythema May be associated with angioedema Causes of drug-induced urticaria: ACE inhibitors - ramipril, lisinopril, captopril - commonest cause Aspirin, NSAIDs may also

Question 63

Amiodarone An anti-arrhythmic medication with a complex multimodal mechanism of action

Answer 63

Amiodarone An anti-arrhythmic medication with a complex multimodal mechanism of action. Mnemonic: Amiodarone is a BITCH of a medication.. Blue slate-like skin 'blue-man syndrome' Interstitial lung disease Thyroid - hypo/hyperthyroidism Corneal microdeposits (reversible on stopping treatment). Drivers may present troublesome glare/being dazzled by headlights at night. Hepatotoxicity

Question 64

Quinolones

Answer 64

E.g. Ciprofloxacin Important side effect: While rare, tendon damage, such as tendon tear/rupture has been reported with quinolone use. Elderly patients are at particularly increased risk. Quinolones may also lower seizure threshold, so should be avoided in those with history of seizures/epilepsy.

Question 65

Cyproterone acetate

Answer 65

A synthetic antiandrogen that used in the treatment of prostate cancer - blocks the androgen receptor (AR) and reduces serum testosterone levels. Complications: Hepatotoxicity and liver failure - hence rarely used today. Monitor LFTs

Question 66

Mefloquine

Answer 66

Mefloquine is an anti-malarial commenced 2-3 weeks prior to departure. Adverse effects: neuropsychiatric symptoms - abnormal behaviour, hallucinations. Contraindicated in patients with a history of psychiatric disorders (including depression) and seizures.

Question 68

Clinical features Mixed respiratory alkalosis (early respiratory centre stimulation) and metabolic acidosis Hyperventilation Tinnitus Hyper or hypoglycaemia N&V

Answer 68

Salicylate poisoning Management Charcoal Urinary alkalinisation with IV bicarbonate (increases excretion) Haemodialysis if: Salicylate concentration > 700 mg/L Seizures Coma Acute respiratory failure Pulmonary oedema Refractory metabolic acidosis

Question 69

CNS depression - drowsiness Impaired balance/ ataxia Slurring of speech Respiratory depression Coma

Answer 69

Benzodiazepine overdose Clinical Features Management Conservative management for most cases Flumazenil can be used in severe cases, or in iatrogenic overdose

Question 70

Early signs/symptoms: anticholinergic in nature – dilated pupils, dry mouth, blurred vision Later: Arrhythmias, metabolic acidosis, seizures, coma ECG changes: Sinus tachycardia Wide QRS (QRS> 100ms – assoc. with seizures; QRS > 160 = increased risk of ventricular arrhythmias). Prolonged QTc

Answer 70

Tricyclic antidepressant overdose Dosulepin and amitriptyline are the most dangerous TCAs in overdose Clinical features Management Intravenous bicarbonate is the mainstay Dialysis is NOT effective in TCA OD

Question 71

Lithium overdose Clinical features Tremor (a fine tremor is a common SE, but a more coarse tremor is suggestive of toxicity/OD) Ataxia Hyperreflexia Nystagmus AKI

Answer 71

Management Mild-moderate - IV 0.9% NaCl fluid resuscitation Haemodialysis if severe. Guidelines vary, but indications include: Serum Lithium > 5mmol Serum Lithium > 4mmol in presence of renal failure Clinical features: Decreased consciousness level, neurological features, seizures, cardiac dysrhythmias

Question 73

Quinine Toxicity - Cinchonism Clinical features Tinnitus Flushing Nausea, vomiting ECG changes Widened QRS Prolonged QTc

Answer 73

Complications Arrhythmias Hypoglycaemia – quinine stimulates pancreatic insulin secretion Flash pulmonary oedema

Question 74

Heparin overdose Management

Answer 74

Protamine sulphate

Question 75

Beta-blocker overdose

Answer 75

Clinical features Bradycardia Hypotension Syncope Hypoglycaemia, hypothermia Management Glucagon

Question 76

Clinical Features There are 3 main features of toxicity in ethylene glycol poisoning: 1. Alcohol-like features – drunk/ confused/ slurred speech/ ataxia 2. High anion gap metabolic acidosis 3. Acute renal failure

Answer 76

Ethylene glycol poisoning (coolant/antifreeze) Ethylene glycol is an industrial compound found in products such as antifreeze. Management 1st line: Fomepizole – inhibits alcohol dehydrogenase

Question 77

Methanol poisoning Clinical features Intoxication Blindness (optic neuritis)

Answer 77

Management Fomepizole and Folinic acid (reduces blindness)

Question 78

Organophosphate insecticide poisoning Mechanism of toxicity Organophosphatase insecticides inhibit acetylcholinesterase, which increases the neurotransmission of acetylcholine

Answer 78

Clinical features - SLUDS Salivation Lacrimation Urination Diarrhoea Small pupils Management Atropine

Question 79

Iron Poisoning

Answer 79

Management Desferrioxamine - iron chelation

Question 80

Investigations Pulse oximetry: may show falsely high SaO2 ABG – carboxyhaemoglobin levels: Normal person < 3% Smoker < 10% Management 100% O2 via a non-rebreathe for 6 hours In severe cases, hyperbaric O2 can be used

Answer 80

Carbon monoxide poisoning Clinical features MCQs may reference a badly maintained house – e.g. a student house Headache N&V Pink skin - often “cherry red” / deeply flushed