Drugs Affecting the Respiratory System: Antitussives and Bronchodilators

When sensory receptors in the airway are stimulated by what

mechanical or chemical irritants

The mechanical or chemical irritants, these receptors send a signal and go where

these receptors send signals through the vagus nerve to the cough center in the medulla oblongata of the brainstem.

Once that message has been sent to the brainsteam it Signals travel

back down to the what

respiratory and abdominal muscles to execute the cough.

While the cough reflex is normally protective, but excessive or chronic coughing can indicate

respiratory diseases.

What are examples of Antitussives

1. Opioid

2. Non-opioid

What is the Mechanism of Action of Opioids as Antitussives!

Agonists of either μ-or κ- opiate receptors directly depress the cough center in the medulla.

Opioid receptors are in what area of the brain

in the medulla oblogata in the cough center

When the opiots interact with the receptor what happens

They are gonna go through the same process by using a G-protein channel!

What is a Gi

• Gi is an inhibitor

• this causes hyperpolarization due to potassium leakage out of the cell when K+ goes out of the cell, the (+) is going to be lower

• when the (+) goes lower then the neuron becomes difficult to stimulate and to send signals

Common Opioid Antitussives are ?

o Morphine: Not common!

o Hydrocodone + Homatropine (added anticholinergic drug to avoid abuse), Extra

label for dogs, Rx

oButorphanol: (Torbutrol®): FDA-approved for use in dogs, Rx

Are opioids abusive ?

All have abuse potential!

What is an example of Non-Opioid Antitussives

Dextromethorphan: Sigma (σ) Opioid Receptor Agonist

Is xylitol toxic to dogs ? If so what does it cause

• Extremely TOXIC to DOGS.

• The safest choice for cats!

• even small doses cause rapid, life- threatening hypoglycemia.

• Higher doses could result is irreversible liver failure.

Which is Antitussives is considered right handed

Non-Opioid Antitussives

Which is Antitussives is considered left handed

Opioids as Antitussives!

What is the MOA of ββ2-Bronchodilators

• Bronchial smooth muscle is innervated by β2-adrenergic receptors.

• Stimulation of β2 receptors leads to increased activity of the enzyme adenylate cyclase (AC), increased intracellular cyclic adenosine monophosphate (cyclic-AMP),

• relaxation of bronchial smooth muscle.

Increasing cyclic AMP causes what

an increase of portein kinase A

If there is an increase of protein kinase A what will happen to the phosphatidyl

the phosphatidyl will decrease in the littel Ca+ concentration and decrease the activity of LLCK which is mysin and light chain kinase lineage

The adrenergic recetors are Alpha 1 what are the results

• vasocontriction

  • increased SVR

The adrenergic recetors are Alpha 2 what are the results

• Inhibits nor-epinephrine release

• inihbitis insulin release

• inhibits acetycholine release

The adrenergic recetors are Beta 1 what are the results

• increased HR

• increased renin

• increased contracility

The adrenergic recetors are Beta 2 what are the results

• vasodilation

  • relaxed smooth muscle bronchodilation

  • increased hlucagon

Beta 1 rectpro goes with what organ

heart

Beta 2 recetpros go with what organ

lungs

What are the indications for ββ2-Bronchodilators-

• In people for the treatment of asthma

• In animals for airway diseases like allergic bronchitis

• feline asthma

• Recurrent airway obstruction (RAO), and inflammatory airway disease (IAD) in horses

What are examples of Short-Acting Nonspecific Bronchodilators

• Epinephrine (Adrenaline)

• Isoproterenol

What is Epinephrine (Adrenaline) and why do we use it

choice for the emergency treatment of life-threatening bronchoconstriction,

such as during an anaphylactic reaction. unsuitable for long-term use.

What is Isoproterenol and why do we use it

for emergency relief of bronchoconstriction in horses, Not suitable for long term due to beta 1 effects.

Which is is not suitable for respiratory therapy.

Norepinephrine

The drug is norepinephrine what is a1, b1, b2

• a1 = +++

• b1 = 1

• b2 = 0

The drug is epinephrine what is a1, b1, b2

• a1 = +++

• b1 = +++

• b2 = ++

The drug is isoproterenol what is a1, b1, b2

• a1 = 0

• b1 = +++

• b2 = ++++

The drug is terbutaline/albuterol what is a1, b1, b2

• a1 = 0

• b1 = +

• b2 = +++

What are examples of Longer-Acting ββ2- Specific Drugs

• Terbutaline

• Clenbuterol

• Albuterol

When do we use Terbutaline

• The injection can be helpful for treatment of acute bronchoconstriction.

• Terbutaline has been used in horses to treat recurrent airway obstruction (RAO). It is not

What kind of medication form is Clenbuterol

Syrup for horses

Clenbuterol is banned in food-producing animals! Why

• The result is increased carcass weight and increased ratio of muscle to fat, while reducing the feed required per kg of weight gain.

• Death in people with heart disease and pregnant women

Adverse Effects of β2-Bronchodilators are

Cardiovascular System: Tachycardia

Skeletal Muscles: Muscle twitching, tremors, sweating

Uterine: Inhibition of contractions

Anticholinergics (Antagonists of Ach) Mechanism of action is what

inhibition of vagal- mediated cholinergic smooth muscle tone in the respiratory tract.

What does Gq do ?

• increase calcium

• theres bronchoconstriction

• antichlorneorgic black ACH which leads to brochodilation

What are examples of Anticholinergic Drugs as Bronchodilators

• Atropine

• N-butylscopolammonium bromide

Atropine is used for what

primarily used to determine prognosis in horses with equine asthma.

N-butylscopolammonium bromide is for what

(Buscopan® injectable solution): Main application to relieve spasmodic colic in horse, iv injection for diagnosis of equine asthma.

Adverse Effects of Anticholinergic Drugs are

Increase in heart rate (tachycardia)decrease in the GI motility. Risk of ileus in horses with Atropine!

Methylxanthines Mechanism of action:

1. Adenosine Receptor Antagonism

2. Phosphodiesterase (PDE) Inhibition

3. Decrease in release of inflammatory mediators from mast cells and increase mucociliary transport.

What are examples of Methylxanthines

• Theophylline:

• Aminophylline:

What is Theophylline:

is available in several formulations, but Theophylline base is poorly soluble

in water and often results in gastrointestinal irritation when administered orally.

What is Aminophylline used for

is a theophylline salt that is more water soluble and results in less gastrointestinal irritation.

What are the common side effects of Methylxanthines

are hyperactivity, inability to sleep, increased heart rate

(tachycardia), gastrointestinal upset (nausea, vomiting, diarrhea)