Guide to Good Prescribing - A Practical Manual
(1994; 115 pages) [French] [Spanish] View the PDF document
Table of Contents
View the documentAcknowledgments
View the documentWhy you need this book
Open this folder and view contentsPart 1: Overview
Close this folderPart 2: Selecting your P(ersonal) drugs
View the documentChapter 2. Introduction to P-drugs
View the documentChapter 3. Example of selecting a P-drug: angina pectoris
Open this folder and view contentsChapter 4. Guidelines for selecting P-drugs
View the documentChapter 5. P-drug and P-treatment
Open this folder and view contentsPart 3: Treating your patients
Open this folder and view contentsPart 4: Keeping up-to-date
Open this folder and view contentsAnnexes
View the documentBack Cover
 

Chapter 3. Example of selecting a P-drug: angina pectoris

Example: patient 2

You are a young doctor, and one of your first patients is a 60-year old man, with no previous medical history. During the last month he has had several attacks of suffocating chest pain, which began during physical labour and disappeared quickly after he stopped. He has not smoked for four years. His father and brother died of a heart attack. Apart from occasionally taking some aspirin he has not used any medication in the past year. Auscultation reveals a murmur over the right carotid artery and the right femoral artery. Physical examination reveals no other abnormalities. Blood pressure is 130/85, pulse 78 regular, and body weight is normal.

You are fairly sure of the diagnosis, angina pectoris, and explain the nature of this disease to him. The patient listens carefully and asks: ‘But, what can be done about it?’. You explain that the attacks are usually self-limiting, but that they can also be stopped by drugs. He responds ‘Well, that's exactly what I need.’ You tend to agree that he might need a drug, but which? Atenolol, glyceryl trinitrate, furosemide, metoprolol, verapamil, haloperidol (no, no that's something else) all cross your mind. What to do now? You consider prescribing Cordacor®1, because you have read something about it in an advertisement. But which dose? You have to admit that you are not very sure.

Later at home you think about the case, and about your problem in finding the right drug for the patient. Angina pectoris is a common condition, and you decide to choose a P-drug to help you in the treatment of future cases.

1A fictitious brandname

Choosing a P-drug is a process that can be divided into five steps (Table 1). Many of these are rather similar to the steps you went through in treating the patient with cough in Chapter 1. However, there is an important difference. In Chapter 1 you have chosen a drug for an individual patient; in this chapter you will choose a drug of first choice for a common condition, without a specific patient in mind.

Each of the steps is discussed in detail below, following an example of choosing a P-drug for angina pectoris.

Table 1: Steps in choosing a P-drug

i Define the diagnosis
ii Specify the therapeutic objective
iii Make an inventory of effective groups of drugs
iv Choose an effective group according to criteria
v Choose a P-drug

Step i: Define the diagnosis

Angina pectoris is a symptom rather than a diagnosis. It can be subdivided into classic angina pectoris or variant angina pectoris; it may also be divided into stable and unstable. Both aspects have implications for the treatment. You could specify the diagnosis of patient 2 as stable angina pectoris, caused by a partial (arteriosclerotic) occlusion of the coronary arteries.

Step ii: Specify the therapeutic objective

Angina pectoris can be prevented and treated, and preventive measures can be very effective. However, in this example we limit ourselves to treatment only. In that case the therapeutic objective is to stop an attack as soon as it starts. As angina pectoris is caused by an imbalance in oxygen need and supply in the cardiac muscle, either oxygen supply should be increased or oxygen demand reduced. It is difficult to increase the oxygen supply in the case of a sclerotic obstruction in the coronary artery, as a stenosis cannot be dilated with drugs. This leaves only one other approach: to reduce the oxygen need of the cardiac muscle. Since it is a life-threatening situation this should be achieved as soon as possible.

This therapeutic objective can be achieved in four ways: by decreasing the preload, the contractility, the heart rate or the afterload of the cardiac muscle. These are the four pharmacological sites of action.2

2 If you do not know enough about pathophysiology of the disease or of the pharmacological sites of action, you need to update your knowledge. You could start by reviewing your pharmacology notes or textbook; for this example you should probably also read a few paragraphs on angina pectoris in a medical textbook.

Step iii: Make an inventory of effective groups of drugs

The first selection criterion for any group of drugs is efficacy. In this case the drugs must decrease preload, contractility, frequency and/or afterload. There are three groups with such an effect: nitrates, beta-blockers and calcium channel blockers. The sites of action are summarized in Table 2.

Table 2: Sites of action for drug groups used in angina pectoris


Preload

Contractility

Frequency

Afterload

Nitrates

++

-

-

++

Beta-blockers

+

++

++

++

Calcium channel blockers

+

++

++

++

Step iv: Choose an effective group according to criteria

The pharmacological action of these three groups needs further comparison. During this process, three other criteria should be used: safety, suitability and cost of treatment. The easiest approach is to list these criteria in a table as in Table 3. Of course, efficacy remains of first importance. Cost of treatment is discussed later.

Efficacy is not based on pharmacodynamics alone. The therapeutic objective is that the drug should work as soon as possible. Pharmacokinetics are therefore important as well. All groups contain drugs or dosage forms with a rapid effect.

Safety

All drug groups have side effects, most of which are a direct consequence of the working mechanism of the drug. In the three groups, the side effects are more or less equally serious, although at normal dosages few severe side effects are to be expected.

Suitability

This is usually linked to an individual patient and so not considered when you make your list of P-drugs. However, you need to keep some practical aspects in mind. When a patient suffers an attack of angina pectoris there is usually nobody around to administer a drug by injection, so the patient should be able to administer the drug alone. Thus, the dosage form should be one that can be handled by the patient and should guarantee a rapid effect. Table 3 also lists the available dosage forms with a rapid effect in the three drug groups. All groups contain drugs that are available as injectables, but nitrates are also available in sublingual forms (sublingual tablets and oromucosal sprays). These are equally effective and easy to handle, and therefore have an advantage in terms of practical administration by the patient.

Cost of treatment

Prices differ between countries, and are more linked to individual drug products than to drug groups. In Table 4, indicative prices for drugs within the group of nitrates, as given in the British National Formulary of March 1994, have been included for the sake of the example. As you can see from the table, there are considerable price differences within the group. In general, nitrates are inexpensive drugs, available as generic products. You should check whether in your country nitrates are more expensive than beta-blockers or calcium channel blockers, in which case they may lose their advantage.

Table 3: Comparison between the three drug groups used in angina pectoris

Efficacy

Safety

Suitability

Nitrates



Pharmacodynamics

Side effects

Contraindictions

Peripheral vasodilatation

Flushing, headaches, temporary tachycardia

Cardiac failure, hypotension, raised intracranial pressure




Tolerance (especially with constant blood levels)

Nitrate poisoning due to long-lasting oral dosage

Anaemia




Pharmacokinetics



High first pass metabolism Varying absorption in the alimentary tract (less in mononitrates)


 


Fast effect dosage forms:

Glyceryl trinitrate is volatile: tablets cannot be kept long


Injection, sublingual tablet, oromucosal spray




Beta-blockers



Pharmacodynamics

Side effects

Contraindications

Reduced heart contractility

Hypotension, congestive heart failure

Hypotension, congestive heart failure

Reduced heart frequency

Sinus bradycardia, AV block

Bradycardia, AV block, sick sinus syndrome




Bronchoconstriction, muscle vasoconstriction, inhibited glycogenolysis
Less vasodilatation in penis

Provocation of asthma Cold hands and feet Hypoglycaemia Impotence

Asthma Raynaud’s disease Diabetes




Pharmacokinetics



Lipophilicity increases passage through blood-brain barrier

Drowsiness, decreased reactions, nightmares

Liver dysfunction



Fast effect dosage forms:
Injection




Calcium channel blockers



Pharmacodynamics

Side effects

Contraindictions

Coronary vasodilatation



Peripheral vasodilatation (afterload)

Tachycardia, dizziness, flushing, hypotension

Hypotension

Reduced heart contractility

Congestive heart failure

Congestive heart failure

Reduced heart frequency

Sinus bradycardia, AV block

AV block, sick sinus syndrome
Fast effect dosage forms:
Injection

Table 4: Comparison between drugs within the group of nitrates


Efficacy

Safety

Suitability

Cost/100 (£)*

Glyceryl trinitrate

NB: volatile




Sublingual tab 0.4-1mg

0.5-30 min

No difference

No difference

0.29 - 0.59

Oral tab 2.6mg, cap 1-2.5mg

0.5-7 hours

between

between

3.25 - 4 28

Transdermal patch 16-50mg

1-24 hours

individual

individual

42.00 - 77.00


NB: tolerance

nitrates

nitrates



Isosorbide dinitrate

Sublingual tab 5mg

2-30 min



1.45 - 1.51

Oral tab 10-20 mg

0.5-4 hours



1.10 - 2.15

Oral tab (retard) 20-40mg

0.5-10 hours



9.52 - 18.95


NB: tolerance





Pentaeritritol tetranitrate

Oral tab 30 mg

1-5 hours



4.45


Isosorbide mononitrate

Oral tab 10-40mg

0.5-4 hours



5.70 - 13.30

Oral tab/caps (retard)

1-10 hours



25.00 - 40.82


NB: tolerance




* Indicative prices only, based on prices given in the British National Formulary of March 1994

After comparing the three groups you may conclude that nitrates are the group of first choice because, with acceptable efficacy and equal safety, they offer the advantages of an immediate effect and easy handling by the patient, at no extra cost.

Step v: Choose a P-drug

Choose an active substance and a dosage form

Not all nitrates can be used in acute attacks, as some are meant for prophylactic treatment. In general, three active substances are available for the treatment of an acute attack: glyceryl trinitrate (nitroglycerin), isosorbide mononitrate and isosorbide dinitrate (Table 4). All three are available in sublingual tablets with a rapid effect. In some countries an oromucosal spray of glyceryl trinitrate is available as well. The advantage of such sprays is that they can be kept longer; but they are more expensive than tablets.

There is no evidence of a difference in efficacy and safety between the three active substances in this group. With regard to suitability, the three substances hardly differ in contraindications and possible interactions. This means that the ultimate choice depends on cost. Cost may be expressed as cost per unit, cost per day, or cost per total treatment. As can be seen from Table 4, costs may vary considerably. Since tablets are cheapest in most countries, these might well be your first choice. In this case the active substance for your P-drug of choice for an attack of angina pectoris would be: sublingual tablets of glyceryl trinitrate 1 mg.

Choose a standard dosage schedule

As the drug is to be taken during an acute attack, there is no strict dosage schedule. The drug should be removed from the mouth as soon as the pain is gone. If the pain persists, a second tablet can be taken after 5-10 minutes. If it continues even after a second tablet, the patient should be told to contact a doctor immediately.

Choose a standard duration of the treatment

There is no way to predict how long the patient will suffer from the attacks, so the duration of the treatment should be determined by the need for follow-up. In general only a small supply of glyceryl trinitrate tablets should be prescribed as the active substance is rather volatile and the tablet may become ineffective after some time.

If you agree with this choice, glyceryl trinitrate sublingual tablets would be the first P-drug of your personal formulary. If not, you should have enough information to choose another drug instead.

Summary

Example of selecting a P-drug: angina pectoris

i. Define the diagnosis

Stable angina pectoris, caused by a partial occlusion of coronary artery

ii. Specify therapeutic objective

Stop an attack as soon as possible


Reduce myocardial oxygen need by decreasing preload, contractility, heart rate or afterload

iii. Make inventory of effective groups


Nitrates


ß-blockers


Calcium channel blockers

iv. Choose a group according


to criteria

efficacy

safety

suitability

cost


Nitrates (tablet)

+

±

++

+


Beta-blockers (injection)

+

±

-

-


Calcium channel blockers (injection)

+

±

-

-

v. Choose a P-drug

efficacy

safety

suitability

cost


Glyceryl trinitrate (tablet)

+

±

+

+


(spray)

+

±

(+)

-


Isosorbide dinitrate (tablet)

+

±

+

±


Isosorbide mononitrate (tablet)

+

±

+

±

Conclusion






Active substance, dosage form:

glyceryl trinitrate, sublingual tablet 1 mg


Dosage schedule:

1 tablet as needed; second tablet if pain persists


Duration:

length of monitoring interval

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