Oral

Anti diabetic drugs:

Ø Treatment for type 2
Ø Only after failed to respond to 3 months of restriction energy and carbohydrate intake and an increase physical activity
Ø Augments diet and exercise does not replace them
Ø If drugs + diet + exercise fails add insulin
Ø When insulin added it is generally added at bedtime as isophane or long acting insulin; when replacing oral drugs given twice a
day of biphasic insulin (or isophane insulin mixed with soluble insulin).
Ø During pregnancy: with pre-existing diabetes treat with metformin (unlicensed use) either alone or in combination with insulin.
Metformin can be continued or replaced with glibenclamide during breastfeeding.
o Women with gestational diabetes may be treated with or without insulin with glibenclamide or metformin (both
unlicensed) from week 11 and treatment should discontinue after giving birth.

Drug Clinical information Side effects Other information
Sulphonylureas Ø Works by augmenting insulin secretion so Glibenclamide long acting > greater
only works if some residual pancreatic beta Hypoglycaemia in excessive risk of hypoglycaemia> avoid in
cell activity is present. dose and persist longer so elderly. (Short acting gliclazide or
Ø Considered for patients who are not always treat in hospital. tolbutamide is preferred)
overweight or in patients whom metformin
is contraindicated or not tolerated.
Biguanides Ø Works by decreasing gluconeogenesis and Ø Abdominal pain, Ø Hypoglycaemia usually does
by increasing peripheral utilisation of anorexia, , diarrhoea , not occur
glucose. nausea, taste Ø Less chances of weight gain
Ø Metformin improves insulin sensitivity, disturbance, vomiting, Ø Can be used for Polycystic
helps with weight reduction, normalise decreased Vit B12 ovary syndrome (UL)
menstrual cycle and may improve absorption, lactic Ø C/I : ketoacidosis & use of
hirsutism acidosis ( withdraw general anesthesia
Ø First choice in overweight people treatment) Ø Iodine containing x-ray
Ø Insulin is almost always necessary in Ø GI side effects are contrast media: can cause
medical and surgical emergencies; insulin initially common and renal failure and lead to
should also be substituted before elective may persist in some lactic acidosis.
surgery (omit metformin on the morning of patients particularly Ø Suspend prior to test and do
the surgery and give insulin if required) with high dose. Dose not restart no earlier than
should be increased 48h after test if renal

slowly. function backs to baseline.
Ø Review eGFR <45 ; avoid <30
Acarbose Ø Reserved for others to fail Ø Abdominal distension Ø C/I: hernia, IBD,
Ø Postprandial hyperglycaemia in Type 1 can and pain; diarrhoea, predisposition to partial
be reduced by acarbose. flatulence and soft stool intestinal obstruction,
Ø An inhibitor of intestinal alpha Ø Antacid not helpful to previous abdominal surgery.
glucosidases, delays the digestion and treat these S/E. Ø Avoid eGFR <25
absorption of starch and sucrose. Ø Counter hypoglycaemia Ø Monitor liver function
use glucose (not sucrose)
Alogliptin Ø Inhibits dipeptidylpeptidase-4 to increase Ø Abdominal pain, GI Ø C/I: ketoacidosis
insulin secretion and lower glucagon reflux, headache, Ø Monitor renal function
secretion. nasopharyngitis, pruritis before and review while on
Ø Usually used in combination or if others rash, URTI treatment
have failed (metformin, pioglitazone,
sulphonylurea or insulin)
Linagliptin Ø M/A Same as alogliptin Ø Cough & nasopharyngitis
Saxagliptin Ø M/A Same as aloglption Ø Dizziness, dyspepsia, Ø Monitor renal function
headache, before and review.
hypoglycaemia,
peripheral odema,
sinusitis, URTI, UTI and
vomiting
Sitagliptin Ø M/A Same as above Ø GI disturbances, Ø C/I: Ketoacidosis
nasopharyngitis, pain, Ø
peripheral odema, URTI
Viladgliptin Ø M/A same as above Ø Asthenia, dizziness, Ø C/ I : Ketoacidosis
headache, nausea, Ø Monitor liver function before
peripheral odema, and every 3 months of first
tremor year and then regularly.
Exenatide Ø Binds to and activates the GLP-1 receptor Ø Abdominal pain and Ø C/I: ketoacidosis and severe
to increase insulin secretion, supresses distension, agitation, GI disease
glucagon secretion and gastric emptying antibody formation, Ø If dose of immediate release
Ø Nice recommendation for triple therapy asthenia, decreased medicine is missed continue
with MR exenatide: (metformin + appetite, disease, with next schedule dose 0 do

sulphonylurea or metformin + headache, not administer after a meal.
thiazolidinedione) hypoglycaemia, weight Ø Woman of childbearing age
Ø BMI > 35 and weight related psychological loss should use of effective
or medical problems contraception during and 12
Ø BMI<35 and insulin would be unacceptable weeks after with MR
for occupational reasons or weight loss exenatide.
would benefit other significant obesity Ø Other drugs taken orally may
related comorbidities. need to be taken at least 1
Ø Treatment only to be continued if hba1c is hour before or 4 hours after
reduced by 1% point and weight loss of 3% injection or taken with a
achieved in 6 months. meal when injection is not
Ø Dual therapy (with metformin or sulphonyl administered in order to
urea) possible interference with
absorption
Liraglutide Ø Same as above (M/A and NICE Ø Abdominal pain and Ø C/I: diabetic gastroparesis,
recommendation) distension, bronchitis, IBD, ketoacidosis, moderate
constipation, decreased to severe congestive heart
appetite, diarrhoea, failure.
dizziness, dyspepsia,
flatulence, disease,
headache,
hypoglycaemia.
Lixisenatide Ø M/A is same as exenatide Ø Diarrhoea, dizziness, Ø C/I: ketoacidosis, severe GI
Ø If a dose is missed, inject within in 1 hour drowsiness, dyspepsia, disease.
before the next meal- do not administer headache, Ø Other drugs taken orally may
after a meal. hypoglycaemia, injection need to be taken at least 1
site reaction, nausea, hour before or 4 hours after
palpitation, vomiting. injection or taken with a
meal when injection is not
administered in order to
possible interference with
absorption

Insulins 1. Rapid-Acting Insulins

Human insulin analogues with a faster onset and shorter duration of action, are classified as rapid-acting insulins. (Joint
Formulary Committee, 2016) Examples of these, include insulin aspart, insulin glulisine and insulin lispro and all of these
have an even faster and shorter duration of action compared to the soluble insulin. (Joint Formulary Committee, 2016)

These special properties of them, make them very suitable for patients who wish to inject just before having a meal, or when
needed just shortly post-meal; they are also of great value for patients who forget to eat after waiting for the soluble short-
acting insulin to take action. (Joint Formulary Committee, 2016)

All three of the rapid-acting insulins listed above, can also be used via the subcutaneous infusion route; and in particular
insulin aspart and insulin lispro could also be given via the intravenously route in emergency situations. (Joint Formulary
Committee, 2016)

Overall, rapid-acting insulin analogues act within 15 minutes and their duration can range between 2 to 5 hours;
consequently this means that they can be injected 5-15 minutes before a meal, with the meal itself or even just after the
meal. (CKS, 2015) (NICE, 2015)

Insulin Aspart (e.g. NovoRapid) = more rapidly absorbed via the subcutaneous route compared to soluble insulin, because of
its reduced tendency to form hexamers in contrast to the soluble human insulin. (Novo Nordisk Limited (a), 2015) The time
taken for insulin aspart to reach its peak concentration is approximately half of that for soluble human insulin (see
upcoming section for more details) and the insulin concentrations usually returns back to the baseline level after about 4 to
6 hours. (Novo Nordisk Limited (a), 2015)

Insulin Glulisine (e.g. Apidra Solostar) = the absorption of insulin glulisine is approximately twice as fast with a maximum
concentration being also twice as high when compared to regular human insulin; it has a mean apparent half-life of 42
minutes. (Sanofi (a), 2013)

Insulin Lispro (e.g. Humalog Kwikpen) = it is rapidly absorbed, achieving a peak concentration within 30 to 70 minutes
when given via the subcutaneous route. (Eli Lilly and Company Limited, 2016)

2. Short-Acting Insulins

Short-acting insulins also have a reasonable quick onset of action (but slightly longer than the rapid-acting insulins) and an
overall short duration of action. Soluble human insulins usually have an onset of action of 30 to 60 minutes when injected

subcutaneously and therefore they are normally injected 30 minutes before food, they reach the maximum peak
concentration between 2 to 4 hours and their duration can last for up to 8 hours. (CKS, 2015)

On the other hand, when these are injected intravenously in emergencies, they have an extremely short half-life of only
approximately 5 minutes and their effect usually vanishes within 30 minutes; examples of soluble insulin, include: Humulin
S, Insuman Rapid and Actrapid. (Joint Formulary Committee, 2016)

3. Intermediate-Acting Insulins

Intermediate-acting insulins aim to mimic the effect of the basal insulin that is normally secreted in continuation
throughout the day. (Joint Formulary Committee, 2016) The onset of action of this subgroup of insulins when given via the
subcutaneous route is approximately 1 to 2 hours and their peak concentration is reached between 4-12 hours with a
duration profile ranging from 16 to 35 hours. (CKS, 2015) (Wiffen et al., 2012)

Examples of intermediate-acting insulins, include: isophane insulin (e.g. Humulin I, Insulatard) which is a suspension of
insulin containing protamine; usually used in twice-daily regimens, where patients normally mix isophane with a soluble
insulin – however, now there are lots of preparations which already contain the appropriate mixture (for example, biphasic
isophane insulin, biphasic insulin aspart (e.g. NovoMix 30), or biphasic insulin lispro). (Joint Formulary Committee, 2016)

Another mixture which normally has a longer duration of action (longer-acting) is the insulin zinc suspension (30%
amorphous, 70% crystalline). (Joint Formulary Committee, 2016) More so, yet another type (longer-acting) is the
protamine zinc insulin which is usually given once a day with soluble insulin; however one of the disadvantages of this one
is that it can bind to the soluble short-acting insulin when mixed in the same syringe, therefore it is not commonly used
anymore. (Joint Formulary Committee, 2016)

The biphasic insulin preparations described above contain a ready-mixed combination of a short-acting insulin and an
intermediate-acting insulin, the former acts to tackle the post-prandial peak in glucose and the latter aims to provide
background insulin to control the basal glucose once the short-acting insulin’s effect has disappeared. (CKS, 2015) (Joint
Formulary Committee, 2016)

There are various combinations with different ratios of short-acting and intermediate-acting insulins to enable different
time-action profiles. Nonetheless, the duration of the action has a similar pattern (approximately 10-16 hours), it is worth
noting that those preparations containing a mixture of the rapid-acting insulins such as insulin aspart (e.g. NovoMix 30) will
unsurprisingly have a more rapid onset of action (less than 20 minutes) than those with a soluble insulin mixture (around
30 minutes). (CKS, 2015) (Gummerson, 2009)

4. Longer-Acting Insulins

Longer-Acting Insulins, when given via the subcutaneous route, usually have an onset of action of 1-2 hours, the topmost
concentration is, in general, reached between 4-12 hours and their duration can range from 16-42 hours. (Joint Formulary
Committee, 2016) Examples of longer-acting insulins include insulin glargine (present in Lantus Solostar) usually given
once a day and insulin detemir (present in Levemir Flexpen) which can be given either once or twice daily. (Joint Formulary
Committee, 2016) Insulin degludec is also a long-acting insulin (human analogue) for once daily subcutaneous use. (Joint
Formulary Committee, 2016)

The above is true as an overall profile of long-acting insulins, however, as a specific example insulin detemir’s
pharmacokinetics particulars are studied in this section. For insulin detemir, the maximum serum concentration is achieved
between 6 and 8 hours after subcutaneous use, and when the patient uses a twice daily regimen then the steady-state serum
concentrations are usually reached after 2-3 doses; and its terminal half-life is between 5-7 hours dependant on the dose
administered. (Novo Nordisk Limited (b), 2015)

Generally, the role of the long-acting insulin analogues is to imitate the basal insulin; they generally achieve a steady-state
level after about 2-4 days (e.g. insulin glargine) and this then leads to a constant level of insulin in the body. (CKS, 2015)
(Sanofi (b), 2015) Lastly, another specific example to touch base on is Insulin degludec (e.g. Tresiba) which has an especially
long half-life of approximately 25 hours independent of the dose administered. (Novo Nordisk Limited (c), 2015)

To complete, there are a few common regimens that can be used, when prescribing insulins but these would depend on the
patient’s diabetic profile overall, a brief overview of each regimen is provided here (Joint Formulary Committee, 2016):
Ø Multiple injection regimen = where a short-acting insulin or rapid-acting insulin analogue is used, usually before
meals and an intermediate-acting or long-acting insulin used either once or twice daily depending on the particular
subtype of insulin within each group;
Ø Short-acting insulin or rapid-acting insulin analogues combined with intermediate-acting or long-acting insulin,
before meals once or twice daily;
Ø Either an intermediate- or long-acting insulin as part of a once or twice daily regimen, this can be with or without a
short- or rapid-acting insulin before meals;
Ø Lastly, a continuous insulin infusion via the use of a portable infusion pump (with short-acting or rapid-acting
insulins) can also be suitable for some patients – this regimen aims to delivers a continuous basal insulin infusion,
and the patient can then activate their bolus doses at meal times as required. (Joint Formulary Committee, 2016)

Drugs with narrow therapeutic drugs:

Drug Clinical information Side effects Other
Digoxin Ø Digoxin is cardiac glycoside that increases Ø It can be hard distinguish Ø When switching from IV to
force of myocardial contraction and between side effect and oral increase the dose by 20-
reduces AV node conductivity deteriorating heart 33% so plasma
Ø Used for controlling ventricular response condition. concentration can be
in persistent and permanent atrial Ø Toxicity progresses maintained.
fibrillation and atrial flutter. Also used in through the range 1.5- Ø C/I: constructive pericarditis,
heart failure. 3mcg/lit. hypertrophic
Ø Dose decided by ventricular rate at rest Ø Regular monitoring not cardiomyopathy,
and persistent rate shouldn’t fall under 60. required unless the intermittent heart block,
Ø Patient with heart failure and sinus rhythm toxicity is suspected. myocarditis, second-degree
doesn’t require loading dose. Ø Arrhythmia, blurred AV block, supraventricular
Ø Has long life so it is once daily. vision, conduction arrhythmias e.g. wolff-
Ø Renal function is the most important in disturbances, parkinson syndrome.
deciding dose. diarrhoea, dizziness, Ø Caution: hyperkalaemia,
Ø Hypokalaemia predisposes the patient to eosinophilia, nausea, hypokalaemia, within others
digoxin toxicity. rash, vomiting, yellow Ø Renal impairment: reduce
vision. dose.
Ø For digoxin assay blood
should be taken at least 6
hours after dose.
Lithium Ø Prophylaxis and treatment of mania, Ø Nytagmus Ø C/I: addison’s disease,
(0.4-1 mmol/lit) hypomania, depression in bipolar disorder Ø Sign of intoxication cardiac insufficiency,
and recurrent unipolar depression. include increasing GI dehydration, F/H of brugada
Ø Thyroid function monitored every 6 disturbance, visual syndrome, low sodium diet,
months. disturbance, polyuria, rhythm disorder, untreated
Ø Caution with concomitant use of drugs that muscle weakness, fine hypothyroidism.
can lower seizure threshold, prolongs QT tremor increasing to Ø Caution: Avoid abrupt
interval and causes sodium depletion (e.g. coarse tremor, CNS withdrawal;

Thiazide diuretics) disturbance (confusion) Ø Mfg advises effective
Ø Sample should be taken 12 hours after abnormal reflexes, contraception during
the dose to achieve a serum lithium myoclonus, incontinence, treatment for women of child
concentration of 0.4-1 mmol/l hypernatremia bearing potential.
Ø Target 0.8-1 mmol/l is recommended for Ø With severe overdose: Ø Avoid during pregnancy if
acute episode of mania and for patients (above 2mmol/l): possible particularly 1st
who have previously relapsed or have sub seizure, cardiac trimester. Dose requirements
syndromal symptoms. arrhythmias, increased during 2nd and 3rd
Ø Weekly after initiation and after each dose bradycardia, first degree trimesters ( but on delivery
change until concentrations are stable then heart block, BP changes, return abruptly to normal)
every 3 months there after. circulatory failure, renal Ø Can affect driving and skilled
Ø Renal function should be monitored at failure, coma and sudden tasks.
baseline and every 6 months thereafter. death. Ø All should be given lithium
Ø If to be discontinued the dose should be treatment pack.
reduced gradually over a period of at least
4 weeks( preferably over 3 months)

Phenytoin Ø Phenytoin sodium is not bioequivalent to Ø Acne, anorexia, Ø C/I:
(10-20mg/lit) those containing phenytoin base. (100mg coarsening of facial Acute porphyrias
is approximately equivalent to 92mg of appearance, With IV use: second and third
base in terms of therapeutic effect) constipation, dizziness, degree heart block, sino-
Ø Pre-treatment screening: HLAB*1502 drowsiness, gingival atrial block, sinus
allele in individuals of Han Chinese or hypertrophy and bradycardia, stokes-adams
Thai origin- avoid unless necessary ( risk hirsutism, insomnia, syndrome
of steven Johnson syndrome) paraeshesia, rash, Ø Cautions: Enteral feeding
Ø Monitoring: transient nervousness, (interrupt feeding 2 hours
In adults: optimum response at 10- tremor, vomiting. before and after dose; more
20mg/lit. In pregnancy, elderly and under Ø With IV : alteration in frequent monitoring
certain disease where protein binding may respiratory function, required)
be reduced, measure carefully or would be arrhythmia, Ø Cross sensitivity reported
more appropriate to measure free plasma- cardiovascular collapse; with carbamazepine.
phenytoin concentration. Ø Symptoms of toxicity: Ø Pregnancy: Changes in
In Children: therapeutic plasma-phenytoin nystagmus, diplopia, plasma protein binding make
concentrations reduced in first 3 months of slurred speech, ataxia, interpretation of plasma
life because of reduced protein binding. confusion, phenytoin concentration

Neonate-3month: 6-15mg/lit hyperglycaemia, difficult.
Child 3months-18 years: 10-20mg/lit Ø Switching between
Ø Blood disorder and their sign and manufacturers is not
symptoms. recommended.

Theophylline: Ø Used in chronic asthma, reversible airway Ø Arrhythmia, CNS Ø Caution: cardiac arrhythmia
10-20mg/lit obstruction, severe acute asthma, stimulation, convulsion, or cardiac disease. Elderly
Ø Dose adjustment is needed if smoking diarrhoea, gastric (increased plasma
started or stopped during treatment. irritation, headache, theophylline concentration),
Ø Concentration increases in heart failure, insomnia, nausea, epilepsy, fever, hypertension,
hepatic impairment and viral infection. palpitation, tachycardia, hyperparathyroidism, peptic
Ø Concentration decreases in smokers, and vomiting. ulcer, risk of hypokalaemia.
by alcohol consumption Ø Hypokalaemia: Ø Neonatal irritability and
Ø Plasma theophylline concentration of 10- potentially serious apnoea been reported.
20mg/lit is required for satisfactory hypokalaemia may result Ø Can be taken normally
bronchodilation. 5-10mg/lit may be from beta 2-agonist during pregnancy as
effective. Frequency and severity increases therapy. Other drugs that important asthma is well
at concentration above 20mg/lit. can cause hypokalaemia: controlled during pregnancy.
Ø Plasma theophylline measured 5 days after corticosteroids, diuretics Ø Present in breast milk:
starting oral treatment and 3 days after and hypoxia. irritability in infant. MR
any dose adjustment. A blood sample Ø Overdose: can cause preparation preferred.
should usually be taken 4-6 hours after an vomiting (severe and Ø Rate of absorption varies
oral dose of MR preparation. intractable), agitation, between brands.
dilated pupils,
restlessness, sinus
tachycardia,
hyperglycaemia,
amongst others.

Oral and parenteral anticoagulants:

Clinical information Side Effects Other information
Drug
(Anticoagulants)
Oral Anti-coagulant: Ø Prevent thrombus formation; Haemorrhage: main adverse Target INR: INR within 0.5 of
Ø Less useful in artery, for in the faster effect of all oral anticoagulants. target is satisfactory.
flowing vessels thrombi are composed of Check INR and omitting doses Ø 2.5: treatment of DVT/PE,
mainly platelets with little fibrin. PRN. AF, cardioversion (target INR
Ø Warfarin sodium, acenocoumarol and If anticoagulant is stopped but 3 weeks before and 4 weeks
phenindione antagonises the effect of not reversed, INR should be after), dilated
vitamin K and takes at least 48-72 hours measured 2-3 days later to cardiomyopathy, mitral
for it to work. ensure its falling. stenosis or regurgitation, bio
Ø If immediate effect is required Ø Major bleeding: stop prosthetic heart valves in
unfractionated or low molecular weight warfaring give mitral position, acute arterial
heparin must be given concomitantly. phytomenadione by embolism requiring
Ø Aspirin is more suitable for risk reduction slow injection; give embolectomy, MI
in TIA. frozen prothrombin Ø 3.5: recurrent DVT or PE in-
Ø Unfractionated or lower molecular weight complex (can give fresh patient currently taking
heparin is usually preferred for frozen plasma but less anticoagulation and with an
prophylaxis if venous effective) INR above 2.
thromboembolism in patients Ø INR>8.0, minor Ø Mechanical prosthetic
undergoing surgery. Warfarin can be bleeding: stop warfarin- heart valves:
continued in selected patients who are give phytomenadione recommendation depends on
currently taking long-term warfarin and slow injection can repeat type and location of the valve
are at high risk of thromboembolism. after 24 hour if still INE and patient risk factors.
Ø Baseline prothrombin time should be high restart warfarin Consider increasing the INR
determined but initial dose should not be once INR<5.0 target or adding an
delayed whilst awaiting result. Ø INR>8.0; no bleeding: antiplatelet drug if an
Ø Peri-operative anticoagulation: stop 5 days stop warfarin, give embolic event occurs whilst
before; phytomenadione orally the day before if phytomenadione by anticoagulated at the target

INR >= 1.5. If haemostasis is adequate , warfarin mouth using parentral INR.
sodium can be resumed at the normal preparation, repeat after Ø Duration: risk of recurrence
maintenance dose on the evening of the surgery 24 hours and restart and anticoagulant related
or next day. warfarin once INR <5.0 bleeding should be
Ø Patient stopping warfarin and at high risk Ø INR 5.0-8.0; minor considered.
of thromboembolism (those with a venous bleeding: stop warfarin 6 weeks for isolated calf-vein
thromboembolism event within last 3 give phytomenadione by deep vein thrombosis.
months, AF with previous stroke or TIA, or slow injection restart 3 months for venous
mitral mechanical valve may require warfarin INR <5.0 thromboembolism provoked
interim therapy ( bridging) with LMWH. Ø INR 5.0-8.0; no by surgery or other transient
Ø LMWH should be stopped 24 hours bleeding: withhold one risk factor
before and if surgery is of high risk or two doses of warfarin atleast 3 months for
bleeding not to be restarted for 48 and reduce subsequent unprovoked proximal DVT or
hours after surgery. maintenance dose. PE; long-term
Ø Patient on warfarin who requires anticoagulation may
emergency surgery that can be delayed for required.
6-12 hours IV phytomenadione can be Ø Combined oral anticoagulant
given. If surgery cant be delayed dried and anti platelet therapy:
prothrombin complex can be given in existing antiplatelet therapy
addition to IV phytomenadione and INR should be continued for the
check before surgery. necessary time for indication
treated. Duration of dual
therapy (aspirin+ warfarin)
or triple therapy ( aspirin+
clopidogrel+ warfarin)
should be kept to minimum.
Risk of bleeding with
aspirin+warfarin is less than
with clopidogrel+ warfarin.
Parenteral Ø Heparin initiates anticoagulation rapidly but short duration of action. It is referred as standard or unfractionated
anticoagulants: heparin.
Ø LMWH has longer duration of action and generally preferred routinely but patient with high risk of bleeding
unfractionated is preferred as it can be withdrawn quickly.
Ø LMWH: dalteparin, enoxaparin, tinzaparin are usually preferred over standard heparin because they are as
effective and less chances of HIT. Standard prophylactic use doesn’t require monitoring and once daily dosage

makes them more convenient.
Ø Danaparoid is heparinoid used in prevention of DVT in general or orho surgery. Providing there is no cross-
reactivity. Also used in patients who develops HIT.
Ø Argatroban can be given with oral anticoagulant only once thrombocytopenia has substantially resolved.
Ø Bivalirudin ( hirudin analogue) is a thrombin inhibitor;
Ø Heparin flushes use should be kept to minimum. For maintain patency of peripheral venous catheter. NACl 0.9% is
as effective as heparin flush.
Ø Epoprostenol (prostacyclin) to inhibit platelet aggregation during renal dialysis when heparins are unsuitable or
contraindicated. Its potent vasodilator with 3 mins half life so should be given as continuous IV infusion.
Ø Fondaparinux sodium is synthetic pentasaccharide that inhibits activated factor X.
Clopidogrel Ø Clopidogrel is recommended Ø Abdominal pain, bleeding Ø C/I: active bleeding.
for patient with and ischemic disorder, diarrhoea, dyspepsia. Ø Caution: discontinue 7 days before
stroke or PAD or elective surgery if antiplatelet effect
multivascular disease or MI; is not desired.

Dipyridamole Ø MR capsules should be Ø Angioedema, dizziness, GI Ø Cautions: aortic stenosis,
dispensed in original effects, hot flushes, severe coagulation disorder, heart failure,
container (contains bronchospasm, tachycardia, hypotension, left ventricular outflow
desiccant) and any capsule thrombocytopenia, urticaria, obstruction; may exacerbate
left after 6 weeks of worsening symptoms of migraine, myasthemia gravis,
opening should be coronary heart disease. rapidly worsening angina, recent MI
discarded. Ø Caution with drug that increases
risk of bleeding.
Apixaban Ø Direct inhibitor of activated Ø Anaemia, bruising, Ø C/I: active bleeding, malignant
factor X (Factor Xa = haemorrhage, nausea. neoplasm, oesophageal varices,
activated Factor X). Ø Regular INR monitoring not recent intracranial haemorrhage,
Ø Duration of treatment should required. significant risk of bleeding, vascular
be determined by balancing Ø Nice Guidelines: aneurysm.
the benefit of the treatment to Ø Apixaban is option for the Ø Cautions: anaesthesia with
risk of bleeding. prevention of stroke systemic postoperative indwelling epidural
Ø NICE guidelines: embolism and in non-valvular catheter (risk of paralysis- monitor
Ø Apixaban is an option in the AF in accordance with one or neurological signs and wait 20-30
prevention of VT in adults more of the following risk: hours after apixaban dose before
after hip or knee replacement previous stroke or TIA, removing catheter and do not give

surgery. symptomatic heart failure, age next dose at least 5 hours after
>=75, diabetes mellitus, catheter removal), prosthetic heart
hypertension. valve, increased risk of bleeding.
Ø Apixaban is an option for the
treatment and prevention of
recurrent DVT and PE in
adults
Fondaparinux Ø Synthetic pentasaccharide Ø Anaemia, bleeding, purpura. Ø C/I: active bleeding, bacterial
sodium that inhibits activated endocarditis.
factor X. Ø Cautions: active GI ulcer, bleeding
disorder, recent intracranial
haemorrhage.
Rivaroxaban Ø Direct inhibitor of activated Ø Abdominal pain, constipation, Ø C/I: active bleeding, in acute
factor X. (Factor Xa = diarrhoea, dizziness, coronary syndrome- previous stroke
activated Factor X). dyspepsia, haemorrhage, or TIA, malignant neoplasm,
Ø Patient should be monitored headache, hypotension, oesophageal varices, recent brain
for bleeding and anaemia. nausea, pain in extremities, surgery, within others.
Stop treatment if bleeding pruritus, rash, renal Ø Cautions: anaesthesia with
occurs. impairment, vomiting. postoperative indwelling epidural
Ø No routine INR monitoring Ø NICE recommendation: catheter ( risk of paralysis –monitor
required. Ø Prevention of venous neurological sign and wait at least
Ø Low dose rivaroxaban in thromboembolism after total 18 hours after rivaroxaban dose
combination with aspirin hip or total knee replacement before removing catheter and do not
alone or aspirin and in adults give next dose at least 6 hours after
clopidogrel, is licenced for the Ø Prevention of stroke and catheter removal); bronchiectasis,
prevention of systemic embolism in AF with prosthetic heart valve, risk of
atherothrombotic events one or more risk factors: bleeding, within others.
following an acute coronary previous stroke or TIA,
syndrome with elevated congestive heart failure, age
cardiac biomarkers. >=75, diabetes mellitus,
hypertension
Ø For treatment of recurrent
DVT and PE in in adults or for
treatment of DVT and PE.
Ø Rivaroxaban for preventing

adverse outcomes after acute
management of acute
coronary syndrome.
Danaparoid Ø Monitor anti factor Xa activity Ø Bleeding, hypersensitivity Ø C/I: Active peptic ulcer, acute
for patient with body weight reaction, rash. bacterial endocarditis, haemorrhagic
over 90 kg. disease, recent cerebral
haemorrhage, etc.
Ø Cautions: antibodies to heparin,
body weight over 90kg, recent
bleeding, risk of bleeding.
Heparins: Ø Monitoring: platelet count Ø If haemorrhage occurs it is Ø C/I: Acute bacterial endocarditis,
Dalteparin, before and regularly if usually sufficient to withdraw after major trauma, epidural
Enoxaparin, treatment to be continued for unfractionated or LMWH, but anaesthesia with treatment doses,
Tinzaparin more than 4 days. if rapid reversal of the side haemophilia and other
Ø Hyperkalaemia: plasma effects of heparin is required, haemorrhagic disorder, peptic ulcer,
potassium level should be protamine sulphate is a recent cerebral haemorrhage, recent
measured in patient with risk specific antidote. surgery to eye, recent surgery to
of hyperkalaemia before Ø HIT: Clinically important HIT nervous system, severe
treatment and regularly if to is immune-mediated and does hypertension, spinal anaesthesia
be treated for longer than 7 not usually develop until after with treatment dose,
days. 5-10 days; it can be thrombocytopenia.
Ø Hyperkalaemia: inhibition of complicated thrombosis. Signs Ø Caution: elderly and renal function;
aldosterone secretion by include: 30% reduction in Ø B/feeding: not excreted in milk due
unfractionated or low platelet count, thrombosis or to high molecular weight.
molecular weight heparin can skin allergy. If HIT is strongly
result in hyperkalaemia. suspected or confirmed, the
Patient with diabetes heparin should be stopped and
mellitus, chronic renal failure, an alternative anti-coagulant,
or those taking potassium- such as danaparoid, should be
sparing diuretics are more given. Ensure platelet counts
susceptible. return to normal range in
those who require warfarin.

Vitamin K Ø Women of childbearing age Ø Alopecia, diarrhoea, Ø C/I: avoid use within 48 hours

Antagonist: should be warned of danger haemorrhage, hepatic postpartum, haemorrhagic stroke,
Acenocumarol of teratogenicity. dysfunction, jaundice, nausea, significant bleeding
Phenindione Ø The base-line prothrombin pancreatitis, purpura, pyrexia, Ø Caution: bacterial endocarditis (use
Warfarin time should be determined rash, skin necrosis, vomiting, only if warfarin otherwise
but the initial dose should not purple toe indicated), conditions in which risk
be delayed whilst awaiting Ø It is essential that INR is of bleeding is increased, history of GI
result. measured daily or on alternate bleeding, peptic ulcer, postpartum
days in early days of (delay warfarin until risk of
treatment, then at longer haemorrhage is low-usually 5-7 days
intervals (depending on after delivery);
response), then up to 12 Ø Pregnancy: should not be given in
weeks. first trimester of pregnancy, can
Ø Provide yellow book to cause placenta and lead to
patient/carer. malformation and placental, fetal or
neonatal haemorrhage, especially
during last few weeks of pregnancy.
So if possible they should be avoided
in pregnancy and mainly during first
and third trimester.
Warfarin Ø See above Ø B/feeding: not present in milk Ø Pregnancy: babies of mothers taking
in significant amount appears warfarin at the time of delivery need
safe. Risk of haemorrhage, to be offered immediate prophylaxis
which is increased by vitamin with intramuscular
K deficiency. phytomenadione.

Antibiotics:
Drug Clinical information Side effects Other information


Ø All aminoglycosides are bactericidal and active against some gm+ve and many gm-ve.
Aminoglycoside: Ø Amikacin, gentamicin and tobramycin are also active against pseudomonas aeruginosa.
Amikacin Ø Streptomycin also active against mycobacterium tuberculosis and now its almost entirely reserved for treatment of
Gentamicin TB.
Neomycin Ø Not absorbed in gut so given by injection for systemic infection.
Streptomycin Ø Gentamicin is broad-spectrum but is inactive against anaerobes and has poor activity against haemolytic streptococci
Tobramycin and pneumococci. Gentamicin is used with another abx for the treatment of endocarditis. Streptomycin where
gentamycin resistant enterococcal endocarditis.
Ø Loading and maintenance dose is based on patient’s weight and renal function and then adjust based on concentration.
Treatment should normally not exceed 7 days.
Ø Amikacin more stable than gentamicin to enzyme inactivation and used mainly for serious infection caused by
gentamicin resistant gm-ve bacilli.
Ø Tobramycin has similar activity to gentamicin. Slightly more active against pseudomonas but less active against some
gm-ve bacteria;
Ø Neomycin too toxic for parenteral use. Used for skin or mucous membrane or to reduce the bacterial population of the
colon prior to bowel surgery or hepatic failure.
Ø Once daily dose is more convenient than multiple doses. Once daily high doses should be avoided in patient’s
endocarditis due to gm+ve bacteria HACEK endocarditis, burns of more than 20% of the body surface area or CrCl less
than 20ml/minute.

Aminoglycosides Ø If there is impairment of renal function, the Ø Nephrotoxicity: occurs Ø C/I: Myasthenia gravis
by injection interval between the doses must be increased. most commonly in Ø Cautions: dose related side
Ø Monitoring: avoids both excessive dose toxicity elderly. effects; Correct the
and sub therapeutic activity. Ø Ototoxicity hydration before starting
Ø In patients with normal renal function, AG the dose. If possible
concentration should be measured after 3 or 4 parenteral treatment
doses of a multiple daily dose regimen and shouldn’t normally exceed 7
after a dose change. For multiple daily dose days.
regimen blood sample should be taken Ø Interactions: shouldn’t be
approximately 1 hour after intramuscular or IV given with drug causing

injection (peak concentration) and also just ototoxicity e.g Cisplatin and
before next dose (trough concentration). If the AG and ototoxic diuretic
pre-dose (trough) concentration high than the (furosemide) should be
interval should be increased if the post dose separated for as long period
(peak) concentration is high than the dose as possible.
must be reduced. Ø Pregnancy: risk of auditory
Ø Renal function should be measured. or vestibular nerve damage
Ø Auditory and vestibular function should be in the infant when given in
monitored during treatment. 2nd or 3rd trimester. Risk is
greatest with streptomycin.
Gentamicin Ø Monitoring: Ø N/A Ø N/A
Ø Multiple daily dose: Peak: 5-10mg/lit, trough
should be less than 2mg/lit
Ø Multiple dose regimen in endocarditis: Peak: 3-
5mg/lit and trough: less than 1mg/lit.
Ø Gentamicin concentration should be measured
after 3 or 4 doses, then every 3 days and after
dose change.
Neomycin Ø Renal function should be assessed before Ø N/A Ø C/I: intestinal obstruction,
starting and during treatment. myasthenia gravis.
Ø Auditory and vestibular function should be Ø Caution: avoid prolonged
measured. use, toxic parenteral use.
Ø Pregnancy: auditory and
vestibular nerve damage in
2nd and 3rd trimester
Streptomycin Ø Used in TB unlicensed Ø N/A Ø N/A
Ø Peak concentration: 15-40mg/lit
Ø Trough concentration: less than 5mg/lit (less
than 1mg/lit in renal impairment or patient
over 50)
Chloramphenicol Ø Potent broad spectrum antibiotic Ø Blood disorder, Ø C/I: acute porphyrias
(Bacterial Ø Monitor plasma concentration mainly in depression, diarrhoea, Ø Caution: avoid repeated
Transpeptidation elderly. Peak plasma concentration 2 hour after dry mouth, erythema courses and prolonged
inhibitors) oral or parenteral dose 10-25mg/lit, pre-dose multiforme, glositis, treatment.

concentration should be less than 15mg/lit. headache, nausea, Ø Pregnancy: Mfg advises
Ø Blood count before and during the treatment haemoglobinuria, optic avoid, neonatal grey baby
neuritis, peripheral syndrome if used in 3rd
neuritis, reversible and trimester.
irreversible aplastic Ø B/feeding: mfg advises
anaemia, avoid, may cause bone
Ø Associated with serious marrow toxicity in infants.
haematological side
effects when given
systemically;
Carbapenems Ø Beta-lactam antibiotics with broad spectrum activity including many gm +ve and –ve bacteria and anaerobes
Ø Imipenem and meropenem have good activity against pseudomonas.
Ø Carbapenems are not active against MRSA and enterococcus facium.
Ø Imipenem and meropenem are used for the treatment of severe hospital acquired infections and polymicrobial
infection including septicaemia, and within others.
Ø Ertapenem is licenced for treating abdominal and gynaecological infections and for community acquired Pneumonia,
but it’s not active against atypical respiratory pathogens and it has limited activity against penicillin resistant
pneumococci.
Ø Unlike other carbapenems, ertapenem is not active against pseudomonas or against acinetobacter spp.
Ø Imipenem is partially inactivated in the kidney by enzymatic activity and is therefore administered in combination
with cilastatin (imipenem with cilastatin), a specific enzyme inhibitor, which blocks its renal metabolism. Meropenem
and ertapenem are stable to renal enzyme, which inactivates imipenem and therefore can be given without cilastatin.
Ø Side effects of imipenem with cilastatin are similar to other beta-lactam antibiotics. Meropenem has less seizure
inducing potential and can be used to treat CNS infections
Cephalosporin Ø Broad-spectrum antibiotics, which are used for the treatment of septicaemia, pneumonia, meningitis, biliary tract
infection, peritonitis and UTI.
Ø Pharmacology is similar to Penicillin and excreted through renal.
Ø Penetrates the cerebrospinal fluid poorly unless inflamed. Cefotaxime and ceftriaxone are suitable for infections of the
CNS (e.g. meningitis)
Ø Principle side effect is hypersensitivity and about 0.5-6.5% of penicillin sensitive patients will also be allergic
to cephalosporin. If a cephalosporin is essential in patient with a history of immediate penicillin hypersensitivity,
because alternative abx is not available then cefixime, cefotaxime, ceftazidime, ceftriaxone or cefadroxil can be used
with caution.
Ø Cefaclor, cefadroxil, cephalexin, cefradine and ceftaroline should be avoided.
Ø Orally active first generation cephalosporins: cephalexin, cefradine, and cefadroxil and the second-generation cefaclor

have similar antimicrobial spectrum. They are useful in UTI, which do not respond to other abx or treatment during
pregnancy, respiratory tract infections, otitis media, sinusitis and skin and soft tissue infections.
Ø Cefaclor has good activity against H. influenza.
Ø Cefuroxime axetil, an ester of the second generation cefuroxime, has the same abx spectrum as parent. It is poorly
absorbed and need to be given with food to maximise absorption.
Ø Cefixime is an orally active third generation. It has longer duration of action than the other cephalosporin that are
active by mouth. It is only licenced for serious infections.
Ø Cefuroxime is a second generation cephalosporin that is less susceptible than the earlier cephalosporin to
inactivation by beta-lactamase so it is active against certain bacteria which are resistant to the other drugs and has
greater H. influenza.
Ø Cefotaxime, ceftazidime and ceftriaxone are third generation with greater activity than the second generation
against certain gm-ve bacteria. However they are less active than cefuroxime against gm+ve bacteria (S. aureus). Their
broad spectrum may encourage superinfection with resistant bacteria or fungi.
Ø Ceftazidime has good activity against pseudomonas. It is also active against other gm-ve bacteria.
Ø Ceftriaxone has a longer life so once daily for serious infection;
Ø Ceftaroline fosamil is a fifth generation cephalosporin with bactericidal activity similar to cefotaxime however
ceftaroline fosamil has an extended spectrum of activity against gm+ve that includes MRSA and multi-drug resistant
streptococcus pneumonia.
Ø Antibiotic associated colitis may occur more frequently with 2nd and 3rd generation.
Ø False positive urinary glucose if tests for reducing substance and false positive coombs test.

Co-trimoxazole Ø Sulfamethoxazole and trimethoprim are Ø Diarrhoea, headache, Ø C/I: acute porphyria
(diaminopyrimidi used in combination (as co-trimoxazole) hyperkalaemia, nausea, Ø Cautions: Asthma, avoid in blood
nes) because of their synergetic activity. rash disorder, avoid in infants under 6
Ø Co-trimoxazole is the drug of choice in Ø Blood disorder or rash: weeks due to risk of kernicterus,
prophylaxis and treatment of associated with rare elderly, G6PD deficiency,
pneumocystis jirovecii pneumonia. but serious side effects, maintain adequate fluid intake,
Monitor blood counts on prolonged discontinue predisposition to folate
treatment. immediately if blood deficiency, predisposition to
disorders or rash hyperkalaemia.
(including stevens Ø Pregnancy: teratogenic risk in
Johnson syndrome) first trimester (trimethoprim a
develop. folate antagonist). Neonatal
haemolysis and
methaemoglobinaemia in third

trimester. Fear of increased risk
of kernicterus in neonates
appears to be unfounded.
Ø B/feeding: small risk of
kernicterus in jaundiced infants
and haemolysis in G6PD deficient
infants
Trimethoprim Ø Unlicenced use: not licenced for Ø Trimethoprim has S/E Ø C/I: blood dyscrasias
treatment of pneumocystis pneumonia, similar to co- Ø Caution: elderly, acute porphyrias
acne resistant to other abx. Not licenced trimoxazole but they Ø Pregnancy: Teratogenic risk in
used for children under 6 weeks. are less frequent and first trimester (folate antagonist).
less severe. Mfg advices avoid

Fusidates: Ø Narrow spectrum antibiotics used for Ø Abdominal pain, Ø Pregnancy: not known to be
Fusidic acid staphylococcal infection diarrhoea, dizziness, harmful; mfg advices avoid unless
drowsiness, dyspepsia; potential benefit outweighs risk;
Vancomycin Ø Has aerobic and anaerobic gm-ve bacteria Ø With IV dose: blood Ø Caution: avoid in history of
including multi-resitant staphylococci. disorders, including deafness; elderly.
Ø Penetration into cerebrospinal fluid is poor. neutropenia (usually Ø Caution if teicoplanin
Ø IV vancomycin has long duration of action and after 1 week or hypersensitivity.
can therefore be given every 12 hours. cumulative dose of 25g)
Ø Vancomycin should not be given orally for interstitial nephritis,
systemic infection because its not absorbed nephrotoxicity,
significantly. ototoxicity (discontinue
Ø All patients require plasma vancomycin if tinnitus occurs), renal
measurement before the 3rd or the 4th failure, RED man
doses if renal function is normal, earlier if syndrome.
renal impairment. Ø Vancomycin is
Ø With IV use: trough concentration: 10- associated with higher
15mg/lit. (15-20mg/lit for endocarditis or incidence of
less sensitive strains of MRSA or S.Aureus) nephrotoxicity than
Ø All patients require regular blood count, urine teicoplanin.
analysis and renal function tests.
Ø Monitor auditory function in elderly.

Clindamycin Ø Active against gm+ve cocci, including Ø IM injection: abscess, Ø Avoid injections containing
streptococci and penicillin resistant induration, and pain. benzyl alcohol in neonates;
staphylococci and also against many Ø IV injection: diarrhoeal states
anaerobes, especially bacteroides fragilis. thrombophlebitis Ø Caution: avoid in acute
Ø Well concentrated in bone and excreted in bile Ø Systemic use: abdominal porphyria; middle aged and
and urine. discomfort, elderly women, especially in
Ø Monitor liver and renal function if treatment anaphylactoid reaction, operation.
exceeds 10 days. antibiotic associated Ø Dalacin 2% cream damages
Ø Monitor renal and liver function in neonates colitis, diarrhoea latex condom and
and infants. (discontinue treatment); diaphragm.
taste disturbances, Ø Pregnancy: not known to be
dermatitis, vomiting, harmful.
within many others; Ø B/feeding: amount too small
Ø Abx associated colitis to be harmful but bloody
could be fatal. Can diarrhoea reported in 1
occur with other Abx too infant.
but more frequent with
clindamycin.
Macrolides Ø Similar spectrum to penicillin but not identical so used in penicillin allergic patients.
Ø Erythromycin is also used in the treatment of early syphilis, uncomplicated genital chlamydial infection and non-
gonococcal urethritis. Has poor activity against H.influenzae.
Ø Azithromycin is a macrolide with slightly less activity than erythromycin against gm+ve bacteria, but enhanced
activity against gm-ve including H.influenzae. Plasma concentration is very low but tissue concentration is very high.
Has long tissue half-life and once daily dose is enough. Also used for treatment of uncomplicated genital chlamydial
infection, non-gonococcal urethritis, and uncomplicated gonorrhoea.
Ø Clarithromycin is an erythromycin derivative with slightly greater activity than the parent compound. Tissue
concentration is higher than erythromycin and it is given twice daily. Clarithromycin is also used for H. Pylori
eradication.
Ø Telithromycin is a ketolide derivative of erythromycin with an antibacterial spectrum similar to penicillin and other
macrolides but also active against penicillin and erythromycin resistant s. pneumoniae.
Ø Caution: electrolyte disturbance (predisposition to QT interval prolongation), may aggravate myasthenia gravis.
Azithromycin Ø Caution with drug that can cause QT Ø Blurred vision, ocular Ø Caution: electrolyte
prolongation. burning, ocular disturbance, may aggravate
Ø Azithromycin tablet can be sold to the public discomfort, ocular myasthenia gravis,
for the treatment of confirmed, asymptomatic pruritus. predisposition to QT

chlamydia trachomatis genital infection in Ø GI side effects are mild prolongation.
those over 16 years of age and the with azithromycin
epidemiological treatment of their sexual compare to
partners, subject to maximum single dose of erythromycin and
1g, maximum daily dose of 1g and a pack size clarithromycin.
of 1g.
Clarithromycin Ø Ø Dyspepsia, headache, Ø Pregnancy: avoid mainly in
hyperhidrosis, insomnia, 1st trimester unless
taste disturbance potential benefit outweighs
the risks;
Erythromycin Ø Caution: avoid in acute
porphyria, neonate under 2
weeks.
Ø Pregnancy: not known to be
harmful.
Ø B/feeding: amount too small
to be harmful.
Telithromycin Ø Visual disturbance and transient loss of Ø Abdominal pain, Ø C/I: congenital history of QT
consciousness may affect performance of diarrhoea, dizziness, interval prolongation, family
skilled tasks. Effect may affect after first dose. flatulence, headache, history of QT interval
Advise patient to take at night-time for nausea, taste prolongation, history of
minimal daytime effect. disturbances, vomiting. Telithromycin associated
Ø Caution: avoid in acute hepatitis, history of
porphyria, bradycardia, Telithromycin associated
coronary heart disease, jaundice, myasthenia gravis,
hypokalaemia, prolonged QT interval.
hypomagnesaemia, and
ventricular arrhythmia.
Metronidazole Ø High activity against anaerobic bacteria and Vaginal use: avoid vaginal Ø Caution: topical use: avoid
protozoa. preparation in girls who are exposure to strong sunlight
Ø Disulfiram like reaction with alcohol. not sexually active, unless or UV light.
Ø Clinical and laboratory monitoring advised for there is no alternative. Not Ø B/feeding: significant
treatment longer than 10 days. recommended during amount in milk; mfg advises
menstruation. avoid large single dose

though otherwise
compatible. May give milk
bitter taste.
Tinidazole Ø High activity against anaerobic bacteria and Ø Anorexia, furred tongue, Ø Caution: avoid in acute
protozoa. GI disturbances, nausea, porphyrias
Ø Has longer duration of action than oral mucositis, taste Ø Pregnancy: avoid in 1st
metronidazole. disturbances, vomiting. trimester.
Ø Disulfiram like reaction with alcohol. Ø B/feeding: avoid bfeeding
Ø Clinical and laboratory monitoring advised for during and 3 days after
treatment longer than 10 days. stopping treatment.
Oxazolidinone
antibacterials
Linezolid Ø Is active against gm+ve bacteria including Ø Diarrhoea, eosinophilia, Ø Caution: acute confusion
MRSA and glycopeptide-resistant enterococci. headache, nausea, taste state, bipolar depression,
Ø Resistance to linezolid can develop with disturbance, vomiting, carcinoid tumour, elderly,
prolonged treatment or if the dose is less than Injection site reaction. history of seizure,
that recommended. Ø Severe optic phaeochromocytoma,
Ø Not active against gm-ve organism; neuropathy may occur schizophrenia,
Ø Blood disorder: haematopoietic disorders rarely, particularly thyrotoxicosis, uncontrolled
(including thrombocytopenia, anaemia, used longer than 28 hypertension.
leucopenia and pancytopenia) have been days. CHM Ø Linezolid is reversible non
reported in patient receiving linezolid. It is recommendation: selective MAO-I (MAO-I
recommended that full blood count monitored o Patient should be food and other restriction
weekly. Close monitoring is recommended in warned to report applies)
patient: visual symptoms Ø Pregnancy: mfg advises use
o Treatment longer than 10-14 days immediately. only if potential benefit
o Have pre-existing myelosuppression. o Experiencing outweighs the risk.
o On drugs that has effect on new visual Ø B/feeding: avoid- present in
haemoglobin, blood counts or platelet symptoms should milk in animal studies.
function. be evaluated and
o Have severe renal impairment. referred.
Ø Monitor full blood count including platelet o Visual function
count weekly. should be
monitored

regularly if
treatment longer
than 28 days.
Penicillin Ø Benzylpenicillin (penicillin G) remains useful but gets inactivated by bacterial beta-lactamase.
Ø Effective against: pneumococcal, gonococcal, meningococcal infection and also for anthrax, diphtheria, gas-gangrene,
leptospirosis and treatment of Lyme disease.
Ø Pneumococci, gonococci and meningococcai, which have reduced sensitivity to penicillin, have been isolated.
Ø Penicillin G is effective in treatment of tetanus, metronidazole is preferred.
Ø Inactivated by gastric acid should be given by injection.
Ø Penicillin V has similar activity as Penicillin G but is less active. Gastric stable so can be used orally. Shouldn’t be used
for serious infection, as concentration is unpredictable and variable. Principally used for respiratory tract infections in
children, for streptococcal tonsillitis and for continuing treatment after one or more injections of Penicillin G when
clinical response has begun.
Ø Flucloxacillin is not activated by penicillinase enzyme so used in penicillin resistant staphylococci. Acid stable
can be given orally or via injection. Well absorbed from gut
Ø Temocillin active against gm-ve bacteria and is stable against beta-lactamase. Reserved for treatment of infection
caused by beta lactamase producing strain of gm-ve bacteria, including those resistant to third generation
cephalosporin. Not active against pseudomonas aeruginosa or acinetobacter spp.
Ø Ampicillin –broad spectrum- active against gm+ve and gm-ve organism but is inactivated by penicillinase including
those produced by S. aureus and by common gm-ve e.coli. Almost all staphylococci, approx. 60% of e.colli strains and
approx. 20% h. influenzae are resitant now and should be careful when selecting for blind treatment.
Ø Ampicillin well excreted in urine and bile.
Ø Amoxicillin is derivative of ampicillin and similar spectrum. Better absorbed and higher plasma and tissue
concentration and not affected by food in gut. Can be used for Lyme disease (unlicenced)
Ø Co-amoxiclav is amoxicillin with beta-lactamase inhibitor clavulanic acid dosen’t have any antibiotic action but by
inhibiting beta-lactamase it makes it works against bacteria resistant to amoxicillin.
Ø Piperacillin only available in combination with beta-lactamase inhibitor tazobactam. Ticarcillin is only available in
combination with clavulanic acid. Both preparations got broad spectrum of activity against gm+ve and gm-ve bacteria
and anaerobes. Piperacillin combination got wider range activity against gm-ve compare to ticarcillin combination and
more active against pseudomonas aeruginosa. Not active against MRSA. For severe pseudomonas infections these anti-
pseudomonal penicillin can be given with an aminoglycoside to get synergistic effect.
Ø Pivmecillinam significant activity against many gm-ve bacteria E.coli, klebsiella, enterobacter and salmonellae.
Pivmecillinam is hydrolysed to mecillinam, which is active drug.
Penicillins Ø Act by inhibiting bacterial cell wall Ø Anaphylaxis, Ø Caution history of allergy.
synthesis. They diffuse well into body tissues angioedema; Ø Allergic reaction occurs to 1-

and fluid but penetration into the Ø Rare but serious toxic 10% of exposed individual.
cerebrospinal fluid is poor except when effect of the penicillin is Anaphylactic reaction can be
meninges are inflamed. Excreted in urine. encephalopathy due to fetal and occurs in 0.05% of
Ø Antibiotics associated colitis. cerebral irritation. treated patients.
Ø The penicillin should not
be given intrathecal
injection because they
can cause
encephalopathy.

Piperacillin with Ø Mechanism of action same for all penicillin. Ø All penicillin side effects Ø Caution: high doses may
tazobactam Ø False positive urinary glucose test Ø Nausea, vomiting. lead to hypernatraemia.
Ticarcillin with Ø Mechanism of action same for all penicillin. Ø All penicillin side effects. Ø Caution: high doses may
clavulanic acid Ø False positive urinary glucose test Ø Eosinophilia, lead to hypernatraemia.
haemorrhagic cystitis, Ø Cholestatic jaundice is
hypokalaemia, injection possibly associated with
site reaction, nausea, clavulanic acid-more
stevens-johnson common in patient over 65
syndrome, toxic and in men. Rarely in
epidermal necrolysis, children. Usually self-
vomiting. limiting and rarely fatal.
Treatment shouldn’t exceed
14 days.
Benzylpenicillin Ø Mechanism of action same for all penicillin. Ø Penicillin side effects Ø Caution: accumulation of
sodium Ø Intrathecal injection of penicillin G is not sodium can occur from high
(Penicillin G) recommended. dose.
Ø False positive urinary glucose
Phenoxymethyl Ø Mechanism of action same for all penicillin. Ø Penicillin side effects Ø Pregnancy not known to be
penicillin Ø False positive urinary glucose harmful;
(Penicillin V)
Amoxicillin Ø Mechanism of action same for all penicillin. Ø Penicillin side effects Ø General caution: acute
Ø Unlicenced used for Lyme disease. Ø Nausea, vomiting. lymphocytic leukaemia, and
Ø If rash occurs related;
discontinue treatment.

Ampicillin Ø Mechanism of action same for all penicillin. Ø All penicillin side effects Ø General caution: acute
Ø Injection: accumulation of electrolytes Ø Nausea and vomiting. lymphocytic leukaemia,
contained in parenteral preparation can occur Ø If rash occurs and chronic lymphocytic
with high doses; discontinue treatment. leukaemia, cytomegalovirus
infection, glandular fever
and maintain adequate
hydration with high doses.
Co-amoxiclav Ø Dose is expressed as amount of amoxicillin Ø Cholestatic jaundice, Ø Caution: history of co-
and clavulanic acid. (x/y) hepatitis, nausea, and amoxiclav jaundice or
Ø Phlebitis at injection site. vomiting. hepatic dysfunction; history
Ø Superficial staining of teeth with suspension. of penicillin associate
Ø Cholestatic jaundice. jaundice or hepatic
dysfunction.
Co-fluampicil Ø Mechanism of action same for all penicillin. Ø Penicillin side effects Ø General caution: acute
Ø False positive urinary glucose test Ø Antibiotic associated lymphocytic leukaemia, and
colitis. related;
Ø GI disturbance, nausea,
vomiting.
Flucloxacillin Ø Penicillinase resistant Ø Penicillin side effects Ø Caution: accumulation of
Ø Mechanism of action same for all penicillin. Ø GI disturbance. electrolytes can occur with
Ø Hepatic disorder: Cholestatic jaundice and high doses. Risk of
hepatitis may occur very rarely, up to 2 kernicterus in jaundice
months after stopping Flucloxacillin. neonates when high doses
Treatment longer than 14 days and given parenteral (in
increasing age can increase the risk. neonates)
o Flucloxacillin should not be used in
patients with a history of hepatic
dysfunction associated with
Flucloxacillin.
o Flucloxacillin should be used with
caution in patients with hepatic
impairment.
o Careful enquiry should be made about
hypersensitivity reaction to beta-

lactam abx.
Ø False positive urine glucose test.

Colistimethate Ø Is active against gm-ve organism including Ø Bronchospasm, cough, Ø C/I: Myasthenia gravis.
sodium (Polymixn pseudomonas aeruginosa, acinetobacter dysphonia, nausea, sore Ø Cautions: acute porphyria,
antibiotics) baumanii and klebsiella pneumoniae. Not throat, taste disturbance severe haemoptysis with
absorbed by mouth has to be given by and vomiting. inhalation.
injection. Ø Major adverse effects Ø Pregnancy: inhalation
Ø IV use monitor renal function. are dose related clinical use suggest probably
Ø Inhalation use monitor: monitor lung function neurotoxicity and safe, intravenous use only if
before and after initial dose and monitor nephrotoxicity. potential benefit outweighs
bronchospasm. If bronchospasm occurs in a the risk.
patient not using bronchodilator repeat test
after using bronchodilator before
Colistimethate.
Quinolones Ø Nalidixic acid and norfloxacin are effective in uncomplicated UTI.
Ø Ciprofloxacin: gm-ve: salmonella, shigella, campylobacter, Neisseria and pseudomonas. gm+ve: S. Pneumonia,
enterococcus faecalis. It should not be used for pneumococcal pneumoniae. It is also active against chlamydia and
some mycobacteria. Can be used for respiratory tract infection, UTI, infection of the GI, bone and joint infections,
gonorrhoea and septicaemia.
Ø Ofloxacin is used for UTI, lower RTI, gonorrhoea and non-gonococcal urethritis and cervicitis.
Ø Levofloxacin active against gm+ve and gm-ve. Better activity at pneumococci than ciprofloxacin. Levofloxacin is
licenced for the treatment of acute sinusitis, acute exacerbation of chronic bronchitis and community acquired
pneumonia and UTI.
Ø Ciprofloxacin, levofloxacin, moxifloxacin and ofloxacin are licenced for skin and soft tissue infection, many
staphylococci are resistant to quinolones and should be avoided in MRSA infection.
Ø Moxifloxacin is associated with QT interval prolongation and life threatening hepatotoxicity. Active against gm+ve
and gm-ve bacteria. Greater activity against gm+ve like pneumococci compare to ciprofloxacin. Moxifloxacin is not
active against psueodmonas aeruginosa and MRSA.
Ø CSM advise: may induce convulsions in Ø Diarrhoea, dizziness, Ø C/I: in patients with history
patient with or without history of convulsions headache, nausea, of tendon disorder related
taking NSAID at same time also may induce vomiting. to quinolone use, over 60
them. Ø The drug should be years and prone to tendon
Ø Tendon damage: including rupture reported stopped if psychiatric damage, risk increases by

in patients receiving quinolones. Normally neurological or concomitant steroid use,
occurs within 48 hours of starting treatment. hypersensitivity tendonitis suspected
Cases have been reported after several reaction (including discontinues treatment.
months. severe rash) occurs. Ø Cautions: can prolong QT
Ø Pregnancy: avoid in interval; conditions that
pregnancy –shown to predispose to seizure;
cause arthropathy in exposure to excess sunlight
animal studies. should be avoided; G6PD
deficiency; history of
epilepsy; myasthenia gravis.

Ciprofloxacin Ø Caution with use of other drugs that can cause Ø Eye: corneal deposit, Ø C/I: acute MI, avoid excess
QT interval prolongation. ocular discomfort, alkalinity in urine,
Ø May interfere with skilled task; effects ocular hyperaemia, taste bradycardia, congenital long
enhanced by alcohol. disturbance. QT syndrome, electrolyte
Ø IV use: flatulence, pain disturbance, ensure
and phlebitis at injection adequate fluid intake, heart
site. failure with reduced left
Ø Oral use: flatulence. ventricular ejection fraction,
history of symptomatic
arrhythmia.
Ø Pregnancy IV or oral:
Eye: mfg advise avoid unless
potential benefit outweighs
the risk.
Levofloxacin Ø Caution with use of other drugs that can cause Ø Eye use: ocular burning, Ø Caution: acute MI, avoid
QT interval prolongation. visual disturbances. excess alkalinity in urine,
Ø IV or oral use: bradycardia, congenital long
constipation, flatulence, QT syndrome, electrolyte
and hyperhidrosis. disturbance, ensure
adequate fluid intake, heart
failure with reduced left
ventricular ejection fraction,
history of symptomatic
arrhythmia.

Moxifloxacin Ø Caution with use of other drugs that can cause Ø Ocular use: hyperaemia, Ø Caution: acute MI, avoid
QT interval prolongation. ocular discomfort, excess alkalinity in urine,
ocular dryness, ocular bradycardia, congenital long
irritation, ocular pain, QT syndrome, electrolyte
taste disturbance. disturbance, ensure
Ø IV use and oral use: adequate fluid intake, heart
angina, arrhythmia, failure with reduced left
constipation, flatulence, ventricular ejection fraction,
gastritis, history of symptomatic
hyperlipidaemia, arrhythmia.
palpitation, sweating, Ø Caution with use in eye in
vasodilation. neonates
Nalidixic acid Ø Caution with use of other drugs that can cause Ø Cranial nerve palsy, Ø Caution: acute MI, avoid
QT interval prolongation. increased intracranial excess alkalinity in urine,
Ø Monitor blood counts, renal and liver function pressure, metabolic bradycardia, congenital long
if treatment exceeds 2 weeks. acidosis, peripheral QT syndrome, electrolyte
neuropathy, toxic disturbance, ensure
psychosis. adequate fluid intake, heart
failure with reduced left
ventricular ejection fraction,
history of symptomatic
arrhythmia.
Norfloxacin Ø Caution with use of other drugs that can cause Ø Epiphora, tinnitus. Ø Caution: acute MI, avoid
QT interval prolongation. excess alkalinity in urine,
Ø May impair skilled task bradycardia, congenital long
QT syndrome, electrolyte
disturbance, ensure
adequate fluid intake, heart
failure with reduced left
ventricular ejection fraction,
history of symptomatic
arrhythmia.
Ofloxacin Ø Caution with use of other drugs that can cause Ø Eye use: eye irritation, Ø Caution: acute MI, avoid
QT interval prolongation. ocular discomfort. excess alkalinity in urine,

Ø Affect the performance of skilled task; Ø IV and oral use: cough, bradycardia, congenital long
enhanced by alcohol. eye irritation, QT syndrome, electrolyte
nasopharyngitis. disturbance, within others
Ø Use in eye caution: corneal
ulcer, epithelial defect.
Rifaximin Ø Rifaximin is a rifamycin that is poorly Ø Abdominal pain, Ø C/I: intestinal obstruction
absorbed from the GI tract and not depression, diarrhoea, Ø Pregnancy: Mfg advices
recommended for systemic infection. dizziness, dyspnoea, avoid –toxicity in animal
Ø Not recommended for diarrhoea associated flatulence, headache, studies.
with invasive organism such as campylobacter muscle spasm, nausea,
and shigella. pruritus, rash, vomiting.
Sulfadiazine Ø Is a sulphonamide with bacteriostatic activity Ø Diarrhoea, headache, Ø C/I: Acute porphyria
against a broad-spectrum of organisms. hyperkalaemia, nausea, Ø Caution: asthma, avoid in
Ø Less importance due to increased resistance rash. blood disorder, avoid in
and alternative which are less toxic and more Ø Pregnancy: risk of infant under 6 weeks
active. neonatal haemolysis and because of the risk of
Ø Monitor blood count on prolonged treatment. methaemoglobinaemia kernicterus, elderly, G6PD
Ø B/feeding: small risk of kernicterus in in third trimester, fear of deficiency, maintain
jaundiced infant and haemolysis in G6PD increased risk of adequate fluid intake,
deficiency. kernicterus appears to predisposition to Folate
be unfounded. deficiency, predisposition to
hyperkalaemia.

Tetracycline Ø Broad-spectrum but importance reduced due to growing resistance.
Ø Treatment of choice for infections caused by chlamydia, rickettsia, brucella (doxycycline with rifampicin or
streptomycin) and the spirochete, borrelia burgdorferi.
Ø They are used in respiratory and genital mycoplasma infection, in acne, in destructive periodontal disease, in
exacerbation of chronic bronchitis and for leptospirosis in penicillin hypersensitivity (as an alternative to
erythromycin)
Ø They also have role in MRSA infection.
Ø Between tetracycline minocycline is broader spectrum and is active against Neisseria meningitides and has been used
for meningococcal prophylaxis but no longer recommended because of side effects including dizziness and vertigo.
Compared to other tetracycline, minocycline is associated with lupus-erythematosus like syndrome and can cause
irreversible pigmentation.

Ø C/I: children under 12 years (deposition in growing bone and teeth, by binding to calcium, causes staining and
occasionally dental hypoplasia)
Ø Caution: Myasthenia gravis, systemic lupus erythematosus.
Ø Interaction: antacids, aluminium, calcium, iron, magnesium and zinc salts decrease the absorption of tetracycline. Use
in caution with those receiving potentially hepatotoxic drugs.
Ø Milk reduces absorption of Demeclocycline, Oxytetracycline and Tetracycline. (DOT)
Ø Pregnancy: should not be given to pregnant woman. Effect on skeletal development have been documented in the first
trimester in animal studies. During 2nd and 3rd trimester use can cause discolouration of the child’s teeth, and maternal
hepatotoxicity has been reported with large parenteral dose.
Ø B/feeding: should not be given to women who are breast-feeding.
Ø Hepatic impairment: should be avoided or used with caution.
Anthrax Ø Inhallation or GI anthrax should be treated with ciprofloxacin or in patient over 12 with doxycycline combined with
amoxicillin, Penicillin G, chloramphenicol, clarithromycin, clindamycin, imipenem with cilastatin, rifampicin and
vancomycin. Once situation is improved and sensitivity of bacillus anthracis found switched to single treatment.
Continue treatment for 60 days.
Ø Cutaneous anthrax should be treated with ciprofloxacin or doxycycline for 7 days. Can be switched to amoxicillin if
sensitive. Treatment for cutaneous infection should be continued for 60 days if it is due to aerosol. A combination of
abx treatment for 14 days if systemic symptoms like extensive oedema or lesions of the head or neck.
Ø Ciprofloxacin or doxycycline can be used for post-exposure prophylaxis. Anthrax vaccine may shortened the duration
of prophylaxis treatment.
Leprosy Ø Drug recommended dapsone, rifampicin and clofazimine. Other drugs active against mycobacterium leprae include
ofloxacin, minocycline and clarithromycin but none as active as rifampicin and reserved for second line.
Ø A three-drug treatment for multibacillary leprosy and a two drugs regimen for paucibacillary leprosy.
Ø Multibacillary leprosy should be treated with combination of rifampicin, dapsone and clofazimine for 2 years for both
type1 (reversal) or type 2 (erythema nodosum leprosum) reactions. During reversal reaction neuritic pain or
weakenss can herald the rapid onset of permanent nerve damage- prednisolone treatment instituted at once. Mild
type II reactions may require corticosteroid. Thalidomide is also useful in patients with corticosteroid dependent.
Thalidomide- only by specialist – teratogen- women of child bearing age- Pregnancy prevention programme. Increased
dose of clofazimine are also useful.
Ø Paucibacillary leprosy should be treated with dapsone and rifampicin for 6 months. If treatment is interrupted the
regimen should be recommenced where it was left off to complete the full course.
Lyme disease Ø Should be treated by specialist with experience. Doxycycline, amoxicillin or cefuroxime are the abx of choice for early
Lyme disease or Lyme arthritis. If these are contraindicated a macrolide can be used.
Ø Intravenous administration of ceftriaxone, cefotaxime or penicillin G is recommended for Lyme disease associated

with cardiac or neurological complications. The duration of treatment is normally 2-4 weeks. Lyme arthritis may
require longer treatment.
MRSA Ø Infection from staphylococcus aureus strains resistant to meticillin (discontinued drug) and to Flucloxacillin are hard
to treat.
Ø Rifampicin or fusidic acid should not be used alone resistance may develop rapidly.
Ø Tetracycline + rifampicin/fusidic acid for skin or soft tissue caused by MRSA. Clindamycin alone is an alternative.
Ø Glycopeptide (e.g. vancomycin) can be used for severe skin or soft tissue infection if unsuitable linezolid can be used
on expert advice. Linezolid is not active against gm-ve bacteria.
Ø Combination of glycopeptide + fusidic acid/rifampicin can be considered for skin or soft tissue infections that have
failed to respond to single abx.
Ø Tigecycline and Daptomycin are licenced for the treatment of complicated skin and soft tissue infections involving
MRSA.
Ø Tetracycline or clindamycin can be used for bronchiectasis caused by MRSA. A glycopeptide can be used for
pneumonia associated with MRSA. If a glycopeptide is unsuitable linezolid can be used on expert advice. Linezolid
must be used with other abx if the infection also involves gm-ve bacteria.
Ø A tetracycline can be used for UTI caused by MRSA. Trimethoprim or nitrofurantoin is alternative. A glycopeptide can
be used for UTI that are severe or resistant to other bacteria.
Ø Glycopeptide can be used for septicaemia associated with MRSA.
Ø Prophylaxis with vancomycin or teicolplanin for surgery if: history of MRSA colonisation or infection without
documented eradication; if there is a risk that the patient’s MRSA carriage has recurred; patient from the area with
high occurrence of MRSA.
Tuberculosis Ø Treated in 2 phases: initial phase- using 4 drugs and then continuation phase using 2 drugs in fully sensitivity
cases.
Ø Initial phase: 4 drugs to reduce the bacterial population as rapidly as possible and to prevent the emergence of drug
resistance. Best given as combination of product unless component is resistant to.
o The treatment of choice: isoniazid, rifampicin, pyrazinamide and ehtambutol.
o Start treatment if suspected without waiting for culture results. Initial phase for 2 months.
o Streptomycin rarely used in UK only when resistant to isoniazid.
Ø Continuation phase: after the initial phase > continuation phase for another 4 months with rifampicin with isoniazid
(preferably combination product). Longer treatment is necessary for meningitis, direct spinal cord involvement and
for resistant organism, which may also require modification of the regimen.
Ø Unsupervised treatment: for patient, who are likely to take anti-TB drugs reliably without supervision. Standard
unsupervised treatment can be given during pregnancy and breast-feeding. Streptomycin should not be given in
pregnancy.
Ø Supervised treatment: fully supervised (direct observation therapy- DOT) with compliance issue. Initial phase

(isoniazid, rifampicin, pyrazinamide and ehtambutol (or streptomycin) three times a week for 2 months followed by
isoniazid and rifampicin three times a week for 4 months.
Ø Immunocompromised patients may present multi-resistant mycobacterium tuberculosis. Organism must be cultured
and confirm its type and sensitivity. Confirmed m. tuberculosis infection sensitive to first line drugs should be treated
with a standard 6 months regimen, after completing treatment monitor patient.
Ø In meningeal or pericardial tuberculosis, a corticosteroid should be started at the same time as anti-tuberculosis
treatment.
Ø Prevention of tuberculosis: may develop tuberculosis due to reactivation of previously latent disease.
Chemoprophylaxis may be required in those who have evidence of latent tuberculosis and are receiving treatment
with immunosuppressant. In this case, chemoprophylaxis involves use of either isoniazid alone for 6 months or
isoniazid and rifampicin for 3 months.
Ø Isoniazid cheap and effective like rifampicin it should always be included in any regimen unless there is a specific
contraindication.
Ø During initial phase rifampicin may transient disturbance of liver function with elevated serum transaminases but no
need to stop treatment. Some time more serious liver toxicity may require change in treatment.
Ø On intermittent treatment six toxicity syndromes have been identified: influenza like, abdominal, and respiratory
symptoms, shock, renal failure and thrombocytopenic purpura-and can occur in 20-30% patients.
Ø Rifabutin, another rifamycin, is indicated for prophylaxis against M. avium complex infections in patients with a low
CD4 count. Also licenced for treatment of non-tuberculosis mycobacterial disease and pulmonary tuberculosis.
Ø Pyrazinamide: only active against intracellular dividing forms of mycobacterium tuberculosis; main effect during first
two three months > good meningeal penetration.
Ø Ehtambutol: included if isoniazid resistance is suspected.
Ø Children treatment same just extra caution with ehtambutol and effect on eye.
Ethambutol Ø Peak concentration: (2-2.5 hours after dose): Ø Ocular toxicity more Ø C/I: optic neuritis; poor
should be 2-6mg/lit. common with excess dose vision.
Ø Trough concentration: should be <1mg/lit. or if renal function is Ø Caution: elderly (in adults)
Ø Renal function should be checked before impaired. and young children (in
treatment. children). Patients who
Ø Visual acuity should be tested by snellen cannot understand caution
chart before treatment with Ethambutol. should be given alternative
Ø Stop treatment at first sign of ocular toxicity. drugs.
Isoniazid Ø Peripheral neuropathy more risk with pre- Ø Peripheral neuropathy. Ø C/I: drug induced liver
existing risk factor such as diabetes, alcohol Ø Hepatitis more common in disease.
dependence, chronic renal failure, those aged over 35 years. Ø Cautions: Acute porphyria,
pregnancy, malnutrition, and HIV infection. Ø B/feeding: Theoretical alcohol dependence,

Ø Patient at increased risk should be given risk of convulsion and diabetes mellitus, epilepsy,
pyridoxine from the start of the treatment; neuropathy. Prophylactic history of psychosis, HIV
Ø When used with tyramine or histamine rich pyridoxine advised. infection, malnutrition, slow
foods, tachycardia, palpitation, hypotension, Ø Renal impairment risk of acetylator status.
flushing, headache, dizziness and sweating ototoxicity and peripheral Ø Pregnancy: not known to be
reported. neuropathy; prophylactic harmful; prophylactic
Ø Monitor renal and hepatic function. Advise pyridoxine. pyridoxine recommended.
patient and carer on signs of hepatic
impairment and discontinuation of
treatment on toxicity.(nausea, vomiting,
malaise or jaundice)
Rifampicin Ø Effectiveness of hormonal contraception is Ø Body secretions coloured Ø C/I: acute porphyria,
reduced. Alternative family planning advice red and orange. Jaundice.
should be offered. Ø Caution: discolouration of
Ø Renal functions should be checked regularly. soft contact lenses.
Ø Hepatic function should be measured before Ø Pregnancy: Mfg advises high
treatment and after only if any sign of liver doses teratogenic in animal
toxicity. studies in first trimester.
Ø Blood count should be monitored in patients Risk of neonatal bleeding
on prolonged therapy. may be increased in third
trimester.

Urinary tract Ø UTI is more common in woman than man. When UTI in man usually underlying abnormality.
infection Ø Recurrent UTI in children should be investigated further – untreated pyelonephritis can lead to permanent kidney
damage.
Ø E.coli is the most common cause of UTI; S. saprophyticus is also common in sexually active woman. Proteus and
klebsiella spp. Less common. Pseudomonas aeruginosa infections usually occurs in hospital settings.
Ø Urine specimen should be collected for culture and sensitivity should be tested before starting abx:
In men, pregnant woman, child < 3 years, suspected UTI, complicated/recurrent infection, resistant organism
suspected, urine dipstick gives a single positive result for leucocyte esterase or nitrile or if clinical symptoms are not
consistant with results from dipstick testing.
Ø Antibacterial for lower UTI: uncomplicated lower UTI is treated with trimethoprim or nitrofurantoin, or amoxicillin,
ampicillin or oral cephalosporin. – 7 day treatment but 3 day treatment is good enough for uncomplicated UTI.
Ø Wide spread resistance ampicillin, amoxicillin and trimethoprim is reported use alternative: co-amoxiclave, an oral
cephalosporin, nitrofurantoin, pivamecillinam hydrochloride or a quinolone.

Ø Fosfomycin – on advise of specialist.
Ø Long term low dose therapy to prevent recurrence of infection; indications include frequent relapses and significant
kidney damage: trimethoprim, nitrofurantoin and cephalexin.
Ø Methenamine hippurate not generally be used in because it requires acidic urine to work and its ineffective in upper
UTI. Has role in recurrent or chronic uncomplicated lower UTI.
Ø Treatment of upper UTI: acute pyelonephritis can lead to septicaemia and is treated initially by injection of a broad
spectrum abx : cefuroxime, quinolone or gentamycin can be used. – suggested treatment duration 10-14 days.
Ø Prostatitis difficult to cure and requires treatment for several weeks with antibacterial which penetrates prostatic
tissues such as some of the quinolones (ciprofloxacin or ofloxacin) or alternatively trimethoprim.- 28 days treatment.
Ø Pregnancy: UTI in pregnancy can be asymptomatic and need prompt treatment to prevent progression to acute
pyelonephritis. Penicillin and cephalosporin are suitable for treating UTI during pregnancy. Nitrofurantoin can be used
but should be avoided at term. Sulphonamide and quinolone should be avoided during pregnancy. Trimethoprim
should also be avoided particularly in first trimester.
Ø UTI in children: should be treated promptly to avoid renal scarring. Uncomplicated lower UTI in children over 3
months of age can be treated with trimethoprim, nitrofurantoin, first generation cephalosporin (cephalexin) or
amoxicillin for 3 days.
Ø Acute pyelonephritis in children over 3 months of age can be treated with a first generation cephalosporin or co-
amoxiclav for 7-10 days. If patient severely ill: better treat initially by injection of a broad spectrum antibacterial such
as cefotaxime, co-amoxiclav or gentamicin is an alternative. Children under 3 months of age transfer to hospital treat
with injection of ampicillin with gentamicin or cefotaxime alone until infection responds, full doses of oral abx given
for further period. Low doses of trimethoprim or nitrofurantoin for prophylaxis in recurrent UTI.
Methenamine Caution: avoid concurrent administration with N/A C/I: gout, metabolic acidosis,
Hippurate sulphonamides (risk of crystalluria) or urinary severe dehydration.
alkalinising agents.

Nitrofurantoin Ø False positive on urinary glucose Ø On long term therapy Ø C/I: acute porphyria, G6PD
Ø Pregnancy: avoid at term-may cause neonatal monitor liver function deficiency, infants less than
haemolysis. and monitor for 3 months old.
Ø B/feeding: avoid, only small amount in milk pulmonary symptoms- Ø Caution: anaemia, diabetes
but enough to produce haemolysis in G6PD discontinue if lung mellitus, electrolyte
deficient infants. function deterioration. imbalance, Folate deficiency,
Ø Caution in vitamin B deficiency. pulmonary disease,
susceptibility to peripheral
neuropathy, urine may be
coloured yellow or brown;

Methotrexate
Methotrexate Clinical information
Ø Methotrexate inhibits the enzyme dihydrofolate reductase, essential for the synthesis of purines and pyrimidines.
It is given by mouth, intravenously, intramuscularly, or intrathecally. Methotrexate inhibits the enzyme
dihydrofolate reductase, essential for the synthesis of purines and pyrimidines. It is given by mouth,
intravenously, intramuscularly, or intrathecally.

Ø Side-Effects: Methotrexate causes myelosuppression, mucositis, and rarely pneumonitis.

Ø It is contra-indicated in significant renal impairment because it is excreted primarily by the kidney. It is also
contra-indicated in patients with severe hepatic impairment. It should also be avoided in the presence of
significant pleural effusion or ascites because it can accumulate in these fluids, and its subsequent return to the
circulation may cause myelosuppression.

Ø Folinic acid following methotrexate administration helps to prevent methotrexate-induced mucositis or
myelosuppression.

Ø Cautions: Blood Count, Liver Toxicity, and Pulmonary Toxicity; extreme caution in blood disorders (avoid if
severe); peptic ulceration, ulcerative colitis, diarrhoea and ulcerative stomatitis (withdraw if stomatitis
develops—may be first sign of gastro-intestinal toxicity); risk of accumulation in pleural effusion or ascites—drain
before treatment; acute porphyria.

Ø Blood count Bone marrow suppression can occur abruptly; factors likely to increase toxicity include advanced
age, renal impairment, and concomitant use with another anti-folate drug (e.g. trimethoprim). A clinically
significant drop in white cell count or platelet count calls for immediate withdrawal of methotrexate and
introduction of supportive therapy

Ø Liver toxicity Liver cirrhosis reported. Treatment should not be started or should be discontinued if any
abnormality of liver function tests or liver biopsy is present or develops during therapy. Abnormalities can return
to normal within 2 weeks after which treatment may be recommenced if judged appropriate

Ø Pulmonary toxicity Pulmonary toxicity may be a special problem in rheumatoid arthritis (patient to seek medical
attention if dyspnoea, cough or fever); monitor for symptoms at each visit—discontinue if pneumonitis suspected.

Ø Aspirin and other NSAIDs If aspirin or other NSAIDs are given concurrently the dose of methotrexate should be
carefully monitored. Patients should be advised to avoid self-medication with over-the-counter aspirin or
ibuprofen

Ø Pregnancy avoid (teratogenic; fertility may be reduced during therapy but this may be reversible); effective
contraception required during and for at least 3 months after treatment in men or women.

Monitoring
In view of reports of blood dyscrasias (including fatalities) and liver cirrhosis with low-dose methotrexate patients
should:
Ø have full blood count and renal and liver function tests before starting treatment and repeated every 1–2 weeks
until therapy stabilised, thereafter patients should be monitored every 2–3 months
Ø be advised to report all symptoms and signs suggestive of infection, especially sore throat
Ø Treatment with folinic acid (as calcium folinate, may be required in acute toxicity

Important
Note that the above dose is a weekly dose. To avoid error with low-dose methotrexate, it is recommended that:
• the patient is carefully advised of the dose and frequency and the reason for taking methotrexate and any other
prescribed medicine (e.g. folic acid);
• only one strength of methotrexate tablet (usually 2.5 mg) is prescribed and dispensed;
• the prescription and the dispensing label clearly show the dose and frequency of methotrexate administration;
• the patient is warned to report immediately the onset of any feature of blood disorders (e.g. sore throat, bruising, and
mouth ulcers), liver toxicity (e.g. nausea, vomiting, abdominal discomfort, and dark urine), and respiratory effects
(e.g. shortness of breath)

Non-Steroidal Anti-Inflammatory drugs

NSAID
Summary
Ø In single doses non-steroidal anti-inflammatory drugs (“NSAIDs”) have analgesic activity comparable to that of
paracetamol, but paracetamol is preferred, particularly in the elderly.
Ø In regular full dosage “NSAIDs” have both a lasting analgesic and an anti-inflammatory effect which makes them
particularly useful for the treatment of continuous or regular pain associated with inflammation.

Choice
Ø Pain relief starts soon after taking the first dose and a full analgesic effect should normally be obtained within a
week, whereas an anti-inflammatory effect may not be achieved (or may not be clinically assessable) for up to 3
weeks.

Ø “NSAIDs” reduce the production of prostaglandins by inhibiting the enzyme cyclo-oxygenase. They vary in their
selectivity for inhibiting different types of cyclo-oxygenase; selective inhibition of cyclo-oxygenase-2 is associated
with less gastro-intestinal intolerance.

Ø Ibuprofen is a propionic acid derivative with anti-inflammatory, analgesic, and antipyretic properties. It has
fewer side-effects than other non-selective “NSAIDs” but its anti-inflammatory properties are weaker.

Ø Other propionic acid derivatives: Naproxen is one of the first choices because it combines good efficacy with a
low incidence of side-effects (but more than ibuprofen)

Ø Drugs with properties similar to those of propionic acid derivatives:

Ø Diclofenac and aceclofenac are similar in efficacy to naproxen.

Ø Etodolac is comparable in efficacy to naproxen; it is licensed for symptomatic relief of osteoarthritis and
rheumatoid arthritis.

Ø Indometacin has an action equal to or superior to that of naproxen, but with a high incidence of side-effects
including headache, dizziness, and gastro-intestinal disturbances.

Ø Mefenamic acid has minor anti-inflammatory properties.

Ø The selective inhibitors of cyclo-oxygenase-2, etoricoxib and celecoxib, are as effective as non-selective
“NSAIDs” such as diclofenac and naproxen. Although selective inhibitors can cause serious gastro-intestinal
events, available evidence appears to indicate that the risk of serious upper gastro-intestinal events is lower with
selective inhibitors compared to non-selective “NSAIDs”; this advantage may be lost in patients who require
concomitant low-dose aspirin.

Ø Celecoxib and etoricoxib are licensed for the relief of pain in osteoarthritis, rheumatoid arthritis, and ankylosing
spondylitis; etoricoxib is also licensed for the relief of pain from acute gout.

Dental and orofacial pain = Those used for dental pain include ibuprofen and diclofenac.

Cautions and contra-indications = “NSAIDs” should be used with caution in the elderly (risk of serious side-effects and
fatalities, in allergic disorders (they are contra-indicated in patients with a history of hypersensitivity to aspirin or any
other “NSAID”—which includes those in whom attacks of asthma, angioedema, urticaria or rhinitis have been
precipitated by aspirin or any other “NSAID”), and in coagulation defects.

Ø Long-term use of some “NSAIDs” is associated with reduced female fertility, which is reversible on stopping
treatment. Caution is also required in patients with connective-tissue disorders. Fluid retention may occur (rarely
precipitating congestive heart failure); blood pressure may be raised.

Ø In patients with cardiac impairment, caution is required since “NSAIDs” may impair renal function.

Ø All “NSAIDs” are contra-indicated in severe heart failure. High-dose noibuprofen (≥ 2.4 g daily) and
dexibuprofen (≥ 1.2 g daily) are contra-indicated in uncontrolled hypertension. Diclofenac, aceclofenac,
ibuprofen (≥ 2.4 g daily), dexibuprofen (≥ 1.2 g daily) and the selective inhibitors of cyclo-oxygenase-2
(celecoxib, etoricoxib, and parecoxib) are contra-indicated in ischaemic heart disease, cerebrovascular disease,
peripheral arterial disease, and mild to severe heart failure.

Ø They should be used with caution in patients with a history of cardiac failure, left ventricular dysfunction,
hypertension, in patients with oedema for any other reason, and in patients with other risk factors for
cardiovascular events.

“NSAIDs” and cardiovascular events = All “NSAID” use (including cyclo-oxygenase-2 selective inhibitors) can, to
varying degrees, be associated with a small increased risk of thrombotic events (e.g. myocardial infarction and stroke)

independent of baseline cardiovascular risk factors or duration of “NSAID” use; however, the greatest risk may be in
those receiving high doses long term.

Cyclo-oxygenase-2 selective inhibitors, diclofenac (150 mg daily) and ibuprofen (2.4 g daily) are associated with an
increased risk of thrombotic events. Naproxen (1 g daily) is associated with a lower thrombotic risk, and low doses of
ibuprofen (1.2 g daily or less) have not been associated with an increased risk of myocardial infarction.

Ø The lowest effective dose of “NSAID” should be prescribed for the shortest period of time to control symptoms
and the need for long-term treatment should be reviewed periodically.

Ø All “NSAIDs” (including cyclo-oxygenase-2 selective inhibitors) are contra-indicated in patients with active
gastro-intestinal ulceration or bleeding. Piroxicam, ketoprofen, and ketorolac are contra-indicated in patients
with any history of gastro-intestinal bleeding, ulceration, or perforation. Other non-selective “NSAIDs” are contra-
indicated in patients with a history of recurrent gastro-intestinal ulceration or haemorrhage (two or more distinct
episodes), and in patients with a history of gastro-intestinal bleeding or perforation related to previous “NSAID”
therapy.

Ø Patients at risk of gastro-intestinal ulceration (including the elderly), who need “NSAID” treatment should receive
gastroprotective treatment.

Hepatic impairment = “NSAIDs” should be used with caution in patients with hepatic impairment; there is an increased
risk of gastro-intestinal bleeding and fluid retention.

Renal impairment = “NSAIDs” should be avoided if possible or used with caution in patients with renal impairment; the
lowest effective dose should be used for the shortest possible duration, and renal function should be monitored.
Sodium and water retention may occur and renal function may deteriorate, possibly leading to renal failure;
deterioration in renal function has also been reported after topical use; see also individual drugs.

Ø Pregnancy = Most manufacturers advise avoiding the use of “NSAIDs” during pregnancy or avoiding them unless
the potential benefit outweighs the risk. “NSAIDs” should be avoided during the third trimester because use is
associated with a risk of closure of fetal ductus arteriosus in utero and possibly persistent pulmonary
hypertension of the newborn. In addition, the onset of labour may be delayed and its duration may be increased.

Ø Side-effects = Gastro-intestinal disturbances including discomfort, nausea, diarrhoea, and occasionally bleeding
and ulceration occur. Systemic as well as local effects of “NSAIDs” contribute to gastro-intestinal damage; taking

oral formulations with milk or food, or using enteric-coated formulations, or changing the route of administration
may only partially reduce symptoms such as dyspepsia.

“NSAIDs” and gastro-intestinal events = All “NSAIDs” are associated with serious gastro-intestinal toxicity; the risk is
higher in the elderly. Evidence on the relative safety of non-selective “NSAIDs” indicates differences in the risks of
serious upper gastro-intestinal side-effects—piroxicam, ketoprofen, and ketorolac are associated with the highest risk;
indometacin, diclofenac, and naproxen are associated with intermediate risk, and ibuprofen with the lowest risk
(although high doses of ibuprofen have been associated with intermediate risk).

Selective inhibitors of cyclo-oxygenase-2 are associated with a lower risk of serious upper gastro-intestinal side-
effects than non-selective “NSAIDs”.

Recommendations are that “NSAIDs” associated with a low risk e.g. ibuprofen are generally preferred, to start at the
lowest recommended dose and not to use more than one oral “NSAID” at a time.

Asthma = Any degree of worsening of asthma may be related to the ingestion of “NSAIDs”, either prescribed or (in the
case of ibuprofen and others) purchased over the counter.

Ø Renal failure may be provoked by “NSAIDs”, especially in patients with pre-existing renal impairment.

Anti-Hypertensive agents:

Anti-hypertensive
Drug treatment of hypertension
A single antihypertensive drug is often inadequate in the management of hypertension, and additional antihypertensive
drugs are usually added in a step-wise manner until control is achieved.

Unless it is necessary to lower the blood pressure urgently (see Hypertensive Crises, below), an interval of at least 4
weeks should be allowed to determine response; response to drug treatment may be affected by age and ethnicity.

Patients under 55 years:

Step 1
• ACE inhibitor; if not tolerated, offer an angiotensin-II receptor antagonist. If both ACE inhibitors and angiotensin-II
receptor antagonists are contra-indicated or not tolerated, consider a beta-blocker; beta-blockers, especially
when combined with a thiazide diuretic, should be avoided for the routine treatment of uncomplicated
hypertension in patients with diabetes or at high risk of developing diabetes
Step 2
• ACE inhibitor or angiotensin-II receptor antagonist in combination with a calcium-channel blocker. If a calcium-
channel blocker is not tolerated or if there is evidence of, or a high risk of, heart failure, give a thiazide-related
diuretic (e.g. chlortalidone or indapamide). If a beta-blocker was given at Step 1, add a calcium-channel blocker in
preference to a thiazide-related diuretic (see Step 1 above)
Step 3
• ACE inhibitor or angiotensin-II receptor antagonist in combination with a calcium-channel blocker and a thiazide-
related diuretic
Step 4 (resistant hypertension)
• Consider seeking specialist advice
• Add low-dose spironolactone [unlicensed indication], or use high-dose thiazide-related diuretic if plasma-potassium
concentration above 4.5 mmol/litre
• Monitor renal function and electrolytes
• If additional diuretic therapy is contra-indicated, ineffective, or not tolerated, consider an alpha-blocker or a beta-
blocker

Patients over 55 years, and patients of any age who are of African or Caribbean family origin:
Step 1

• Calcium-channel blocker; if not tolerated or if there is evidence of, or a high risk of, heart failure, give a thiazide-related
diuretic (e.g. chlortalidone or indapamide)
Step 2
• Calcium-channel blocker or thiazide-related diuretic in combination with an ACE inhibitor or angiotensin-II receptor
antagonist (an angiotensin-II receptor antagonist in combination with a calcium-channel blocker is preferred in
patients of African or Caribbean family origin)
Steps 3 and 4
Treat as for patients under 55 years (see above)

ACE Inhibitors
Ø Angiotensin-converting enzyme inhibitors (ACE inhibitors) inhibit the conversion of angiotensin I to angiotensin
II. Renal function and electrolytes should be checked before starting ACE inhibitors (or increasing the dose) and
monitored during treatment (more frequently if features mentioned below present); hyperkalaemia and other
side-effects of ACE inhibitors are more common in those with impaired renal function and the dose may need to
be reduced.
Ø Concomitant treatment with NSAIDs increases the risk of renal damage, and potassium-sparing diuretics (or
potassium-containing salt substitutes) increase the risk of hyperkalaemia. ACE inhibitors can cause profound
hypotension (see Cautions) and renal impairment (see Renal effects above), and a persistent dry cough.

Calcium Channel Blockers
Ø Calcium-channel blockers (less correctly called ‘calcium-antagonists’) interfere with the inward displacement of
calcium ions through the slow channels of active cell membranes. They influence the myocardial cells, the cells
within the specialised conducting system of the heart, and the cells of vascular smooth muscle.
Ø There are important differences between verapamil, diltiazem, and the dihydropyridine calcium-channel blockers
(amlodipine, felodipine, lacidipine, lercanidipine, nicardipine, nifedipine, and nimodipine).
Ø Side-effects associated with vasodilation such as flushing and headache (which become less obtrusive after a few
days), and ankle swelling (which may respond only partially to diuretics) are common.

Beta-Blockers
Ø Beta-adrenoceptor blocking drugs (beta-blockers) block the beta-adrenoceptors in the heart, peripheral
vasculature, bronchi, pancreas, and liver.
Ø Atenolol, celiprolol, nadolol, and sotalol are the most water-soluble; they are less likely to enter the brain, and
may therefore cause less sleep disturbance and nightmares. Water-soluble beta-blockers are excreted by the
kidneys and dosage reduction is often necessary in renal impairment.
Ø Atenolol, bisoprolol, metoprolol, nebivolol, and (to a lesser extent) acebutolol, have less effect on the

beta2 (bronchial) receptors and are, therefore, relatively cardioselective, but they are not cardiospecific. They have
a lesser effect on airways resistance but are not free of this side-effect.
Ø Beta-blockers can precipitate bronchospasm and should therefore usually be avoided in patients with a history
of asthma.

Opiates:

Opiates
Opioid analgesics are usually used to relieve moderate to severe pain particularly of visceral origin. Repeated
administration may cause dependence and tolerance;

Cautions: Opioids should be used with caution in patients with impaired respiratory function (avoid in chronic
obstructive pulmonary disease) and asthma (avoid during an acute attack);

Ø Repeated use of opioid analgesics is associated with the development of psychological and physical dependence;
Ø Avoid abrupt withdrawal after long-term treatment.
Ø Transdermal preparations (fentanyl or buprenorphine patches) are not suitable for acute pain or in those
patients whose analgesic requirements are changing rapidly because the long time to steady state prevents rapid
titration of the dose.

Renal Impairment: The effects of opioid analgesia are increased and prolonged and there is increased cerebral
sensitivity when patients with renal impairment are treated with opioid analgesics; avoid use or reduce dose.

Strong Opioids
Ø Morphine is the opioid of choice for the oral treatment of severe pain in palliative care. It is given regularly every 4
hours (or every 12 or 24 hours as modified-release preparations).
Ø Buprenorphine has both opioid agonist and antagonist properties and may precipitate withdrawal symptoms,
including pain, in patients dependent on other opioids.
Ø Dipipanone used alone is less sedating than morphine but the only preparation available contains an antiemetic
and is therefore not suitable for regular regimens in palliative care.
Ø Diamorphine (heroin) is a powerful opioid analgesic. It may cause less nausea and hypotension than morphine.
In palliative care the greater solubility of diamorphine allows effective doses to be injected in smaller volumes and
this is important in the emaciated patient.
Ø Alfentanil, fentanyl and remifentanil are used by injection for intra-operative analgesia; fentanyl is available in
a transdermal drug delivery system as a self-adhesive patch which is changed every 72 hours.
Ø Methadone is less sedating than morphine and acts for longer periods. In prolonged use, methadone should not
be administered more often than twice daily to avoid the risk of accumulation and opioid overdosage.
Ø Oxycodone has an efficacy and side-effect profile similar to that of morphine.
Ø Tramadol produces analgesia by two mechanisms: an opioid effect and an enhancement of serotonergic and
adrenergic pathways. It has fewer of the typical opioid side-effects (notably, less respiratory depression, less

constipation and less addiction potential).

Weak Opioids
Ø Codeine can be used for the relief of mild to moderate pain where other painkillers such as paracetamol or
ibuprofen have proved ineffective.
Ø Dihydrocodeine has an analgesic efficacy similar to that of codeine.
Ø Meptazinol is claimed to have a low incidence of respiratory depression. It has a reported length of action of 2 to
7 hours with onset within 15 minutes.

Pain Management with Opioids

Ø Recommended starting doses vary but, generally, a starting dose between 20–30 mg daily is safe for opioid-
naïve patients and 40–60 mg daily for patients being switched from a regular weak opioid. The dose is given
either as an immediate-release preparation 4-hourly or as a modified-release preparation 12-hourly, in addition
to rescue doses.

Ø If pain occurs between regular doses of morphine (‘breakthrough pain’), an additional dose (‘rescue dose’) of
immediate-release morphine should be given. An additional dose should also be given 30 minutes before an
activity that causes pain, such as wound dressing.

Ø The standard dose of a strong opioid for breakthrough pain is usually one-tenth to one-sixth of the regular
24-hour dose, repeated every 2–4 hours as required (up to hourly may be needed if pain is severe or in the last
days of life). Review pain management if rescue analgesic is required frequently (twice daily or more).

Ø When adjusting the dose of morphine, the number of rescue doses required and the response to them should be
taken into account; increments of morphine should not exceed one-third to one-half of the total daily dose
every 24 hours.

Ø Thereafter, the dose should be adjusted with careful assessment of the pain, and the use of adjuvant analgesics
should also be considered. Upward titration of the dose of morphine stops when either the pain is relieved or
unacceptable adverse effects occur, after which it is necessary to consider alternative measures.

Cytotoxic Drugs:
Ø Cytotoxic drugs works on cancerous cells but can also damage the normal tissue cells. Most cytotoxic drugs are
teratogenic.
Ø Guideline for handling cytotoxic drugs:
o Trained personal should reconstitute the drug.
o Reconstituted should be carried out in designated area.
o Protective clothing should be worn.
o Eyes should be protected and means of first aid should be specified.
o Pregnant staff should avoid exposure and all females of childbearing age should be informed of reproductive hazard.
o Use local procedures for dealing with spillage and disposal of cytotoxic waste material.
o Staff exposure should be monitored.
Ø Safe system for cytotoxic medicine:
o Should be given as a part of wider pathway of care coordinated by multidisciplinary team.
o Cytotoxic drugs should be prescribed, dispensed and administered only in context of a written protocol.
o Injectable cytotoxic drugs should only be dispensed if they are prepared for administration.
o Oral medicine should only be dispensed with clear written instruction.
Ø Safety:
o Non-specialist who prescribe or administer on-going cytotoxic medication should have access to written protocol and
treatment plan.
o Staff dispensing cytotoxic drug should confirm that prescribed dose is appropriate for the patient. Patient should have
access to this written information and so should the dispensing staff and get advice from cancer specialist pharmacist on
initiating hospital.
Ø Dose: dose is adjusted by body weight or surface area. Dose may be adjusted based on neutrophil count, renal and hepatic
function and previous side effects.
Ø Side effects:
o Extravasation of intravenous drugs: can cause severe tissue necrosis if leakage into the extravascular compartment.
o Oral mucositis: sore mouth is very common complication of cancer therapy; associated with fluorouracil, methotrexate
and anthracyclines. Good oral hygiene or with fluorouracil ice chips during infusion helps.
o Tumour lysis syndrome: secondary to rapid destruction of malignant cells. Non-hodgkin’s lymphoma, burkitts
lymphoma, acute lymphoblastic lymphoma, acute lymphoblastic leukaemia, acute myeloid leukaemia are more at risk. Pre-
existing hyperuricaemia, dehydration and renal impairment are predisposing factors.
o Hyperuricaemia: High-grade lymphoma and leukaemia – allopurinol start 24hours before treatment and keep patient
hydrated. Dose of mercaptopurine or azathioprine should be reduced if needs to be given at same time as allopurinol.
Rasburicase is licenced for hyperuricaemia in patient with haematological malignancy.

o Bone marrow suppression: all cytotoxic except vincristine sulphate and bleomycin can cause bone marrow suppression.
Can occur after 7-10 days of administrations but can be delayed with carmustine, lomustine and melphalan. Peripheral
blood count to be checked before each treatment-reduce dose if the bone marrow has not recovered. Cytotoxic drugs C/I in
patients with acute fever. Clear infection before or when starting treatment. Fever in neutropenic patient (neutrophil
count < 1.06 X 109.
o Alopecia: reversible hair loss is a common complication.
o Thromboembolism: VTE can be complication of cancer and increased risk with chemotherapy.
o Pregnancy and reproductive function: most cytotoxic drugs are teratogenic and shouldn’t be used in pregnancy,
especially during first trimester. Regimens that do not contain alkylating drug or procarbazine may have less effect on
fertility but alkylating drugs or procabazine can cause permanent male sterility (no effect on potency). Women are less
effective but premature menopause can occur.
o Nausea and vomiting: nausea and vomiting can cause distress.
§ Mildly emetogenic treatment: fluorouracil, etoposide, methotrexate (<100mg/m2), the vinca alkaloids and
abdominal radiotherapy.
§ Moderately emetogenic treatment: taxanes, doxorubicin, intermediate and low dose of cyclophosphamide,
mitoxantrone and higher dose methotrexate.
§ Highly emetogenic treatment: Cisplatin, dacarbazine and high dose cyclophosphamide.
§ Acute symptoms: patient with low risk can be treated with dexamethasone or lorazepam and for patients with high
risk treat with 5HT-3 receptor antagonist combined with dexamethasone and the neurokinin receptor antagonist
aprepitant is effective.
§ Delayed symptoms: dexamethadone + 5HT-3 receptor antagonist or dexamethasone+apretitant or metoclopramide
is also effective.
o Anthracycline-induced side effects: dose associated, cumulative and potentially life threatening cardio-toxicity.
Ø Treatment for cytotoxic-induced side effects:
o Chemotherapy induced mucositis and myelosuppression: folinic acid (given as calcium folinate) to counteract folate-
antagonist action of methotrexate. It doesn’t counteract the antibacterial activity of trimethoprim.
o Urothelial toxicity: haemorrhagic cystitis common with oxazaphophorines, cyclophosphamide and ifosfamide- caused by
metabolite acrolein. Mesna works particularly against this metabolite.
Ø Anthracyclines and other cytotoxic drugs:
o Widely used. Many cytotoxic antibiotics act as radiomimetics and simultaneous use of radiotherapy should be avoided
because it may increase toxicity.
o Doxorubicin is available as both conventional and liposomal formulation.
o Other anthracyclines includes: epirubicin, idarubicin, Daunorubicin, mitoxanthrone, pixanthrone, belomycin and
mitomycin.
Ø Vinca alkaloid: vinblastine, vincristine and vindesine are used to treat leukaemia, lymphomas and some solid tumours.

Vinorelbine semisynthetic vinca alkaloid used for breast cancer.
Ø Antimetabolite: incorporated with new nuclear material or combine irreversibility with cellular enzymes, preventing normal
cellular division.
Ø Alkylating drugs: act by interfering with cell replication by DNA damaging. Examples include cyclophosphamide, ifosfamide,
melphalan, lomustine, carmustine, estramustine. Mitobronitol is used for chronic myeloid leukaemia, available on named patient
basis from specialist importing company.



References:

www.bnf.org
https://www.medicines.org.uk/emc/