Respiratory - Respiratory Drugs

Question 1

What is the methyxanthine,

Etamiphylline camsylate

used for in treating respiratory failure?

Answer 1

Etamiphylline camsylate is a methylxanthine, which means it is is PDE III inhibitor.

PDE III, or phosphodiesterase III, degrades cAMP in vascular & bronchial smooth-muscle cells, where increased cAMP leads to decreased intracellular calcium levels, and therefore vasodilation. PDE III reduces cAMP levels, and therefore leads to vasoconstriction. **A PDE III inhibitor such as etamiphylline would relax smooth muscle in arterioles as well as in bronchioles. **

• Etamiphylline camsylate stimulates central chemoreceptors in medulla, mimicking normal physiological response to too much CO₂, for example

Indications:

• promote respiration in apnoeic newborn or pre- term animals
• reverse respiratory depression after overdose eg. of general anaesthetic

Question 2

What type of respiratory ailments are treated with opioid-receptor agonists and opioids?

What are they meant to do, and what are some examples?

Answer 2

Cough.

Opioid-receptor agonists are also known as anti-tussives.

Agonists bind to opioid receptors within the medulla’s cough centre, depressing the cough reflex.

They mimic enkephalins & endorphins, which are natural, endogenous opioid agonists

Negative feedback for irritant receptors in respiratory tract.

Examples:

Butorphanol

Codeine

Dextromethorphan

Question 3

What are three classes of drug to treat accumulation of mucous in the respiratory tract?

Answer 3

1. Mucolytics
2. Expectorants
3. Nasal decongestants

Question 4

What do mucolytic drugs do, and what are some examples?

Answer 4

They break up mucus in the airways.

Bromhexine - makes mucus less viscous so it can move

Dembrexine - causes secretory glands to produce more fluid, watery, serous mucous.

Question 5

What are expectorants and what are some examples?

Answer 5

They’re supposed to make you cough up mucus by irritating mucus membranes & causing increased clearance of mucus. ie., Supposed to help mucociliary mechanism work better, but it isn’t proven & as such they are of limited value.

Oral treatments:

• Ipecacuana - root of a flowering plant; also an emetic
• Squill / Scilla (herb)
• *- Camphor
• Aniseed**
• Ammonium chloride - Guaiacol
• Liquorice extract

Inhaled treatments:

Eucalyptus oil - supposed to increase secretion of watery mucus, but not proven

Question 6

How do nasal decongestants work and what is one example?

Answer 6

They reduce mucus production in upper respiratory tract & in conditions associated with profuse secretion eg., allergic rhinitus in cats

Pseudoephedrine (Sudafed) - indirectly-acting sympathomimetic that causes release of endogenous norepinephrine from presynaptic nerve terminals, resulting in vasoconstriction (constriction of smooth muscles in nasal mucusa & trachea to constrict secretory glands in airways); these act on alpha-1 & alpha-2 adrenoreceptors

Question 7

What drugs could be used to relieve bronchoconstriction by antagonising action at M₃ receptors?

NB M₃ cholinergic receptors typically vasoDILATE arterioles in most organs and skeletal muscle as a parasympathetic response, when bound to their natural ligand, Ach. Their vasodilatory activity is achieved via the release of nitric oxide (NO) from endothelial cells.

HOWEVER, M₃ activation by Ach directly on SMOOTH MUSCLE CELLS - include in the bronchioles - results in CONSTRICTION. (Normally, this vasoconstriction effect is overridden by the vasodilatory effect of NO).

Answer 7

M3 receptor antagonists include Atropine & Ipratroprium bromide.

Atropine is well-known as an antagonist to the muscle-constricting effects parasympathetic nervous system; it is used also to dilate pupils. As a bronchodilator, it antagonises the muscle-constricting effects of the M₃ receptor.

Ipratroprium bromide - can be inhaled

Adverse effects:

• Antagonising the parasympathetic system can cause a lack of motility in the GIT and enable uncontrolled stimulation of the sympathetic system
• Bronchodilators interfere with mucociliary clearance but if inhaled it is ok as it targets lungs

Question 8

What drugs could be used to relieve bronchoconstriction by agonising action at ß₂ receptors?

NB ß₂ receptors, when bound to norepinephrine or epinephrine are vasodilatory because they relax smooth muscle, and so they are bronchodilatory as well.

Answer 8

Sympathomimetics, their binding to ß2 receptors leads to phosphorylation events that reduce Ca++, promoting relaxation of muscle. Just as β2 receptors work in vascular smooth muscle, & OPPOSITE to β1 receptors in cardiac muscle

β2-selective drugs/ agonists:

**Clenbuterol - ** very good example of a β2 agonist bronchodilator; good for horses & cattle

Terbutaline: cats & dogs

Salbutamol/Salmeterol: for horses via inhalation

Non-selective beta agonists:

**epinephrine **(adrenaline) - for emergency treatment - isoprenaline

Question 9

What are the adverse effects of using ß₂ adrenergic receptor agonists or non-selective ß-receptor agonists to treat bronchconstriction?

Answer 9

Since agonists of any ß adrenergic receptor would be a sympathomimetic – ie., mimicking norepinephrine or epinephrine – it is possible that these drugs could also bind to other adrenergic receptors to cause very different effects throughout the body.

For example, the use of clenbuterol, a ß₂ sympathomimetic, could also lead to hypotension due to too much vasodilation of coronary & skeletal-muscle arterioles, which could also experience muscle tremors.

A non-selective sympathomimetic could bind to ß₁receptors, causing tachycardia.

**Hypokalaemia (increased metabolism of potassium by liver) **

Question 10

What classes of drugs could be used to treat airway inflammation?

Answer 10

Inflammation can be treated with

1. Glucocorticoids - NSAIDs: aspirin, naproxen
2. Methylaxanthines - etamiphylline
3. Histamine (H₁) antagonists (antihistamines)
4. 5-HT aka seratonin antagonists
5. leukotriene (LT) D₄- receptor antagonists
6. (Prophylactic) sodium cromoglycate & medocromil sodium