Prescribing

Dr Andrew Smith

Outline – from 2014

• Rules of Prescribing

• Prescribing Controlled Drugs

• Liver/Renal Disease

• Pregnancy/Breastfeeding

• Prescribing in the Elderly

• Allergies

• Adverse Drug Reactions

• Drug Level Monitoring

• Drug Interactions

• Practice Questions

Outline - Revised

Outline - Revised

Covered in other

lectures

I’ll leave the detailed slides in for your own use,

but will focus more on examples

These areas will come up in

finals (OSCEs and written)

as well as your prescribing

exam!

Slides on the theory and considerations for prescribing are contained at the end.

Prescribing Controlled Drugs• Doctors have the ability to prescribe controlled (Class A-C)

drugs. Some are limited to those with special licences.

• In order to meet the legal requirements for prescriptions, you must:• Include the name and address of the patient.

• State the name and strength of the formulation

• State the dose and frequency

• State the total amount to be supplied in words and figures.

• Doctors have a wider responsibility to avoid introducing dependence producing drugs unless clinically needed as well as monitoring for the signs of dependence and overuse.

Prescribing Controlled Drugs – Which is correct?

MORPHINE SULPHATE 10mg oral tabletsTake one tablet, three times dailyPlease supply 28 (TWENTY-EIGHT) tablets.

MORPHINE SULPHATE 10mg oral tabletsTake one tablet, three times daily.Please supply 28 10mg(TEN MILLIGRAM) tablets.

?? Will Dooley

?/?/?? Perrin Lecture Theatre

?? Will Dooley

?/?/?? Perrin Lecture Theatre

Prescribing Controlled Drugs – Which is correct?

?? Will Dooley

?/?/?? Perrin Lecture Theatre

MORPHINE SULPHATE 10mg oral tabletsTake one tablet, three times dailyPlease supply 28 (TWENTY-EIGHT) tablets.

?? Will Dooley

?/?/?? Perrin Lecture Theatre

MORPHINE SULPHATE 10mg oral tabletsTake one tablet, three times daily.Please supply 28 10mg (TEN MILLIGRAM) tablets.

It’s the ‘total amount’ that you need to specify

Prescribing Controlled Drugs – Which is correct?

MORPHINE SULPHATELiquid (10mg/5ml)

Take 10mg when required

Please supply 100ml(ONE HUNDRED)

MORPHINE SULPHATELiquid (10mg/5ml)

Take 10mg (TEN MILLIGRAM) when required

Please supply 100ml

?? Will Dooley

?/?/?? Perrin Lecture Theatre

?? Will Dooley

?/?/?? Perrin Lecture Theatre

Prescribing Controlled Drugs – Which is correct?

MORPHINE SULPHATELiquid (10mg/5ml)

Take 10mg when required

Please supply 100ml(ONE HUNDRED)

MORPHINE SULPHATELiquid (10mg/5ml)

Take 10mg (TEN MILLIGRAM) when required

Please supply 100ml

It’s the ‘total amount’ that you need to specify – Including the units. It should read:

Please supply 100ml (ONE HUNDRED MILLILITRES)

?? Will Dooley

?/?/?? Perrin Lecture Theatre

?? Will Dooley

?/?/?? Perrin Lecture Theatre

Outline - Revised

Adverse Drug Reactions

• These are unwanted reactions to drugs that occur with normal use of the drug.

• They can be reported to the Medicines and Healthcare Products Regulations Agency (MHRA) by professionals and patients by the Yellow Card Scheme.

• Two main types:• Type A (Augmented) – Common, predictable and often

dose dependent. Can be severe and delayed.

• Type B (Idiosyncratic) – No link to expected pharmacological effects. Often serious but rare.

Adverse Drug Reactions - Examples

Drug Reaction

Type A (Augmented)

Anticoagulants Bleeding

Insulin Hypoglycaemia

Antipsychotics Parkinsonism

Cytotoxics Bone Marrow Suppression

Type B (Idiosyncratic)

Penicillin Anaphylaxis

Isoniazid Hepatotoxity

Anaesthetics Malignant Hyperthermia

Sulphonamides Toxic Epidermal Necrolysis

Allergies• Type 1 allergy (e.g anaphylaxis) to medications is not that common.• Many reports of allergy are in fact just intolerances or side-effects of

the medication (e.g. nausea).• It is important to discern the exact reaction as else important

medications may be unnecessarily withheld.• True allergic symptoms are urticaria, swelling, laryngeal oedema,

anaphylaxis. • They can take up to 72 hours to appear and may not appear on the

first exposure to the drug.• Common culprits: Penicillin, Sulfa drugs, Tetracycline, Codeine,

NSAIDs, Phenytoin, Carbamazepine.• There is a reported 10% cross-over of penicillin allergy to

cephalosporins

Penicillin Allergy• Which of the following are safe, or useable with caution, in a

patient with true penicillin allergy?

AugmentinAmikacinCeftriaxoneGentamicinTazocinDoxycyclineFlucloxacillinMetronidazoleTrimethoprimMeropenem

Penicillin Allergy• Which of the following are safe, or useable with caution, in a

patient with true penicillin allergy?

AugmentinAmikacin

CeftriaxoneGentamicin

TazocinDoxycycline

FlucloxacillinMetronidazoleTrimethoprim

Meropenem

CONTRAINDICATED WITH CAUTION SAFE

Allergic Reaction Management

A patient recently given Tazocin despite a Type 1 Penicillin allergy develops shortness of breath, stridor and a widespread urticarial rash.

Which are appropriate treatments:

A) Chlorphenamine 4mg, PO

B) Adrenaline 10ml of 1:10000, IV

C) Adrenaline 10ml of 1:10000, IM

D) Adrenaline 0.5ml of 1:1000, IV

E) Adrenaline 0.5ml of 1:1000, IM

F) Hydrocortisone 200mg, IV

G) Chlorphenamine 10mg, IV

Allergic Reaction Management

A patient recently given Tazocin despite a Type 1 Penicillin allergy develops shortness of breath, stridor and a widespread urticarial rash.

Which are appropriate treatments:

A) Chlorphenamine 4mg, PO – only after resuscitation

B) Adrenaline 10ml of 1:10000, IV – cardiac arrest, 1mg

C) Adrenaline 10ml of 1:10000, IM – never used

D) Adrenaline 0.5ml of 1:1000, IV – never used

E) Adrenaline 0.5ml of 1:1000, IM – e.g. 0.5mg

F) Hydrocortisone 200mg, IV

G) Chlorphenamine 10mg, IV

Allergic Reaction Management

A patient recently given Tazocin despite a Type 1 Penicillin allergy develops shortness of breath, stridor and a widespread urticarial rash.

Which are appropriate treatments:

A) Chlorphenamine 4mg, PO – only after resuscitation

B) Adrenaline 10ml of 1:10000, IV – cardiac arrest, 1mg

C) Adrenaline 10ml of 1:10000, IM – never used

D) Adrenaline 0.5ml of 1:1000, IV – never used

E) Adrenaline 0.5ml of 1:1000, IM – e.g. 0.5mg

F) Hydrocortisone 200mg, IV

G) Chlorphenamine 10mg, IV

Drugs Expressed as Ratios

weight (g) : volume (ml)

1:1000 = 1g in 1000ml = 1000mg in 1000ml

Therefore, 1mg in 1ml 0.5mg in 0.5ml

1:10000 = 1g in 10,000ml = 1000mg in 10,000ml

Therefore, 1mg in 10ml

Higher concentrations are given IM so less volume has to be given(IM injections are unpleasant)

Used in anaphylaxis

Used in Cardiac Arrest

Adverse Reactions – Management Examples

• 76 year old on Warfarin for recurrent DVTs. Recent check showed an INR of 7. She is otherwise well

• 64 year old on Warfarin for Atrial Fibrilliation. Recent check showed an INR of 8.4. He is suffering from epistaxis.

• 83 year old on Warfarin for a replacement heart valve. Recent check shows INR of 8.7. She is suffering from an upper GI bleed.

Warfarin Overtreatment Management

Depends on patient factors:• High risk patients are age >65, severe hypertension, organ failure,

falls risk, trauma, etc.

And Bleeding Factors• Minor bleeding, e.g. haematuria, epistaxis.• Major bleeding, e.g. intracranial, intra-abdominal etc.• Any bleed can be major if deemed so by the clinician

Mx Options include:• Withold Warfarin• Vitamin K – oral (effect within 24 hours), or IV (4-6 hours)• Prothrombin Complex Concentrate (PCC. E.g. Beriplex/Octaplex)

– immediate action (still need to give Vit K)• Fresh Frozen Plasma

Adverse Reactions – Management Examples

• 76 year old on warfarin for recurrent DVTs. Recent check showed an INR of 7. She is otherwise well• Withhold warfarin. Recheck in 24 hours. If patient is high risk

consider oral Vit K.

• 64 year old on warfarin for atrial fibrilliation. Recent check showed an INR of 8.4. He is suffering from epistaxis.• Withhold warfarin. Oral Vitamin K.

• 83 year old on warfarin for a replacement heart valve. Recent check shows INR of 8.7. She is suffering from an upper GI bleed.• Withhold Warfarin. Immediate reversal with Vit K and PCC.

Consider why the INR was so high! ?drug interaction

Outline - Revised

Drug Level Monitoring• For some drugs, the therapeutic range (or window) is narrow. I.e.

They can be easily under-or-overdosed.

• Other indications include:• Potential compliance issue.• Benefit (and adverse reactions) which cannot be judged by clinical

parameters alone.• Drug levels in overdose/self-harm.

• Drug levels are typically measured as a trough level (pre-dose). However, for drugs with short half-lives peak and trough levels should be taken.

• They should be taken once a steady-state has been achieved (typically after 3-5 doses)

Drug Level Monitoring - Examples

DrugHalf-life

TimingTherapeutic

Range*ToxicLevel*

Extra CareMajor Toxic

Effects

Gentamicin 2h TroughAfter 2-3

doses<2mcg/ml >2mcg/ml

Renal disease, elderly, obesity

Nephrotoxity,irreversible ototoxicity

Phenytoin 20-40h TroughAfter 2-3

days

Total 10-20mcg/ml

Free 1-2mcg/ml

Total >20mcg/ml

Free>2mcg/ml

NB: Zero-orderkinetics. Elderly,

pregnancy, altered protein states

Nystagmus, diplopia, ataxia,

confusion, hyperglycaemia

Aminophylline4-16hr

N/A4-6hrs after starting IV infusion

10-20mcg/ml

>20mcg/ml

Inc. in: Liverdisease, elderly

Dec. in: Smokers, alcohol

Arrhythmias, convulsions, hypotension

Theophylline Trough 5 days

Digoxin 24-36h Trough 1 week0.5-

1.9ng/ml>2ng/ml

Elderly, hypokalaemia

Arrhythmias, visual disturbance,

anorexia

*can vary between labs/assays

Other Drug Monitoring

• The effects of other drugs need to be monitored also.

For example:

• Warfarin – monitor INR

• Levothyroxine – monitor TFTs

• When starting, monitor TFTs every 4 weeks and titrate

dose up in increments of 25-50micrograms.

• ACE Inhibitors/Diuretics – monitor U+Es

• Clozapine – monitor FBC

Drug InteractionsDrug interactions may be caused by a variety of effects:• Drug Absorption• Altering gastric pH (Omeprazole/Ranitidine)• Chelation (e.g. Aluminium salts)• Gastric motility (e.g. Metoclopromide)

• Drug Distribution (not typically clinically significant)• Drug Excretion • Urinary pH (e.g. Salicylates, Diuretics, Sodium Bicarbonate)

• Additive effects of drugs• E.g. Multiple anticoagulants• Increased side-effects (ACE inhibitors and K-sparing diuretics)

• Antagonistic effects• Competing effects (e.g. Steroids and anti-hypertensives)• Confounding effects (e.g Furosemide and Digoxin, Metronidazole and

Alcohol)

• Enzyme Induction/Inhibition

Enzyme Inducers/Inhibitors• A major cause of drug interactions is the inhibition/induction of the

cytochrome P450 family of enzymes (there are 6 main subtypes).

• Inhibition/induction may occur via direct action on the enzymes or by altering the genes involved in their expression.

• Inhibitors increase the levels of drug metabolised by the enzymes.

• Inducers decrease the levels of drugs metabolised by the enzymes.

Inducers Inhibitors

Carbamazepine Macrolides (e.g. Clarithromycin)

Phenytoin Grapefruit juice (flavinoids)

Omeprazole Imidazoles (e.g. Fluconazole)

Nifedipine Quinolones (e.g. Ciprofloxacin)

Rifampicin Amiodarone

Smoking Isoniazid

Chronic Alcohol Use Acute Alcohol Use

Courtesy of www.apotential.wordpress.com

Outline - Revised

Spot the mistakes

Spot the mistakes

No details of reaction

No unique patient identifier or DOB

Allergy No signature

How many charts? Good practice to fill this in

How should you alter this prescription?

FUROSEMIDE

PREDNISOLONE25/2/15

PO

25/2/15PO

40mg

40mg

FUROSEMIDE

PREDNISOLONE25/2/15

PO

25/2/15PO

40mg

40mg

Should be given in morning – will keep patient awake!

Should be given in morning – will keep patient awake!

What dose should you prescribe?

What dose should you prescribe?

Spot the mistakes

Spot the mistakes

Incorrect dose – Should be 62.5 MICROgrams

Write Units (not just ‘U’) – technically should be prescribed on the insulin area of the chart!

Write “micrograms” in full

What type?

What should you monitor in this patient?

Spot the mistake.

What should you monitor in this patient?

Spot the mistake.

POTASSIUM – both drugs can cause hyperkalaemia

Dose alteration is not signed for

What should you monitor in this patient?

Spot the mistake.

POTASSIUM – both drugs can cause hyperkalaemia

Dose alteration is not signed for

Some drugs causing HYPERKALAEMIA• ACE Inhibitors• Amiloride• Angiotensin Receptor Blockers (ARB)• Antifungals (Ketoconazole, Fluconazole)• Beta Blockers• Cyclosporine• Digoxin• Heparin• NSAIDs• Spironolactone• Tacrolimus• Transfusions of RBC• Trimethoprim

What is this patient at risk of ?

What is this patient at risk of ?

PHENYTOIN TOXICITY

Enzyme inhibitor

Enzyme inducer(but relatively less so)

What is this patient at risk of ?

OMEPRAZOLE

PAROXETINE25/2/15

PO

25/2/15PO

20mg

40mg

What is this patient at risk of ?

OMEPRAZOLE

PAROXETINE25/2/15

PO

25/2/15PO

20mg

40mg

Drugs commonly causing HYPONATRAEMIA

• Thiazide diuretics• Amiloride• Carbamazepine• Sulphonylureas (but not gliclazide)• Proton pump inhibitors• Antidepressants, particularly SSRIs• ACE inhibitors and ARBs• Opiates

Fluid chart errors

25/2/15 0.9% Saline 1 litre KCl 40mmol STAT A.L.S

25/2/15 Red Blood Cells 2 units ----------------- 4 hours A.L.S

25/2/15 50% Dextrose 1 litre 12 hours A.L.S

Fluid chart errors

25/2/15 0.9% Saline 1 litre KCl 40mmol STAT A.L.S

25/2/15 Red Blood Cells 2 units ----------------- 4 hours A.L.S

25/2/15 50% Dextrose 1 litre 12 hours A.L.S

This amount of potassium must be given over at least 4 hours due to risk of arrhythmias

Each unit needs to be prescribed separately

Has to be discarded after 4 hours (from leaving the lab)

50% Dextrose is irritant to veins. It should only be given in small volumes (10% or

20% should preferably be used if trying to reverse hypoglycaemia)

• Some of the theory summarised…

Rules of Prescribing• Prescriptions must be written legibly, in CAPITALS!

• Ensure the patient’s name, DOB and hospital/NHS number is present.

• The dose and route of administration should be specified.

• Avoid using decimal places. If mandatory, make them clear e.g. 0.5

rather than .5

• “Micrograms” should be written in full. Not mcg or µg.

• Write “Units” in full. Not “U”.

Rules of Prescribing Continued• Some drug charts will have specific places for insulin, antimicrobials

and anticoagulants – use them!

• If stopping a drug, make it clear and sign and date it.

• Avoid abbreviations in drug names e.g. “Isosorbide Mononitrate”

rather than “ISMN”.

• Accepted abbreviations for routes of administration are often printed

on the drug chart.

Rules of Prescribing Continued• Trade-names should be avoided apart from in special

circumstances (e.g. modified release preparations).

• Ensure special instructions are clear, especially if it is an

uncommon drug (e.g. Methotrexate weekly).

• Use the BNF – including the appendices on interactions, and info

on hepatic/renal failure, pregnancy and breast-feeding.

• Don’t prescribe a drug you don’t know (read about it first).

Common AbbreviationsAbbreviation Meaning Abbreviation Meaning

PO Orally/By mouth OD Once Daily

IV Intravenous BD Twice Daily

IM Intramuscular TDS X3 Daily

SC Subcutaneous QDS X4 Daily

TOP Topical PRN When Required

SL Sub-lingual MANE Morning

INH Inhaled NOCTE At Night

NEB Nebulised Others routes (e.g. buccal, intradermal) should be written in full. It is good practice to try and avoid using the Latin frequency

abbreviations on formal prescriptions.

PV Vaginally

PR Rectally

Prescribing in Liver Disease• Many drugs are metabolised by the liver, but there is a large hepatic

reserve. LFTs are a poor indicator of drug metabolism.

• Some drugs (e.g. Rifampicin) are excreted unchanged in bile and can accumulate in obstructive disorders.

• Hypoalbuminaemia is associated with decreased drug binding and therefore increased free toxic levels of highly protein bound drugs (e.g. Phenytoin, Prednisolone).

• Patients with abnormal clotting will be more sensitive to anticoagulants.

• In severe disease, sedative drugs, opioids, and drugs causing constipationwill increase the risk of encephalopathy.

Prescribing in Liver Disease

Some examples of Hepatotoxic drugs:

• Amiodarone

• Isoniazid

• Coamoxiclav

• NSAIDs

• Statins

• Anti-fungals

• Anti-retrovirals

• Consult the BNF for dose alterations

Prescribing in Renal Failure• Dose adjustments required in renal failure vary depend on the extent of renal

excretion and toxicity of the drug.

• For many drugs, empirical dose reductions will suffice. For drugs with narrow therapeutic ranges, or in patients with extremes of weight, doses based on creatinine clearance should be used. Plasma levels should then be monitored.

• Some drugs should be avoided altogether.• Consult the BNF!

Some examples of nephrotoxic drugs: • ACE Inhibitors• Aminoglycosides• NSAIDs• Methotrexate.

Prescribing in Pregnancy• Harm can be caused at any time during

pregnancy.

• Teratogenesis occurs in the first trimester

(during organogenesis), but growth and

functional disorders can occur throughout

pregnancy.

• Even those prescribed just prior to labour can

have an effect on foetus and neonate

(e.g. morphine).

• Drugs should be prescribed only if the

expected benefit is thought to be greater than

the risk to the foetus.

Prescribing in Pregnancy• Tried and tested drugs should be used before

newer ones, and at lower doses.

• There is some impact on fertility and risk of paternal teratogenesis for certain medications used by the father near the time of conception (mostly chemotherapeutic agents).

Examples of teratogens:

• Sodium Valproate

• Warfarin

• ACE inhibitors

• Tetracyclines

• Lithium

• Alcohol

Prescribing in Breast Feeding• The amount of drug transferred to the infant via breast-milk is often very

small; especially for drugs with poor enteral absorption.• ‘Basic’ drugs transfer more easily due to the more acidic nature of breast

milk compared to plasma.• Large molecules (e.g. heparin) do not transfer into the milk.• Some drugs are known to be present in high levels (e.g. Fluvastatin).• Some medications can have effects on lactation (e.g. Bromocriptine) or on

the sucking reflex (e.g. Phenobarbital).• Insufficient evidence does not equal safety!

Examples of drugs to avoid:• Aspirin• Carbimazole• Tetracyclines• Fluoroquinolones• Lamotrogine• Diazepam.

Prescribing in the Elderly - Issues• Poly-pharmacy increases the risk of drug interactions (but poly-pharmacy

does not just occur in the elderly!).

• Patient compliance decreases as the number of drugs increases.

• Hepatic and renal excretion decline with age. These are exacerbated by acute illness.

• There may be exaggerated pharmacodynamic effects on certain systems. E.g.:• ß-blockers and bradycardia• Nitrates/diuretics and postural hypotension• Anticholinergics/hypnotics/opioids and confusion/sedation• NSAIDs and gastric erosions.

• It may be appropriate to change the formulations of medications.

Prescribing in the Elderly - Guidelines• Always consider whether a drug is indicated at all• Limit the range from which you prescribe so your knowledge of

each increases• Reduce drug doses (consider starting 50% of recommended dose)• Review the need for medications regularly.• Simplify regimens, minimises doses. Blister packs may help.• Explain clearly.

Read the PSA Blueprint – it gives examples of what to expect!https://prescribingsafetyassessment.ac.uk/resource/PSA-Blueprint-December2015/pdf

There is a free practice paper at: www.prepareforthepsa.com

Good Luck!

Any Questions?