Make your own free website on Tripod.com
pharmacology115
Blank page3
Home
Blank page6
Nervous Systems
New Page Title
Blank page1
Blank page2
Blank page3
Blank page4
Blank page5

Enter subhead content here

Parasympatholytic bronchodilators

Clinical indications

Anticholinergic bronchodilators:

Maintenance treatment in COPD, including chronic bronchitis and emphysema.

Combined anticholinergic + β adrenergic bronchodilators:

COPD patients who require additional bronchodilation for airflow obstruction relief.

Nasal spray: Perennial rhinitis and colds.

Use in asthma

Anticholinergic bronchodilators do not have a labeled indication for asthma in the U.S.

If used in combined therapy, the effect is additive.

Special uses for asthmatic patients are:

- nocturnal asthma

- psychogenic asthma (P fibers involved?)

- asthma + glaucoma, angina or hypertension

- alternative to theophyllines

- acute severe episodes not responding well to β agonists

 

Mode of action.

Parasympatholytic bronchodilators are

antimuscarinic: they compete against ACH

for the muscarinic receptors located in the

parasympathetic neuroeffector sites, M3 in

the lungs.

Why COPD?

Bronchoconstriction seen in COPD is partially caused by an

autonomic arc reflex which responds to stimuli such as

irritant aerosols, cold air, tobacco smoke, noxious fumes and

inflammatory mediators.

Muscarinic receptors in the lung

M1

Facilitators of the cholinergic transmission. They "help" the nicotinic receptors at the ganglionic synapse.

M2

"Autoreceptors"; they inhibit further release of ACH.

M3

Located in the bronchial smooth muscle, in contact with parasympathetic fibers. its blockade prevents bronchoconstriction.

Antimuscarinic agents block both M1 and M3 receptors.

Ipratropium bromide

IB is a non-selective antagonist of M1, M2

and M3 receptors.

Brand name: Atrovent

Dosage forms Adult dosage

MDI 18 μg/puff 2 puffs qid

SVN .02% 2.5 ml tid-qid

          Structure-activity relation:

IB is a quaternary ammonium compound.

It is fully ionized (fig 7.1, p. 140) and doesnt distribute well across lipid membranes, limiting its distribution mostly to the lung when inhaled.

It isnt rapidly removed from the aerosol site and doesnt reach the CNS (less side effects).

          Pharmacokinetics:

Onset of action: Within a few minutes

Peak effect: 1-2 hours

Half life: 6 hours (asthma) and 8 hours (COPD)

Tiotropium bromide

Brand name: Spiriva

Dosage form: DPI 18 μg/dose

Adult dosage: 18 μg daily

Advantages:

Longer half life

Low side effect profile

Greater FEV1 improvement than IB

Combined therapy: Albuterol + Ipratropium bromide

Brand name: Combivent

Dosage form: MDI (18 μg IB + 90 μg

Albuterol/puff)

Adult dosage: 2 puffs qid

Advantages:

Action sites are complementary

Mechanisms of action are different and complementary

Effect is additive (less amount of each, less side effects)

Pharmacokinetics are somewhat complementary

Combined therapy may prevent systemic steroid use.

Side effects

MDI and SVN (common)

Dry mouth

Cough

MDI (occasional)

Nervousness Palpitations

Irritation Rash

Dizziness

Headache

          SVN

Pharyngitis Eye pain

Dyspnea Urinary retention

Flu-like symptoms

Bronchitis

Upper respiratory infections

Nausea

Occasional bronchoconstriction

< The eyes must be protected from drug over-spraying

to prevent mydriasis. >

Enter supporting content here