Sustained effects have also been obtained from subcutaneous
injections by using oily suspensions or by implanting a pellet
subcutaneously (e.g. oestrogenortestosteronefor hormone
replacement therapy).
INTRAVENOUS INJECTIONThis has the following advantages:
- rapid action (e.g. morphinefor analgesia and furosemide
in pulmonary oedema);
2.presystemic metabolism is avoided (e.g. glyceryl trinitrate
infusion in patients with unstable angina);
3.intravenous injection is used for drugs that are not
absorbed by mouth (e.g. aminoglycosides (gentamicin)
and heparins). It is also used for drugs that are too painful
or toxic to be given intramuscularly. Cytotoxic drugs must
not be allowed to leak from the vein or considerable local
damage and pain will result as many of them are severe
vesicants (e.g. vincristine,doxorubicin);
4.intravenous infusion is easily controlled, enabling
precise titration of drugs with short half-lives. This is
essential for drugs such as sodium nitroprussideand
epoprostenol.
The main drawbacks of intravenous administration are as
follows:
- Once injected, drugs cannot be recalled.
2.High concentrations result if the drug is given too rapidly –
the right heart receives the highest concentration.
3.Embolism of foreign particles or air, sepsis or
thrombosis.
4.Accidental extravascular injection or leakage of toxic drugs
(e.g.doxorubicin) produce severe local tissue necrosis.
5.Inadvertent intra-arterial injection can cause arterial
spasm and peripheral gangrene.
INTRATHECAL INJECTIONThis route provides access to the central nervous system for
drugs that are normally excluded by the blood–brain barrier.
This inevitably involves very high risks of neurotoxicity, and
this route should never be used without adequate training. (In
the UK, junior doctors who have made mistakes of this kind
have been held criminally, as well as professionally, negligent.)
The possibility of causing death or permanent neurological
disability is such that extra care must be taken in checking that
both the drug and the dose are correct. Examples of drugs used
in this way include methotrexateand local anaesthetics (e.g.
levobupivacaine) or opiates, such as morphineandfentanyl.
(More commonly anaesthetists use the extradural route to
administer local anaesthetic drugs to produce regional analge-
sia without depressing respiration, e.g. in women during
labour.) Aminoglycosides are sometimes administered by
neuro-surgeons via a cisternal reservoir to patients with Gram-
negative infections of the brain. The antispasmodic baclofenis
sometimes administered by this route.
Penicillinused to be administered intrathecally to patients
with pneumococcal meningitis, because of the belief that it
penetrated the blood–brain barrier inadequately. However,
when the meninges are inflamed (as in meningitis), high-dose
intravenouspenicillinresults in adequate concentrations in
the cerebrospinal fluid. Intravenous penicillinshould now
always be used for meningitis, since penicillinis a predictable
neurotoxin (it was formerly used to produce an animal model
of seizures), and seizures, encephalopathy and death have
been caused by injecting a dose intrathecally that would have
been appropriate for intravenous administration.points22 DRUG ABSORPTION AND ROUTES OF ADMINISTRATION
Key points- Oral – generally safe and convenient
- Buccal/sublingual – circumvents presystemic metabolism
- Rectal – useful in patients who are vomiting
- Transdermal – limited utility, avoids presystemic
metabolism - Lungs – volatile anaesthetics
- Nasal – useful absorption of some peptides (e.g.
DDAVP; see Chapter 42) - Intramuscular – useful in some urgent situations (e.g.
behavioural emergencies) - Subcutaneous – useful for insulin and heparin in
particular - Intravenous – useful in emergencies for most rapid and
predictable action, but too rapid administration is
potentially very dangerous, as a high concentration
reaches the heart as a bolus - Intrathecal – specialized use by anaesthetists
Case history
The health visitor is concerned about an eight-month-old
girl who is failing to grow. The child’s mother tells you that
she has been well apart from a recurrent nappy rash, but
on examination there are features of Cushing’s syndrome.
On further enquiry, the mother tells you that she has been
applyingclobetasone, which she had been prescribed her-
self for eczema, to the baby’s napkin area. There is no bio-
chemical evidence of endogenous over-production of
glucocorticoids. The mother stops using the clobetasone
cream on her daughter, on your advice. The features of
Cushing’s syndrome regress and growth returns to normal.
Comment
Clobetasoneis an extremely potent steroid (see Chapter
50). It is prescribed for its top-ical effect, but can penetrate
skin, especially of an infant. The amount prescribed that is
appropriate for an adult would readily cover a large frac-
tion of an infant’s body surface area. If plastic pants are
used around the nappy this may increase penetration
through the skin (just like an occlusive dressing, which is
often deliberately used to increase the potency of topical
steroids; see Chapter 50), leading to excessive absorption
and systemic effects as in this case.