A Textbook of Clinical Pharmacology and Therapeutics

caused by timololeyedrops given for open-angle glaucoma.

However, such absorption is not sufficiently reliable to make

use of these routes for therapeutic ends.

INTRAMUSCULAR INJECTION

Many drugs are well absorbed when administered intramus-

cularly. The rate of absorption is increased when the solution is

distributed throughout a large volume of muscle. Dispersion is

enhanced by massage of the injection site. Transport away from

the injection site is governed by muscle blood flow, and this

varies from site to site (deltoidvastus lateralisgluteus max-

imus). Blood flow to muscle is increased by exercise and absorp-

tion rates are increased in all sites after exercise. Conversely,

shock, heart failure or other conditions that decrease muscle

blood flow reduce absorption.

The drug must be sufficiently water soluble to remain in

solution at the injection site until absorption occurs. This is a

problem for some drugs, including phenytoin, diazepamand

digoxin, as crystallization and/or poor absorption occur when

these are given by intramuscular injection, which should there-

fore be avoided. Slow absorption is useful in some circum-

stances where appreciable concentrations of drug are required

for prolonged periods. Depot intramuscular injections are

used to improve compliance in psychiatric patients (e.g. the

decanoate ester of fluphenazinewhich is slowly hydrolysed to

release active free drug).

Intramuscular injection has a number of disadvantages:

1. pain – distension with large volumes is painful, and
   injected volumes should usually be no greater than 5 mL;
   2.sciatic nerve palsy following injection into the buttock –
   this is avoided by injecting into the upper outer gluteal
   quadrant;
   3.sterile abscesses at the injection site (e.g. paraldehyde);
   4.elevated serum creatine phosphokinase due to enzyme
   release from muscle can cause diagnostic confusion;
   5.severe adverse reactions may be protracted because there
   is no way of stopping absorption of the drug;
   6.for some drugs, intramuscular injection is less effective
   than the oral route;


2. haematoma formation.

SUBCUTANEOUS INJECTION

This is influenced by the same factors that affect intramuscular

injections. Cutaneous blood flow is lower than in muscle so

absorption is slower. Absorption is retarded by immobiliza-

tion, reduction of blood flow by a tourniquet and local cooling.

Adrenaline incorporated into an injection (e.g. of local anaes-

thetic) reduces the absorption rate by causing vasoconstriction.

Sustained effects from subcutaneous injections are extremely

important clinically, most notably in the treatment of insulin-

dependent diabetics, different rates of absorption being

achieved by different insulin preparations (see Chapter 37).

Transdermal absorption is sufficiently reliable to enable system-
ically active drugs (e.g. estradiol,nicotine,scopolamine) to be
administered by this route in the form of patches. Transdermal
administration bypasses presystemic metabolism. Patches are
more expensive than alternative preparations.

LUNGS

Drugs, notably steroids, β 2 -adrenoceptor agonists and mus-
carinic receptor antagonists, are inhaled as aerosols or particles
for their local effects on bronchioles. Nebulized antibiotics are
also sometimes used in children with cystic fibrosis and recur-
rent Pseudomonasinfections. Physical properties that limit sys-
temic absorption are desirable. For example, ipratropiumis a
quaternary ammonium ion analogue of atropine which is
highly polar, and is consequently poorly absorbed and has
reduced atropine-like side effects. A large fraction of an
‘inhaled’ dose of salbutamolis in fact swallowed. However,
the bioavailability of swallowed salbutamolis low due to inac-
tivation in the gut wall, so systemic effects such as tremor are
minimized in comparison to effects on the bronchioles.
The lungs are ideally suited for absorption from the gas
phase, since the total respiratory surface area is about 60 m^2 ,
through which only 60 mL blood are percolating in the capil-
laries. This is exploited in the case of volatile anaesthetics, as
discussed in Chapter 24. A nasal/inhaled preparation of insulin
was introduced for type 2 diabetes (Chapter 37), but was not
commercially successful.

NOSE

Glucocorticoids and sympathomimetic amines may be admin-
istered intranasally for their local effects on the nasal mucosa.
Systemic absorption may result in undesirable effects, such as
hypertension.
Nasal mucosal epithelium has remarkable absorptive
properties, notably the capacity to absorb intact complex pep-
tides that cannot be administered by mouth because they
would be digested. This has opened up an area of therapeutics
that was previously limited by the inconvenience of repeated
injections. Drugs administered by this route include desmo-
pressin(DDAVP, an analogue of antidiuretic hormone) for
diabetes insipidus and buserelin(an analogue of gonadotrophin
releasing hormone) for prostate cancer.

EYE, EAR AND VAGINA

Drugs are administered topically to these sites for their local
effects (e.g. gentamicinorciprofloxacineyedrops for bacterial
conjunctivitis, sodium bicarbonate eardrops for softening wax,
andnystatinpessaries for Candidainfections). Occasionally,
they are absorbed in sufficient quantity to have undesirable sys-
temic effects, such as worsening of bronchospasm in asthmatics

ROUTES OFADMINISTRATION 21