1 Introduction to

pharmacology and
drug administration

INTRODUCTION

Pharmacology is the study of drugs or chemicals used to treat and cure disease
and their interactions in the body. Within the study of pharmacology there are a
number of separate areas to consider, but for nurses the most important aspects
are pharmacokinetics (PK) and pharmacodynamics (PD). Pharmacokinetics
describes what the body does to a drug through the movement and distribution
of that drug around the body. This is important because to be therapeutically
useful, drugs must be absorbed into the body and transported to the desired site
for action. Drugs will be therapeutically ineffective if they do not reach the
target organ (site) to exert their activity. Pharmacodynamics considers what a
drug does to the body – that is, the mechanism of drug action in the body. It
describes the biochemical and physical effects of a drug and how it interacts
with its desired target (such as a cell surface receptor, enzyme or DNA).
Nurses should understand the PK/PD principles of the drugs they are admin-
istering to patients. This includes the mode of action of drugs, dose responses,
and potential interactions with other treatments (pharmacological or non-
pharmacological) that the patient may be undergoing. Serious and adverse side-
effects can arise from drug treatment (sometimes very quickly) and it is
essential that the nurse can recognize these and act quickly to minimize their
potential life-threatening effects.

Useful resources
Nurses! Test Yourself in Essential Calculation Skills
Chapters 1 and 2

Nurses! Test Yourself in Anatomy and Physiology

Chapters 1 and 2

Nurses! Test Yourself in Non-Medical Prescribing

Chapters 4 and 6

25302.indb 1 13/09/2013 12:00

 QUESTIONS Pharmacology and drug administration

LABELLING EXERCISE

1–9 Identify the routes of administration in Figures 1.1 and 1.2 using the
terms provided in the box below

intramuscular rectal intradermal

oral subcutaneous intravenous

topical inhalation transdermal

Figure 1.1 Common routes for the administration of medicines

25302.indb 2 13/09/2013 12:00

 Pharmacology and drug administration QUESTIONS

Figure 1.2 Position of the needle for common injection routes

25302.indb 3 13/09/2013 12:00

 QUESTIONS Pharmacology and drug administration

TRUE OR FALSE?

Are the following statements true or false?

10 In pharmacology, the word ‘agonist’ describes a drug that binds or inter-

acts with its biological receptor but produces no effect.

11 An antagonist may be described as competitive or non-competitive.

12 The pharmacological action of a drug varies significantly among

individuals.

13 A pro-drug describes a drug that is pharmacologically inactive until it

reaches the liver and is metabolized.

14 Drugs administered intravenously (IV) are considered to have 100%

absorption into the systemic circulation.

15 Free, unbound drug molecules cannot exert a pharmacological effect.

16 Most drugs are excreted in the urine.

25302.indb 4 13/09/2013 12:00

 Pharmacology and drug administration QUESTIONS

MULTIPLE CHOICE

Identify one correct answer for each of the following.

17 The time required for the onset of a drug’s action depends on its delivery
to the site of action. Which of the following is not an important consid-
eration in drug delivery?
a) route of administration
b) rate of absorption
c) rate of elimination
d) distribution of drug

18 How many factors are associated with a drug’s distribution?

a) 1
b) 2
c) 3
d) 4

19 Which of the following describes the amount of drug absorbed by the

body and distributed systemically?
a) bioavailability
b) first-pass metabolism
c) biotransformation
d) pharmacokinetics

20 Most drugs and drug molecules are excreted by the:

a) liver
b) kidneys
c) gall bladder
d) lungs

25302.indb 5 13/09/2013 12:00

 QUESTIONS Pharmacology and drug administration

21 The ability of the kidneys to excrete drugs is called:

a) renal excretion
b) renal filtration
c) renal secretion
d) renal clearance

22 The time taken for the concentration of a drug to fall to half its original
level is called:
a) half-life
b) steady state
c) elimination
d) clearance

23 When the amount of drug excreted equals the amount being absorbed,
the condition is called:
a) toxicity
b) half-life
c) therapeutic limit
d) steady state

24 Sometimes drug metabolism processes become more effective, which

can lead to:
a) drug toxicity
b) drug tolerance
c) drug overdose
d) liver failure

25302.indb 6 13/09/2013 12:00

 Pharmacology and drug administration QUESTIONS

FILL IN THE BLANKS

Fill in the blanks in each statement using the options in the box below.
Not all of them are required, so choose carefully!

urine faeces

receptors formulation

enzymes concentration

slowly lipid solubility

enterohepatic recirculation carriers

perfusion specificity

infusion first-pass metabolism

ion channels distribution

water solubility affinity

second-pass metabolism systemic circulation

25 Drug __________ describes how well a drug binds to its specific target.

26 The ability of drugs to cross cell membranes depends on their ________

___________.

27 Tissue ____________ has a significant role in the initial distribution of a

drug.

28 The physical and chemical composition of a drug is called its

______________.

25302.indb 7 13/09/2013 12:00

 QUESTIONS Pharmacology and drug administration

29 Drugs direct their effects at molecular targets within the body. The four
most common molecular targets are: ________, __________, and _____
__________.

30 The products of bilary excretion are eliminated from the body via the
_______.

31 Some drugs undergo __________ _____________, which prolongs their

effect.

32 ______ – _______ _____________ occurs in the liver.

33 Sustained release drugs are delivered _____________ into the blood.

25302.indb 8 13/09/2013 12:00

 ANSWERS
LABELLING EXERCISE

Figure 1.3 Common routes for the administration of medicines

25302.indb 9 13/09/2013 12:00

 ANSWERS Pharmacology and drug administration

Figure 1.4 Position of the needle for common injection routes

1 Inhalation: drugs targeting the respiratory tract may be inhaled to

produce a rapid, local effect on the respiratory system. Drugs that
are absorbed by the lungs to produce a general effect may also be
administered by inhalation (for example, some general anaesthetics).
2 Oral: this is the most common route of administration because it is the
easiest for both the patient and the person administrating the medicine.
There are many formulations available for the oral administration of
drugs, including tablets, capsules, caplets, elixirs, linctus, lozenges,
oral powders, and suspensions. The absorption of orally administered
medicines is affected by several factors, including:
G the drug formulation
G the presence of food in the stomach
G the rate of gastric emptying
G possible drug interactions (especially if drugs are administered
together).

The formulation of tablets, capsules, and caplets affects the absorption

of drugs; for example, many enteric-coated tablets are now available to

10

25302.indb 10 13/09/2013 12:00

 Pharmacology and drug administration ANSWERS

protect the lining of the stomach by preventing the release of the active
ingredient until it reaches the duodenum. Sublingual tablets are placed
under the tongue for absorption, while buccal tablets are administered
between the cheek and gum. Like tablets, capsules and caplets deliver a
measured dose of medication (for example 250 mg), although capsules
and caplets are generally considered easier to swallow than tablets. They
differ in their shape and rate of absorption of the medicine each contains.
A capsule has a cylindrical-shaped shell (often made of gelatine), while
a caplet is an oval (or capsule)-shaped tablet. Elixirs are alcohol-based
solutions. A lozenge is designed to dissolve slowly in the mouth, since it is
absorbed here it generally has a local effect. A linctus is a sweet, sucrose
syrup often prescribed when administering drugs to children who may
find it difficult to swallow tablets; a sugar-free formulation is preferable
when available. An oral powder is usually dissolved in juice or water
before administration, while an oral suspension is mixed with, but not
completely dissolved in, a liquid. It must be shaken before administration
to distribute and suspend the drug particles equally. A disadvantage of
liquid preparations over solid dosage forms is that liquid preparations
rely on the patient, carer or other administrator to measure the dose
accurately and subsequently could result in the incorrect dose being given.
3 Transdermal: active drug ingredients may be delivered via the skin for
systemic distribution, often using a transdermal patch. For example,
nicotine patches are used in nicotine replacement therapy as a smoking
cessation aid. A transdermal analgesic patch (such as buprenorphine or
fentanyl) may be applied to the skin to relieve moderate to severe pain.
4 Rectal: certain drugs may be absorbed from the rectum and may be
administered as a suppository or enema. A suppository is a bullet-shaped
formulation that melts at body temperature, dispersing the drug. The drug
in an enema is suspended in a solution and infused into the rectum. This
route is useful to avoid first-pass metabolism (see Answer 19).
5 Topical (local): drugs may be applied topically (locally) to the skin,
mucous membranes or surface wounds, usually in the form of creams,
ointments or gels. Topically applied medicines are primarily active at
the site of application, although some drugs (for example, non-steroidal
anti-inflammatory drugs (NSAIDs)) are also absorbed into the systemic
circulation and can therefore cause side-effects.
6 Intravenous (IV): this route has the most rapid action since the drug is
applied directly into the bloodstream and has a bioavailability of 100%
(see Answers 14 and 19). It may be used for drugs that are too irritating
to be administered intramuscularly. This procedure is technically quite
difficult and the nurse must be careful not to inadvertently inject into an
artery, which can lead to arterial spasm and tissue damage.
7 Intramuscular (IM): this route is easier than the intravenous one but
can be quite painful, so the maximum volume for delivery depends on

11

25302.indb 11 13/09/2013 12:00

 ANSWERS Pharmacology and drug administration

the muscle being injected. Some common muscles should only receive
1mL intramuscular injection. Higher volumes may be injected depending
on muscle size and its capacity to cope with the volume being injected.
Absorption from the site is variable and depends on the blood flow but can
be increased by exercise and rubbing the injection site. Usually absorption
is greatest from the deltoid muscle and least from the buttock.
8 Subcutaneous (SC): this route is widely used. The common areas for
subcutaneous injections are the forearm, outer aspect of the thigh or the
abdominal wall. Absorption is slower than with an intramuscular injection
(see Figure 1.5) and the area should not be massaged after administration.
When a local effect is required (for example, with a local anaesthetic), a
vasoconstrictor may be added to the injection to narrow the blood vessels
and prevent the drug being distributed away from the site of injection.

Figure 1.5 The effect of route of administration on plasma concentrations

of drug after one dose

9 Intradermal (ID): this is the route often used when administering

immunizations. A very small volume is injected at an angle, just under the
skin in the dermis, commonly in the upper arm. The injection site should
not be massaged when the needle is removed.

12

25302.indb 12 13/09/2013 12:00

 Pharmacology and drug administration ANSWERS

TRUE OR FALSE?

10 In pharmacology, the word ‘agonist’ describes a drug that

binds or interacts with its biological receptor but produces
no effect. 
An agonist is a drug that binds to, or interacts with, its specific biological
receptor (such as a cell surface receptor, an enzyme or a section of DNA),
stimulating the receptor to trigger a response by the cell. The response is
produced in a similar manner to that of the natural physiological ligand
(or chemical), such as a hormone or neurotransmitter – that is, the action
of an agonist mimics that of the receptor’s natural ligand (see Figure
1.6). For example, a beta2 (β2) agonist drug (such as salbutamol) mimics
the action of the natural ligand for the β2 adrenergic receptors (for
example adrenaline) on the muscles surrounding the airways. Activation
of β2 adrenergic receptors relaxes the muscles surrounding the airways,
causing bronchodilation, which opens the airways. Dilation of the airways
helps to relieve the symptoms of dyspnoea (shortness of breath).

Figure 1.6 Mechanism of ligand/agonist–receptor binding

13

25302.indb 13 13/09/2013 12:00

 ANSWERS Pharmacology and drug administration


11 An antagonist may be described as competitive or
non-competitive.
An antagonist drug may compete with the natural ligand to bind with the
cell surface receptor. When it binds with the natural ligand an antagonist will
not produce a cellular response, thus an antagonist inhibits the action of the
natural ligand. Sometimes the inhibition of the cellular response is desirable
in therapeutics and many drugs utilize this mode of action. For example, the
cells of some breast cancer patients possess many receptors that will bind
to the natural oestrogen hormone circulating in the body. Since oestrogen
stimulates breast cancer cells to grow, the continued binding of oestrogen to
these receptors will allow the cancerous cells to multiply rapidly, enabling
the malignant tumour to grow and spread. Competitive antagonists work
by competing with the natural oestrogen ligand to bind with the receptor
and once bound they inhibit the cellular response. When the competitive
antagonist drug is bound to the receptor, it effectively blocks the oestrogen
receptors on the cell surface, which prevents the natural oestrogen ligands
from binding to the same receptors and hence tumour cell growth is
prohibited. This is how a ‘competitive antagonist’ works. Tamoxifen is an
example of a competitive antagonist used in the treatment of breast cancer.


12 The pharmacological action of a drug varies significantly
among individuals.
Generally, the body’s response to the pharmacological action of a certain
drug does not vary significantly among individuals; however, the intensity
and duration of the drug response may vary considerably. This is due to
two main factors: (1) the bioavailability of the drug (plasma concentration
of the absorbed drug) within the body may vary significantly, and (2) the
sensitivity and responsiveness of the necessary cell surface receptors may
differ. Usually these individual differences are not significant enough to cause
concern, although some drugs have a narrow margin between therapeutic
effect and toxicity and with these it is important for the nurse to consider
the factors that may modify an individual’s response to specific drugs.


13 A pro-drug describes a drug that is pharmacologically
inactive until it reaches the liver and is metabolized.
A pro-drug may be used if the bioavailability of the orally administered
drug is quite poor. It may also be used to increase the selectivity of
the drug for its intended target. Pro-drugs only become active when they
have undergone metabolism in the liver. Many chemotherapy treatments
utilize pro-drugs to specifically target malignant cells and reduce the
adverse effects of the treatment.


14 Drugs administered intravenously (IV) are considered to
have 100% absorption into the systemic circulation.
Drugs administered intravenously are considered to have 100%
absorption because they are delivered directly into the bloodstream. The
blood plasma concentration of orally administered drugs is compared

14

25302.indb 14 13/09/2013 12:00

 Pharmacology and drug administration ANSWERS

against the concentration of the same IV-administered drug to determine

the bioavailability of the oral dosage.


15 Free, unbound drug molecules cannot exert a
pharmacological effect.
Drugs are considered free and unbound when they are not bound to
plasma proteins in the blood. Only free drug molecules, which are not
bound to plasma proteins, can leave the bloodstream and enter the
interstitial (tissue) fluid to exert a pharmacological effect. While bound
to plasma proteins such as albumin, drug molecules cannot leave the
blood and therefore remain pharmacologically unreactive (inert).

16 Most drugs are excreted in the urine. 

Most drugs are excreted in the urine either unchanged or as a metabolite.
Three renal processes are involved in excretion of drugs. In the first
stage, glomerular filtration, small drug molecules are forced across the
membrane of the glomerulus by the high pressure in the renal arteries
and enter the filtrate in the renal tubule at a concentration equal to that
of the blood plasma. Drugs bound to plasma proteins are not filtered. As
water is reabsorbed from the filtrate, the concentration of drug in the
urine increases. Drug molecules that are not filtered out of the blood in
the glomerulus are secreted into the filtrate in the proximal convoluted
tubule. The process of secretion is highly effective and can remove most
of the drug from the blood in just one passage through the kidneys. Other
routes of excretion include the lungs and biliary excretion.

MULTIPLE CHOICE
Correct answers identified in bold italics.

17 The time required for the onset of a drug’s action depends on

its delivery to the site of action. Which of the following is not an
important consideration in drug delivery?
a) route of administration b) rate of absorption
c) rate of elimination d) distribution of drug
For many drugs, the time taken for the onset of drug action is an
important consideration because its desired effect is required within a
certain timeframe. The time to the onset of drug action can be modified
in a number of ways. For example, if drug action is required quickly
an intramuscular or intravenous route of administration may be taken.
For patients who suffer chronic pain, analgesia (pain relief) may be
administered through a transdermal patch which provides a more
continuous plasma drug level to control the pain and reduce the amount
of oral medication required; this is particularly important in older adults
and patients who may have difficulty swallowing tablets or capsules. The

15

25302.indb 15 13/09/2013 12:00

 ANSWERS Pharmacology and drug administration

rate of drug elimination will determine the duration of the drug effect:
the quicker the drug is removed from its target site, the shorter the drug’s
therapeutic effect.

18 How many factors are associated with a drug’s distribution?

a) 1 b) 2 c) 3 d) 4
Once a drug has been administered and absorbed by the body, it must
be distributed to the correct site of action. For some drugs the desired
site of action is known (thus a drug may be administered locally at the
site) but when the site of action is unknown, drugs must be distributed
systemically (throughout the body) to ensure they reach the necessary
target. Four factors need to be considered regarding drug distribution
in the body: (1) distribution into the body fluids; (2) uptake of drugs by
body tissues (organs); (3) the extent of plasma protein binding; and (4)
passage through barriers (such as the blood–brain barrier).

19 Which of the following describes the amount of drug absorbed by

the body and distributed systemically?
a) bioavailability b) first-pass metabolism
c) biotransformation d) pharmacokinetics
Bioavailability refers to the quantity of the administered drug that is
absorbed into the body and distributed by the systemic blood circulation.
Bioavailability is affected by incomplete absorption and first-pass
metabolism, so the route of administration is significant in determining the
bioavailability of a drug. For example, drugs that are administered orally
may not be fully absorbed from the stomach or intestinal tract (if there
is a lot of food present or there is GI disturbance), which will reduce the
amount of drug entering the bloodstream. Some drugs are significantly
metabolized in their first transit through the liver (first-pass metabolism),
which also reduces bioavailability (see Answer 32). Drugs administered
intravenously are considered to have 100% absorption (because they
are delivered directly into the bloodstream) and so the blood plasma
concentration of orally administered drugs is compared against the
concentration of IV-administered drugs to determine the bioavailability
of the oral dosage. Biotransformation describes the metabolism of drugs
in the body. It mainly occurs in the liver. Pharmacokinetics describes what
the body does to drugs from administration to excretion.

20 Most drugs and drug molecules are excreted by the:

a) liver b) kidneys c) gall bladder d) lungs
Excretion of drugs occurs primarily through the kidneys, although small
quantities of drug may be detected in the faeces. Drugs that are detected
in the faeces are eliminated from the body through the bile. Drugs may
also be detected in sweat, saliva, hair, tears, and exhaled air, although
these are not considered routes of excretion since the quantities usually
detectable are very low.

16

25302.indb 16 13/09/2013 12:00

 Pharmacology and drug administration ANSWERS

21 The ability of the kidneys to excrete drugs is called:

a) renal excretion b) renal filtration
c) renal secretion d) renal clearance
Renal clearance is determined by dividing the amount of drug excreted
in the urine by the plasma concentration of the drug. In a healthy adult,
the kidneys filter 120 mL of plasma every minute. Based on this figure,
if a drug has a renal clearance value considerably lower than 120 mL
per minute, it means the drug is either (1) not well filtered as it passes
through the glomeruli of the kidneys or (2) the drug is filtered and then
mostly reabsorbed into the plasma at the kidney tubules. Renal clearance
values of more than 120 mL per minute indicate that the drug is filtered
by the glomeruli and actively secreted by the tubules. Drugs with high renal
clearance values rely on the healthy functioning kidneys to eliminate them
from the body, otherwise the drug will accumulate in the body – this is
particularly important when prescribing such drugs to patients with kidney
disease or individuals at risk of renal complications from other illnesses
(such as diabetes). Drugs with low renal clearance rates rely on other
elimination mechanisms, usually by the liver with bile. Doses of drugs with
low renal clearance need not be modified for patients with kidney disease.
The renal clearance rate in newborn babies and older adults is significantly
lower and these patients need to receive lower drug doses (see Chapter 12).

22 The time taken for the concentration of a drug to fall to half its
original level is called:
a) half-life b) steady state c) elimination d) clearance
The half-life (or elimination half-life) of a drug is the time taken for the
plasma concentration of a drug to decrease by half. The half-life indicates
the speed of elimination of a drug and therefore implies the duration of
action of a drug. The faster the elimination of a drug, the shorter its half-
life will be because plasma concentrations will decrease relatively quickly
(see Figure 1.7). When the half-life of a drug is known, it can be used to
help determine the intervals between drug doses in patients.

23 When the amount of drug excreted equals the amount being

absorbed, the condition is called:
a) toxicity b) half-life c) therapeutic limit d) steady state
Ideally a therapeutic effective concentration of a drug (or steady state)
would be achieved and maintained with a single dose. Unfortunately this is
rarely possible so to maintain a steady state, doses have to be administered at
intervals. A steady state may be reached quickly by initially administering a
higher dose of the drug – known as a loading dose – followed by a maintenance
dose. Some antibiotics are administered using this loading–maintenance dose
regimen to rapidly attack bacteria and produce desired levels of the drug
in the body immediately to combat infection. Rapidly excreted drugs (with
relatively short half-lives) require frequent administration or a continuous
infusion to maintain a reasonably steady state in the body (see Figure 1.8).

17

25302.indb 17 13/09/2013 12:00

 Figure 1.7 The half-life of a drug after one IV injection

Figure 1.8 Influence of excretion on achieving a steady-state blood

concentration of a drug

18

25302.indb 18 13/09/2013 12:00

 Pharmacology and drug administration ANSWERS

24 Sometimes drug metabolism processes become more effective,

which can lead to:
a) drug toxicity b) drug tolerance
c) drug overdose d) liver failure
Drug tolerance may develop when the metabolic processes become more
effective. In this situation, repeatedly larger doses of the drug will be
required to produce the same therapeutic effect. Patients taking anti-
epileptic drugs can sometimes develop drug tolerance, so their initial
prescriptions should be as low a dose as necessary to control seizures
and still allow for an increased dose in the future.

FILL IN THE BLANKS

25 Drug affinity describes how well a drug binds to its specific target.
Drugs with a high affinity bind preferentially to their specific physiological
target compared with other drug molecules that may be present. The
higher the affinity, the tighter the drug will bind to its target. Even
low concentrations of very high affinity drugs will bind to their targets
preferentially, which can be useful with drugs that are toxic at higher
doses.

26 The ability of drugs to cross cell membranes depends on their

lipid solubility.
Lipid-soluble drugs can easily enter cells from the interstitial tissue
fluid by crossing the cell membranes.This is due to the phospholipid nature
of cell membranes, which separates the intracellular and extracellular
fluid compartments and facilitates the movement of lipids through the
cell membrane. Water-soluble drugs will not cross cell membranes as
easily. Due to their relatively favourable solubility, lipid-soluble drugs
(such as warfarin) will be widely distributed throughout the body fluids
and compartments, whereas the distribution of water-soluble drugs tends
to be restricted to the extracellular fluid compartments of the plasma
and interstitial fluid.

27 Tissue perfusion has a significant role in the initial distribution

of a drug.
Organs and tissues that are richly perfused with blood will initially receive
more drug molecules than regions that do not have a rich blood supply.
This is because the drug molecules are transported around the body in the
blood, so that areas such as the brain, heart, and kidneys, which receive
a rich supply of blood, will initially receive more drug molecules quickly.
Bone and adipose (fat) tissue are less well perfused and therefore receive
less drug during the initial distribution; even very lipid-soluble drugs will
not initially be detected in significant quantities in adipose tissue. After

19

25302.indb 19 13/09/2013 12:00

 ANSWERS Pharmacology and drug administration

initial distribution, drugs become redistributed to the tissues for which

they have highest affinity.

28 The physical and chemical composition of a drug is called its

formulation.
The formulation of a drug describes all physical and chemical aspects of
a medicine, including the active ingredients and any excipients (inactive
substances that serve as the vehicle or medium for a drug). Excipients can
be responsible for adverse drug reactions and may vary between brands,
therefore the rate of release of the active ingredient may be different.

29 Drugs direct their effects at molecular targets within the body.

The four most common molecular targets are: receptors, enzymes,
carriers, and ion channels.
Many drugs target and bind to protein molecules located on cell
membranes. The phospholipid bilayer of the cell membrane is selectively
permeable and has protein molecule receptors embedded throughout
the surface that facilitate the movement of substances in and out of
the cell. Certain molecules called ligands bind to specific receptors
and produce a response. Drugs may bind to receptors agonistically to
mimic the response of a natural ligand or antagonistically to inhibit the
natural response. Salbutamol and morphine are examples of common
drugs that interact with receptors. Many drugs act by targeting
natural enzymes and inhibiting their activity. For example, angiotensin
converting enzyme (ACE) inhibitor drugs reduce blood pressure by
preventing the action of angiotensin converting enzyme which converts
angiotensin I to angiotensin II. In the absence of angiotensin II, blood
pressure falls. Carrier proteins (or transport systems) may be targeted
by drugs to prevent the normal physiological recycling of certain
chemical transmitters. An example is the inhibition of the re-uptake of
the neurotransmitter serotonin by certain antidepressant drugs, causing
an accumulation of serotonin at the synapse, which enhances mood.
Ion channels in the cell membrane may be targeted by drugs in two ways:
(1) channels are blocked, as in calcium channel blockers, which block
the entry of calcium into cells, or (2) channels may be regulated by
drugs that bind to the channel, altering the channel’s response to its
normal target.

30 The products of bilary excretion are eliminated from the body via
the faeces.
Drugs are often broken down or combined with other chemicals by
enzymes in the liver making them inactive. These metabolites then pass
out of the liver, mix with the bile, and enter the gastrointestinal (GI)
tract. They pass through the GI tract with other unwanted products and
are eventually eliminated from the body in the faeces.

20

25302.indb 20 13/09/2013 12:00

 Pharmacology and drug administration ANSWERS

31 Some drugs undergo enterohepatic recirculation, which prolongs

their effect.
During bilary excretion, some drugs are reabsorbed from the GI tract
back into the blood and travel to the liver again where they are further
metabolized. This helps to maintain constant circulating levels of the
drug, which prolongs the drug’s effect until the next dose is administered.
The combined oral contraceptive pill (COCP) is an example of a drug
that undergoes this process; this enables the COCP to maintain constant
high levels of the hormones required to prevent fertilization of the egg or
implantation of a fertilized egg, thus preventing pregnancy. It is also the
reason why the COCP should be taken at the same time each day.

32 First-pass metabolism occurs in the liver.

The first-pass metabolism (or effect) describes the breakdown
(metabolism) of drugs by enzymes in the liver before the drug has
entered the general circulation. After an oral drug is absorbed in the
digestive tract, it passes to the liver via the hepatic portal vein. A family
of enzymes in the liver, known as cytochrome P450 (or microsomal)
enzymes, specialize in metabolism and certain enzymes within the family
target drugs for metabolism. Each time a drug passes through the liver,
it undergoes a certain amount of metabolism, which varies depending
on the drug. The amount of metabolism the drug undergoes during its
first passage through the liver will determine how much of the drug
actually enters the circulation (known as the drug’s bioavailability). If a
drug undergoes extensive first-pass metabolism in the liver, very little of
the drug will remain when it is released into the circulation, which will
limit its therapeutic efficacy. The anti-angina medicine, glyceryl trinitrate
(GTN), is a drug that undergoes almost complete first-pass metabolism,
which is why it is usually administered sublingually. From this site, it is
directly absorbed into the blood, which gives it sufficient time to exert
its therapeutic effect before it is metabolized in the liver. Each time a
drug passes through the liver, it undergoes further metabolism by the
cytochrome P450 enzymes. Some drugs induce certain cytochrome P450
enzymes, which increases their metabolic activity; while other drugs
inhibit specific cytochrome P450 enzymes, which reduces their metabolic
activity. This is the basis for many drug interactions (see Chapter 13).

33 Sustained release drugs are delivered slowly into the blood.

Sustained (prolonged) release formulations are delivered slowly, but at a
steady rate, into the blood. This maintains a prolonged therapeutic action.
It usually means a patient requires fewer tablets (if the drug is in tablets
form) and side-effects may be reduced because peak plasma levels of the
drug are reduced.

21

25302.indb 21 13/09/2013 12:00