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Chapter 1 Pharmacodynamics and pharmacokinetics

dosing schedules. It is vital that nurses know the

normal dosing schedules for the drugs they are

administering (this can easily be found in the Brit-

ish National Formulary, or BNF) so that the cor-

rect regimen is implemented. Drugs need to be

given more than once to have continued effect.

Some drugs need to be given daily, while others

need to be given two, three or four times per day

to maintain their effective action.

First pass metabolism

Some drugs undergo destruction by first pass

metabolism. When absorbed through the stomach

after oral administration, a drug enters blood ves-

sels that lead directly to the liver. We call this the

portal circulation. This means that drugs which

are largely destroyed by liver enzyme systems

will not enter the general systemic circulation.

An example of such a drug is glyceryl trinitrate

(GTN), which is metabolized completely by the

liver at this stage. Therefore, you will find GTN

being given via routes other than orally.

The concept of affinity

Drugs have what is termed an affinity for their

receptors, or chemical targets. This is a measure of

how well a drug can bind to its chemical target. The

tighter the bond, the better the drug action. Some

drugs have a higher affinity for their chemical tar-

gets than others. Those with a higher affinity will

bind first, in preference to any other drug molecule

present. Some drugs have a higher affinity for their

targets than even the normal physiological mole-

cule. This can be very useful in drug action, espe-

cially where the normal molecule is abundant and

is the cause of the problem or symptom the patient

is experiencing. Higher affinity means that even

small amounts of the drug will bind preferentially.

Agonistic and antagonistic drug action

Drugs can either be agonists or antagonists at

their target sites. This is best explained using

receptors as an example (see Figure 1.2). When

agonists or antagonists bind to receptors, they

are said to occupy the receptor site. The amount

of drug occupying the receptor site relates to the

magnitude of response to the drug itself. In simple

terms, the more of an agonist drug occupying a

receptor, the greater the response.

Agonists are drugs that bind to their targets and

form a drug–receptor complex. Agonists activate

the receptors to produce a response (known as full

agonists) and have what is termed positive efficacy.

Antagonists are drugs that bind to their targets and

form a drug–receptor complex, but without causing

activation or response. They can block the recep-

tor to its endogenous activator, thereby blocking

normal function. They have what is termed zero

efficacy. Receptor occupancy by antagonists is

important if the drug is a competitive antagonist,

i.e. it competes for occupancy with another drug or

with the receptor’s normal mediator. The amount of

drug occupying will determine any response.

AGONISTS

DRUG

DRUG–RECEPTOR

COMPLEX

ACTIONS

INDIRECT

RECEPTOR

ANTAGONISTS

DRUG

DRUG–RECEPTOR

COMPLEX

ACTIONS

RECEPTOR

DIRECT

enzyme action

ion channel modulation

DNA action e.g.

anti-cancer drugs

no effect / endogenous mediators blocked

ion channel

Figure 1.2 Basic receptor theory

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Chapter 1 Pharmacodynamics and pharmacokinetics

This is a simplistic view of the concepts of ago-

nism and antagonism, as the response of a drug

at its chemical target is graded. For agonists we

have:

■ Partial agonists: drugs that bind to their

targets and activate them to produce less of

a response than we would expect from a full

agonist. They have what is termed partial effi-

cacy. Taking opioid drugs as an example, mor-

phine is a full agonist but buprenorphine is a

partial agonist.

■ Inverse agonists: drugs that bind to their

targets and can reduce the normal activity of

that chemical target. They have what is termed

negative efficacy. Naltrexone is an example of

a drug with inverse agonist properties.

For antagonists we have:

■ Competitive antagonists: drugs that bind to

the chemical targets and prevent activation by

the normal target agent. Naloxone is a com-

petitive antagonist at opioid receptors and can

reverse adverse effects in opioid overdose.

■ Non-competitive antagonists: drugs that

do not necessarily bind to the chemical target

but at a point in the chain of events block tar-

get activation. Ketamine is a non-competitive

antagonist.

Drug specificity

Very few drugs are specific for their intended tar-

gets within the body. A prescriber will give a drug

with a specific action in mind, for example salbuta-

mol. Salbutamol is a beta2 adrenoceptor agonist.

This means it has its main action at beta2 adreno-

ceptors in the bronchi. This gives us its desired

effect as a bronchodilator, which eases breathing

in asthma. However, the action of salbutamol is not

that specific and can act on other beta2 adreno-

ceptors in the body as well as on beta1 adrenocep-

tors, especially if given in high doses leading to

increased receptor occupancy. This is the reason

for some of the side-effects of drugs. In the case

of salbutamol, action at other beta adrenoceptors

can lead to palpitations, while increased occu-

pancy at non-bronchial beta adrenoceptors can

cause tremor.

The concepts in this chapter relate to the NMC

Standards of Proficiency for Registered Nurses

(NMC 2018):

Platform 4: Providing and evaluating care

4.15 demonstrate knowledge of pharmacology

and the ability to recognise the effects of medi-

cines, allergies, drug sensitivities, side effects,

contraindications, incompatibilities, adverse

reactions, prescribing errors and the impact

of polypharmacy and over the counter medi-

cation usage

and

Platform 3: Assessing needs and planning care

3.2 demonstrate and apply knowledge of body

systems and homeostasis, human anatomy

and physiology, biology, genomics, pharmacol-

ogy and social and behavioural sciences when

undertaking full and accurate person-centred

nursing assessments and developing appropri-

ate care plans

Case studies

Mrs Asamoah is a 72-year-old woman who has been admitted to the medical unit

following a general deterioration in her mobility and ability to carry out most of the

activities of living independently. She has suffered from rheumatoid arthritis for many years

→

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Chapter 1 Pharmacodynamics and pharmacokinetics

and takes co-codamol with moderate effect. On admission she looks pale and lethargic and is

complaining of pain in her knees and hands. She informs you that she has also been taking

atenolol 50 milligrams (mg) daily for the past 5 years.

Following a discussion with her daughter, you learn that she has recently commenced a course

of trimethoprim to treat a urinary tract infection but has been reluctant to take it as she claims

that she has too many tablets to take and has difficulty swallowing them. What information from

Mrs Asamoah’s assessment could you now obtain which would help you identify factors influenc-

ing the absorption and distribution of the medication she is taking?

Mr Mambety is a 42-year-old man who is recovering from emergency gastric surgery. He has a

history of heavy drinking and cigarette smoking. His post-operative pain is being controlled by a

patient-controlled analgesic device and he is beginning to mobilize with assistance. What factors

are likely to influence Mr Mambety’s ability to metabolize and excrete any drugs he is prescribed

during his post-operative recovery?

Ben Brown is aged 45 and has Down’s syndrome. He currently takes regular Gaviscon as he

suffers from indigestion. He has developed a respiratory infection and is to be commenced on

erythromycin 250mg four times per day. Erythromycin comes with cautionary labels 5, 9 and 25.

Label 5 warns that the erythromycin should not be taken within 2 hours (before or after) antacid

preparations and label 9 dictates that the doses be split evenly throughout the day. Label 25

states the drugs should be swallowed whole.

Thinking about the principles of absorption, what do you need to find about from Ben regard-

ing his Gaviscon taking, and what advice and education would you give to Ben to ensure that he

takes the medications appropriately?

→

Key learning points

Introduction

▶

Pharmacology is the study of drugs.

▶

Pharmacodynamics is the effect that drugs have on the body.

▶

Pharmacokinetics is the effect the body has on the drugs.

▶

Pharmacokinetics includes absorption, distribution, metabolism and excretion of drugs.

Absorption

▶

The main factor relating to absorption of drugs is the route of administration.

▶

Physiological considerations in absorption are blood flow, total surface area, time of arrival

of the drug and time of drug at absorption site.

▶

Other considerations for absorption are solubility, chemical stability and how soluble the

drug is in lipids.

→

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Chapter 1 Pharmacodynamics and pharmacokinetics

Distribution

▶

Drugs are distributed into major body fluids (e.g. plasma).

▶

Specific tissues may take up certain drugs (e.g. iodine is taken up by the thyroid gland).

▶

Drug distribution is affected by the extent that the drug binds to plasma proteins.

▶

Drug distribution is affected by barriers (e.g. the placenta and the BBB).

Biotransformation

▶

This is the process of metabolizing drugs in the body.

▶

It occurs mainly in the liver and is therefore often called hepatic metabolism.

▶

Some drugs are activated by this hepatic metabolism – these are called pro-drugs.

▶

Drug metabolism is split into two phases in the liver.

▶

An example of phase I metabolism is oxidation.

▶

An example of phase II metabolism is conjugation.

Excretion

▶

Excretion includes renal elimination and faecal elimination.

▶

The main method of renal elimination is by active glomerular filtration.

▶

Drugs can also be eliminated by passive methods in the distal tubules.

▶

Drugs can be eliminated from the body in bile and so removed in the faeces.

General and molecular aspects

▶

Drugs exert their effects at molecular (chemical) targets (e.g. adrenaline receptors).

▶

Drugs can also act by stopping or partially stopping important ions entering the cell

(e.g. calcium channel blockers).

▶

Drugs can interfere with enzymes that are produced by the body.

▶

Drugs can work on the transport of chemicals into and out of cells.

Drug action

▶

Drug action relies on the route of administration, rate of absorption and manner of distribution.

▶

The duration of drug effect involves how quickly it is removed from the body.

▶

Some drugs when absorbed from the stomach enter the portal circulation and pass through

the liver. This is called the first pass effect.

▶

Drug action can also be affected by drug affinity.

▶

The greater the affinity, the better the drug action.

Agonistic and antagonistic drug action

▶

Agonists activate receptors to produce a response.

▶

Antagonists bind with receptors but do not activate them or cause a response. They can actu-

ally block the activation of receptors.

▶

Partial agonists produce a response. However, this is less than would be expected from a full

agonistic drug.

→

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Chapter 1 Pharmacodynamics and pharmacokinetics

▶

Inverse agonists are drugs that can reduce the normal activity of the cell.

▶

Competitive antagonists are drugs that prevent activation of the cell by their normal agent.

▶

Non-competitive antagonists are drugs that may block the receptor but not in a perma-

nent way.

→

Multiple-choice questions

Try answering these multiple-choice questions to test what you have learned from reading this

chapter. You can check your answers at the end of the book.

1. A drug that binds to a cell receptor and affects a response is called …

a) An agonist

b) An antagonist

c) A receptor blocker

d) A channel blocker

2. Most drugs and metabolites are excreted by …

a) The kidneys

b) The lungs

c) Bile

d) Saliva

3. The four processes in pharmacokinetics are …

a) Stomach, liver, kidney and lungs

b) Receptors, ion channels, transport systems and enzymes

c) Administration, absorption, metabolism and elimination

d) Absorption, distribution, metabolism and excretion

4. Pharmacodynamics is defined as …

a) The effect our body has on drugs

b) The action of the liver on drug molecules

c) The effect a drug has on our bodies

d) The movement of a drug around the body

5. The main method of renal elimination of a drug is by …

a) Passive distal excretion

b) Active glomerular filtration

c) Selective reabsorption

d) Active secretion into the collecting duct

→

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Chapter 1 Pharmacodynamics and pharmacokinetics

6. How many phases of hepatic metabolism are there?

a) 1

b) 2

c) 4

d) 10

7. What route should drugs subject to complete destruction by first pass metabolism

not be given by?

a) Intravenous

b) Intramuscular

c) Sublingual

d) Oral

8. Which of the following is a plasma protein?

a) Prostacyclin

b) Albumin

c) Protamine

d) Meatamine

9. A pro-drug is …

a) A drug given to promote growth

b) A drug given in its active form

c) A drug given to prevent metabolism of another drug

d) A drug given in its inactive form, requiring metabolism

10. An antagonist can be …

a) Competitive and non-competitive

b) Competitive and complementary

c) Competitive and comparative

d) Competitive and conjugated

→

Recommended further reading

Adverse drug reactions and

interactions

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Chapter 2 Adverse drug reactions and interactions

Introduction

The aim of this chapter is to introduce you to the

concepts of adverse drug reactions and drug inter-

actions and side-effects. According to Veeren and

Weiss (2016), emergency hospital admissions due

to adverse drug reactions (ADRs) are an increas-

ing problem in the National Health Service (NHS).

The likelihood of drug interactions and adverse

reactions is increased in patients on more than one

medicine, and highest in those who take more than

four medications (polypharmacy). The incidence

is also increased in elderly patients. As many

elderly people are on several medicines, they as a

group are often at higher risk of interactions and

adverse reactions.

Main mechanisms of drug interactions

Drug interactions can be:

■ pharmacokinetic; and/or

■ pharmacodynamic.

Pharmacokinetic interactions can occur in any of

the four pharmacokinetic processes:

■ absorption;

■ distribution;

■ metabolism;

■ excretion.

Absorption

The most common absorption interactions occur

when medicines are taken by the oral route. Many

drugs require precise conditions for optimal

absorption in the stomach and upper gastroin-

testinal (GI) tract. Anything which disrupts these

conditions can affect drug absorption. Examples

include:

■ Taking medication with or after a meal: the

presence of food in the stomach can delay

drug absorption. Sometimes we use this to our

advantage, but some drugs need to be taken

on an empty stomach.

■ Taking medication at the same time as an ant-

acid preparation. Antacids such as Gaviscon

coat the stomach and delay drug absorption,

thus taking them at the same time as some

drugs must be avoided.

■ Crushing or splitting tablets. Some tablets need

to travel intact through the stomach before be-

ing absorbed optimally in the small intestine,

or have a coating that delays their absorption.

Crushing or splitting tablets may change the

rate of absorption of these drugs.

■ Be aware of anaphylaxis.

■ List three common drugs that are frequently implicated in drug reactions.

■ Discuss the steps taken in minimizing drug interactions in patient care.

■ Describe why elderly people and children are at a higher risk of drug interaction than other

age groups.

Clinical tip

Do not crush or tamper with tablets or

capsules: many are specially designed to

be absorbed in a specific manner in a spe-

cific time frame. If in doubt how a medicine

should be taken, consult your pharmacist.

Always follow any instructions given with oral

medicines to ensure their optimal absorption.

Distribution

Some drugs are bound to plasma proteins during

their distribution through body fluids. The efficiency

of a drug can be affected by the degree to which it

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Chapter 2 Adverse drug reactions and interactions

binds to proteins within the blood plasma. The less

a drug binds to a plasma protein, the more efficient

it is in diffusing and crossing cell membranes. An

example of a common blood protein that drugs

can bind to is albumin. Due to protein binding of

a drug, the drug exists in two forms, namely pro-

tein bound and unbound (free), the unbound form

being the active component of the drug. The bound

portion remains inactive unless displaced from the

protein. Any medications that may displace other

medicines from plasma proteins could change the

level of free drug in the plasma. Drugs associated

with this sort of interaction are usually listed as

incompatible in Appendix 1 of the British National

Formulary (BNF).

and the effects should be monitored. Having the

pharmacist on the ward on a daily basis, mon-

itoring prescriptions while liaising with both the

medical and nursing staff, is of great importance

in identifying any such problems.

Metabolism

Some drugs can interfere with the effectiveness

of drug metabolizing enzymes in the liver. These

drugs can have one of two effects:

Enzyme inducer: this is where the drug in-

creases the effectiveness of the enzymes and

metabolizes more quickly. This means that

the effectiveness of other drugs and their du-

ration of action may be reduced.

Enzyme inhibitor: this is where the drug

decreases the effectiveness of the enzymes

and metabolizes more slowly. This means

that the effectiveness of other drugs and their

duration of action may be increased.

Drugs that modify metabolizing enzymes should be

given with caution to patients on other medicines,

Clinical tip

When working in the clinical setting it

is important to be thinking of the age of the

person you are dealing with. For example,

neonates, infants and older people have

a reduced amount of plasma proteins,

therefore doses of drugs in these patients

should reflect physiological differences.

Clinical tip

When nursing neonates and infants,

you will notice that certain drugs are given

at a reduced dose. This is because of the

immature liver’s poorer ability to metabolize

drugs.

Excretion

Relatively few drugs have a dramatic effect on

drug excretion. Non-steroidal anti-inflammatory

drugs (NSAIDs) can affect the kidney tubule and

modify the excretion and reabsorption of some

drugs. Pharmacodynamic interactions are more

common and fall into two categories.

Additive effects of drugs with similar

actions. For example, giving an angioten-

sin-converting enzyme (ACE) inhibitor (e.g.

Lisinopril) with a diuretic (e.g. bendroflume-

thiazide) may lead to an adverse fall in blood

pressure.

Competing effects of drugs with opposite

actions. For example, giving a beta blocker

drug for hypertension (e.g. propranolol) to

an asthmatic patient may render their beta

agonist drug (e.g. salbutamol) ineffective in

managing their asthma symptoms.

Clinical tip

As a nurse you should keep accurate

fluid balance records because patients’

renal function needs to be optimal to avoid

toxicity. Often, the first indicator of renal

insufficiency is a change in urinary output.

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