2019/2020 REVISION TOOL: Short Guides For Key Therapeutic Areas

2019/2020 REVISION TOOL
Short Guides for Key Therapeutic Areas
Acknowledgment for Victoria Bowles (Rotational Pharmacist, Cambridge University Hospitals) for writing the content
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CONTENTS
Cardiovascular System 2 Corticosteroids 35

Cardiovascular Disease 2 Osteoporosis: Bisphosphonates 36
Cardiovascular Disease Treatment 3 Thyroid Disorder 37
Nervous System 5 Diabetes Insipidus 38
Epilepsy 5 Infection 39
Depression 9 Antibiotics 39
Lithium 12 Tuberculosis 43
Antipsychotics 14 Antifungals 44
o Antipsychotics - Side Effects 15 Genito-Urinary Tract System 45
Clozapine 16 Genitourinary Medicine 45
Dementia 17 Contraception 46
Parkinson’s Disease 18 Gastro-Intestinal System 48
Benzodiazepines 20 Constipation 48
Nausea and Vomiting 21 Diarrhoea 50
Pain 22 Inflammatory Bowel Disease 51
o Opioids 22 Crohn’s Disease 54
o Neuropathic Pain & Lower Back Pain 24 Ulcerative Colitis 56
Respiratory 25 H. Pylori 58
Asthma 25 Immune System and Malignant Disease 59
COPD 28 Cytotoxic Drugs 59
Endocrine System 30 Immunotherapy 63
Diabetes Overview 30 Oncological Emergencies 64
o Diabetes Treatment 32 Breast Cancer 65
o Antidiabetic Agents 33 Lung Cancer 66
Prostate Cancer 67
Please note: This revision guide is intended for use only as an aide memoire. Please use with caution as the content may not go into the depth of learning required for the GPhC assessment
copyright of UEA (2020)
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CARDIOVASCULAR SYSTEM – CARDIOVASCULAR DISEASE
HYPERTENSION HEART FAILURE

ATRIAL FIBRILLATION
First-line treatment: (most common type of arrhythmia)
<55yrs – ACEI or ARB First-line treatment:
>55yrs – CCB ACE I/ARB + BB
Rate control:
Afro-Caribbean – CCB BB – ‘start low go slow’
First-line: BB
DM – ACE I or ARB MRA -
Second-line: rate-limiting CCB
Spironolactone/eplerenone
Note: digoxin only effective for controlling ventricular
Targets: rate at rest (use as monotherapy in sedentary patients Loop diuretic – “acute
<80 yrs 140/90 only) phase” or symptom
>80 yrs 150/90 control with fluid overload
In Type 1 diabetes aim Rhythm control (pharmacological)
for<135/85 (or <130/80 if First-line: BB Add on options:
other risk factors). Type 2 Second-line: dronedarone/amiodarone/other Ivabradine
diabetes same as non- antiarrhythmic agent Hydralazine + nitrate
diabetic Rhythm control (electrical cardioversion) Digoxin
Preferred if AF >48hrs Sacubitril + valsartan
Pregnancy:
Anticoagulate for 3 weeks before and at least 4 weeks
Labetolol, methyldopa and after Symptoms
MR nifedipine considered safe Fatigue, dyspnoea, orthopnoea,
pink frothy sputum, nocturnal
Stoke risk- assessment tools
cough, weight loss…
CHA2DS2VASc of 1+ in males and 2+ in females
requires anticoagulation
STABLE ANGINA HAS-BLED of 3+ bleeding risk too high (often
modifiable factors)
PRIMARY / SECONDARY
Acute attacks: PREVENTION
S/L GTN spray
For primary prevention offer
Long-term management: STROKE atorvastatin 20mg to people who have
First-line: BB or CCB a 10% or greater 10-year risk of
Second-line: BB+CCB or long- Thrombolysis – alteplase within 4.5hrs of symptom onset developing CVD (QRISK3)
acting nitrate, ivabradine,
ranolazine or nicorandil (nicorandil Aspirin 300mg for 2 weeks (initiated 24hrs after thrombolysis) For secondary prevention offer
last resort due to risk of ulceration) atorvastatin 80mg to people with CVD
Nicorandil – can cause ulceration Long-term treatment with clopidogrel (or anticoagulant if AF) and aim for a 40% reduction in LDL-C
TIA-> same regardless of baseline.
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CARDIOVASCULAR SYSTEM – CARDIOVASCULAR DISEASE TREATMENT
ACS PROTOCOL ANTICOAGULANTS

Initial management of STEMI/NSTEMI Warfarin
Oxygen if hypoxic Takes approx. 5 days to become therapeutic (unless loading dose
Nitrates – to relieve ischaemic pain used)
Opioids – for ischaemic pain AF – slow loading with no bridging appropriate
Antiemetic – to prevent opioid-induced N&V DVT/PE – bridging required with LMWH/UFH
Aspirin Target INR usually 2.5
Clopidogrel (ticagrelor + prasugrel = alternatives) Target of 3.5 for recurrent VTE whilst on anticoagulation and mitral
valve replacement
Long-term management
Aspirin (+ clopidogrel/ticagrelor/prasugrel for 12 Food interactions: maintain constant levels of dietary vitamin K and
months) (ticagrelor 60mg bd after 12 months for avoid cranberry juice
further 3 years in high risk patients) DOACs
Beta blocker Not licensed post valve replacement
ACE inhibitor Caution in renal impairment
Nitrates – if angina present (all patients prn GTN) Bridging not required as fast onset of action
Spironolactone/Eplerenone – if HF present
LMWHs/UFH
Atorvastatin 80mg
S/E: haemorrhage, HIT (more common with UFH) and hyperkalaemia
UFH – administered as a continuous infusion requiring APTT
monitoring
Pregnancy – LMWHs preferred as do not cross placenta and have less
AMIODARONE risk of HIT
Loading – 200mg TDS 1 week; 200mg BD 1 week; 200mg OD
thereafter (alternative unlicensed fast loading 400mg tds 3 days
then 200mg od thereafter)
DIGOXIN
Adverse effects: pulmonary toxicity, thyroid dysfunction,
hepatotoxicity, peripheral neuropathy, corneal microdeposits, Take levels at least 6 hours post-dose (or pre-dose) once reach steady state reached (7-
phototoxicity 14 days)
Monitoring: TFTs, LFTs, CXR, serum K+
Signs of toxicity – nausea, blurred /yellow vision, bradycardia
Long half-life therefore potential for drug interactions for months Increased risk of toxicity – hypercalcaemia, hypokalaemia, hypoxia hypomagnesaemia, renal
after cessation impairment. Interaction with amiodarone => reduce digoxin dose by 50%
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CARDIOVASCULAR SYSTEM – CARDIOVASCULAR DISEASE TREATMENT
BETA BLOCKERS DIURETICS
Heart Failure Loop diuretics

‘Start low go slow’ Potent diuretics, act within 1 hour and complete diuresis within 6
Bisoprolol, carvedilol and nebivolol licensed in HF hours. First line for CCF.
IV furosemide maximum 4mg/min due to risk of ototoxicity
Contraindications
2nd and 3rd-degree AV block
Thiazide diuretics
Caution Produce a weaker diuresis within 1-2hrs and diuresis is complete
COPD/asthma (cardioselctive BB frequently used with within 12-24hrs
caution) Ineffective if CrCL <30ml/min
Chlortalidone and indapamide (thiazide-like) used in hypertension
Side effects Metolazone produces a profound diuresis (atypical thiazide – only
Bradycardia, bronchospasm, cold extremities, fatigue, used in CCF in combination with LOOP diuretic
hyperglycaemia
May mask symptoms of hypoglycaemia Both loop and thiazide diuretics can cause hyperglycaemia (LOOPs less),
Nightmares (more common in lipid soluble e.g. exacerbation of gout and potassium loss
propranolol)
Potassium-sparing diuretics First line for CCF. Step 4 for HT.
Other uses: Contraindicated in Addison’s disease, anuria and hyperkalaemia
Anxiety, thyrotoxicosis, migraine prophylaxis, glaucoma
NITRATES
STATINS
1o prevention: Atorvastatin 20mg 2o prevention: Atorvastatin 80mg S/E – flushing, throbbing headache, dizziness, postural hypotension
High intensity statin – ‘the dose at which a reduction in LDL-C of
>40% is achieved Tolerance – remove patch for 8-12hrs per day, take BD plain tablets morning and
Atorvastatin 20-80mg; rosuvastatin 10-40mg; early afternoon and take MR formulations 8 hours apart (instead of 12-hourly) or
simvastatin 80mg preferably once daily to ensure “nitrate-free period”
S/E: g.i.; myopathy & rhabdomyolysis; hepatic disorders (only stop
if>3xULN); GTN tablets – supply in glass containers, closed with foil-lined cap containing no
cotton wool and discard after 8 weeks (N.B. spray more commonly used)
Simvastatin + pravastatin require doses at night
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NERVOUS SYSTEM - EPILEPSY
Overview of management Considerations Driving
When monotherapy with a 1st-line AED If a driver has a seizure of any type, they
has failed, monotherapy with another 1st Antiepileptic hypersensitivity syndrome must inform the DVLA and stop driving
or 2nd-line drug should be tried immediately
Rare and potentially fatal
Symptoms occur 1-8 weeks after exposure
When changing from one drug to 1st unprovoked seizure – must not drive
(fever, rash, lymphadenopathy, liver
another, slow cross tapering should for 6 months and until they have been
dysfunction, haematological, renal and
occur – slowly withdraw the first drug assessed by a specialist as fit to drive
pulmonary abnormalities)
once the new regimen has been
established Drug should be withdrawn immediately
Established epilepsy – must be seizure
Associated with carbamazepine, lamotrigine,
free for at least 1 year (or 6 months if
A single AED should be used whenever phenobarbital, phenytoin and others
seizure due to change in AED) (or
possible established pattern of seizures that do not
influence their level of consciousness).
Suicidal thoughts and behaviour
DVLA advises not to drive during
MHRA warning – all AEDs associated with risk medication changes or during AED
Can occur as early as 1 week after starting withdrawal periods
Advise patients to seek medical advice
Brand-specific prescribing
3 risk-based categories: Interactions

+++ (particularly with older generation
1 – Should always be prescribed by
AEDs) Breastfeeding
brand (phenytoin, carbamazepine,
phenobarbital, primidone) Carbamazepine and phenytoin = enzyme
inducers Monotherapy – should generally be
Sodium valproate = enzyme inhibitor encouraged to BF
2 – Need for brand-specific prescribing
Combination therapy – specialist advice
should be based on clinical judgement
(sodium valproate, lamotrigine,
Withdrawal Monitor infants for sedation, feeding
clobazam, topiramate, clonazepam)
difficulties, adequate weight gain
Avoid abrupt withdrawal
3 – Not usually necessary to prescribe Should be a gradual reduction in dose
Phenobarbital & lamotrigine may
by brand (levetiracetam, lacosamide, (months)
accumulate in infant therefore monitor
gabapentin, pregabalin) If on multiple AEDs, withdraw one at a time closely for s/e
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Pregnancy Hormonal Contraceptive Advice

Sodium Valproate and Pregnancy
MHRA – Valproate Use by Women and Girls
Increased risk of teratogenicity associated Enzyme inducing AEDs, that reduce
with the use of AEDs, particularly in the the effect of the combined oral
first trimester or if the patient takes 2 or contraceptive pill:
Associated with significant risk of birth defects and
more agents developmental disorders (4 in 10 risk of developmental Primidone (metabolised to
disorders and 1 in 10 risk of birth defects) phenobarbital)
The highest risk is with sodium valproate Phenobarbital
(see right) Valproate must no longer be used in any women or girl Phenytoin
able to have children unless she has a pregnancy Carbamazepine
There is also an increased risk of prevention programme in place (HCPs must ensure
phenytoin, primidone, phenobarbital, Breakthrough bleeding, spotting and
patients are enrolled on this – signed risk unplanned pregnancy can occur.
lamotrigine and carbamazepine acknowledgement form should be completed at least
annually with a review by a specialist) Advice: require at least 50mcg
Topiramate = increased risk of cleft
palate ethinylestradiol per day (2 x 30mcg
Valproate use is banned for migraine and bipolar during tablets or 1 x 20mcg and 1 x 30mcg
pregnancy and for treating epilepsy during pregnancy tablet)
General advice -Effective contraception to unless there is no alternative treatment option.
avoid unplanned pregnancy The use of a hormonal patch or
vaginal ring are not recommended as
Smaller pack sizes to be introduced to encourage monthly 2 patches / 2 rings are not
-If planning pregnancy, need referral to prescribing
specialist appropriate.
See: Stockley’s Drug Interactions for
A pictogram/warning imagine to be added to packaging more information
-Unplanned pregnancy: usually too late to
make changes to medication; do not stop EHC – A copper-bearing intrauterine
A patient card, patient booklet, booklet for HCPs and a device is the preferred option.
AEDs unless advised by specialist; folate valproate annual risk acknowledgement form is available
supplementation (5mg) advised during 1st However, if the woman insists on
here: https://www.gov.uk/guidance/valproate-use-by- hormonal contraception, or cannot
trimester (to reduce risk of neural tube women-and-girls
defects) be fitted with an IUD: Prescribe
double dose levonorgestrel 3 mg (that
-Routine injection of vitamin K at birth is two tablets of levonorgestrel 1500
minimises risk of neonatal haemorrhage micrograms) to be taken as a single
in women taking enzymeinducing AEDs dose as soon as possible and within
72 hours of unprotected sexual
intercourse. Ulipristal acetate is not
recommended
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SODIUM VALPROATE PHENYTOIN
Indications – all forms of epilepsy; migraine prophylaxis; BPAD Indications – tonic clonic seizures, focal seizures (which are not controlled by
(generally valproic acid used due to licensing) other 1st line AEDs), prevention/treatment of seizures following head
injury/neurosurgery – now rarely used.
Brands – Epival, Episenta, Epilim Status epilepticus (adults) – loading dose of 20mg/kg (IV) then 100mg (IV/PO)
every 6-8hrs
Safety Information – as per MHRA guidance above Conversions – phenytoin sodium is not equivalent to phenytoin base
(100mg phenytoin sodium = 92mg phenytoin base)
CIs – acute porphyria’s; personal/family hx of severe hepatic
dysfunction, mitochondrial disorders Safety information – ‘risk of death and severe harm with injectable phenytoin’
Patient Safety Alert due to risk of error
Caution – consider Vitamin D supplementation in patients who
are immobilised for long periods/have inadequate sun exposure/ Cautions – enteral feeding: interrupt feed for 2 hours before and after dose.
reduced dietary intake of calcium due to reduced BMD s/e. SLE With IV use: hypotension, respiratory depression, HF (resuscitation facilities must
Liver toxicity has occurred, especially in patients <3yrs. be available); formulation is irritant therefore given via central line using a filter.
Discontinue treatment if abnormally prolonged prothrombin time. Vitamin D supplementation as with sodium valproate. Highly protein bound:
Raised liver enzymes are usually transient. therefore caution in patients with low albumin
Monitoring – LFTs, FBC S/E – acne, hirsutism, coarsening of facial appearance, gingival hypertrophy and
tenderness (maintain good oral hygiene)
S/E – transient hair loss, weight gain, nystagmus, blood disorders Overdose signs: nystagmus; diplopia; slurred speech; confusion;
(thrombocytopenia) and bone marrow suppression, hepatic hyperglycaemia; ataxia
dysfunction, pancreatitis, tremor
Monitoring – pre-treatment screening in Han Chinese and Thai patients
Counselling – as per MHRA warning for females; to withdraw (HLAB*1502 allele increases risk of SJS); HR and BP during IV administration;
treatment and seek medical attention if signs of blood disorders, LFTs, FBC; TDM: 10-20mg/L = target In pregnancy, the elderly, and certain
hepatic dysfunction or pancreatitis develop e.g. abdominal pain, disease states where protein binding may be reduced, careful interpretation of
jaundice total plasma-phenytoin concentration is necessary
Counselling – how to recognise blood disorders and skin disorders and to seek
Interactions – carbapenems decrease the concentration of immediate medical attention; maintain good oral hygiene; signs of toxicity and to
sodium valproate (increasing the dose does not counteract this seek immediate medical attention
interaction), lamotrigine, phenytoin, topiramate and primidone. Interactions – enzyme inducer, number of interactions
Pharmacokinetics – zero order – small increase in dose can result in large
PO vs IV – when switching between oral and IV therapy, no increase in plasma drug concentration
conversion required (dosage is the same)
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LAMOTRIGINE
CARBAMAZEPINE
Indications – for many seizure types
Indications – many seizure types; trigeminal neuralgia; prophylaxis of
BPAD unresponsive to lithium (unlicensed, not recommended by NICE); Titration – dose must be increased very slowly (e.g. every 1-2 weeks)
adjunct in acute alcohol withdrawal (unlicensed); diabetic neuropathy due to risk of skin reactions (slower when used as adjunctive treatment)
If a patient misses lamotrigine for 5 half-lives (dependent on
Formulations – MR tablet, tablet suppository (dose equivalents are concomitant AEDs), dose titration needs to be repeated.
noted in BNF), oral suspension (note – no injectable formulation)
Cautions – may exacerbate Parkinson’s Disease; may exacerbate
Contra indications - Acute porphyria’s ; AV conduction abnormalities myoclonic seizures.
(unless paced); history of bone-marrow depression
Skin reactions – serious skin reactions, including SJS, have occurred
Cautions – cardiac disease, skin reactions, vitamin D supplementation especially in children and usually occur in the first 8 weeks. The risk is
as per valproate/ phenytoin. Blood, hepatic and skin disorders – increased with concomitant use of valproate and following rapid dose
withdraw immediately. Can aggravate absence or myoclonic seizures. escalation.
S/E – Dose related s/e: headache, ataxia, drowsiness, N&V, blurred Counselling – how to recognise signs and symptoms of blood and skin
vision, dizziness, unsteadiness, allergic skin reactions (can offer MR disorders and to seek immediate medical attention
preparations, as per NICE recommendation). Serious s/e: blood Interactions – increased levels with valproate; reduced levels with
disorders, SJS, hepatic impairment, cardiac conduction disorders carbamazepine; reduces efficacy of COC
Monitoring – TDM 4-12mg/L measured after 1-2 weeks. This is to
measure for optimum response but is not usually used unless compliance
is an issue. Blood counts; hepatic function; renal function; Pre-treatment
screening for Han Chinese and Thai patients (HLA-B*1502 allele LEVETIRACETAM
increases risk of SJS). U&Es – can rarely cause hyponatremia due to
SIADH. Indications – many types of seizures
Interactions – a potent enzyme inducer (reduces effect of combined PO vs IV – when switching between oral and IV therapy, no conversion is
contraceptive and warfarin); concurrent use of MAOIs is contraindicated; required (dosage is the same)
macrolides may increase carbamazepine concentration (increased risk of
toxicity) S/E- can cause anxiety and irritability; rarely causes blood disorders and
Pharmacokinetics – exhibits autoinduction – needs to start with low skin disorders, depression (more acceptable ADR profile compared to
dose and titrate slowly over 4 weeks other AEDs)
No monitoring required! No important interactions!
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NERVOUS SYSTEM - DEPRESSION
Overview Switching Antidepressants

Monitoring Therapy
Antidepressant drugs are useful for Evidence for switching between or
moderate to severe depression and within classes is weak.
If side effects develop:
dysthymia (low grade, chronic
depression). Initially switch to a different SSRI or
Can stop the antidepressant a better tolerated newer-generation
They should not be used for mild Can switch to a different antidepressant antidepressant
depression (psychological therapy first Can consider short-term treatment with a
line; could be tried if psychological benzodiazepine if anxiety, agitation and/or insomnia Subsequently, switch to an
therapy ineffective) are problematic (can occur in first couple of weeks) antidepressant of a different class
however this should be limited to 2 weeks to prevent that may be less well tolerated (e.g.
First-line is usually an SSRI dependence venlafaxine, TCA, MAOI)
Antidepressants work gradually not
immediately therefore patients must be No improvement in symptoms: Switching can usually be achieved in
counselled on taking the medication 1 week for drugs with shorter half-
continuously for 3-4 weeks If response is absent/minimal after 3-4 weeks: lives, however consider the following:
Consider increasing the dose
Antidepressants may be associated Switching to another antidepressant Fluoxetine to other drugs – caution
with discontinuation symptoms due to long half-life of fluoxetine
If there is some improvement at 4 weeks:
Augmentation is the term used when a Continue treatment for another 2-4 weeks Fluoxetine/paroxetine to TCAs –
non-antidepressant drug is used in Consider above if response still inadequate caution as both of these inhibit the
combination with an antidepressant to metabolism of TCAs (start with a
enhance its effects. Examples include Monitoring for increased risk of suicide: lower dose of TCA)
lithium, aripiprazole, olanzapine,
quetiapine, risperidone (specialist use There is an increased risk of suicide when treatment with an Switching to an MAOI – caution
only) antidepressant is started, particularly for patients <30yrs. because of the risk of serotonin
syndrome
Patients should continue treatment For patients at high risk, see within 1 week of starting therapy
with antidepressants for at least 6 Non-reversible MAOI to another
months after remission to prevent For patients at lower risk, see within 2 weeks of starting antidepressant – a 2 week wash
relapse (for at least 2 years if they are therapy out period is required
at high risk of relapse or have a history
of recurrent depression)
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Serotonin Syndrome SSRIs
An uncommon ADR caused by too much central and peripheral Recommended first-line for depression in adults due to being as effective
serotonin. as other agents with less side effects.
Symptoms can occur within hours to days following the initiation, dose Common s/e include – GI symptoms (more common at the start of
increase or overdose of a serotonergic drug, switching between treatment); anxiety (more common at start of treatment); insomnia and
serotonergic drugs or the addition of a new serotonergic drug. sexual side effects. SSRIs also increase the risk of GI bleeding.
3 categories of symptoms: All antidepressants can cause hyponatraemia however, this is most
common with the SSRIs.
1 – Neuromuscular hyperactivity
Tremor Drug specific points:
Hyperreflexia
Clonus and myoclonus Citalopram – risk of QTc prolongation; has fewer drug interactions
Rigidity compared to other SSRIs
2 – Autonomic dysfunction Escitalopram – S enantiomer of citalopram therefore also causes QTc

Tachycardia prolongation and has fewer drug interactions
BP changes
Fluoxetine – more drug interactions compared to other SSRIs, long half-
Hyperthermia
life; only antidepressant licensed for children
Shivering
Diarrhoea Paroxetine – more drug interactions compared to other SSRIs; short
half-life therefore risk of withdrawal symptoms upon stopping (withdraw
3 – Altered mental state slowly)
Agitation
Confusion Sertraline – few drug interactions; antidepressant of choice for patients
Mania who have a history of MI / unstable angina
Treatment – withdrawal of the drug; supportive care Interactions to bear in mind – NSAIDs, anticoagulants, antiplatelets,
triptans
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TCAs MAOIs
MOA – block the reuptake of 5HT and NA to different extents depending Used much less frequently than TCAs, SSRIs and SNRIs due to the
on the drug dangers of dietary and drug interactions.
Sedating TCAs vs Non-sedating TCAs
Sedative: better for agitated and anxious patients (e.g. Irreversible (e.g. phenelzine) vs reversible (e.g. moclobemide MAO A
clomipramine) selective). Irreversible should be reserved for specialist use only.
Non-sedative: better for withdrawn and apathetic patients (e.g.
lofepramine) Food interactions - MAOIs can potentiate the pressor effect of tyramine,
S/E – antimuscarinic (dry mouth, blurred vision, constipation, urinary causing a hypertensive crisis (first sign is a throbbing headache) therefore
retention) and cardiotoxic in overdose counsel patients on the need to avoid foods high in tyramine (mature
Lofepramine: lower incidence of s/e, less dangerous in overdose cheese, game, Bovril, Oxo, Marmite) and to avoid alcohol and foods
but can be hepatotoxic suspected of ‘going off’.
Imipramine – more marked antimuscarinic s/e
Amitriptyline + dosulepin: particularly dangerous in overdose, Drug interactions – Lots! e.g. inhibit the metabolism of indirect-acting
not recommended in depression sympathomimetic contained in many cough and cold medicines (e.g.
Dosulepin should not be prescribed pseudoephedrine) hypertensive crisis
TCAs are not recommended first line due to potential harm in overdose
Danger of interactions persists for up to 2 weeks after an MAOI is
withdrawn therefore a 2 week wash out period is required when switching
from a non-reversible MAOI to another antidepressant.
SNRIs
S/E – similar to SSRIs, particularly GI related. Can also cause sweating, Mirtazapine
headaches, BP changes and palpitations.
MOA – a presynaptic alpha2-antagonist; increases central NA and 5HT
Venlafaxine – marginally more effective than SSRIs; BP monitoring transmission
required; short half-life therefore slow withdrawal required. Higher doses
may exacerbate cardiac arrhythmias. S/E – sedation (useful for patients with insomnia); oedema; increased
appetite (useful for patients with reduced appetite) and weight gain. Can also
Duloxetine – licensed for depression, diabetic neuropathy and moderate- cause blood disorders (rare)
severe stress urinary incontinence in women. Lower doses used for
depression. Counselling – counsel patients on how to recognise signs of blood
disorders
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NERVOUS SYSTEM - LITHIUM
Indications Monitoring
Acute management of mania and hypomania RFTs (95% renally excreted) and U&Es (Na+ affects lithium
clearance and electrolyte disturbances will predispose to QT
Prophylaxis against bipolar affective disorder (BPAD) prolongation/arrhythmias) (3/12ly)
Control of aggressive behaviour or intentional self-harm TFTs (can affect thyroid function) (6/12ly)
Treatment and prophylaxis of recurrent depression Body weight/BMI (can cause weight gain) (12/12ly)
Brands FBC (12/12ly)
Brand specific prescribing e.g. Priadel*, Camcolit, Liskonum Cardiac function (can cause arrhythmias) (12/12ly)
Different salt forms have different bioavailability’s (carbonate vs Calcium (can cause hypercalcaemia) (12/12ly)
citrate)
*Discontinuation planned for April 2021 TDM (3/12ly)
Take a level 12 hours post dose (therefore dosing at night for

Side Effects level in the morning)
Below 0.4mmol/L is usually thought not to work for most people,
GI disturbances (particularly at initiation) although some people still seem to do well on very low doses
0.4-0.6mmol/L – may have lower side effects but is probably
Metallic taste in mouth slightly less effective than the higher levels
0.6-0.8mmol/L – the usual effective range, although side effects
Weight gain will increase with increased levels
0.8-1.2mmol/L – usually only needed for people for whom mania
Ankle oedema or hypomania is more of a problem
1.2 and above – generally thought to be the toxic or dangerous
Polyuria and polydipsia (due to inhibition of ADH) levels. These are higher levels than needed in most people, with
more risk of worse side effects.
Neurotoxicity (can occur at therapeutic levels [paraesthesia, Take a level weekly at initiation and after each dose change until
ataxia, tremor, cognitive impairment) stable
Take a level every 3 months once stable for the first year
13
NERVOUS SYSTEM - LITHIUM
Lithium Toxicity
Usually due to dehydration, reduced renal function, infection, treatment with interacting medicines (e.g. diuretics and NSAIDs)
Early Signs Following signs Severe signs
Non-specific Vomiting Convulsions

Restlessness Diarrhoea Coma
Apathy Ataxia Renal failure
Confusion Weakness Electrolyte imbalance
Drowsiness Dysarthria Hypotension
Muscle twitching Cardiac arrhythmias
Tremor
Visual disturbances
Polyuria, incontinence
Interactions Patient Counselling
Rise in lithium levels Importance of adherence and monitoring

ACEIs and ARBs
Diuretics Avoid dehydration and big changes to the level of salt in your diet
NSAIDs
Importance of effective contraception (inform doctor immediately if unplanned
Drugs that prolong the QT-interval pregnancy / planning pregnancy)
Phenothiazines
Citalopram Inform pharmacist before buying OTC products (e.g. ibuprofen / aspirin)
Clarithromycin
Antiarrhythmics Seek medical advice if you experience diarrhoea and vomiting ( dehydration
increased risk of lithium toxicity)
Sodium (e.g. antacids)
Increased Na+ intake decreases lithium levels How to recognise signs of toxicity, hypothyroidism, renal dysfunction and benign
Decreased Na+ intake increases lithium levels intracranial hypertension
See Stockley’s Drug Interactions for explanation
14
NERVOUS SYSTEM - ANTIPSYCHOTICS
Antipsychotic Drugs (APDs) Extrapyramidal S/E (EPS)

First Generation APDs
1st generation VS 2nd generation Most common with group 3
Phenothiazine derivatives
phenothiazines, the butyrophenones
1st generation – predominantly block and the first-generation depots.
D2 receptors in the brain and are not 1 – Chlorpromazine, levomepromazine, promazine
selective for any of the 4 dopamine Pronounced sedative effects Parkinsonian symptoms
pathways, therefore cause a range of Moderate antimuscarinic and EPS Includes tremor, which may appear
side effects gradually. Can be treated with
2 – Pericyazine antimuscarinic drugs e.g. procyclidine
2nd generation – act on a range of Moderate sedative effects
different receptors. Are less likely to Fewer EPS than groups 1 and 3 Dystonia
caused extrapyramidal side effects Abnormal face and body movements.
3 – Fluphenazine, perphenazine, prochlorperazine, Occur more commonly in children and
trifluoperazine young adults and can appear after a
Fewer sedative and antimuscarinic effects few doses
More pronounced EPS than groups 1 and 2
Second Generation APDs Akathisia
Butyrophenones Restlessness, which occurs after large
Risperidone initial doses.
Benperidol and haloperidol
Olanzapine Same clinical properties as group 3 phenothiazines Tardive dyskinesia
Rhythmic, involuntary movements of
Quetiapine Thioxanthenes the tongue, face and jaw. Usually
develops on long-term therapy or with
Clozapine high doses. This is the most serious
Flupentixol and zuclopenthixol
Moderate sedative, antimuscarinic and EPS manifestation of EPS and may be
Aripiprazole irreversible on drug withdrawal.
Diphenylbutylpiperidines
Paliperidone
Pimozide – reduced sedative, antimuscarinic and EPS
Lurasidone
Substituted benzamides
These are generally better for treating
the negative symptoms of
schizophrenia compared to the 1st Sulpiride – reduced sedative, antimuscarinic and EPS
generation.
15
NERVOUS SYSTEM - ANTIPSYCHOTICS SIDE EFFECTS
Hyperprolactinaemia Sexual Dysfunction APD Monitoring
Occurs with all APDs to some One of the main causes of non-adherence FBC, U&Es, LFTs – start and then
extent apart from aripiprazole, Mechanisms causing sexual dysfunction: annually
which reduces prolactin due to its Decreased dopamine transmission and hyperprolactinaemia lead
partial dopamine-receptor to decreased libido Blood lipids and weight – start, 3
agonist effects. Antimuscarinic effects lead to disorders of arousal months and then yearly
Alpha1-adrenoceptor antagonist properties can lead to erection
Clinical symptoms of high and ejaculation problems Fasting blood glucose – start, 6
prolactin: months and then yearly
Sexual dysfunction
Reduced bone mineral ECG and BP – start and during dose
density Hyperglycaemia and Weight Gain titration
Menstrual disturbances
Breast enlargement Less likely with first generation APDs Prolactin – start, 6 months then where
Galactorrhoea Hyperglycaemia and sometimes DM can occur with APDs – clozapine, clinically indicated, annually for known
olanzapine, quetiapine and risperidone = most common prolactin elevating APDs
All APDs can cause weight gain but to different extents (clozapine and
olanzapine = most)
Other Uses of APDs

Cardiovascular S/E Hypotension and Interference with Temperature Regulation
Nausea and vomiting
Include: These are dose-related side effects, which can cause falls and
hypo/hyperthermia in the elderly. Chorea (abnormal involuntary
Tachycardia movement disorder)
Arrhythmias Postural hypotension may be associated with syncope.
Hypotension Motor tics
Intractable hiccup
QT-prolongation is a particular
concern with: Neuroleptic Malignant Syndrome Deviant antisocial sexual behaviour
Symptoms – hyperthermia, fluctuating levels of consciousness, muscle Psychomotor agitation

Haloperidol
rigidity, autonomic dysfunction, tachycardia, labile BP, sweating, urinary
Pimozide Severe agitation and restlessness in
incontinence, elevated creatine kinase levels.
Any IV preparation the elderly
Requires immediate withdrawal and admission to hospital
16
NERVOUS SYSTEM - CLOZAPINE
Overview Blood Tests Additional Points
2nd generation APD Clozapine can cause neutropenia and agranulocytosis and Missed Doses
therefore FBC monitoring is required
Used for treatment-resistant Also risk of eosinophilia If doses have been missed for >48hrs,
schizophrenia (only APD licensed for Incidence of neutropenia = 2% the dose will need to be re-titrated.
this and with proven efficacy), 30-60% Incidence of agranulocytosis = 0.8%
of patients will respond If >72hrs missed, FBC monitoring
FBC monitoring requirements: frequency may need to be altered
All patients treated with clozapine must Newly started: weekly for 18 weeks
be registered with an approved 18-52 weeks of treatment: fortnightly
clozapine monitoring service >52 weeks of treatment: monthly Smoking
Maximum quantity of clozapine that can be supplied: Dose adjustment needed in smoking
Weekly FBCs = 10 days cessation and increase/decrease in
Fortnightly FBCs = 21 days smoking habits (dose related effect).
Monthly FBCs = 42 days Levels not affected by nicotine
replacement therapy.
Clozapine drug history taking
Other Monitoring
Due to enzyme induction.
What brand?
As for other APDs above.
Clozapine blood level monitoring appropriate in some clinical Particular care needed during
The current frequency of FBC tests
situations (including smoking cessation and acute severe illness) transfers of care
and when the last one was
An ECG before treatment is vital due to risk of myocarditis and Other indications
The current dose
cardiomyopathy. Persistent tachycardia, particularly in the first 2
months should prompt observation for indicators of myocarditis and Clozapine is also indicated for
Patient’s adherence – have they
cardiomyopathy psychosis in Parkinson’s Disease
missed any doses? When did they last
take a dose?
Frequent monitoring of BP, pulse and temperature during initiation
Who supplies the clozapine? and slow dose titration required due to risk of BP changes,
tachycardia and pyrexia.
Have they brought a supply into
hospital with them? Patients should be monitored for constipation due to the risk of
potentially fatal intestinal obstruction, faecal impaction and
paralytic ileus
17
NERVOUS SYSTEM - DEMENTIA
Overview Memantine
Acetylcholinesterase Inhibitors (AChEI)
A number of conditions cause the A glutamate receptor antagonist
Donepezil, galantamine and rivastigmine
symptoms of dementia: Alzheimer’s
disease, vascular dementia, dementia Side effects:
Reversible inhibitors of acetylcholinesterase (increase the Balance disorders
with lewy bodies
concentration of acetylcholine) Constipation
Cognitive symptoms Hypertension
Recommended for the treatment of cognitive symptoms of mild
to moderate dementia to due Alzheimer’s Disease
Consider cholinergic burden and Can be used as monotherapy or in
review drugs that have anticholinergic combination with AChEIs in
effects. moderate/severe disease (Alzheimer’s
General side effects:
or Lewy body dementia).
Drugs used to treat the cognitive
symptoms of dementia are not GI – diarrhoea, GI discomfort, nausea
recommended for vascular dementia. Syncope
Treatment should be assessed on a Urinary incontinence
regular basis and only be continued Arrhythmias Treatment of aggression, violence
when it is considered to be having a and extreme agitation
worthwhile effect on symptoms.
For galantamine An antipsychotic drug or a
Non-cognitive symptoms benzodiazepine can be given (high
Serious skin reactions can occur, including SJS, so doses / combinations should be
e.g. delusions, anxiety, aggression treatment must be discontinued at the first appearance avoided)
and agitation of a rash
Pharmacological treatment should If IM administration is required, options
only be offered if the symptoms cause include:
severe distress or if there is immediate Rivastigmine Lorazepam
risk of harm to the patient or to others. Haloperidol
The MHRA reports a clear increased Available as a transdermal patch – less likely to cause Olanzapine
risk of stroke when antipsychotics are GI side effects
used in elderly patients with dementia Also indicated in dementia of Parkinson’s Disease IV should only be used in exceptional
therefore risk: benefit ratio must be circumstances.
assessed Avoid antipsychotics where possible in
lewy body or Parkinson’s dementia
due to risk of severe adverse effects.
18
NERVOUS SYSTEM - PARKINSON’S DISEASE
Overview
Drug Treatment
PD occurs due to the degeneration of
dopaminergic neurons, resulting in a Levodopa – gold standard treatment – most effective oral symptomatic treatment
deficiency of dopamine within the
basal ganglia. Cannot use dopamine replacement as dopamine does not cross the blood brain barrier however its precursor,
levodopa, does.
Classical symptoms of motor
symptoms: Levodopa is converted to dopamine via the enzyme dopamine decarboxylase, which would not be ideal in the
Bradykinesia periphery due to side effects (e.g. nausea, tachycardia, postural hypotension) therefore a dopamine
Rigidity decarboxylase inhibitor is combined with levodopa (carbidopa / benserazide)
Tremor – approx. 70% of
patients has a resting tremor Carbidopa and benserazide do not cross the blood brain barrier therefore they prevent the conversion to
Postural instability dopamine in the periphery but not within the brain – allows lower dose of levodopa to be administered.
Non-motor symptoms Levodopa usually improves symptoms for 6-18 months and then after approx. 2yrs, a slow decline occurs
Sleep disturbances Dyskinesias – develop in 30-40% of patients after 4–6 years of treatment.
Hallucinations
Dementia Motor fluctuations – occur in due course and cause ‘on/off’ symptoms (fluctuations between symptom control
Restless legs and flares)
REM sleep behaviour disorder
End of dose deterioration (‘wearing off’) – the effects of levodopa wear off before the next dose is due.
Depression
MR preparations have a limited role in preventing or reducing wearing off, but does have important therapeutic
Visual and olfactory disturbances
role in managing night time akinesia and simplifying dosing regimens.
Dysphagia, which can contribute to
Dispersible tablets are often used first thing in the morning for their fast onset of action to help the patient get
mortality from pneumonia; sialorrhoea
up from bed
Autonomic dysfunction
Side effects: Nausea (can take with food initially), postural hypotension, somnolence, urine discoloration. All
CV disorders (postural
dopaminergic drugs are associated with the risk of impulse control disorders (ICDs – see dopamine agonists)_
hypotension)
Impaired sweating
Constipation
Bladder disturbance
19
NERVOUS SYSTEM - PARKINSON’S DISEASE
Monoamine oxidase type B inhibitors – useful mild symptomatic effect in

Dopamine Agonists – less effective at controlling motor symptoms
early disease, and levodopa-sparing effect in later disease
than levodopa
Selegeline (may cause insomnia due to amphetamine-like metabolites),
Ergot derivatives – rarely used due to risk of fibrotic reactions (not
rasagiline, safinamide
recommended by NICE)
Bromocriptine, cabergoline, pergolide MOA – selectively inhibit the oxidative metabolism of levodopa and dopamine
and therefore potentiate the effects of levodopa, allowing for levodopa dose
Non-ergot derivatives reduction
Pramipexole, ropiniorle, rotigotine (transdermal patch) Interactions – hypertension is predicted to occur when high-doses of selegiline
are taken with tyramine-rich foods; caution with SSRIs – may precipitate
Can be added to levodopa therapy to increase the ‘on’ time or they can serotonin syndrome.
be used as monotherapy, particularly in younger patients whose QoL is S/E – increased levodopa side effects, therefore reduce levodopa dose
not affected to delay the use of levodopa
Side effects
Sudden onset of sleep
Catechol-O-Methyltransferase (COMT) Inhibitors
Hypotensive reactions, oedema, hallucinations
Impulse control disorders (e.g. pathological gambling, hyper- Entacapone – Prevents the peripheral breakdown of levodopa, allowing more to
sexuality, punding, binge eating, excessive shopping) – strong enter the brain. May colour the urine reddish-brown
association with dopamine agonists – risk factors: young age, Tolcapone – more potent than entacapone (rarely used, can cause hepatotoxicity)
alcohol abuse, smoker, past history of mental health disorder –
adjust dose or discontinue drug. Needs to be taken 2-3hrs apart from iron preparations
Apomorphine
Potent dopamine agonist
Used in advanced disease for unpredictable ‘off’ periods Antimuscarinics
S/C injection or continuous infusion pump
Trihexiphenidyl, procyclidine, orphenadrine
Once treatment is established, other PD medication may be
able to be reduced/withdrawn
MOA – restore the cholinergic-dopamine balance
High incidence of N&V therefore it is important to establish a
patient on domperidone (a peripheral D2 blocker) at least 2 days
Useful in drug-induced PD but are of little benefit in idiopathic PD (no longer
prior to commencement
recommended by NICE – increased risk of cognitive impairment)
May be useful in controlling excessive saliva
20
NERVOUS SYSTEM - BENZODIAZEPINES
Overview
Withdrawal of BZDs
BZDs are the most commonly used anxiolytics and hypnotics
BZD withdrawal syndrome
Dependence occurs, leading to difficulty withdrawing the drug, particularly if
taken regularly for more than a few weeks May develop at any time up to 3 weeks after stopping a long-acting BZD
and within 1 day of stopping a short-acting BZD. May continue for
BZDs are indicated for short-term relief (2-4 weeks) of anxiety that is weeks/months after stopping the BZD
severe, disabling or causing the patient unacceptable distress.
Features:
It is inappropriate to use a BZD to treat short-term ‘mild’ anxiety Insomnia and agitation
Loss of appetite and loss of body weight
BZDs should be used to treat insomnia only when it is severe, disabling or Tremor
causing the patient extreme distress Perspiration
Tinnitus
Perceptual disturbances
For short term use of 2-4 weeks, withdrawal can occur over 2-4 weeks
Side Effects however after long-term use, withdrawal may take longer than several
months
General
Drowsiness Protocol for withdrawing:
Confusion Transfer the patient to an equivalent daily dose of diazepam
Dependence Reduce the dose by 1-2mg every 2-4 weeks
Muscle weakness If uncomfortable withdrawal symptoms occur, maintain this dose
until symptoms lessen
Reduce the diazepam dose in smaller steps of 500mcg towards
Paradoxical effects the end of withdrawal
A paradoxical increase in hostility and aggression may occur The addition of beta blockers, antidepressants and antipsychotics
Increased anxiety and perceptual disorders can also occur to treat withdrawal symptoms should be avoided where possible
Effects range from talkativeness and excitement to aggressive and
antisocial acts
Adjustment of the dose sometimes attenuates the impulses
21
NERVOUS SYSTEM - NAUSEA AND VOMITING
Antihistamines
D2 antagonists
MOA – D2 antagonists
E.g. cyclizine 50mg TDS
Metoclopramide
S/E – drowsiness and antimuscarinic side effects
Crosses the BBB therefore not suitable in PD
MHRA warning – neurological s/e such as extrapyramidal symptoms
and tardive dyskinesia; max 5 days
10mg TDS
Phenothiazines and Other Antipsychotics
Domperidone
E.g. prochlorperazine, chlorpromazine, haloperidol, levomepromazine
Does not cross the BBB therefore safe in PD
MOA – dopamine receptor antagonists MHRA warning – risk of cardiac s/e; max 7 days
10mg TDS
S/E – extrapyramidal and anticholinergic side effects, drowsiness
Prochlorperazine can be administered as a buccal tablet

5HT3 antagonists
E.g. ondansetron, granisetron
Caution – prolong the QT interval

Corticosteroids
S/E - constipation
E.g. dexamethasone
Used for N&V associated with cancer chemotherapy

Neurokinin1 receptor antagonists
Can be used alone or in combination with other antiemetics
E.g. aprepitant, fosaprepitant, rolapitant
Also has use in reducing intracranial pressure due to tumours
Used for chemotherapy-induced nausea and vomiting
22
NERVOUS SYSTEM - PAIN: OPIOIDS
Opioids Overview Opioid Side Effects
Mostly used for analgesia but can also be used as cough suppressants, to Respiratory
reduce intestinal motility and opioid dependence Bronchoconstriction due to opioid-induced histamine release
(asthmatic patients are particularly prone)
Generally they are full agonists at opioid receptors but some have mixed Respiratory depression – rare but serious
agonist-antagonist activity e.g. buprenorphine and pentazocine
Skin
Tramadol also has noradrenergic and serotonergic properties
Pruritis – due to cutaneous release of histamine
Flushing – due to histamine-stimulated dilation of cutaneous blood
Opioids are suitable for moderate-severe pain
vessels (increased risk with epidural opioids)
Little evidence to support use of antihistamines
Other
Opioid Side Effects Urinary retention – increased with epidural opioids
Miosis (pinpoint pupils are characteristic of opioid toxicity)
Gastrointestinal
N&V occur very commonly – this often diminishes as tolerance
develops
Constipation – due to reduced peristalsis and increased anal Special Precautions for Transdermal Patches
sphincter tone. For long-term use, the combination of an osmotic
and stimulant laxative should be used. A bulk-forming laxative is These points are particularly important if around children:
not appropriate as it increases the risk of faecal impaction Store out of reach and sight of children
Dry mouth
Affix the patch securely
CNS & Psychiatric
Drowsiness + sedation – dose dependent effects which often Follow the PIL for disposal instructions (may require folding the patch
diminish when tolerance devleops back on itself) and discard so that it cannot be retrieved by a child or a
Confusion, delirium, dizziness pet
Mood changes – euphoria and dysphoria
Hyperalgesia – increased sensitivity to pain can occur with long- Be alert of opioid side effects in children and get medical help if
term use contact is suspected
Cardiovascular
Postural hypotension
23
NERVOUS SYSTEM - PAIN: OPIOIDS
Dependence and Withdrawal

Strong Opioids
Dependence can be psychological and physical
Morphine
Withdrawal symptoms: Most valuable opioid for severe pain
Nausea, vomiting, diarrhoea Standard for which other opioids are compared
Sweating, anxiety, agitation Can be given 4-hourly as standard release or 12/24-hourly as
modified release
Restlessness, yawning, insomnia
Dilated pupils, increased tear production, rhinorrhoea Buprenorphine
Bone and muscle pain, abdominal cramps Agonist-antagonist activity therefore can precipitate withdrawal
Gooseflesh (pimply state of skin with erect hairs) Much longer duration of action compared to morphine
Available as patches and SL
To treat withdrawal, switch to a long-acting opioid (buprenorphine / methadone)
and very slowly reduce the dose over time Diamorphine
Less N&V and hypotension compared to morphine
Note that buprenorphine can provoke withdrawal reactions in those still under the Greater solubility that morphine so useful in palliative care as it
influence of opioid drugs or those dependent on high doses due to its agonist- can be injected in a smaller volume in emaciated patients
antagonist activity. To prevent this reaction, the first dose of buprenorphine
should coincide with the appearance of withdrawal effects. Fentanyl
Available as a 72-hourly TD patch
Methadone
Weak Opioids Less sedating than morphine and has a longer duration of
action
Codeine
Codeine is a pro-drug, metabolised to morphine by CYP2D6 – poor Oxycodone
metabolisers will not get sufficient analgesia from codeine and rapid Metabolite is not active and therefore used in renal impairment
metabolisers are at risk of toxicity instead of morphine (morphine’s metabolites are active and
accumulate in renal impairment)
Dihydrocodeine
Analgesic efficacy similar to codeine Tramadol
Noradrenergic and serotonergic activity
Meptazinol Fewer typical opioid s/e but psychiatric reactions have been
Claimed to have lower incidence of respiratory depression reported
Weak opioid of choice in renal impairment
24
NERVOUS SYSTEM - PAIN: NEUROPATHIC PAIN & LOWER BACK PAIN
Neuropathic Pain Overview

Lower Back Pain and Sciatica
Can be due to several causes:
Non-drug treatments (e.g. exercise programs, psychological therapies) should be
Phantom limb pain
offered for people with lower back pain with or without sciatica
Compression neuropathies
Peripheral neuropathies (e.g. diabetic peripheral Paracetamol alone is ineffective for managing low back pain
neuropathy, chemotherapy)
Trauma An NSAID should be considered for managing acute, low back pain
Central pain (e.g. spinal cord injury)
Post-herpetic neuralgia A weak opioid may be combined with paracetamol to manage acute low back pain
Trigeminal neuralgia only if an NSAID is contraindicated, not tolerated or ineffective
Management (except trigeminal neuralgia) For chronic low back pain, NSAIDs should be offered first-line if non-drug treatments
First-line: offer a choice of amitriptyline, duloxetine, are ineffective. Opioids should be the last treatment option.
gabapentin or pregabalin
Second-line: offer one of the 3 remaining drugs and NSAIDs and CV events
consider switching again if this is ineffective All NSAIDs can be associated with a small increased risk of thrombotic events,
Tramadol – only consider if acute rescue therapy is independent of baseline CV risk
needed (not long term unless under specialist advice) Greatest risk in high dose, long term therapy
Capsaicin cream – can be considered for localised COX-2 inhibitors, diclofenac 150mg/day + ibuprofen 2.4g/day have an
neuropathic pain in people who cannot tolerate oral increased risk
treatment Naproxen 1g/day has a lower risks
Low dose ibuprofen 1.2g/day have not been associated with an increased risk
NSAIDs and GI events

Trigeminal Neuralgia All NSAIDs are associated with GI toxicity (higher risk in elderly)
Selective COX-2 inhibitors have a lower risk compared to non-selective NSAIDs
TN is severe, episodic facial pain, in the distribution of one or Highest risk: piroxicam, ketoprofen, ketorolac trametamol
more branches of the 5th cranial nerve (the trigeminal nerve). Intermediate risk: diclofenac, naproxen, indomethacin
Lowest risk: ibuprofen
Offer carbamazepine 100mg BD and titrate by 100-200mg every
2 weeks until pain is relieved. Once pain is relieved, the dose NSAIDs and hepatic impairment
should be reduced to the lowest maintenance dose for controlling Caution – increased risk of GI bleeding and fluid retention
pain
25
RESPIRATORY MEDICINE - ASTHMA
Overview Diagnosis – Spirometry

Asthma is a disease with many variations (phenotypes),
usually characterised by chronic airway inflammation. All patients with suspected asthma should undergo objective testing including
Described as “A chronic, inflammatory disorder of the Spirometry (evidence of obstruction and reversibility) and peak flow monitoring (evidence of
airways, which causes an increase in airway hyper- variability).
responsiveness that leads to recurrent episodes of
wheezing, breathlessness, chest tightness and coughing.” The 3 most important spirometric measures for the assessment of asthma:
Causes
No single cause but there are several environmental and 1) Forced vital capacity (FVC) – total volume expelled by forced exhalation after a
genetic risk factors: maximal inhalation
- Family history of asthma or other atopy (e.g. 2) Forced expiratory volume in 1 second (FEV1) – the volume exhaled in the first second
eczema, allergic rhinitis), potentially corroborated of an FVC
by a previous record of raised allergen-specific 3) FEV1/FVC ratio – the proportion of FVC that can be expelled during the first second of
IgE levels, positive skin-prick tests to expiration (normally at least 70%. <70% suggests airway obstruction)
aeroallergens or blood eosinophilia.
- Having bronchiolitis as a child Peak expiratory flow (PEF) –Is a useful way of monitoring variability in asthma. It may be used
- Being exposed to tobacco smoke as a child to aid diagnosis in those unable to perform spirometry or in monitoring asthma control.
- Being born prematurely
- Being born with low birth weight If an obstruction is found, a patient should be tested again to establish whether the obstruction is
reversible – i.e. after an inhaled bronchodilator or a trial of inhaled corticosteroids. A change in
Signs & Symptoms FEV1 of >12% and 200ml confirms reversibility and supports an asthma diagnosis. Testing may
- Wheezing need to be repeated during symptoms, in the early morning, or after withholding bronchodilator
- Short of breath (SOB) medications.
- Coughing – particularly at night and early morning
- Chest tightness Asthma Treatment Aims:
People with asthma generally have >one of these
symptoms. The symptoms occur variably over time and 1) No daytime symptoms
vary in intensity 2) No night-time awakening due to asthma
3) No need for rescue medication
Triggers 4) No asthma attacks
- Airbourne irritants (cigarette smoke, chemical 5) No limitations on activity, including exercise
fumes) 6) Normal lung function (FEV1 and/or PEF >80% of predicted)
- Allergens (pollen, house dust mites, animal 7) Minimal side effects from medication
dander)
- Respiratory tract infections (RTIs) Before initiating new drug therapy check adherence and optimise inhaler technique. Whenever
- Weather conditions (e.g. cold air) possible do not mix MDIs and DPIs as they require different inhaler techniques (slow and steady
- Foods containing sulphites (beer, wine, shrimp) vs quick and deep). All inhalers should also be prescribed by brand.
- Emotion (stress, laughter)
- -Exercise
26
Asthma Treatment – Stepwise Approach

BTS vs NICE guidelines
Asthma is an inflammatory condition and recent guidelines have highlighted the need to treat all individuals symptomatic of asthma with inhaled corticosteroids. The practice of using a
short acting bronchodilator (SABA) as monotherapy is now outdated and reports such as the National Review of Asthma Deaths (NRAD) have highlighted the potential dangers of this
practice with underuse of inhaled corticosteroids and over reliance on beta-agonists a contributory factor in a number of deaths.
BTS/SIGN (2019) NICE (2017)
Low dose inhaled corticosteroid (ICS)

Inhaled SABA prn (e.g. salbutamol/terbutaline)
E.g. Clenil MDI 100 2 doses BD
Move down to lowest controlling therapy
Initial add- on therapy:

Low dose ICS
Low dose ICS + LABA
E.g. Clenil MDI 100 2 doses BD
E.g. Seretide MDI 50 2 doses BD
Move up to improve control
Additional add-on therapy:

Low dose ICS + Montelukast 10mg ON
Option 1 – increase ICS (as part of ICS/LABA) to medium dose
Option 2 – add in theophylline/ LRTA (montelukast)/ LAMA
Low dose ICS + LABA (with/without Montelukast)
(Spiriva (tiotropium) Respimat -only LAMA licensed in asthma)
High dose therapy Consider MART* regime
High dose ICS – e.g. Seretide MDI 250 2 doses BD Increase ICS dose
Increase ICS dose to moderate
Patients should be referred to a respiratory specialist at this step Moderate dose ICS + LABA +/-
Continue MART* regime
LRTA
Continuous oral steroids at lowest effective dose (patient should be under
Option 1- Increase ICS to high dose
specialist care)
Option 2- Trial theophylline/ LAMA
Maintain high dose ICS
Consider referral to a respiratory specialist
Think about – bone prophylaxis, risk of diabetes
*MART = maintenance and reliever therapy
Note – for children under 5 years, NICE recommends the following:

1) SABA prn
2) Paediatric low dose ICS
3) Low dose ICS + montelukast for children
Refer to a specialist if not adequately controlled at step 3
27
ICS Equivalence
Long-acting beta agonists (LABA)
Historically potency described in relation to Formoterol – rapid onset of action within 5 minutes, Salmeterol slower onset of 15-20
beclometasone dipropionate (BDP). Now see table for minutes. Both effects last >12hrs.
comparison of doses: Formoterol is licensed for symptomatic relief as well as maintenance due to its rapid onset.
https://www.nice.org.uk/guidance/ng80/resources/inhale NB: the LABA, Indacaterol is licensed for COPD only
d-corticosteroid-doses-pdf-4731528781 MUST be prescribed as a combination product with ICS to obviate the risk of patients
inadvertently taking the LABA as mono-therapy, which has been associated with increased
Qvar (beclomethasone) has extra fine particles so should risk of mortality.
be prescribed as approximately half the dose as other If no benefit is seen with a LABA, it should be discontinued as there is a possible increased
BDP inhalers risk of respiratory-related, asthma-related deaths
S/E – as for SABAs
Fluticasone furoate (Relvar®) and fluticasone propionate
are more potent than BDP inhalers Theophylline/Aminophylline (a methylxanthine)
Brand specific prescribing – e.g. Neulin SA, Uniphyllin Continus
Ciclesonide is the only once daily ICS (without a TDM required - Therapeutic range – 10-20mg/L (sometimes 5-15mg/L is effective)
combined LABA) Plasma concentration…
Increased in: congestive HF, hepatic impairment, viral infections, drugs p450
inhibitors
Decreased in: smokers and by alcohol consumption care and monitoring
required during smoking cessation, drugs p450 inducers
Short-acting beta agonists (SABAs) Cautions – HT, arrhythmias, CVD, hyperthyroidism

Overdose – (think caffeine/coffee): vomiting, agitation, restlessness, dilated pupils,
Salbutamol and terbutaline tachycardia, hyperglycaemia
Onset of action within 5 mins and a peak effect at 4-6hrs

Montelukast (Leukotriene-receptor antagonist)
Should only be used PRN as do not improve outcomes Achieves bronchodilation within 2 hour of administration, anti-inflammatory effect seen
and monitoring SABA use is a good indicator of asthma within 4 weeks
control Taken ON
S/E – GI disturbances, MHRA reminder of the risk of neuropsychiatric reactions
S/E – arrhythmias (due to effect on beta receptors on (September 2019) Healthcare professionals are advised to be alert for neuropsychiatric
cardiac tissue), fine tremor, hyperglycaemia, reactions, including speech impairment and obsessive-compulsive symptoms, in adults,
hypokalaemia (more common with nebulised/IV therapy), adolescents, and children taking montelukast.
muscle cramps Formulations – tablets, chewable tablets and granules (good for paediatric population)
28
RESPIRATORY MEDICINE - COPD
Overview Medical Research Council (MCR) Dyspnoea Scale
Airflow obstruction which is progressive, not fully 1 Not troubled by breathlessness except during strenuous exercise
reversible and does not change markedly over several 2 Short of breath when hurrying or walking up a slight hill
months
3 Walked slower than contemporaries on the level because of breathlessness, or
has to stop for breath when walking at own pace
Similar symptoms to asthma, however the symptoms in 4 Stops for breath after walking about 100m or after a few minutes on the level
COPD are constant (as opposed to intermittent in
asthma). In most patients, COPD is associated with 5 Too breathless to leave the house, or breathless when dressing or undressing
significant concomitant chronic disease, which increase
its morbidity and mortality.
Diagnosis
Risk Factors
Post-bronchodilator FEV1/FVC ratio of <0.7 indicates airflow obstruction
-Smoking (pack years = no. cigarettes smoked x number
of years you have smoked / 20) Stage 1 – mild. FEV1 80% predicted or higher
-Air pollution/occupational exposure (e.g. dust,
chemicals, gases, particles) Stage 2 – moderate. FEV1 50-79% of predicted
-Genetics – e.g. alpha1 antitrypsin deficiency
Stage 3 – severe. FEV1 30-49% of predicted
Symptoms
Stage 4 – very severe. FEV1 <30% of predicted
-Dyspnoea
-Chronic cough Diagnosis of an acute exacerbation of COPD
-Sputum: change in volume and/or colour may indicate
Defined as a sustained worsening of a person’s symptoms from their usual stable state, which is
exacerbation
beyond normal day-to-day variations and is acute in onset.
-Wheeze
-Chest tightness Commonly reported symptoms: Other symptoms:
Increased breathlessness Increased wheeze and chest tightness
Increased cough Upper respiratory tract symptoms e.g.
Increased sputum production sore throat
Change in sputum colour Reduced exercise tolerance
Ankle swelling
Increased fatigue
Acute confusion
29
RESPIRATORY MEDICINE - COPD
Antimuscarinic Drugs
Treatment of COPD – NICE approach
Overview
Block cholinergic nerves in the airways therefore prevent
bronchoconstriction (known as bronchodilators)
Ipratropium – a short-acting muscarinic antagonist (SAMA)

with maximal effects between 30-60mins. It has a slower
onset of action to short-acting beta agonists (SABA). Duration
of action = 3-6 hours.
Tiotropium, aclidinium,glycopyrronium and umeclidinium

= long-acting muscarinic antagonists (LAMAs).
Tiotropium: available as Spiriva Handihaler (18mcg/dose),

Braltus Zonda inhaler (10mcg/Dose ) and Spiriva Respimat
nebulised solution (2.5mcg/dose). Duration of action = 24
hours.
SAMAs should not be used alongside LAMAs (in

exacerbations, hold the LAMA)
Cautions
Prostatic hyperplasia and bladder outflow obstruction –
worsened urinary retention reported
CKD stage 3+ - risk of drug toxicity
Angle-closure glaucoma – nebulised mist can

precipitate/worsen. Use a mouthpiece rather than a mask
For Spiriva Respimat – caution in patients with arrhythmias
S/E
Generally well tolerated
Nasal congestion, nasal dryness, dry mouth, abnormal taste
30
ENDOCRINE SYSTEM – DIABETES OVERVIEW
TARGETS DRIVING RULES

5-7mmol/L on waking/fasting HYPOGLYCAEMIA
4-7mmol/L before meals Check blood glucose before driving
5-9mmol/L 90mins after eating Blood glucose <4mmol/L – ‘4 is the floor’ (within 2 hours) and every 2 hours.
> 5mmol/L when driving
Requires fast-acting form of glucose e.g.: Blood glucose must be >5 to drive
HbA1c <48mmol/mol (<6.5%),
Fruit juice
or < 53mmol/mol in T2DM on
treatment associated with Non-diet soda drink If hypo when driving, pull over,
hypoglycaemia Dextrose tablets or sugary sweets e.g. Jelly babies switch off the engine, remove the
40% Glucose gel (Hypostop, Glucogel) keys from ignition and move from the
driver’s seat. Take a fast-acting
Or if decreased level of consciousness: carbohydrate and wait for 45mins
DKA IM glucagon (don’t repeat: give IV glucose) after BG has returned to normal
IV glucose 20%, 100ml over 15 minutes
Involves hyperglycaemia, acidosis and Recheck blood glucose and repeat above until in range. Keep fast-acting carbohydrates
ketosis. Sometimes can occur without available in easy reach in the car,
hyperglycaemia Once above 4mmol/l, have long-acting carbohydrate e.g. slice and keep snacks for longer journeys.
of toast, or a meal.
1 - Fixed rate intravenous insulin
infusion (0.1units/kg/hr) – suppresses Beta blockers can mask the symptoms of hypoglycaemia
ketogenesis, reduces blood glucose
Repeated hypoglycaemic episodes can reduce awareness COMPLICATIONS
2 – Fluid replacement –Starting with (awareness of hypo’s can be measured using the Clarke
0.9% Sodium Chloride (with K+ to score or Gold score). To restore the warning signs, episodes Retinopathy
maintain K+ in range, corrects of hypoglycaemia need to be reduced.
Neuropathy
electrolyte disturbances) Nephropathy
Causes of hypoglycaemia:
Cardiovascular disease (MI,
3 – IV glucose 10% - once blood Too much insulin
stroke, PVD)
glucose <14mmol/L – to prevent Sulphonylureas, glinides
hypoglycaemia whilst insulin is still Infections that can lead to
Skipping meals/eating less carbohydrates than usual
running and to clear ketones amputations
Exercise
Cardiovascular disease – offer
Alcohol (binge drinking) atorvastatin 20mg in T1DM if aged
If patient is established on a long- Self harm over 40yrs or diagnosis of T1DM for
acting insulin, continue this as normal
>10yrs. Offer atorvastatin 20mg in
alongside FRIII.
T2DM based on QRISK2.
31
ENDOCRINE SYSTEM – DIABETES OVERVIEW
BLOOD GLUCOSE TESTING PRESENTATION

INSULIN TYPES
At least 4 times a day advised in T1DM; Polyuria
increased in periods of illness and Rapid acting
Polydipsia
during long drives Novorapid (insulin aspart), Humalog (insulin lispro) and
Apidra (insulin glulisine)
Given immediately before a meal (within 10 mins) More commonly in T1DM: lethargy,
Equipment: meter (from DM clinic) with stupor, acetone breath, nausea,
Onset 5-15mins; peak 0.5-1.5hrs; duration 3-5hrs
test strips and lancets (FP10) or vomiting, abdominal pain, weight loss
Fiasp = extra fast acting (within 2mins)
continuous glucose monitor; sharps bin
Short acting/soluble
Actrapid and Humulin S (soluble insulin)
Administered 15-30mins prior to a meal
SICK DAY RULES Onset 30mins; peak 2-4hrs; duration 6-8hrs ADDITIONAL MONITORING
Actrapid used in a VRIII – immediate onset
Do not stop insulin therapy – dose Annual foot check and eye check
Isophane insulin/intermediate acting
may need to be altered according to
Insulatard, Humulin I and Insuman basal BP: target 135/85 adults <80 years old
BG levels
Protamine slows down the onset of action and increases the 145/85 adults >80 years old
duration of action
Monitor BG more frequently, including 130/80 in CKD
Onset 2- 4 hours, peak 4-8 hrs, duration 14-16hrs
throughout the night Given OD or BD
Cholesterol: if diagnosed with T1DM
Consider ketone monitoring (blood / Long-acting for 10yrs+ commence atorvastatin
urine) Lantus, Abasaglar, Toujeo (insulin glargine – once or twice 20mg OD. If T2DM, use QRISK2 to
daily) calculate CV risk.
Aim to maintain normal meal pattern Levemir (insulin detemir – once or twice daily)
even if appetite is reduced (could Onset 0-2hrs; duration 18-42hrs; no peak Kidney function: measure ACR and
replace with carbohydrate containing Tresiba (insulin degludec): extra-long acting, available in 2 CrCL. Start an ACE I in adults with
drinks) strengths confirmed nephropathy
Mixed insulins BMI: aim for 18.5-24.9 (18.5-22.9 in
Aim to drink at least 3L of fluid to Humulin M3; Novomix; Humalog mix; Insuman Comb
prevent dehydration patients of Asian ethnicity)
Mixture of an intermediate acting insulin with a rapid acting
or a soluble insulin
Seek urgent medical attention if Thyroid: check TSH annually in T1DM
violently sick, unable to keep fluids Xultophy (increased risk of other autoimmune
down or if drowsy. Insulin degludec with liraglutide diseases)
32
ENDOCRINE SYSTEM – DIABETES TREATMENTS
INSULIN REGIMENS
T2DM TREATMENT
1 – Basal bolus regimen
1st-line therapy in T1DM Note: NICE guideline for the treatment of T2DM (2017) is undergoing review
Long acting insulin with rapid acting insulin at mealtimes as it does not include the latest evidence and is not fit for purpose. Use ADA
E.g. BD Levemir with mealtime Novorapid or OD Tresiba with guideline together with NICE advice.
mealtime Fiasp
Advantages: better glucose control and allows for mealtime If HbA1c rises to 48mmol/mol on lifestyle interventions
flexibility
Disadvantages: multiple daily injections
Offer standard-release metformin
2 – Continuous glucose infusion First intensification: if HbA1c rises to 58mmol/mol, consider dual
Used with continuous glucose monitoring therapy adding one of the following (treatment choice is based on
T1DM only presence of cardiovascular disease, heart failure, renal disease or need
3 – Twice daily biphasic regimen
for glucose control):
Can be used in T1DM if basal bolus not suitable GLP-1, SGLT-2 inhibitor, DPP-4 inhibitor, sulphonylurea or
Can be used in T2DM also pioglitazone
1st-line is soluble mixed – Humulin M3
2nd-line is rapid-acting mixed – Novomix 30 Second intensification: if HbA1c rises to 58mmol/mol, consider triple
Advantages: fewer injections compared to basal-bolus regimen therapy with metformin and 2 of the agents above
Disadvantages: does not allow for mealtime flexibility
4 – Intermediate acting/basal only regimens Or consider insulin-based treatment (intermediate or basal only
Only used in T2DM regimen)
1st step of insulin treatment in T2DM
NICE recommends using an intermediate acting insulin such as If triple therapy is ineffective, not tolerated or contraindicated consider:
once or twice-daily Insulatard
Reassess patient for compliance
Remember that insulin should be prescribed by brand! Consider weight management and exercise levels
Be aware of clinical inertia – are we choosing the best therapy
Be aware of high strength insulin. Most insulin devices contain for this patient when considering their co-morbidities?
100units/ml. High strength insulins are defined as insulin products
that contain more than 100units/ml (e.g. Toujeo 300units/ml or
Tresiba 200units/ml). This creates an increased risk of error
33
ENDOCRINE SYSTEM – ANTIDIABETIC AGENTS
METFORMIN PIOGLITAZONE DPP-4 INHIBITORS
MOA: increases insulin sensitivity; Alogliptin, linagliptin, saxagliptin,

MOA: a PPAR agonist – increases insulin sensitivity and
inhibits gluconeogenesis and sitagliptin, vildagliptin
reduces hepatic glucose output
glycogenolysis
S/Es: Weight gain (fluid retention), bladder cancer, HF, MOA: DPP-4 usually breaks down
Dose: 500mg OD with breakfast for 1 GLP-1 (which stimulates insulin
week; 500mg BD with breakfast and increased risk of bone fractures, LF (rare)
release and lowers glucagon
dinner for 1 week; 500mg TDS with secretion). By inhibiting DPP-4, GLP-
breakfast, lunch and dinner thereafter. CV safety: incidence of HF is increased when combined with
1 activity increases
This reduces the risk of GI s/e. If GI s/e insulin therapy. Closely monitor for signs of HF and discontinue
are still problematic, MR preparations treatment if any deterioration in cardiac status occurs
can be used. DPP-4
CI: Heart failure; previous or active bladder cancer; GLP-1
S/E: GI disturbances (very common); inactivates
uninvestigated macroscopic haematuria.
lactic acidosis (rare, increased risk of GLP-1
renal impairment); decreased absorption Review safety and efficacy after 3-6 months and stop treatment
of vitamin B12 (rare) in patients who do not receive any benefit. Advise patients to
promptly report haematuria, dysuria or urinary urgency during
CI: CrCL <30, metabolic acidosis
treatment.
Weight neutral; does not cause hypos
Stimulates
Interactions: contrast media (increased insulin
risk of AKI) secretion and
SULPHONYLUREAS suppresses
glucagon
Gliclazide, tolbutamide, glipizide, glimepiride secretion
ACARBOSE
MOA: stimulate insulin secretion therefore taken with or
Very rarely used after meals. Note that glibenclamide is a long-acting agent
MOA: inhibits alpha glucosidases thereby delays therefore has an increased risk of hypoglycaemia, No weight gain; less hypoglycaemia
starch and sucrose absorption (must use especially at night. compared to sulphonylureas
glucose to treat hypos)
S/E: hypoglycaemia, weight gain. S/E: pancreatitis – discontinue if
S/E: GI disturbances; liver failure (rare) symptoms occur.
Note that gliclazide is principally metabolised in the liver Vildagliptin – discontinue if signs of
Take directly before meal/with 1st mouthful liver toxicity
therefore can be used with caution in renal impairment
34
ENDOCRINE SYSTEM – ANTIDIABETIC AGENTS
MEGLITINIDES GLP-1 AGONISTS

SGLT-2 INHIBITORS
Nateglinide; repaglinide More widely used now due to CVD benefits
Canagliflozin, dapagliflozin, empagliflozin
Rarely used Liraglutide, dulaglutide, semaglutide,
Excellent evidence for reducing HF and CVD. Canagliflozin exenatide, lixisenatide
MOA: have a rapid onset of has evidence for preventing deterioration in renal function and
action and short duration of can be initiated if eGFR >30ml/min. It can be continued in MOA: bind to GLP-1 receptor to increase
action. They work similarly to patients already on it if their eGFR drops below this. insulin secretion and suppress glucagon
sulphonylureas in that they secretion. They also delay gastric emptying.
stimulate insulin secretion MOA: inhibit sodium-glucose co-transporter-2 in the proximal Can help with weight loss – sometimes
convoluted tubule in the nephron to reduce glucose significantly
Administration: 1-30 minutes reabsorption and increase urinary glucose excretion
before meals. Omit dose if Initiation: in patients on insulin the insulin
omit meal. Cautions: elderly (risk of hypotension); hypotension; correct dose should be reduced but blood glucose
hypovolaemia before treatment levels monitored closely to prevent DKA or
S/E: hypoglycaemia, pruritis, hypoglycaemia
rash, urticaria Risk of DKA: DKA can present atypically with raised ketones
but only moderately raised BG (these agents cause glucose to Administration: subcutaneous injection.
These agents can be used be excreted in the urine but not ketones). Counsel patients on Some formulations must be given before
flexibly around mealtimes signs and symptoms of DKA and to seek immediate medical meals
however they are generally attention if these occur. Discontinue and do not restart if DKA
less preferred than occurs with no other identified cause. Exenatide – antibiotics and GR
sulphonylureas formulations should be taken at least 1 hour
S/E: polyurea, polydipsia, genital infection, UTI, dehydration, before or 4 hours after exenatide.
dysuria, hypotension, hypovolaemia
CI: severe GI disease
Monitoring: renal function before treatment and then annually
S/E: pancreatitis (discontinue permanently if
this develops); GI side effects
35
ENDOCRINE SYSTEM – CORTICOSTEROIDS
USES OTHER POINTS TO NOTE

IBD MINERALCORTICOID SIDE EFFECTS
Rheumatoid arthritis Infections – long courses of steroids
Oncology Anxiety, osteoporosis, peptic ulceration increase infection risk and infection
Pain/symptoms due to nerve compression Hypertension, impaired healing severity
Respiratory tract infections Na+ and water retention, most marked with
Replacement – e.g. Addison’s disease fludrocortisone (therefore can be used for Chickenpox – immunisation required for
Asthma postural hypotension) patients who have been exposed to
And many others K+ and Ca2+ loss chickenpox and whom are not already
Psychiatric disorders immune
Negligible with dexamethasone Measles – particular care required to
avoid exposure
TREATMENT CESSATION GLUCOCORTICOID SIDE EFFECTS
Psychiatric reactions – advise patients
Gradual withdrawal is required in the Diabetes mellitus, muscle wasting to seek medical advice if they experience
following circumstances: Osteoporosis, avascular necrosis of the psychiatric symptoms (rare possibility on
femoral head (high doses) withdrawal of treatment also)
More than 40mg prednisolone daily (or
equivalent) for more than 1 week Peptic ulceration, electrolyte imbalance
Headache, impaired healing Adrenal suppression/ non-functional –
adrenal atrophy can develop during
Repeat doses of steroids in the evening Skin reactions, Cushing’s syndrome
prolonged therapy. For patients on long-
Psychiatric reactions, anxiety term steroids (including inhaled), acute
More than 3 weeks treatment High potency glucocorticoids include illness, trauma or surgery requires a
dexamethasone and betamethasone temporary increase in dose. Patients
Recently received repeated courses
may need a hydrocortisone emergency
MHRA/CHM ADVICE – CORTICOSTEROIDS IM injection kit to prevent adrenal crisis
A short course within 1 year of stopping
long-term therapy
Rare risk of central serous chorioretinopathy Growth restriction – in paediatric
Patients should report any blurred vision or patients, less likely with recommended
If patient has other possible causes of
other visual disturbances with corticosteroid doses of inhaled therapy (initial growth
adrenal suppression
velocity may be reduced however).
treatment given by any route
Note that abrupt withdrawal can cause
Steroid card – for patients on long-term
acute adrenal insufficiency, hypotension
treatment
and even death
36
ENDOCRINE SYSTEM – OSTEOPOROSIS: BISPHOSPHONATES
USES ALENDRONIC ACID

MHRA/CHM ADVICE – ALL BISPHOSPHONATES
Prophylaxis and treatment of Dose: 10mg daily or 70mg weekly
osteoporosis (including post- Atypical femoral fractures
menopausal and corticosteroid-induced) Reported rarely, mainly in patients receiving long- CIs: abnormalities of the oesophagus;
hypocalcaemia, delayed gastric emptying
term treatment for osteoporosis
Treatment of Paget’s disease, Re-evaluate use based on risk vs benefit after 5 Cautions: dysphagia; surgery of the
hypercalcaemia of malignancy and in years of use upper GI tract; GI disorders (e.g. ulcers,
bone metastases in breast cancer Advise patients to report thigh, hip or groin pain gastritis, bleeding) especially in elderly
patients – STOPP criteria
Osteonecrosis of the jaw Correct vitamin D deficiency or
Higher risk in patients receiving IV therapy for the hypocalcaemia before initiating
DRUGS treatment of cancer
Risk factors: potency of drug (zoledronate highest), S/E: GI s/e are common
Alendronic acid – most commonly route of admin, cumulative dose, duration and type
seen; oral agent Oesophageal reactions have been
of malignant disease, concomitant treatment,
reported and patients should stop taking
smoking, history of dental disease and seek advice if they develop
Zoledronic acid – intravenous Dental check-up required before treatment dysphagia, new or worsening heartburn
infusion
Patients should maintain good oral hygiene and or retrosternal pain
Risedronate sodium – oral agent receive regular routine dental check ups
Renal: avoid if CrCL <35ml/min
Patients should report any dental mobility, pain or
Ibandronic acid – intravenous swelling, non-healing sores or discharge Counselling: for all PO bisphosphonates
infusion Ensure dentures fit correctly
Patients should be given a patient reminder card if Tablets should be swallowed whole with
Pamidronate disodium – intravenous receiving IV bisphosphonates plenty of water whilst sitting or standing,
infusion on an empty stomach at least 30mins
before breakfast or other medication.
Osteonecrosis of the external auditory canal Remain upright for at least 30mins.
Denosumab, teriparatide and Reported very rarely, mainly in patients receiving
raloxifene are non-bisphosphonate long-term therapy (>2 years) Interactions:
alternatives Al3+, Ca2+, Mg2+, Zn2+ containing
Risk factors: steroid use, chemotherapy, infection,
medicines - take 30mins apart.
ear operation, cotton-bud use Gastric irritants
Advise patients to report any ear pain, discharge or
ear infections
37
ENDOCRINE SYSTEM – THYROID DISORDERS
HYPERTHYROIDISM
HYPOTHYROIDISM
Blood results:
Blood results: High T3, high T4 and low TSH
Low T3, low T4 and raised TSH
Signs and Symptoms:
Signs and symptoms: Breathlessness, neck pressure, heat intolerance, increased sweating,
Fatigue, cold intolerance, weight gain, arthralgia, myalgia, constipation, increase appetite, weight loss, diarrhoea, agitation, mood changes, fine
depression, coarse dry hair and skin, goitre, mood changes tremor, goitre, bulging eyes (exophthalmous).
Can lead to AF and HF
Treatment:
Levothyroxine Thyroid storm - rare
Adults 18-49yrs – 50-100mcg OD (adjusted by 25-50mcg every 3-4 Emergency situation with tachycardia, fever, D&V, high BP
weeks) Treatment includes – IV fluids, IV propranolol, IV hydrocortisone, oral
Adults 50yrs+, with cardiac disease or severe hypothyroidism – 25mcg iodine and carbimazole/propylthiouracil
OD (adjusted by 25mcg every 4 weeks)
Maintenance 50-200mcg OD – can be higher in pregnancy Long-term therapy
Carbimazole
Caution in CV disorders (baseline ECG valuable) Used alone or in blocking-replacement regimen
Safety info – can cause neutropenia and agranulocytosis.
Take at least 30mins before breakfast, caffeine-containing liquids or Counsel patients on recognising signs/symptoms such as a sore
other medication throat and to seek urgent medical help
Rashes and pruritis are also common (use antihistamines)
S/E: if dose is too high, may cause signs of hyperthyroidism (see right) Propylthiouracil
Reserved for those intolerant of carbimazole and in 1st trimester
Liothyronine of pregnancy (switch to carbimazole in 2nd)
For severe hypothyroid states when a rapid response is required (e.g. Can cause hepatotoxicity (including liver failure resulting in
hypothyroid coma) transplantation) – counsel patients to report anorexia, nausea,
Given IV vomiting, abdominal pain, dark urine
Rapid effect that lasts 24-48hrs
Note: if switching from levothyroxine to liothyronine, dosage is not Curative treatment options:
equivalent (20-25mcg of liothyronine is approx. equivalent to 100mcg of Surgery
levothyroxine) Radioactive iodine
38
ENDOCRINE SYSTEM – DIABETES INSIPIDUS
DIABETES INSIPIDUS
Signs and Symptoms:

Passing of large volumes (>3L/24hrs) of dilute urine (polyuria),
nocturia and thirst
Treatment:
Maintain fluid intake
Desmopressin (vasopressin analogue) PO, SL, intranasal or SC, IV
or IM injection
Cautions:
Fluid overload, cardiovascular disease, heart failure, hypertension
Monitoring:
Serum sodium levels
Urine output
Fluid balance
Interactions:
Chlorpromazine, lamotrigine and medications that increase the risk
of hyponatraemia
Side effects:
Hyponatraemia, especially if fluid intake is not restricted
NB – omission of desmopressin in patients with moderate or

severe diabetes insipidus can result in death within hours
39
INFECTION - ANTIBIOTICS
AMINOGLYCOSIDES GLYCOPEPTIDES
START SMART THEN FOCUS
Bactericidal, activity against many gram-negative Vancomycin and Teicoplanin
Start smart: (including Pseudomonas aeruginosa) and some gram-
positive infections Broad spectrum against gram positive only
Do not start antimicrobial therapy unless
(cannot penetrate porins of gram-negative
clear evidence of infection Not absorbed from the GI tract therefore given IV or
topically
organisms)
Check allergies
S/E: Active against MRSA
Nephrotoxicity – more common in renal Vancomycin – infusion
Sepsis – ‘golden hour’
impairment. Therefore dosage interval should Teicoplanin -bolus
Comply with local antimicrobial guidelines be increased in pts with renal impairment
(more time for drug to be excreted) S/E
Ototoxicity Red man syndrome (if infused too fast)
Hypocalcaemia, hypokalaemia, Nephrotoxicity
Then focus: hypomagnesaemia Ototoxicity
May impair neuromuscular transmission
Stop abx if no evidence of infection (therefore CI in myasthenia gravis)
Vancomycin
Switch from IV to oral route Gentamicin IV usually give a loading dose and then 12hrly
Not active against anaerobes therefore when used dosing (less frequently and at reduced dose in
for empirical therapy, it is often used in combination renal impairment)
Change abx to a narrower spectrum (or with a penicillin or metronidazole
broad spectrum if required) Usual dose 3-7mg/kg/day (ideal body weight used
to calculate to avoid excessive doses in obese Pre-dose trough level should be 10-15mg/L (15-
Continue and document new review or patients (aminoglycosides are hydrophilic). Dosage 20mg/L in more severe/deep seated infections
interval extended in pts with renal impairment from e.g. endocarditis, osteomyelitis)
stop date 24 hourly to 36 or 48 hourly
OPAT – outpatient parenteral abx therapy TDM: Used PO for C.diff 125mg QDS for 10-14 days.
For once daily dose regimens pre-dose trough Dose can be increased in severe C. diff
<1mg/L or monitor again a gentamicin nomogram
(see individual Trust guidelines)
More info: Start Smart- Then Focus For multiple daily dose regimens 1 hour peak 5-
Antimicrobial Stewardship Toolkit for 10mg/L (3-5mg/L in endocarditis) and trough levels
English Hospitals <2mg/L (<1mg/L in endocarditis)
Tobramycin
Can be nebulised – often used for 28 day
cycles in cystic fibrosis
40
CARBAPENEMS CEPHALOSPORINS
Beta-lactam antibiotics (caution if penicillin allergy) therefore inhibitors of cell Beta-lactam antibiotics (caution if penicillin allergy) therefore inhibitors of
wall synthesis cell wall synthesis
Broad spectrum – gram positive, negative and anaerobes Approx. 0.5-6.5% of penicillin-sensitive patients will also be allergic to
cephalosporins.
Meropenem and Imipenem – active against Pseudomonas aeruginosa
1st generation – e.g. cephalexin (often used in UTI, safe in pregnancy)
Meropenem is least likely to induce seizures (therefore used for CNS
infections). Higher doses in CNS infections to ensure reaches CSF. 2nd generation – e.g. cefuroxime (more activity against gram negative
bacteria)
Ertapenem – Once daily - not active against Pseudomonas aeruginosa
3rd generation – e.g. ceftriaxone and ceftazidime (ceftazidime active
Interactions – carbapenems decrease the concentration of sodium valproate against pseudomonas)
to as low as 10%. Increasing the dose of sodium valproate does not counteract
this interaction 4th generation – e.g. cefepime (broad spectrum)
QUINOLONES
MACROLIDES
Ciprofloxacin – only oral agent active against Pseudomonas aeruginosa; may
decrease phenytoin levels Similar spectrum to penicillins therefore can be used in penicillin allergy
and often used to cover atypical organisms. Good bioavailability so should
Safety information https://www.gov.uk/drug-safety-update/fluoroquinolone-antibiotics- be given orally where possible
new-restrictions-and-precautions-for-use-due-to-very-rare-reports-of-disabling-and-
potentially-long-lasting-or-irreversible-side-effects Erythromycin has more GI side effects compared to clarithromycin
Tendon damage and rupture has been reported rarely therefore CI if hx of
tendon disorders following quinolone use. Concomitant use of corticosteroids increases Erythromycin = QDS Clarithromycin = BD
the risk
Interactions – inhibitors of CYP3A4 therefore can increase the
Convulsions may be induced and taking NSAIDs at the same time increases the risk
concentration of statins, warfarin, CCBs, apixaban, ciclosporin and digoxin
Cautions
QT-interval prolongation; can cause arthropathy in children; hx of epilepsy; avoid Cautions – can prolong the QT interval
excessive exposure to sunlight
41
PENICILLINS
Overview
Inhibitors of bacterial cell wall synthesis; bactericidal

Allergic reactions occur in 1-10%; anaphylaxis occurs in <0.05%
Benzylpenicillin (Pen G) & phenoxymethylpenicillion (Pen V)
Penicillin G – inactivated by gastric acid therefore given parenterally

Penicillin V – similar spectrum but less active than pen G; active orally; should be taken on an empty stomach
Penicillinase-resistant penicillins
Flucloxacillin –used to treat skin and soft tissue infections caused by Staphylococcus aureus; not inactivated by penicillinases therefore active
against penicillin-resistant staphylococci; must be taken on an empty stomach; QDS dosing
Temocillin – active against beta-lactamase-producing gram-negative bacteria
Broad-spectrum penicillins
Should not be used for the blind treatment of sore throats as often cause a maculopapular rash in people with glandular fever
Ampicillin – active against gram-positive and gram-negative but inactivated by penicillinases (if used in hospital, should check sensitivity first)
Amoxicillin – better absorbed PO compared to ampicillin
Co-amoxiclav – amoxicillin plus clavulanic acid therefore active against beta-lactamase producing organisms (reduce dose of IV in renal impairment)
Anti-pseudomonal penicillins
Piperacillin + tazobactam (tazocin) – usual dosage 4.5g TDS (reduce in renal impairment)
Synergistic effect when combined with an aminoglycoside
Tip – it is worth learning amoxicillin doses in paediatric patients (age banded)
42
TRIMETHOPRIM / CO-TRIMOXAZOLE METRONIDAZOLE

MOA – a pro-drug whereby the nitro-group must be reduced (can only be achieved
Serious Interaction – with MTX (folate antagonist) by anaerobes – therefore spectrum limited to anaerobes)
Trimethoprim Dose – 400 TDS (oral), 500mg TDS (IV). Good bioavailability so give by oral route if
Most commonly used for UTIs 200mg BD available
Sometimes 100mg ON for UTI prophylaxis
Counselling – take with food; avoid alcohol during treatment and for 48hrs after;
Contra-indicated if blood disorders present may darken the urine
Co-trimoxazole
Trimethoprim + sulfamethoxazole NITROFURANTOIN
Treatment/prevention of PCP
Prophylactic dose often MON/WED/FRI MOA – requires excretion into the urine for effect against UTI therefore may be
ineffective if CrCL <45ml/min
Caution in sulphonamide allergy
Monitor for blood disorders (leucopenia, thrombocytopenia, anaemia) Dose – IR 50-100mg QDS; MR 100mg BD
and rash (SJS, TEN reported)
Counselling – may turn urine yellow-brown
Safety Information- risk of peripheral neuropathy. Acute, subacute and chronic
pulmonary reactions have been observed in patients treated with nitrofurantoin. If
LINEZOLID these reactions occur, nitrofurantoin should be discontinued immediately.
Monitoring – Can cause myelosuppression. FBC (including platelets); blood disorders

more likely if treatment >10-14 days
TETRACYCLINES
Safety information – can cause optic neuropathy so patients should report any visual
disturbances Broad spectrum; active against MRSA
Interaction - can cause serotonin syndrome with the co-administration of linezolid and CI - <12yrs due to deposition in teeth and bones
serotonergic agents, including antidepressants such as selective serotonin reuptake
inhibitors (SSRIs). Check interactions closely Counselling – swallow whole with plenty of water whilst sitting or standing; take during
meals; avoid exposure to sunlight / sunlamps
Dose – doxycycline usually 200mg STAT followed by 100mg OD
CHLORAMPHENICOL
Use – broad spectrum; used IV for life-threatening infections CLINDAMYCIN
Infants – can cause ‘grey-baby syndrome’ (avoid in pregnancy) S/E – associated with antibiotic-associated colitis, which could be fatal (more common
than with other abx). D/C treatment if this occurs
S/E – can cause blood disorders, optic neuritis, peripheral neuropathy, stomatitis
43
INFECTION - TUBERCULOSIS
TREATMENT OVERVIEW TYPES OF TB

Latent vs Active
Treated in two phases Latent
Initial phase (usually 2 months) Dormant infection; more likely to progress to active in patients who
To eradicate bacteria as quickly as possible and reduce the are HIV positive, immunocompromised and elderly
chance of resistance emerging The Mantoux skin test can be used to test for latent TB and if
4 drugs – isoniazid, rifampicin, ethambutol, pyrazinamide (Rifater positive, a CXR can be used to rule out active TB
+ ethambutol) Offer chemoprophylaxis to patient’s with latent TB if they are
healthcare workers, close contacts of a person with active TB,
Continuation phase (usually 4 months) immunocompromised (6 months isoniazid or 3 months isoniazid +
Isoniazid + rifampicin (Rifinah) rifampicin)
Longer duration required for TB meningitis and for resistant Active
strains Active infection, usually affecting the lungs but it can affect many
other body systems
Two choices of regimen Treated in 2 phases (see box to left)
Unsupervised
Daily treatment
For patients who are likely to be compliant
RIFAMPICIN
Supervised (DOT – directly observed therapy)
For patients who cannot comply reliably Interactions – potent enzyme inducer (warfarin, COCs)
Important they are treated effectively to stop spread of the
infection Counselling – discolours soft contact lenses, turns secretions orange-red,
report sx of hepatic disorders (abdominal pain, nausea, vomiting)
If daily supervision not appropriate, can have 3 x weekly
Monitoring – renal function; liver function; blood counts
ISONIAZID
PYRAZINAMIDE S/E – peripheral neuropathy (increased risk in DM, renal impairment, alcohol
dependence, malnourished pts, uraemic pts, pregnancy, HIV – give
Monitoring – liver and renal function (can cause hepatoxicity) prophylactic pyridoxine)
ETHAMBUTOL Monitoring – acetylator status (slow = increased risk of peripheral

neuropathy); renal function; liver function
Monitoring – visual acuity (can cause ocular toxicity); renal function
Counselling – tyramine + histamine rich foods can cause tachycardia,
Counselling – d/c treatment immediately and seek medical attention if visual hypotension, flushing, headache, dizziness; report sx of hepatic disorders
disturbances occur
44
INFECTION - ANTIFUNGALS
IMIDAZOLES
TRIAZOLES
Clotrimazole, miconazole, econazole, ketoconazole
Fluconazole, itraconazole, posaconazole, voriconazole
Mainly topical treatments e.g. ketoconazole shampoo; clotrimazole pessary
Fluconazole
Can purchase OTC for candida infection Miconazole oral gel – interacts with warfarin (can increase INR)
Can cause QT-interval prolongation
Less commonly associated with liver damage
Interactions mostly relate to prolonged treatment (enzyme inhibition)
Itraconazole
Liver damage – avoid in patients with liver disease POLYENES
Can be used to treat pityriasis versicolor
High doses and long treatment durations are associated with HF (avoid in Amphotericin B
patients with a history of HF)
Highly protein bound
Capsules – take with food
Solution – take on an empty stomach Toxic and commonly causes s/e (abnormal liver function,
anaemia, arrhythmias, blood disorders, hypoK+ and
Posaconazole hypoMg2+
Used for invasive fungal infections unresponsive to other treatments Lipid formulations reduce toxicity (e.g. Ambisome)
Voriconazole Test dose required before first dose and patient should be
Used for invasitve fungal infections, in possible life-threatening infections observed for 30mins for anaphylaxis
IV and oral Infused slowly as rapid infusion can cause arrhythmias
Lots of interactions
Non-linear pharmacokinetics Monitoring
Monitor LFTS Liver and renal function
Associated with phototoxicity
Blood counts
K+ and Mg2+
ECHINOCANDINS Nystatin
Caspofungin, Micafungin
Used for oral infections – swirled around the mouth
IV only. Not effective against fungal CNS infections

Only active against Aspergillus and Candida
45
GENITO-URINARY MEDICINE
Urinary Frequency Urinary Retention
Antimuscarinic Drugs Antimuscarinics, tricyclic antidepressants and sympathomimetics may

Increase bladder capacity and decrease symptoms of urgency and urge contribute to urinary retention
incontinence. Their use should be reviewed every 4-6 weeks until stable
and then every 6-12 months Urinary retention and benign prostatic hyperplasia
Alpha blocker = treatment of choice: relaxes smooth muscle
Contraindications and produces an increase in urinary flow rate
GI obstruction; paralytic ileus; toxic megacolon; severe UC 5a-reductase inhibitor = considered when there is raised
Urinary retention; bladder outflow obstruction prostate specific antigen and a high risk of progression
Both can be combined if symptoms remain problematic
Cautions
CVD (MI, HF, CAD) Alpha blockers
Susceptibility to angle-closure glaucoma Doxazosin – 1mg OD, can be increased to 8mg OD
Tamsulosin – 400micrograms OD
S/E Contraindications – postural hypotension
‘Can’t spit, can’t see, can’t poo, can’t pee’ – dry mouth, blurred
vision, constipation, urinary retention 5a-reductase inhibitors
Dilated pupils Dutasteride – 500micrograms OD
Finasteride – 5mg OD. MHRA warning: reports of depression
Oxybutynin and suicidal thoughts
MR preparations may also reduce side effects
Available as a transdermal patch S/E – breast enlargement, breast tenderness, decreased
Dose 5-20mg per day libido, ejaculation disorders, impotence
Cases of male breast cancer have been reported – patients
Solifenacin should report any lumps, tenderness or nipple discharge
5-10mg per day (max 5mg If CYP3A4 inhibitors prescribed) Women of childbearing age should avoid handling
Condoms recommended if women is pregnant or could
Tolterodine become pregnant
1-2mg BD
Can cause peripheral oedema
Beta3 Agonist – Mirabegron

Common side effect – tachycardia and UTI
46
GENITO-URINARY MEDICINE - CONTRACEPTION
Combined Oral Contraceptive Pill (COC) Combined Oral Contraceptive Pill (COC)
MOA – prevent ovulation, cause thickening of the mucus in the womb and A missed pill is defined as >24hrs later
thin the endometrium. Contain an oestrogen and a progesterone.
One Missed Pill
Minor S/E – mood changes, nausea, breast tenderness, headaches Take the pill as soon as you remember, even if it means taking
2 pills at the same time
Major S/E (rare) – VTE, cervical cancer Carry on taking the rest of the pack as normal
Take your 7-day PFI as normal (unless you have the everyday
1 – Monophasic 21-day pills pill)
Each pill has the same content of hormone No extra contraception required
Take one pill OD for 21 days, followed by a 7-day pill-free interval
(PFI) Two or more missed pills
E.g. microgynon, marvelon, yasmine, cilest This is 48hrs or more without a pill
Take the last pill missed as soon as you remember, even if
2 – Phasic 21-day pills this means taking 2 at the same time
One pill OD for 21 days, following by a 7-day PFI Leave any earlier missed pills
Pills must be taken in the correct order as they contain differing Carry on the rest of the pack like normal
hormone contents Use extra contraception for next 7 days
E.g. logynon If there are 7 or more pills left in the pack after the last missed
pill, finish the pack and take your 7-day PFI as normal (or
3 – Everyday pills inactive pills if everyday pill)
21 active pills and 7 placebo pills (different appearance) If there are <7 pills left in the pack after the missed pill, finish
Pills must be taken in the correct order the pack and start a new pack the next day (i.e. miss the 7-day
E.g. microgynon ED PFI or miss the inactive pills in the everyday pill)
Who should not take the COC? – see BNF for full list Vomiting and Diarrhoea
35yrs + and a smoker (or stopped smoking <1yr ago) If you vomit within 2hrs of taking, take another pill straight
Overweight – BMI 35+ away
Previous VTE or family history of VTE at <45yrs old If you continue to vomit, use extra protection for 7-days after
Previous stroke the vomiting has stopped
Hypertension Severe diarrhoea – use extra protection for 2-days after the
Severe migraines, especially with aura diarrhoea has finished
History of breast cancer
47
GENITO-URINARY MEDICINE - CONTRACEPTION
COC – interactions
Progestogen-Only Pill (POP)
Rifampicin
Reduces contraceptive effect MOA – thicken the mucus in the cervix; if desogestrel-containing, also
stop ovulation.
Antiepileptics
Carbamazepine How to take
Oxycarbazepine ‘3-hour POP’ – must be taken within 3hrs of the same time each day
Phenytoin
’12-hour POP’ – contains desogestrel. Must be taken within 12-hours
Phenobarbital + primidone
of the same time each day
Topiramate
These reduce the contraceptive effect A pack contains 28 days, one must be taken each day. There is no
See Stockley’s for management advice break between packs
If the pill is started on days 1-5 of the menstrual cycle, it will work
immediately and no additional contraception will be required.
Advantages of COC
If started on any other day, additional contraception will be required for
2 days
Reliable and reversible
Missed Pills – i.e. 3 hours or 12 hours late
Reduced dysmenorrhoea and menorrhagia Take the pill as soon as you remember
Take the next pill at the usual time (may mean taking 2 on the
Reduced incidence of pre-menstrual tension same day)
Carry on taking remaining pills as normal
Less fibroids and ovarian cysts Use extra contraception for 48hrs
Less benign breast disease Side Effects

Acne
Reduced risk of ovarian and endometrial cancer Breast tenderness and enlargement
Ovarian cysts
Reduced risk of pelvis inflammatory disease Increased / decreased libido
NOTE – should be discontinued 4 weeks before major elective surgery
48
GASTROENTEROLOGY - CONSTIPATION
Self-Help Advice for Constipation Management of short-term constipation
Diet Rule out secondary causes and review drug regime

Healthy, balanced diet with regular meals First-line: lifestyle measures (see left). If these are ineffective, offer laxatives in a stepped
Whole grains approach as follows:
Fruits high in sorbitol (apples, apricots, grapes, 1 – Bulk-forming laxative: e.g. ispaghula. Provide advice on adequate fluid intake
peaches)
2 – Osmotic laxative: e.g. macrogol. Should be substituted or added if stools remain
Vegetables
hard/difficult to pass. Lactulose is second-line to macrogol
Fibre intake should be increased gradually
minimise flatulence and bloating – adults
3 – Stimulant laxative: e.g. senna. If stools are soft but difficult to pass or if there is a sensation
should aim for 30g/day
of inadequate emptying, add a stimulant.
Fluid
For opioid-induced constipation: offer an osmotic + a stimulant laxative (or docusate). Do not
Adequate fluid intake, especially if risk of offer a bulk-forming laxative due to risk of faecal impaction
dehydration
Laxative use should be gradually reduced and stopped once the person is produced soft stools
Exercise
without straining at least 3 x per week
Increase exercise activity to 30mins 5 x per
week
Helpful toileting routines

Regular, unhurried toilet routine, giving time to Faecal Impaction
fully defecate
Respond immediately to the sensation of This is a solid, immobile mass of faeces that can develop in the rectum due to chronic constipation
needing to defecate
Ensure access to supported seating if the 1 – High dose oral macrogol if stools are hard
person is unsteady on the toilet
2 – If there are soft stools or stools remain hard after a few days, add an oral stimulant laxative
Red flag symptoms 3 – If response is still inadequate or too slow, consider prescribing a suppository (e.g. bisacodyl
Unexplained weight loss for soft stools or glycerol with/without bisacodyl for hard stools) or a mini enema (e.g. docusate
Abdominal pain or sodium citrate)
Rectal bleeding 4 – If response is still inadequate, consider prescribing sodium phosphate or arachis oil
retention enema
49
GASTROENTEROLOGY - CONSTIPATION
Types of Laxatives Contra-indications to laxatives
Bulk-forming laxatives Intestinal obstruction or perforation

Contain soluble fibre Paralytic ileus
Act by retaining fluid within the stool and increasing Colonic atony or faecal impaction – bulk-forming laxatives
faecal mass Crohn’s disease or Ulcerative Colitis
Also stimulant peristalsis Toxic megacolon
E.g. ispaghula, methylcellulose, sterculia Severe dehydration – bisacodyl
Osmotic Laxatives Galactosaemia – lactulose
Increase amount of fluid in the large intestine producing History of hypersensitivity to peanuts – arachis oil enema
distension, which leads to the stimulation of peristalsis
Lactulose and macrogols have stool softening
properties Cautions for the prescribing of laxatives
E.g. lactulose, macrogols (polyethylene glycols),
phosphate and sodium citrate enemas Fluid and electrolyte disturbances
Stimulant Laxatives History of prolonged use – risk of electrolyte imbalance e.g. hypoK+
Stimulate colonic nerves (senna) or colonic and rectal CVD – do not prescribe >2 sachets of full-strength macrogol compound oral
nerves (bisacodyl, sodium picosulfate) to cause powder in any one hour
peristalsis Lactose intolerance – lactulose may cause diarrhoea
E.g. senna, bisacodyl, docusate
Docusate is a surface wetting agent, which reduces
surface tension of the stool, allowing water to penetrate
and soften it
Naloxegol is used in opioid-induced constipation Constipation in Pregnancy
PEGylated derivative of the mu-opioid receptor
antagonist naloxone, it works as a peripheral receptor First-line: lifestyle measures
antagonist without diminishing the analgesic effects of
opioids. Second-line: bulk-forming laxative
For use where treatment failure with at least two different laxatives
from different classes at highest tolerated recommended dose for Third-line: osmotic laxative – add or switch
at least six months and where invasive treatment is being
considered:
Prokinetic Laxatives If stools are soft but difficult to pass or there is a sensation of incomplete
emptying, consider a stimulant laxative (short-course)
Prucalopride – a selective 5HT4 receptor agonist, which
stimulates intestinal motility
Fifth-line: glycerol suppository
50
GASTROENTEROLOGY - DIARRHOEA
Overview
Clostridium Difficile Infection
Definition: The abnormal passing of stools with
increased frequency, increased volume or both. Risk factors: >65yrs; antibiotic treatment (most common: clindamycin, cephalosporins,
Acute <28 days ciprofloxacin, norfloxacin, co-amoxiclav, ampicillin, amoxicillin); long duration of antibiotic
treatment; previous abdominal surgery; cancer; chronic renal disease; tube feeding; PPI or H 2-
Causes: drugs, IBD, infection, altered intestinal receptor antagonist use
motility
Severity
Red flag symptoms: unexplained weight loss, rectal Mild – not associated with an increase in WCC. <3 episodes of loose stools/day
bleeding, persistent diarrhoea, systemic illness, Moderate – increase in WCC (<15 x 109/L). 3-5 loose stools per day
recent antibiotic treatment, following foreign travel, Severe – increased WCC (>15 x 109)/L) or increased serum creatinine (>50% above baseline)
recent hospital treatment, blood/pus in stool, or temperature >38.5, evidence of severe colitis. Number of stools may be a less reliable
dehydration, nocturnal symptoms indicator at this stage
Life-threatening – hypotension, partial or complete ileus, toxic megacolon or CT evidence of
Treatment: most episodes of acute diarrhoea settle severe disease
spontaneously without treatment. Attempt to
determine underlying cause Treatment
Stop antibiotic if appropriate, where not appropriate review to narrow spectrum and seek
Oral rehydration therapy (disodium specialist advice
hydrogen citrate with glucose, KCl and NaCl; First episode of mild-moderate
KCl with NaCl; KCl with rice powder) Oral metronidazole 10-14 days – 400mg TDS
If severe dehydration – immediate 2nd or subsequent episodes / severe infection / infection not responding to metronidazole
admission to hospital and IV fluid Oral vancomycin 10-14 days – 125-500mg QDS
replacement required Fidaxomicin is an alternative 10 days – 200mg BD
Loperamide – standard treatment when rapid Infection not responding to vancomycin or fidaxomicin / life-threatening infection / ileus present
control of symptoms required. It is also first- Oral vancomycin + IV metronidazole 10-14 days – 125-500mg QDS and 500mg
line for faecal incontinence. TDS
Dose 4mg initially followed by 2mg after each Note – vancomycin injection can be given orally
loose stool, max. 16mg per day
Avoid giving antimotility drugs such as loperamide and ensure hygiene measures in place.
Consider impact of diarrhoea/dehydration on Review other medications with GI activity e.g. iron, laxatives, proton pump inhibitors
medicines (e.g. lithium, diuretics)
51
GASTROENTEROLOGY – INFLAMMATORY BOWEL DISEASE
Aminosalicylates
Azathioprine
Mesalazine, sulfasalazine, olsalazine, balsalazide
MOA –Azathioprine (AZA) is broken down enzymatically to 6-mercaptopurine, which
Sulfasalazine antagonises purine metabolism, thereby inhibits synthesis of DNA, RNA and proteins. The
Broken down by colonic enzymes to 5- mechanism of therapeutic effect however is largely unknown.
aminosalicylic acid (5-ASA) and
therapeutically inactive sulfapyridine Pre-treatment screening – thiopurine methyltransferase (TPMT)
Sulfapyridine causes systemic side effects This enzyme metabolises thiopurine drugs
May stain soft contact lenses, yellow Patients with diminished TPMT activity are at an increased risk of myelosuppressive
discolouration of body fluids side effects
Formulations:tablets, GR tablets, oral Azathioprine is contraindicated when TPMT activity if absent or very low and it is
suspension, suppository cautioned in reduced TPMT activity
Patients are also screen for TB and vaccination status is confirmed
Mesalazine Some patients metabolise azathioprine in such a way that efficacy of treatment is reduced,
Free 5-ASA only whilst the risk of side-efffects is higher. In these patients you may see allopurinol prescribed
Medicines which lower stool pH (e.g. concomitantly, with a reduced dose of azathioprine (25-33% lower dose)
lactulose) might prevent the release of
GR/MR preparations Side Effects
Hypersensitivity reactions – may include malaise, dizziness, vomiting, diarrhoea, fever, rigors,
Formulations: MR tablets, GR tablets,
prolonged release granules, enemas, rectal myalgia, arthralgia, rash, hypotension, renal dysfunction. Immediate withdrawal required
foams. Delivery characteristics may vary Neutropenia & thrombocytopenia – neutropenia = dose-dependent side effect. If these occur,
with different brands monitoring and dose adjustment necessary
Nausea – this is common at the start of therapy and usually resolves after a few weeks.
Side Effects of Aminosalicylates Nausea can be reduced by dividing the daily dose, taking the dose after food or with the use
Common - Leucopenia, GI side-effects, pruritis, of antiemetics.
headache
Monitoring – FBC, creatinine clearance/eGFR, LFTs
Uncommon - Alopecia, dyspnoea, photosensitivity,
thrombocytopenia Every 2 weeks until dose is stable for 6 weeks. Then monthly for 3 months. Thereafter, at
Rare - Agranulocytosis, bone marrow disorders, least every 12 weeks.(More frequent monitoring is appropriate in patients at higher risk of
toxicity). Dose increases: Every 2 weeks until dose is stable for 6 weeks, then revert to
neutropenia, pancreatitis, renal impairment
previous schedule
Counselling – report any unexplained bleeding,
Counselling – Report signs or symptoms of bone marrow suppression – unexplained
bruising, purpura, sore throat, fever or malaise
bruising / bleeding and infection
Monitoring – FBC, Creatinine clearance/eGFR,
LFTs
52
Methotrexate
Dose in Crohn’s Disease– up to 25mg weekly
MOA in Crohn’s unclear

Important Safety information
Advise patient the dose is a weekly dose
Explain the rationale for taking folic acid alongside MTX (decreases mucosal and GI effects of methotrexate and may prevent hepatotoxicity. Usually
taken on a different day of the week, or up to 6 days weekly if side-effects experienced)
Only one strength of MTX tablets should be dispensed (2.5mg usually)
Contraindications
Active infection; significant pleural effusion, ascites; immunodeficiency syndromes
Cautions
Blood Count – bone marrow suppression can occur; increased age, renal impairment and the addition of other anti-folate drugs increase the risk; if a
clinically significant drop in WCC or platelets occurs, immediately withdraw MTX and commence supportive therapy
GI toxicity – if stomatitis occurs, withdraw treatment immediately as this could be the first sign of GI toxicity
Liver toxicity – liver cirrhosis reported. Do not start treatment / stop treatment if abnormal LFTs or liver biopsy
Pulmonary toxicity – may be a particular problem in rheumatoid arthritis; discontinue if pneumonitis suspected
Monitoring
FBC, renal function, LFTs every 2 weeks until a stable dose is maintained for 6 weeks. Then monthly for 3 months*. Thereafter, at least every 12 weeks.
More frequent monitoring is appropriate in patients at higher risk of toxicity.
Dose increases: Every 2 weeks until dose is stable for 6 weeks, then revert to previous schedule. (monthly monitoring should continue if used in combination
with leflunomide).
Counselling
Report immediately signs of blood disorders (sore throat, bruising, mouth ulcers), liver toxicity (nausea, vomiting, abdominal pain, dark urine), respiratory
effects (shortness of breath)
Avoid self-medication with aspirin or ibuprofen
Read treatment booklet – available here for extra revision: https://www.sps.nhs.uk/wp-content/uploads/2018/02/2006-NRLS-0267-Oral-
methotrexaosage-record-2006-v1.pdf
53
Ciclosporin
Unlicensed use, last line in steroid-resistant UC (usually in an attempt to prevent surgery)
Brands – patients should be stabilised on one brand of oral ciclosporin as switching between brands may lead to important changes in blood-ciclosporin levels
Contraindications (in non-transplant indications)

Abnormal baseline renal function
Malignancy
Uncontrolled hypertension and uncontrolled infections
Cautions
Elderly (monitor renal function)
Hyperuricaemia
Malignancies
Food interactions
Pomelo/grapefruit juice is predicted to increase ciclosporin exposure and purple grape juice decreases ciclosporin exposure
Side Effects
Electrolyte imbalance, gingival hyperplasia, hepatic disorders,
Hyperglycaemia, hyperlipidaemia, hypertension, hyperuricaemia,
Leucopenia, paraesthesia, peptic ulcer, renal impairment
TDM – Monitor whole blood ciclosporin concentration (trough) – target level is dependent on the indication
Other monitoring
Liver function and renal function, FBC, blood glucose and BP – discontinue if hypertension develops that cannot be controlled by antihypertensives.
Ciclosporin levels weekly until dose is stable for 6 weeks, then monthly. People who have been stable for 12 months can be considered for reduced
monitoring frequency (every 3 months) on an individual basis. More frequent monitoring is appropriate in patients at higher risk of toxicity.
Serum K+/Mg2+and blood lipids at baseline – risk of seizures with hypomagnesemia, and toxicity with cholesterol <3mmol/L
Dose increases: Every 2 weeks until dose is stable for 6 weeks, then revert to previous schedule.
54
Crohn’s Management
Add-on treatment
Acute exacerbation – Monotherapy
2 or more inflammatory exacerbations in a 12-month period or
1st presentation or a single inflammatory exacerbation in 12-months
the glucocorticoid cannot be tapered
1st line Glucocorticosteroid Glucocorticosteroid (or budesonide) + azathioprine or
mercaptopurine
Prednisolone Assess TPMT activity before
Methylprednisolone Do not offer if this is very low or absent
IV hydrocortisone Consider using lower dose if TPMT below normal (but not
deficient)
Consider enteral nutrition as an alternative to above to induce Monitor for neutropenia
remission for children in whom there is concern about growth or
s/e and young people in whom there is concern about growth Consider adding methotrexate
In people who cannot tolerate azathioprine or MP
2nd line Budesonide – if above CI, decline or not tolerated In people who have deficient TPMT activity
Less effective
Less s/e Adalimumab or infliximab (Anti-TNF monoclonal antibody)
Do not offer for severe presentations/exacerbations Under specialist supervision
If inadequate response to conventional therapies or
3rd line 5-ASA intolerance or C
If above declined, not tolerated or CI Vedolizumab ( α4β7 integrin monoclonal antibody)
Fewer s/e Treatment option for moderate-severe active Crohn’s when
Less effective adalimumab or infliximab is unsuccessful, CI or not
Do not offer for severe presentations/exacerbations tolerated
Do not offer azathioprine, MP or MTX as monotherapy to induce remission
55
Active Fistulating Crohn’s Disease

Metronidazole and/or ciprofloxacin
Metronidazole – usually given for 1 month (maximum 3 months due to risk of peripheral neuropathy)
Abx
Ciprofloxacin - unlicensed
Or as guided by Microbiology
Azathioprine or MP
Immuno-
suppressants
To control inflammation
Continued for maintenance for at least 1 year
For patients with active, fistulating Crohn’s disease:
Who have not responded to conventional therapy (abx, drainage and immunosuppressants)
Infliximab
Who are intolerant of or have Cis
For 12 months or until treatment failure – whichever is first
Maintenance of Remission – Crohn’s Disease

As monotherapy
Azathioprine
Can be used when previously used with a corticosteroid to induce remission
or MP
Can also be used in patients who have not previously received these drugs
Only in patients who required MTX to induce remission
MTX
Or patients intolerant of or are not suitable for AZA or MP for maintenance
Maintaining Remission After Surgery
Consider Azathioprine or MP to maintain remission after surgery in people with adverse prognostic factors e.g. More than one resection OR
Previously complicated or debilitating disease
Other treatments
Loperamide
To manage diarrhoea in those who do not have colitis
or codeine
Colestyramine Relief of diarrhoea associated with Crohn’s disease
56
Ulcerative Colitis - Acute Exacerbations

Step 1 Step 1 Step 1 Step 1
Mild-moderate - proctitis Mild-moderate proctosigmoiditis or Extensive disease Acute Severe UC
left-sided disease (person admitted to hospital)
1st Topical aminosalicylate 1st Topical aminosalicylate 1st Topical aminosalicylate 1st Give IV corticosteroids
line (suppository or enema) line line and high-dose oral line
aminosalicylate
2nd If a topical aminosalicylate 2nd If topical treatment is 2nd Where aminosalicylates 2nd Consider IV ciclosporin or
line is declined line declined, consider: line are not tolerated offer a line surgery for people who
Consider oral High-dose oral time-limited course of decline, cannot tolerate
aminosalicylate – not as aminosalicylate alone – not corticosteroids or have CI to IV
effective as effective corticosteroids
rd rd
3 If cannot tolerate 3 If aminosalicylates are CI, not
line aminosalicylates: line tolerated or declined:
Consider a time-limited Give topical or oral
course of topical or oral corticosteroid
corticosteroid
Step 2 Step 2 Step 2 Step 2
If there is no improvement within 4 If there is no improvement within 4 1st If no response, worsening or
If admission not achieved within 4 weeks of starting step 1 weeks, stop topical line little improvement
weeks aminosalicylate therapy or if aminosalicylates and offer a high- within 72hrs of starting IV
Consider adding oral symptoms worsen despite treatment: dose oral aminosalicylates with a corticosteroids
aminosalicylate or a time- Consider adding a high-dose oral time-limited course of an oral Add IV ciclosporin to
limited course of oral or aminosalicylate or corticosteroid IV corticosteroids
topical corticosteroid where Switching to a high-dose oral or consider surgery
oral aminosalicylate is used aminosalicylate and a time-limited
as 1st line therapy 2nd If ciclosporin is CI or
course of a topical corticosteroids
line inappropriate:
Step 3 Infliximab is recommended
If further treatment required, add
a time-limited course of a topical
or oral corticosteroid (where not
already prescribed)
57
Maintenance of Remission- Ulcerative Colitis
Maintaining Remission All extents of disease

Proctitis and Proctosigmoiditis (after mild-moderate exacerbation) Maintaining remission after a single episode of acute-severe UC
1st line Topical aminosalicylate (daily or intermittent) 1st line Oral azathioprine or MP
In people who cannot tolerate, have CIs or decline

Topical aminosalicylate + oral aminosalicylate (daily or
nd
2 line 2nd line azathioprine or MP:
intermittent)
Oral aminosalicylates
Disease refractory to immunomodulatory therapy despite dose

3rd line Oral aminosalicylate alone – not as effective
optimization or where conventional treatment is not tolerated or CI
Maintaining remission - All extents of disease

After 2 or more exacerbations in 12 months that require treatment Infliximab, adalimumab or golimumab (choice made on
1st line
with systemic corticosteroids individual basis)
Or if remission is not maintained with aminosalicylates
1st line Azathioprine or MP 2nd line Vedolizumab
Tofacitinib (where conventional therapy or a biological agent

Maintaining remission
3rd line cannot be tolerated or disease response is inadequate/has
Left-sided and Extensive UC (after mild-moderate exacerbation)
been lost)
1st line Low maintenance dose of an oral aminosalicylate
Consider OD dosing regimen (although no difference in
efficacy vs divided dosing and can result in more s/e)
58
GASTROENTEROLOGY – HELICOBACTER PYLORI
Description
One of the most common causes of peptic ulcer disease, associated with 95% of duodenal and 70–80% of gastric ulcers.
There is an additive risk of peptic ulceration where non-steroidal anti-inflammatory drugs (NSAIDs) are used in patients with co-existent H. pylori infection.
H. pylori is also associated with acute and chronic gastritis, gastric cancer, and gastric mucosa associated lymphoid tissue (MALT) lymphoma.
Aims of treatment
To eradicate H. pylori, reduce the risk of peptic ulcer disease, ulcer bleeding and gastric malignancy, and the recurrence of gastritis and peptic ulcers.
Testing for H. pylori

Testing by the urea (13C) breath test, Stool Helicobacter Antigen Test (SAT), or laboratory-based serology
- NB: 13C test and SAT should not be performed within 2 weeks of treatment with a proton pump inhibitor (PPI), or within 4 weeks of antibacterial
treatment (as this can lead to false negatives)
Who to treat
Patients with uncomplicated dyspepsia, and no alarm symptoms who are unresponsive to lifestyle changes and antacids, following a single 1 month
treatment course with a PPI
Those at high risk (older people, those of North African ethnicity or those living in a high risk area) should be tested before trial of PPI
Previously untested patients with a history of peptic ulcers or bleeds, prior to initiating NSAIDs in patients with a prior history of peptic ulcers or bleeds,
unexplained iron-deficiency anaemia after endoscopic investigation has excluded malignancy, and other causes have been investigated
Drug treatment
Usually involves triple therapy comprising a PPI and 2 antibacterial agents (choice of regimen should consider the patient’s antibacterial treatment history
and consideration to resistance)
Example regimens (these will vary depending on local guidance):
No penicillin allergy (1st line) True penicillin allergy (2nd line)

Omeprazole PO 40mg BD + amoxicillin PO 1g BD + clarithromycin PO 500mg BD 7 Omeprazole PO 40mg BD + clarithromycin PO 500mg BD +
days metronidazole PO 400mg TDS 7 days
Repeat course of an alternative combination of antibiotics if first line fails
59
IMMUNE SYSTEM AND MALIGNANT DISEASE - CYTOTOXIC DRUGS
Alkylating Agents Anti-tumour antibiotics
Alkylating agents work transferring an alkyl group to the purine Anthracyclines: doxorubicin, daunorubicin, epirubicin, idarubicin
bases of DNA (adenine and guanine) which results in the formation
of cross links within the DNA chain. This ultimately leads to Specific mechanism of action is unclear but have several effects:
apoptosis. Act on signal transduction
Generate free radicals
These agents are non-specific and will therefore act on all rapidly Target topoisomerase II which leads to DNA strand breaks and cell death
dividing cells. There are several dose limiting acute toxicities:
Myelosuppression
Side effects: anaemia, pancytopenia, amenorrhea, mucosal Mucositis
damage, alopecia, increased risk of malignany. Alopecia
N.B. these side effects are due to the non-specific action of alkylating agents.
Cumulative cardiotoxicity – due to generation of free radicals in the heart. ECHO
required before treatment with anthracyclines and periodically during treatment
Melphalan: derivative of nitrogen mustard and the amino acid
to check heart function. Due to this risk, life time cumulative doses cannot be
phenylalanine which make it more likely to be taken up by rapidly
exceeded.
dividing cells resulting in some selectivity.
Dactinomycin: binds to DNA and inhibits the synthesis of RNA and proteins.
Cyclophosphamide: extensively used. Major toxicities include
bone marrow suppression, alopecia, nausea and vomiting.
Mitomycin: toxicity includes myelosuppression, especially thrombocytopenia.
Ifosfamide: isomer of cyclophosphamide. Side effects include
alopecia and haemorrhagic cystitis which can be overcome by the
co-administration of mesna which combines with the metabolite
responsible for causing this toxicity. Plant Alkaloids
Cyclophosphamide and ifosfamide are pro-dugs which are These are tubulin-interactive agents that act by binding to tubulin (protein that forms
activated through cytochrome P450 enzymes cellular microtubules used cell division – specifically metaphase)
Chlorambucil: a well absorbed derivative of nitrogen mustard Vinka alkaloids: Vinblastine, vincristine, vinorelbine
Cause neurotoxicity, extravasation, myelosuppression
Carmustime: a small lipophilic molecule used in CNS tumours and Must not be given intrathecally – can cause severe neurotoxicity, which is usually fatal
haematological malignancies (multiple myeloma and lymphoma).
Licenced for use as intralesional implants for treatment of recurrent Taxanes: Docetaxel, paclitaxel, cabazitaxel
glioblastoma and malignant glioma Can cause severe hypersensitivity reactions therefore may require steroids and
antihistamines pre-treatment
60
Antimetabolites
Antimetabolites are structurally related to natural compounds. They interfere with cell metabolism of nucleic acids which are necessary for DNA, RNA and protein
synthesis. They specially act within the S-phase of the cell cycle.
Methotrexate: inhibits folate metabolism thereby inhibiting the synthesis Cytarabine: a cytosine analogue which competes with cytosine for
of purines and pyrimidines required for DNA and RNA synthesis. incorporation into RNA and DNA
Common toxicities include mucositis, myelosuppression and Toxicities include vomiting, myelosuppression and alopecia.
nephrotoxicity. “Rescue” folinic acid is administered after high dose MTX
to promote clearance and reduce toxicities. Due to its rapid clearance, cytarabine acts more effectively when given as
a continuous infusion.
Fluorouracil: pro-drug which is activated within the cell. Metabolites act
by inhibiting pyrimidine synthesis. It has a relatively short half life with Gemcitabine: also a cytosine analogue. It has better cell permeation and
significant hepatic, renal and lung clearance. affinity than cytarabine.
Toxicities include myelosuppression, stomatitis, cardiotoxicity,
Toxicities include myelosuppression, oedema, flu-like symptoms and
neurotoxicity and diarrhoea. Prolonged infusion can result in hand-foot
nephrotoxicity
syndrome.
Can be administer over longer periods of time (e.g. 48 hours or over 1 Fludarabine: an adenosine analogue which competes with adenosine for
week) via an infusion pump. incorporation into RNA and DNA. Before incorporation, it is
phosphorylated.
Capecitabine: orally administered pro-drug of fluorouracil which is
activated within the tumour itself and in the liver. It can potentially be used Toxicities include myelosuppression and haemolytic anaemia.
to replace prolonged and continuous infusion of fluorouracil. Dose limiting
diarrhoea can affect treatment and can result in dosage reductions or Hydroxycarbamide: reduced the availability of nucleotides by inhibiting
treatment cessation. the enzyme ribonucleotide reductase
Pemetrexed: an anti-purine which acts as an antagonist against enzymes Toxicities include myelosuppression, GI toxicity and hyperpigmentation of
involved in folate dependent pathways which result in a decrease of the skin.
intracellular purines
Toxicity is reduced by co-administration of B12 and folate supplements.
61
Topoisomerase inhibitors
Platinum complexes
Topoisomerase enzymes are involved in the regulation of the winding of
Platinum agents interfere with and disrupt the structure of the DNA DNA. In eukaryotic cells there are two types:
double helix. They also form cross links which are similar to those of Topoisomerase I cleaves apart the double strand of DNA. These
alkylating agents. Electrolyte imbalances are caused, particularly low relaxed strands are then used for replication, transcription and
magnesium. recombination.
Topoisomerase II cuts both strand of DNA simultaneously
Cisplatin: bind directly to DNA and forms cross links within the strands allowing another strand of double helix DNA to pass through the
which ultimately inhibits DNA synthesis by altering its structure. cut thereby stopping tangles.
Toxicity include dose dependent nephrotoxicity, peripheral neuropathy
and ototoxicity. It is also highly emetogenic. Topoisomerase I inhibitors
Irinotercan and Topotecan: both block the action of Topoisomerase I
Initial clearance of cisplatin is fast followed by a reduced rate which is whose action is increased in cancer cells
due to plasma binding. Renal impairment affects clearance.
Toxicities include neutropenia, diarrhoea, nausea, vomiting, anaemia,
Carboplatin: is an analogue of cisplatin thrombocytopenia and alopecia
Toxicities include thrombocytopenia, nephrotoxicity, ototoxicity, Topoisomerase I inhibitors

neurotoxcity, alopecia and nausea and vomiting. Carboplatin is Etoposide and Teniposide: both inhibit the action of Topoisomerase II
considered less toxic compared to cisplatin (other than higher rates of through various mechanisms:
thrombocytopenia). Preventing the enzyme from regulating cleaved DNA
Clearance is dependent on renal function and therefore dosage is Generating large amounts of DNA with a high number of DNA
dependent on creatine clearance. breaks
Creating irreversible double stranded breaks
Oxaliplatin: platinum analogue differing from carboplatin and cisplatin Causing inconceivable recombination
(has a broader spectrum of activity). Apoptosis
Can cause dose limiting peripheral neuropathy which can reverse upon Toxicities include blood pressure changes (related to the infusion),
withdrawal of oxaliplatin. Other toxicities experienced include diarrhoea, neutropenia, alopecia, mucositis and hypersensitivity reactions. They
nausea, vomiting, bone marrow suppression and ototoxicity. are both heavily protein bound which leads to higher toxicities in those
with low serum concentrations of albumin.
62
IMMUNE SYSTEM AND MALIGNANT DISEASE - CYTOTOXIC DRUGS (SIDE EFFECTS)
Side effects of cytotoxic medications

Oral mucositis Alopecia
Commonly caused by anthracyclines, fluorouracil and methotrexate Usually occurs 3 – 6 weeks after first dose of chemotherapy
Also effect of radiotherapy to head and neck area Reversible hair loss is common
Prevention: good oral hygiene, use of soft toothbrush, sucking ice No pharmacological methods available for prevention/treatment
chips during infusion (reduced blood flow to mouth due to Cold caps can be worn during treatment to minimise
vasoconstriction meaning less drug will travel to the area), using concentration of cytotoxic drug reaching hair follicles through
artificial saliva mouth washed and gels. vasoconstriction
Treatment: anti-inflammatory mouthwashes (e.g. Benzydamine),
saline mouthwashes, palifermin (human keratinocyte growth factor),
pain medications (such as paracetamol, codeine and morphine)
Poor oral hygiene can cause fungal infections and also lead to
system infections
Nausea and vomiting

Acute: within 24 hours of treatment
Delayed: occurs 24 hours after treatment has finished
Anticipatory: occurs prior to treatment (treatment includes use of an
anxiolytic agent e.g. lorazepam)
Prophylaxis vital in reducing symptoms experienced – steroid
commonly used prior to treatment for this reason
Different cytotoxic medications have different emetogenic
properties – treatment based upon this
Common anti-emetic agents used: metoclopramide, ondansetron, Asparagine – neurotoxicity
dexamethasone, aprepitant, cyclizine and domperidone Cisplatin – nephrotoxicity
Vincristine/Vinblastine – peripheral neuropathy
Pregnancy and reproduction
Most cytotoxic drugs are teratogenic Vinblastine – bone marrow toxicity
Effective contraception is required both during and after treatment Bleomycin – pulmonary fibrosis
Alkylating agents affect fertility to the greatest extent – can cause Doxorubicin – cardiac toxicity
permanent male sterility
Women are affected less than men however their reproductive life Cyclophosphamide – haemorrhagic cystitis
span may be reduced due to early menopause Methotrexate – hand-foot syndrome
63
IMMUNE SYSTEM AND MALIGNANT DISEASE – IMMUNOTHERAPY
Background
Immunotherapy toxicities
Immunotherapy uses a person’s own immune system to Skin toxicity
fight cancer. Immunotherapy works by: Most commonly caused by ipilimumab, nivolumab and pembrolizumab
Training the immune system to recognise and Can cause rash, pruritus, and vitiligo and rarely alopecia, stomatitis, dry skin and
attack cancer cells photosensitivity
Boost person’s immune system to fight cancer Management: topical emollients, oral antihistamines, and topical corticosteroids.
Provide a person with additional components to Systemic steroids to be used to high severity rash
enhance the immune response to cancer
Thyroid toxicity
Some treatments help the immune system to
Hyperthyroid disorders more common than hyperthyroid disorders
slow down or stop the growth of cancer
Management: thyroid hormone for hypothyroidism. Beta-blockers, carbimazole or
Others help the immune system to destroy
steroids can be used for hyperthyroidism
cancer cells to stop it from metastasising
Hepatotoxicity
Immunotherapy allows for more targeted treatment. Can occur in those being treated with ipilimumab, nivolumab and pembrolizumab
All patients should have serum transaminases and bilirubin measured prior to
Monoclonal antibodies treatment to assess for presence of hepatotoxicity
E.g. ipilimumab, nivolumab, pembrolizumab, Management for moderate hepatotoxicity includes withholding immunotherapy.
atezolizumab, avelumab Steroid may be required for persistent toxicity. If no response to steroids,
Can be used to block activity of abnormal mycophenolate mofetil can be used
proteins that are produced by cancer cells
target a cancer’s specific genes, proteins, or the Gastrointestinal toxicity
tissue environment Diarrhoea is the most common immunotherapy related toxicity
some are checkpoint inhibitors which work by Management: non-severe diarrhoea should be treated with antidiarrheals, fluid and
stopping the ability of cancer cells to bypass an electrolyte supplementation. Severe diarrhoea would require immunotherapy
immune response treatment cessation and systemic steroids. Infliximab can be used in those who do
not respond to steroid
Other types of immunotherapy include:
Oncolytic virus therapy Pneumonitis
T-cell therapy Patients who are being treated with immunotherapy that present with h pulmonary
Cancer vaccines symptoms, such as an upper respiratory infection, new cough, shortness of breath or
hypoxia should be assessed for presence of pneumonitis
Immunotherapy does not work for everyone and can Management: steroids and antibiotics if signs of infection. If not response to
cause some very severe toxicities steroids, infliximab, mycophenolate mofeti or cyclophosphamide can be used
64
IMMUNE SYSTEM AND MALIGNANT DISEASE – ONCOLOGICAL EMERGENCIES
Oncological Emergencies
Hypercalcaemia Spinal cord compression
Most common metabolic complication of malignancy Causes include vertebral tumour, collapse of vertebra or spinal
Common in multiple myeloma and solid tumours cord tumour
Majority of cases due to the production of parathyroid hormone Diagnosis confirmed through urgent MRI scan
related peptide (PTHrP) by tumours which will act on bone, kidney Signs and symptoms include vertebral pain, sensory changes ,
and the GI tract to increase serum calcium levels motor weakness, numbness
Also due to the reabsorption of bone by osteoclasts Patient should immediately be started on high dose steroids (e.g.
Treatment: rehydration, bisphosphonates (e.g. pamidronate), oral dexamethasone 8mg BD)
calcitonin, octreotide Treatment can also involve radiotherapy or surgery
Patients should be advised to lie flat and rest whilst investigations
Tumour lysis syndrome are taking place
Caused by the rapid destruction of malignant cells resulting in the
release of cellular contents into the blood stream Superior vena cava (SVC) obstruction
Most commonly associated with lymphomas and leukaemias Most commonly occurs with lung cancer
Signs: hyperuricaemia, hyperphosphataemia, hyperkalaemia, Signs and symptoms include: headaches, skin discolouration,
hypocalcaemia, hypomagnesaemia, acute renal failure and oedema and distended neck and arm veins.
metabolic acidosis Patient should be sat upright and given oxygen therapy for
Prevention: rasburicase for high risk patients, allopurinol for breathlessness
intermediate/low risk patients Treatment includes opioids for pain and high dose steroids to
Treatment: rasburicase reduce oedema
Optimal treatment is stenting of the SVC and radiotherapy
Bone marrow suppression/neutropenic sepsis
Causes by all cytotoxics apart from vincristine and bleomycin Syndrome of inappropriate antidiuresis
Blood counts required before each treatment Diagnosis is based in plasma osmolarity, plasma sodium, urine
Neutropenia is a neutrophil counts of < 0.5 x 109/L osmolarity, urinary sodium
Fever in a neutropenic patient = immediate broad-spectrum Treatment includes fluid restriction, hypertonic saline (if symptoms
antibiotics severe or rapid in onset), demeclocycline
Treatment of neutropenia can also include to use of filgrastim Loop diuretics can correct hyponatraemia but should be used in
(GCSF) caution
65
IMMUNE SYSTEM AND MALIGNANT DISEASE – BREAST CANCER
Background
Hormone Treatment
The most frequent cancer in women and the Trastuzumab (Herceptin)
commonest cause of death in women aged 35-54 years For HER2+ breast cancer
in England Can cause cardiotoxicity – cardiac function must be monitored before and during treatment
Should not be given with anthracycline-containing regimens due to risk of cardiotoxicity
Both genetic and hormonal factors are involved in the Luteinising hormone releasing hormone (LHRH) analogues
aetiology of BC E.g. Goserelin, leuprorelin, buserelin
Used to induce chemical castration in females (oestrogen and progesterone) and males
Hormonal risk factors – prolonged exposure to (testosterone) via continuous stimulation of the pituitary gland
oestrogen (e.g. early menarche, late menopause, late Initial treatment can cause a tumour flare
first pregnancy), combined contraceptive pill, HRT Required in pre-menopausal women (not required in post-menopausal women as they no longer
produce oestrogen)
Clinical presentation involves: Side effects – breast abnormalities, gynaecomastia, hot flushes, altered mood, sexual
Mass in breast or underarm area dysfunction, vulvovaginal dryness
Nipple discharge
Selective oestrogen receptor modulators (SERMs)
Skin discolouration or changes in texture
E.g. tamoxifen, raloxifene
Staging based on TNM Partial agonists at oestrogen receptors
Can be used in both pre- and post-menopausal women
Tumour size, location
Side effects – endometrial changes (hyperplasia, polyps, uterine sarcoma prompt
Lymph nodal involvement
investigation if abnormal vaginal bleeding), increased risk of VTE, vaginal dryness, hot flushes,
Metastases – most common areas are bone, mood changes
lung, liver, pleura, adrenal glands, skin, and Tamoxifen = pro-drug, which requires activation by CYP2D6 therefore interaction with SSRIs
brain (inhibitors of CYP2D6)
Treatment options include: Selective oestrogen receptor down-regulators (SERDs)

Surgery and adjuvant radiotherapy E.g. fulvestrant
Surgery and adjuvant hormonal therapy (for Block the ER as well as downregulate it
tumours that express the oestrogen receptor Side effects – hot flushes, VTE
[ER+]) Aromatase Inhibitors (AIs)
Surgery and adjuvant chemotherapy (for E.g. anastrazole, letrozole, exemestane
patients at high risk of recurrence) Aromatase is the enzyme which facilitates the conversion of androgens into oestrogens
AIs inhibit this conversion, thus reducing levels of oestrogen
Used in post-menopausal women (contra-indicated in pre-menopausal women)
Side effects – hot flushes, vulvovaginal dryness, osteoporosis, vaginal haemorrhage
66
IMMUNE SYSTEM AND MALIGNANT DISEASE – LUNG CANCER
Treatment
Background
Lung cancer is the most common worldwide cancer with most patients over 65 years. Small cell lung cancer
Despite government initiatives to reduce smoking, lung cancer remains the highest death Surgery has a limited role and chemotherapy
caused by cancer in both the UK and USA. required
Etoposide with carboplatin or cisplatin
Risk factors:
Non-small cell lung cancer
Smoking (most significant risk factor)
Treatment depends on staging
Previous radiotherapy to the chest
Stages 1, 2 and 3a – curative surgery to remove
Occupational exposure to chemicals such as asbestos primary tumour with adjuvant chemotherapy
Hereditary risk factors Stages 3b and 4 – inoperable and chemotherapy
is used. Double therapy with carboplatin or
Small cell lung cancer (SCLC): cisplatin with gemcitabine or vinorelbine.
Treated as an emergency and requires immediate treatment Second line- docetaxel
Cancer in the larger airways which presents as systemic disease and frequently
metastasises (commonly to the liver, bones, bone marrow, brain and adrenal glands) EGFR tyrosine kinase inhibitors
E.g. gefitinib, erlotinib
Non-small cell lung cancers (NSCLC):
EGFR is over mutated and overexpressed in
All other lung cancers classified as non-small cell cancer cells (especially in NSCLC)
Arise from epithelial cells from the bronchi and alveoli Inhibit the epidermal growth factor receptor
Divided into three main types: (EGFR) pathway which prevents cancer cell
o Squamous cell – present as obstruction to the bronchus and tend to grow growth
slowly, spreading locally Side effects – diarrhoea, rash (acne-like)
o Adenocarcinoma – occurs in bronchial mucosal glands. Can originate from
scar tissue and have a high risk of metastasising Radiotherapy
o Large cell carcinoma – presents as large mass that grow rapidly and Aims to shrink the size of the tumour
metastasise early
Often given during chemotherapy treatment to
make tumour more susceptible to chemotherapy
Clinical presentation involves:
Radical radiotherapy used to actively treat the
Chronic cough
cancer
Chest pain
Palliative radiotherapy given to help manage
Haemoptysis
symptoms of lung cancer (e.g. chest pain, cough,
Breathlessness airway obstruction)
Recurrent chest infections
67
IMMUNE SYSTEM AND MALIGNANT DISEASE – PROSTATE CANCER
Background
Treatment
Prostate cancer is the most common cancer in men in
the UK. The incidence increases with age with more Early-stage disease (T1, T2)
than 60% of cases in men over the age of 70 years.
Watchful waiting
Risk factors: Varies from waiting until patient presents with symptoms to more active follow ups with
Family history regular PSA testing. It is the best option for men with low-grade tumours with a life
expectancy of <10yrs
Inherited mutations (BRCA 1 and BRCA 2)
Ethnicity
Radical radiotherapy
Diet Most common treatment in the UK. May cause damage to adjacent organs, acute diarrhoea,
chronic proctitis.
Clinical presentation involves:
Many asymptomatic Radical prostatectomy
Locally advanced disease presents with urinary For younger patients, surgery is a better option but may cause complete incontinence and
frequency, poor urine flow or difficulty starting or impotence.
stopping urination
There may also be bone pain (due to metastatic Locally advanced disease (T3, T4) & Metastatic Disease
disease), lethargy and weight loss
Treated with hormonal therapies – LHRH analogues with/without antiandrogens
Screening:
Men over 50 years can choose to have a PSA LHRH analogues
(prostate specific antigen) test e.g.leuprorelin, goserelin
o A raised PSA can indicate PC but it can cause a chemical castration (orchidectomy) via testosterone production.
also indicate a UTI, prostatitis or an Side effects - hot flushes, sexual dysfunction and impotence.
enlarged prostate, therefore it is not LHRH analogues can cause an initial tumour flare in the first 1-2 weeks, leading to.
specific Spinal cord compression, ureteric obstruction or increasing bone pain.
Rectal examination
Survey for focal bone tenderness Antiandrogens
X-ray of chest and any sites of bone pain e.g. bicalutamide, flutamide, cyproterone
Transrectal ultrasound are started 3-7 days prior to therapy to prevent the tumour flare
Bone scan side effects - breast tenderness, gynaecomastia, haematuria, sexual dysfunction

2019/2020 REVISION TOOL: Short Guides For Key Therapeutic Areas

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2019/2020 REVISION TOOL

Short Guides for Key Therapeutic Areas

Cardiovascular System 2 Corticosteroids 35

CARDIOVASCULAR SYSTEM – CARDIOVASCULAR DISEASE

HYPERTENSION HEART FAILURE

CARDIOVASCULAR SYSTEM – CARDIOVASCULAR DISEASE TREATMENT

ACS PROTOCOL ANTICOAGULANTS

CARDIOVASCULAR SYSTEM – CARDIOVASCULAR DISEASE TREATMENT

BETA BLOCKERS DIURETICS

Heart Failure Loop diuretics

NERVOUS SYSTEM - EPILEPSY

Overview of management Considerations Driving

3 risk-based categories: Interactions

NERVOUS SYSTEM - EPILEPSY

Pregnancy Hormonal Contraceptive Advice

NERVOUS SYSTEM - EPILEPSY

SODIUM VALPROATE PHENYTOIN

NERVOUS SYSTEM - EPILEPSY

No monitoring required! No important interactions!

NERVOUS SYSTEM - DEPRESSION

Overview Switching Antidepressants

NERVOUS SYSTEM - DEPRESSION

Serotonin Syndrome SSRIs

2 – Autonomic dysfunction Escitalopram – S enantiomer of citalopram therefore also causes QTc

NERVOUS SYSTEM - DEPRESSION

NERVOUS SYSTEM - LITHIUM

Brands FBC (12/12ly)

*Discontinuation planned for April 2021 TDM (3/12ly)

Take a level 12 hours post dose (therefore dosing at night for

NERVOUS SYSTEM - LITHIUM

Early Signs Following signs Severe signs

Non-specific Vomiting Convulsions

Interactions Patient Counselling

Rise in lithium levels Importance of adherence and monitoring

NERVOUS SYSTEM - ANTIPSYCHOTICS

Antipsychotic Drugs (APDs) Extrapyramidal S/E (EPS)

NERVOUS SYSTEM - ANTIPSYCHOTICS SIDE EFFECTS

Hyperprolactinaemia Sexual Dysfunction APD Monitoring

Other Uses of APDs

Symptoms – hyperthermia, fluctuating levels of consciousness, muscle Psychomotor agitation

NERVOUS SYSTEM - CLOZAPINE

Overview Blood Tests Additional Points

NERVOUS SYSTEM - DEMENTIA

NERVOUS SYSTEM - PARKINSON’S DISEASE

NERVOUS SYSTEM - PARKINSON’S DISEASE

Monoamine oxidase type B inhibitors – useful mild symptomatic effect in

May be useful in controlling excessive saliva

NERVOUS SYSTEM - BENZODIAZEPINES

NERVOUS SYSTEM - NAUSEA AND VOMITING

Prochlorperazine can be administered as a buccal tablet

E.g. ondansetron, granisetron

Caution – prolong the QT interval

Used for N&V associated with cancer chemotherapy

NERVOUS SYSTEM - PAIN: OPIOIDS

Opioids Overview Opioid Side Effects

NERVOUS SYSTEM - PAIN: OPIOIDS

Dependence and Withdrawal

NERVOUS SYSTEM - PAIN: NEUROPATHIC PAIN & LOWER BACK PAIN

Neuropathic Pain Overview

NSAIDs and GI events

RESPIRATORY MEDICINE - ASTHMA

Overview Diagnosis – Spirometry

RESPIRATORY MEDICINE - ASTHMA