Page 144 - Basic _ Clinical Pharmacology ( PDFDrive )

130 SECTION II Autonomic Drugs

■ CLINICAL PHARMACOLOGY conjunctival application. However, glycopyrrolate, a quaternary
OF THE MUSCARINIC RECEPTOR- agent, is as rapid in onset and as long-lasting as atropine.
Antimuscarinic drugs should never be used for mydriasis unless
BLOCKING DRUGS cycloplegia or prolonged action is required. Alpha-adrenoceptor
stimulant drugs, eg, phenylephrine, produce a short-lasting
Therapeutic Applications mydriasis that is usually sufficient for funduscopic examination
(see Chapter 9).
The antimuscarinic drugs have applications in several of the major A second ophthalmologic use is to prevent synechia (adhesion)
organ systems and in the treatment of poisoning by muscarinic formation in uveitis and iritis. The longer-lasting preparations,
agonists. especially homatropine, are valuable for this indication.

A. Central Nervous System Disorders
1. Parkinson’s disease—The treatment of Parkinson’s disease C. Respiratory Disorders
(see Chapter 28) is often an exercise in polypharmacy, since no The use of atropine became part of routine preoperative medi-
single agent is fully effective over the course of the disease. Most cation when anesthetics such as ether were used, because these
antimuscarinic drugs promoted for this application (see Table 28–1) irritant anesthetics markedly increased airway secretions and were
were developed before levodopa became available. Their use is associated with frequent episodes of laryngospasm. Preanesthetic
accompanied by all of the adverse effects described below, but the injection of atropine or scopolamine could prevent these hazard-
drugs remain useful as adjunctive therapy in some patients. ous effects. Scopolamine also produces significant amnesia for the
events associated with surgery and obstetric delivery, an adverse
2. Motion sickness—Certain vestibular disorders respond to effect that was considered desirable. On the other hand, urinary
antimuscarinic drugs (and to antihistaminic agents with anti- retention and intestinal hypomotility following surgery were often
muscarinic effects). Scopolamine is one of the oldest remedies exacerbated by antimuscarinic drugs. Newer inhalational anesthet-
for seasickness and is as effective as any more recently introduced ics are far less irritating to the airways.
agent. It can be given by injection or by mouth or as a transder- Patients with COPD, a condition that occurs more frequently
mal patch. The patch formulation produces significant blood in older patients, particularly chronic smokers, benefit from
levels over 48–72 hours. Useful doses by any route usually cause bronchodilators, especially antimuscarinic agents. Ipratropium,
significant sedation and dry mouth. tiotropium (see Figure 8–3), aclidinium, and umeclidinium,
synthetic analogs of atropine, are used as inhalational drugs
B. Ophthalmologic Disorders in COPD either alone or in combination with a long-acting
Accurate measurement of refractive error in uncooperative β-adrenoceptor agonist. The aerosol route of administration has
patients, eg, young children, requires ciliary paralysis. Also, the advantage of maximal concentration at the bronchial target
mydriasis greatly facilitates ophthalmoscopic examination of the tissue with reduced systemic effects. This application is discussed
retina. Therefore, antimuscarinic agents, administered topically as in greater detail in Chapter 20. Tiotropium (t 25 hours) and
1/2
eye drops or ointment, are very helpful in doing a complete exami- umeclidinium (t 11 hours) have a longer bronchodilator action
1/2
nation. For adults and older children, the shorter-acting drugs are than ipratropium (t 2 hours) and can be given once daily
1/2
preferred (Table 8–2). For younger children, the greater efficacy because they dissociate slowly from M receptors. Aclidinium
3
of atropine is sometimes necessary, but the possibility of antimus- (t 6 hours) is administered twice daily. Glycopyrrolate is now
1/2
carinic poisoning is correspondingly increased. Drug loss from the available in inhalational form for twice daily treatment of COPD.
conjunctival sac via the nasolacrimal duct into the nasopharynx Tiotropium reduces the incidence of COPD exacerbations and is
can be diminished by the use of the ointment form rather than a useful adjunct in pulmonary rehabilitation to increase exercise
drops. Formerly, ophthalmic antimuscarinic drugs were selected tolerance. The hyperactive neural bronchoconstrictor reflex pres-
from the tertiary amine subgroup to ensure good penetration after ent in most individuals with asthma is mediated by the vagus,
acting on muscarinic receptors on bronchial smooth muscle cells.
Ipratropium and tiotropium are also used as inhalational drugs in
asthma.
TABLE 8–2 Antimuscarinic drugs used in
ophthalmology.
D. Cardiovascular Disorders
Usual Marked reflex vagal discharge sometimes accompanies the pain of
Drug Duration of Effect Concentration (%) myocardial infarction (eg, vasovagal attack) and may depress sino-
Atropine 5–6 days 0.5–1 atrial or atrioventricular node function sufficiently to impair car-
Scopolamine 3–7 days 0.25 diac output. Parenteral atropine or a similar antimuscarinic drug
is appropriate therapy in this situation. Rare individuals without
Homatropine 12–24 hours 2–5
other detectable cardiac disease have hyperactive carotid sinus
Cyclopentolate 3–6 hours 0.5–2
reflexes and may experience faintness or even syncope as a result
Tropicamide 15–60 min 0.5–1 of vagal discharge in response to pressure on the neck, eg, from a