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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5230_Библиотеки_им_академика_М_И_Перельмана.pdf
Drug monitoring
For drugs which have a narrow therapeutic window, or where eective
treatment of a condition is imperative, it is important to ensure that drug
concentrations are within the therapeutic target range and adjust the drug
dose or dosing interval accordingly. Some prescriptions are based on ideal
body weight and some require you to calculate the creatinine clearance
(using the Cockroft–Gault equation). Online calculators are available to
work these out. Commonly prescribed drugs requiring monitoring are
outlined in Table 4.2. Therapeutic monitoring requirements are listed
under specic drugs in Chapter 5, in theBNF, and in the local protocols of
many hospitals. If in doubt, discuss with a senior or pharmacist.
Table4.2 Commonly used drugs requiring therapeutic drug monitoring
2+
†
, lipids
Drug Monitoring tests
Gentamicin Trough level immediately before next dose, peak levels h
Vancomycin Trough level immediately before next dose. Check U+E
Digoxin Trough level >6h after last dose. Monitor U+E
Phenytoin Trough level immediately before next dose
Theophylline Variable depending on drug route and patient factors
Lithium Level taken 2h after dose. Check U+E, TFTs, and ECG
Carbamazepine Trough level immediately before next dose.
Ciclosporin Trough level immediately before next dose. Check U+E,
†
The frequency of these tests depends on the indication for the drug, the dosing regimen, and
patient factors such as renal function. Check BNF/local protocols.
post dose. Monitor U+E
LFTs, Mg
173CONTROLLED DRUGS
Controlled drugs
Controlled drugs (CDs) CDs are those drugs which are addictive and
most often abused or stolen, and are subject to the prescription and storage
requirements of the Misuse of Drugs Regulations 200. See Box 2.6 for a list
of commonly used CDs. These agents are stored in a locked cabinet and a
record of their use on a named patient basis is required to be kept by law.
Some other drugs may be kept in the CD cupboard such as concentrated
KCl, ketamine, benzodiazepines, and anabolic steroids, but this is not a legal
requirement and will depend upon local policy. The weaker opioids (codeine) are not treated as CDs though they are still often misused.
Prescribing controlled drugs Prescribing for in- patients is just like pre-
scribing any other drug and the benets should be balanced against potential
side eects for each individual patient. Morphine, diamorphine, and tramadol
are the most commonly prescribed CDs on the ward. As with all prescriptions,
write the details clearly and make sure a maximum dose and a minimal interval
between doses is documented (E pp. 92–95 for management ofpain).
Controlled drugs forTTOs Epp. 82–3.
174 CHAPTER4 Prescribing
Night sedation
Patients develop tolerance to and dependence on hypnotics (sedating
drugs) if they are taken long term. They are only licensed for short- term
use and should be avoided if possible.
Causes of insomnia Anxiety, stress, depression, mania, alcohol,
pain, coughing, nocturia (diuretics, urge incontinence), restless leg
syndrome, steroids, aminophylline, SSRIs, benzodiazepine/ opioid
withdrawal, sleep apnoea, poor sleep hygiene, levothyroxine.
Try to dose regular medications so that stimulants (steroids, SSRIs,
aminophylline) are given early in the day, while sedatives (tricyclics, antihistamines) are given at night. Encourage sleep hygiene, ear plugs, eye
shades, and treat any causes of insomnia.
Sleep hygiene Avoid caeine in evening (tea, coee, chocolate), al-
cohol, nicotine, daytime naps, phone use or cerebral activity before
sleep; encourage exercise, light snack – 2h before bed, comfortable
and quiet location (ear plugs and eye shades), routine.
If the patient is still unable to sleep and there is a temporary cause (eg postop pain, noisy ward) then it is appropriate to prescribe a one- o or short
course (≤5d) of hypnotics (Table4.3). Some patients may be on long- term
hypnotics; these are usually continued in hospital. If long- term hypnotics
are stopped, the dose should be weaned to minimize withdrawal.
Table4.3 Common oral hypnotics
Zopiclone 3.75– 7.5mg/
Diazepam 5– 5mg/ 24h Signicant hangover eect, useful for anxious
Temazepam 0– 20mg/ 24h Shorter action than diazepam, less hangover
Lorazepam –2mg/24h May be more readily available on the wards
24h
Less dependence and risk of withdrawal
than diazepam and less hangover eect
patients
ContraindicationsRespiratory/ hepatic failure and sleep apnoea.
Side eectsThese include hangover (morning drowsiness), confusion,
ataxia, falls, aggression, and a withdrawal syndrome similar to alcohol
withdrawal if long- term hypnotics are stopped suddenly.
DischargeIf a patient is not on hypnotics when they enter hospital, they
should not be on hypnotics when they leave. It is bad practice to discharge
patients with supplies of addictive and unnecessary medications.
Violent/ aggressive patients E p. 02 for emergency sedation.
Pre- op sedation Should only be prescribed after discussion with
the anaesthetist and is rarely oered these days. Lorazepam, diazepam,
and temazepam are options. Midazolam is a rapidly acting IV sedative; it
should only be used by experienced doctors under monitored conditions
(sats, RR, and BP) with a crash trolley available. Give – 2mg boluses then
wait 0min for the full response before repeating; >5mg is rarely needed.
Steroid therapy
2 Steroids given for >3wk should never be abruptly discontinued as this
can precipitate an Addisonian crisis (E p. 346). Patients can need >60mg
prednisolone per day for severe inammatory disease and this must be
converted to an appropriate IV corticosteroid dose if they are unable to
take regular PO doses (Table 4.4, Box 4.4). Long- term steroid use should
prompt consideration of osteoporosis prophylaxis (Ep. 459).
Table4.4 Conversion oforal prednisolone toIV hydrocortisone
Normal prednisolone dose Suggested hydrocortisone dose
≥60mg/ 24h PO 00mg/ 6h IV
20– 50mg/ 24h PO 50mg/ 6h IV
≤20mg/ 24h PO 25mg/ 6h IV
†
If patients with known adrenal insuciency, or those who have been on any dose of oral corticosteroids for >3wk, present unwell, consider an initial dose of 00– 200mg hydrocortisone IV
STAT, then d/ w senior as to regular steroid dose. If unable to tolerate PO administration, ensure
equivalent IV steroids given, as per Box4.4.
Box 4.4 Steroid conversion
These are equivalent corticosteroid doses compared to 5mg prednisolone, but
do not take into account dosing frequencies or mineralocorticoid eects:
• Hydrocortisone 20mg; usually given IV6– 8h
• Methylprednisolone 4mg; usually given oncedaily
• Dexamethasone 750micrograms; usually given oncedaily.
Withdrawing steroid therapyThis is an art and must be performed
gradually if steroids have been used for >3wk. Large doses (>20mg prednisolone or equivalent) can be reduced by 5– 0mg/ wk until dose is 0mg
prednisolone/ d. Thereafter the doses must be reduced more slowly, eg
by 5mg/ wk. If the patient has been on long- term steroids and there is
signicant concern about adrenal insuciency then omit a single morning
dose and arrange a short Synacthen
®
test. Resume dosing immediately
after while awaiting results. If these show an adequate adrenal response, it
is safe to stop steroid therapy; if not, discuss with endocrinology.
See Table4.5 for side eects of steroids and treatment and monitoring options.
Table4.5 Steroid side eects and treatment and monitoring options
GI ulceration Consider PPI or H
Infections and reactivation of TB Low threshold for culturing samples or CXR
Skin thinning/ poor wound healing Pressure care and wound care
+
Na
and uid retention Regular BP, uid balance charts, and daily
Hyperglycaemia Twice- daily blood glucose if taking high- dose
Osteoporosis (E p. 459) Bone protection (Ca
Hypertension Twice- daily BPs
weighing of patients
steroids
- receptor antagonist
2
2+
+ bisphosphonate)
†
175STEROID THERAPY
176 CHAPTER4 Prescribing
Topical corticosteroids
Topical steroidsThese are used in the treatment of many inamma-
tory skin diseases. As with corticosteroids given orally or intravenously,
the mechanism of action is complex. Corticosteroids oer symptomatic relief but are seldom curative. The least potent preparation (see
Table 5.22 E p. 217) possible should be used to control symptoms.
Withdrawal of topical steroids often causes a rebound worsening of
symptoms and the patient should be warned about this. The amount of
steroid needed to cover various body parts is shown in Fig.4.4. Always
wash hands after applying topical steroids.
Side eectsLocal thinning of the skin, worsening local infection, striae
and telangiectasia, acne, depigmentation, hypertrichosis, systemic rarely
adrenal suppression, Cushing’s syndrome (subsequent withdrawal of topical steroids can precipitate an Addisonian crisis).
Potency E p. 217 for a list of the common topical steroids used ar-
ranged by potency.
ONE adult
ngertip
unit (FTU)*
Age
Adult
Children:
3–6 months
1–2 years
3–5 years
6–10 years
Fig.4.4 Amount of topical steroid required to treat various body parts. *One
adult ngertip unit (FTU) is the amount of ointment or cream expressed from a
tube with a standard 5mm diameter nozzle, applied from the distal crease on the
tip of the index nger.
Reproduced with permission from Long, C.C. and Finlay, A.Y. (99) Clinical and
Experimental Dermatology, 6:444– 7. Blackwell Publishing.
3
Number of ngertip units (FTUs)
Arm
& hand
Leg
Trunk
& foot
4
8
(front)
7
Trunk (back)
inc. buttocks
7
3
See these NICE Clinical Knowledge Summaries for an excellent resource in prescribing topical corticosteroids for dierent ages and body areas:Mhttps://cks.nice.org.uk/topics/
corticosteroids-topical-skin-nose-eyes/
Empirical antibiotic treatment
Local antibiotic guidelines These will be your key resource for
antibiotic treatment. They are written to ensure the most appropriate
antibiotics are used prior to knowing the pathogen and its antimicrobial
sensitivities. Always seek advice from the microbiologists if deviating
from the guidelines; their choice of suitable antibiotic will depend upon
the likely pathogen and its usual antimicrobial sensitivity, patient factors
(age and coexisting disease), and drug availability. Some common infections and suggested antibiotic regimens are listed in Tables4.6 and 4.7
(suitable for an otherwise healthy 70kg adult); more detailed options,
including choices for patients with penicillin allergies, are listed elsewhere,
E OHCM11 p. 382–3.
Taking culturesprior to commencing antibiotic therapy is important as
they allow subsequent therapy to be more specically tailored. However,
cultures should not delay treatment in the septic patient.
Table4.6 Common examples
Lower UTI Nitrofurantoin or trimethoprim
Pyelonephritis Cefalexin or ciprooxacin
Cellulitis Flucloxacillin g/ 6h PO/IV
Wound
infection
Meningitis Ceftriaxone 2g/ 2h IV. Consider adding amoxicillin 2g/
Encephalitis As for meningitis + aciclovir 0mg/ kg/ 8h IV (to cover
Septic arthritis Flucloxacillin. Base therapy on Gram stain of joint aspirate
Sepsis Broad-spectrum antipseudomonal penicillin, eg piperacillin/
As for cellulitis if after ‘clean’ surgery; for ‘dirty’ surgery or
trauma, use co- amoxiclav .2g/ 8h IV
4h IV if patient >50yr, pregnant, or immunocompromised
and/ or vancomycin g/ 2h IV if penicillin- resistant
pneumococcal meningitis is suspected
herpes simplex virus encephalitis)
tazobactam 4.5g/8h IV until source identied or culture
positive. Consider addition of metronidazole if anaerobes
suspected, vancomycin if MRSA suspected
177EMPIRICAL ANTIBIOTIC TREATMENT
Table4.7 Pneumonia
Community- acquired
(CAP), CURB65 = 0–
CAP, CURB65 = 2 Amoxicillin g/ 8h PO/ IV + clarithromycin 500mg/
CAP, CURB65 ≥ 3 Co- amoxiclav .2g/ 8h IV + clarithromycin 500mg/ 2h
Hospital- acquired
aspiration pneumonia
Amoxicillin 500mg– g/ 8h PO
2h PO/ IV
PO/IV
There is considerable variation between hospitals so
always consult local guidelines. Gram- negative cover
is important
Chapter 5
Pharmacopoeia
Pharmacopoeia 80
179
180 CHAPTER 5 Pharmacopoeia
Pharmacopoeia
Users are advised to always check local guidelines and formularies and to
consult the BNF when prescribingdrugs.
ACEi $ Angiotensin- converting enzyme inhibitor. Dose See Tables5.
and 5.2 on how to commence a patient on an ACEi
failure, hypertension, diabetic nephropathy, prophylaxis of cardiovascular events
Caution Pregnancy and breastfeeding, patients already
taking diuretics, renal artery stenosis/ renal impairment, aortic stenosis, hyperkalaemia, known allergy to ACEi. May not be eective in
African- Caribbean patients
SE Postural hypotension, renal impairment
and hyperkalaemia, dry cough, taste disturbance, urticaria, and angiooedema. If cough is problematic for the patient, consider AT II receptor
antagonist (E p. 86), or other antihypertensiveagent.
Table5. ACEi
Enalapril Dose Initially 5mg/ 24h PO up to max 40mg/ 24h PO
Fosinopril Dose Initially 0mg/ 24h PO up to max 40mg/ 24h PO
Lisinopril Dose Initially 5– 0mg/ 24h PO up to max 80mg/ 24h PO
Perindopril
erbumine
Perindopril
arginine
Ramipril Dose Initially .25– 2.5mg/ 24h PO up to max 0mg/ 24h PO
Dose Initially 4mg/ 24h PO up to max 8mg/ 24h PO
Dose Initially 5mg/ 24h PO up to max 0mg/ 24h PO
Table5.2 Starting anACEi
Patients with signicant comorbidity and/ or taking other antihypertensive
medications, as well as the frail and elderly, may need more cautious
management when starting an ACEi and when increasing the dose
Before starting Check U+E, document starting BP, identify target BP
First dose Start with lowest dose and consider giving at bedtime to
In hospital Increase dose daily/ alternate days as BP allows, monitor
In community Check U+E and BP at 7– 0d after starting therapy or increasing
limit any problems with rst- dose hypotension
U+E daily/ alternate days
dose. Increase dose every 4d until target BP reached
Indications Heart
Acetylcysteine (eg Parvolex®) $ Acetylcysteine helps replace
0.8
Plasma-paracetamol concentration (mmol/litre)
Plasma-paracetamol concentration (mg/litre)
120
Time (hours)
02
the substrates necessary to eliminate the toxic products formed when
normal hepatic metabolism of paracetamol is overwhelmed.
DoseIn adults, 3 doses of acetylcysteine are given (5% glucose is preferred):
• 50mg/ kg IV infusion in 200mL 5% glucose or 0.9% saline overh
• 50mg/ kg IV infusion in 500mL 5% glucose or 0.9% saline over4h
• 00mg/ kg IV infusion in 000mL 5% glucose or 0.9% saline over 6h.
Indication Mainly used in known or suspected paracetamol overdose
(E p. 499). It should be commenced immediately in all patients calculated to have ingested >75mg/ kg, those with a staggered overdose, or a
blood paracetamol level above the treatment threshold on the nomogram
in Fig.5.. Start treatment within 8h of ingestion— do not wait for level if
patient presents close to or after this time as ecacy of acetylcysteine will
decline rapidly after 8h. Discontinue treatment if the plasma concentration
is later reported as below the treatment line and patient is asymptomatic with normal LFTs, creatinine, and PT. Discuss patients with acidosis, encephalopathy, worsening renal function, or PT prolongation with
hepatologist on call (or at nearest liver centre if not available locally).
SEFlushing, rash, pruritus, urticaria, nausea, and vomiting are all relatively
common during treatment. More severe anaphylactoid reactions (dBP,
iHR, bronchospasm) should be managed as per E pp. 474–5 with in-
fusion slowed or stopped.
110
Treatment line
100
90
80
70
60
50
40
30
20
10
0
1412108642
22201816
181PHARMACOPOEIA
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
4
Fig.5. Paracetamol overdose treatment nomogram.
Reproduced from Mhttps://www.gov.uk/drug-safety-update/treating-
paracetamol-overdose-with-intravenous-acetylcysteine-new-guidance Contains
public sector information licensed under the Open Government Licencev3.0.
182 CHAPTER 5 Pharmacopoeia
Actrapid
®
$ Insulin. See insulin.
Adenosine $ Nucleoside (antiarrhythmic). Dose 6mg rapid IV bolus;
if needs repeated dose 2mg rapid IV bolus, then 2mg rapid IV bolus
Indication Supraventricular tachycardiaCI 2nd/ 3rd- degree heart block, sick
sinus syndrome (unless pacemaker tted), long QT syndrome, COPD/
asthma
CautionPregnancy, recent MI, pericarditis, heart block, bundle branch
block, accessory pathway, hypovolaemia, valvular lesions
SE Nausea, sinus
pause, bradycardia/ asystole, ushing, angina, dizziness.
Adrenaline (epinephrine); anaphylaxis $ Catecholamine.
Dose 0.5mg/ STAT IM (0.5mL of :000); repeat after 5min if inad-
equate response
Caution Cerebro- and cardiovascular disease SE iHR, iBP, anxiety,
it
Indication Suspected anaphylaxis; if in doubt give
sweats, tremor, arrhythmias.
Adrenaline (epinephrine); cardiac arrest $ Catecholamine.
Dose mg/ STAT IV (0mL of :0,000); repeat as per ALS algorithm
Indication Cardiac arrest Caution As for ‘Adrenaline (epinephrine); ana-
phylaxis’
SE As for ‘Adrenaline (epinephrine); anaphylaxis’.
Aggrastat
®
$ Glycoprotein IIb/ IIIa inhibitor. See tiroban.
AlogliptinSee DPP-4 inhibitors.
Alteplase $ Plasminogen activator. See brinolytics.
Amiloride $ Potassium- sparing diuretic. Dose5– 0mg/ 24h PO (max
20mg/ 24h PO)
Indication Oedema, potassium conservation when used
as an adjunct to thiazide or loop diuretics for hypertension, congestive
cardiac failure, hepatic cirrhosis with ascites
Addison’s disease
feeding
SE Abdominal pain, GI disturbances including bleeding.
Caution Renal impairment, DM, pregnancy, and breast-
CI Hyperkalaemia, anuria,
Aminophylline; IV $ Theophylline/ methylxanthine. Dose Loading
5mg/ kg (based on ideal body weight) in 00mL 0.9% saline IVI over
20min;
Maintenance 0.5mg/ kg/ h, make up 500mg in 500mL 0.9% sa-
line (concentration=mg/ mL)IVI
severe acute asthma
Caution Avoid loading dose if patient taking oral
theophylline; cardiac disease, hypertension, epilepsy
palpitations, arrhythmia, convulsions
Indication Reversible airways disease,
SE Tachycardia,
Info Theophylline is only available
as an oral preparation; aminophylline consists of theophylline and ethylenediamine which simply improves the drug’s solubility.
Monitoring
aminophylline
(theophylline)
Stop infusion 5min prior to sampling, take sample
commencing an infusion
2
Toxic >20mg/ L (>0micromol/ L)
Signs of toxicity Arrhythmia, anxiety, tremor, convulsions
2
(E OHAM4 p. 740)
0– 20mg/ L (55– 0micromol/ L)
4– 6h after
Amiodarone; cardiac arrest $ Class III antiarrhythmic. Dose
300mg IV/ STAT after third shock if patient remains in VF/ pulseless
VT
IndicationVF/ pulselessVT.