Respiratory Drugs

pharmacology 1-7 Midterm review

mixed agonists drug

alpha 1, beta 1 and beta 2 receptor agonists

-bronchodilation

-inotropic and chronotropic effect

-vasoconstriction (increased blood pressure)

epinephrine

Uses of mixed agonists - epinephrine

anaphylaxis, acute episodes of bronchospasm, mucous membrane decongestion (topical nasal spray

what are toxicities associated with mixed agonists- epinephrine

tremors, tachyarrhythmia, hypertension, hypertension

when do you not use mixed agonists - epinephrine

animals with a known heart condition

Beta Agonists -Beta 1 and Beta 2 - adrenergic

-bronchodilator

-short duration of action < 1 hour

can be given SLOW IC but must dilute in saline (0.2mg/50mL)

Isoproterenol

when is Beta Agonists - Isoproterenol mainly used

Inhalation to treat bronchospasms in horses in an EMERGENCY, not for long term use

when should you discontinue Beta Agonists - Isoproterenol

When heart rate doubles

Beta Agonists - beta 2 selective

-similar to isoproterenol but longer acting and more selective (lasts 6-8 hours)

PO BID

Terbutaline

What is the Beta Agonists - Terbutaline used for?

For cats not having severe bronchoconstriction episodes despite corticosteroids

When to not use Beta Agonists - Terbutaline

In cats with cardiomyopathy or glaucoma

Beta Agonists

Short use ONLY

MDI or Nebulization for acute bronchoconstriction

Long-term use results in beta 2 receptor down-regulation (less effective)

Albuterol

What species is Beta agonists - Albuterol used as a rescue inhaler for?

Cats, Horses, Cattle

Beta agonists

Not used in dogs/cats

-use caution in race horses and food producing animals

short term unless concurrent with anti-inflammatories

Clenbuterol

What is Beta Agonists -Clenbuterol generally used for?

equine asthma only

What does Beta Agonists - Clenbuterol do regarding horses and cattle.

inhibits uterine contractions

What does Beta Agonists - Clenbuterol do regarding dystocia

results in uterine relaxation

Beta Agonists drug (inhalation)

• long acting albuterol analog (lipophilic)

Salmeterol

-Horses and cats to improve airway conduction in bronchial asthma and bronchospasm due to bronchitis or emphysema, and for COPD and pneumonia in horses

common uses for Beta Agonists - Salmeterol

What specifically is a toxicity regarding to Beta Agonists - Albuterol toxicosis in dogs

they chew on albuterol-containing inhalers and liquid vials used in nebulizers for humans

What are class toxicity regarding Beta Agonists

-beta 2 receptor stimulation in skeletal muscle

-high doses(terbutaline), _because of beta-adrenergic effect

Tremors, tachycardia

Decongestants (drug)

Alpha -1 agonists

-Oral formulation : low bioavailability, often combined w/ other ingredients toxic to our patients

-IV, increases blood pressure via peripheral vasoconstriction

-Topical (ophthalmic, nasal spray)

• topical vasoconstriction

Phenylephrine

Why would you avoid using Decongestants - Phenylephrine in pregnant animals?

Causes uterine vasoconstriction

Xanthine Bronchodilator

Dose depends on the percent

-Bronchodilator (may increase cAMP via inhibition of phosphodiesterase)

-Anti-inflammatory (inhibits mast cells degranulation)

-Increases mucociliary clearance

Theophylline

What does Xanthine Bronchodilator- Theophylline due to the strength of respiratory muscles

Increased

What is Xanthine Bronchodilator - Theophylline used for? (prophylactic and treatment)

Chronic asthma, myocardial failure, and pulmonary edema

What is Xanthine Bronchodilator - Theophylline used for in cats specifically with asthma used as?

sustained release oral theophylline because of short half life

What is the toxicity signs of Xanthine Bronchodilator - Theophylline?

sympathic activity, agitation, tremors, seizures

Xanthine Bronchodilator

eg. used IV with O2 therapy in foals with respiratory distress

Aminophylline

What drugs class?

-compete with acetylcholine at muscarinic receptors

-antagonize vagally-mediated bronchoconstriction

-reduce sensitivity to irritant receptors

-augment the bronchodilator effect of beta-adrenergics

Side Effects: Can’t see, pee, spit, sh”t

Anticholinergics

Anticholinergics

-Aerosol (central airways) or IV (central and Peripheral airways)

-increases heart rate (common in Ax)

-facilitates bronchodilation in dyspneic animals

-Drug of choice for respiratory distress caused by anti-cholinesterases

-Do not use chronically

Atropine

What are systemic side effects of Anticholinergics - Atropine?

reduces mucociliary clearance, induces tachycardia, urine retention, decreases gastric motility

Anticholinergic drug

-less systemic effects than atropine (not absorbed as well as atropine following aerolization)

-No reduction of mucociliary clearance or drying of mucus secretions

-May be given chronically (adjusted to other bronchodilator therapy)

Ipratropium bromide

Anticholinergics drug

-Bronchodilator in small animal

-Longer duration of action compared to atropine and fewer side effects

-Twice as potent as atropine when used as an aerosol

Glycopyrrolate

Stimulus for cough comes from irritation in the larynx, trachea, bronchi, and bronchioles → sends signal to the cough center in the brainstem

motor impulses travel down to diaphragm and respiratory muscles to produce a forceful expiration

mechanisms of a cough

What type of cough?

-Larynx and upper trachea produces a sudden, retching cough

gagging cough (maybe laryngospasm)

What type of cough?

-Lower trachea, bronchi, larger bronchioles, more controlled

Coordinated deep cough

Stimulus of what does NOT produce a cough?

terminal bronchioles or alveoli

What are the different classifications of a cough?

Productive or non-productive

What classification of cough is this?

-mucus being coughed up and expelled

• excessive fluid/mucus secretion stimulated by inflammation (secondary to infection or irritant substances)

Productive cough

What classification of cough is this?

-sharp cough but no mucus brough up

• early staged of respiratory disease

• Inspissated mucus (dried out mucus)

  • dehydrated animals

non-productive cough

These are all signs to do what

-mechanical irritation of bronchi

-infectious diseases if non-productive

-exhaustion associated with coughing

-collapsing trachea

suppress the cough

What drugs are used to suppress a cough?

Central acting cough suppressants(for non-productive cough), Bronchodilators, Mucokinetic drugs and expectorants (removal of the irritant)

What drug class is this?

-Inhibit medullary cough center by reducing its sensitivity to stimuli

-Do NOT use if productive cough

Toxicity: opioid effects on CNS (eg.,sedation, constipation)

Centrally Acting Antitussives

Centrally acting antitussives : Opioids (narcotic)

-good antitussive, LOW bioavailability

-Limited side effects

-risk of respiratory depression in a patient at risk or with high doses

Codeine

Centrally acting antitussives : Opioids (narcotic)

-most common abused prescription opioid in oct 2019

-Commonly used in dogs with a collapsing trachea

-more potent than codeine and less respiratory depressive effects

Hydrocodone with homatropine

Centrally acting antitussives: Opioids (narcotic)

-Agonist activity for analgesia and cough suppression

-injection possible

Butorphanol

Centrally acting antitussives (non-opioid)

-low potency, (over-the-counter drug)

Dextromethorphan

Other Cough Suppressants

-to remove secretions

• increase ciliary action (beta-receptor agonists, methylxanthines)

• decrease viscosity of secretions (acetylcysteine that disrupts linkages in mucus; used in bronchitis, COPD, asthma..)

Mucokinetic drugs

Other cough suppressants

-Stimulate tubulo-acinar cells indirectly (via gastric mucosa receptors) or directly and thus, decrease viscosity of secretions

Used with infectious disease, allergy, or chronic irritation

Expectorants

Other cough suppressants

What drugs are expectorants?

saline expectorants, guaifenesin, volatile oils- no evidence of clinical efficacy

Anti-inflammatory and immunosuppressant drugs

-inhibit phospholipase A2

-(stabilize cell membranes, reduce edema, help suppress immune reactions)

-Sensitize smooth muscle to the action of adrenergic drugs

-Stimulate epinephrine synthesis and inhibits its destruction

-usual caution for use

Corticosteroids

Anti-inflammatory and immunosuppressant drugs - Corticosteroids: medications

-orally for chronic or allergic bronchitis, asthma in patients unresponsive to bronchodilators

Prednisone/Prednisolone

Anti-inflammatory and immunosuppressant drugs - Corticosteroids: medications

-Inhaled: for patients that require beta 2 - agonist treatment more than twice a day

Triamcinolone

Anti-inflammatory and immunosuppressant drugs - Corticosteroids: medications

-e.g., several inhalations per day in foals

Fluticasone, beclomethasone dipropionate

Anti-inflammatory and immunosuppressant drugs -

Mast Cell stabilizers

-but ineffective for acute asthma

Chromolyn sodium

-it is possible to encounter resistance to corticosteroids

-It is recommended to use long-acting beta 2 agonist (LABA) in combination with corticosteroids

Resistance to therapy in case of asthma and COPD

Diuretics

Indications: primary pulmonary edema or secondary to heart disease; edema associated with choking

-OK to use in kidney disease

-Side Effects: PU/PD, hyperglycemia (do not use in diabetics), ototoxicity (cats ++)

Furosemide

Furosemide is commonly used in horses displaying what

frequent exercise-induced pulmonary hemorrhage (EIPH)

-with vasodilator (wait for stabilization of kidney function and electrolyte balance)

-with digitalis derivatives: risk of arrhythmia

-with theophylline: should decrease dosage of theophylline

-with prednisone: potassium loss ++

-with aminoglycoside antibiotics: ototoxicity enhanced

these are all serious contraindications of Furosemide with other drugs

Respiratory Stimulants

Used in drug-induced CNS depression; obstructive airway disease; neonatal asphyxia; functional laryngeal examination

Side effects: hyperexcitability, convulsiosns

Doxapram

-clinically evident inability to adequately ventilate and/or oxygenate

-Abnormal sounds, posture, mucus color; weakness, altered respiration effort, resistance to restraint

possible symptoms of respiratory distress

conscious perception of shortness of breath

dyspnea

greater than normal respiratory rate

tachypeea

increased respiratory distress when the patient is lying down or the chest is compressed

orthopnea

ventilation that exceeds metabolic demand (PaCO2 <35mHg at sea level)

hyperventilation

ventilation that does not meet metabolic demand (paCO2 >45mmHg at sea level)

hypoventilation

Initial: re-establish adequate oxygenation, prevent cardiac arrest

-establish airway, ventilation, supplemental oxygen

-put cats in oxygen cage ASAP

respiratory distress treatment

-pleural space disease

-asthma (cats++)

-pulmonary edema and contusion

-Pneumonia

-pulmonary thromboembolism

-laryngeal edema or paralysis

-foreign body

-aspiration

Respiratory distress be because of

Minimize cardiac work, improve oxygenation, resolve pulmonary edema (diuretics, vasodilators)

Acute cardiogenic edema

(increased capillary permeability)

-Oxygen is a key element, mechanical ventilation, cautious fluid therapy, only use diuretics and vasodilators if the patient is normovolemic, inotropic support

noncardiogenic edema

Emergency:

-oxygen

-corticosteroids as injection (dexamethasone)

-Bronchodilators (e.g., aminophylline IM or sloe IV, albuterol nebulized)

Acute Small airway disease (cat asthma)

Acute Small Airway Disease (cat asthma)

-Epinephrine (only temporary to avoid cardiac side effects)

-beta-adrenergic agonists (e.g., Terbutaline)

-Parasympatholitics (atropine)(only temporary to avoid inspissation of secretions)

If the first line of treatment fails or if severe respiratory distress

-is indicated for animals that are hypoxic from inadequate oxygenation (either animal is not ventilating properly or respiratory control is depressed)

-Remember oxygen is very dry

• this will reduce effectiveness of mucociliary apparatus by making the mucus less runny

• gas should be humidified

-Using an oxygen cage is preferable to mask in animals that are not recumbent or markedly depressed because they may fight the mask (increase heart rate, increase demand by heart for oxygen which is not available → heart problem)

Oxygen

-life threatening form of respiratory failure (e.g. acute lung injury, noncardiogenic pulmonary edema)

• severe respiratory distress refractory to supplemental oxygen

• clinical signs of severe pulmonary edema and inflammatory response

Acute respiratory distress (ARDS)

-correct hypoxemia (mechanical ventilation, transfusion), fluid and nutritional therapy)

-Furosemide IV (caution!) and vasodilators if capillary pressure increases

Acute respiratory distress (ARDS) treatment

-oxygen therapy, rapidly acting corticosteroids, cough suppressants and light tranquilization

Collapsing trachea emergency care

-airway dilators (aminophylline, theophylline), cough suppressant (hydrocodone with homatropine), antibiotics only if indicated

collapsing trachea long term treatment

-antibiotics

-bronchodilators (e.g., methylxanthine derivatives, theophylline or aminophylline, beta 2 - adrenergic agonists sometimes administered by inhalation)

-NSAIDs to control hyperthermia (in case of severe pneumonia)

-oxygen delivery (when severe hypoxia)

-Nutrition supplementation if not nursing

foal pneumonia example of treatment

upper respiratory tract expels foreign objects (dust foreign bodies) by what?

sneezing and excessive nasal mucus production (runny nose)

stimulation of larynx, trachea, bronchi, and larger bronchioles elicits a what response

coughing response

-vocal folds in the larynx can slam shut if anything stimulated the larynx (laryngospasm)

-trachea and larger bronchioles have a sheet of sticky mucus that traps particles

-constriction of bronchioles (bronchospasm)

-macrophages engulf particles in alveoli

Respiratory protective mechanisms

-Parasympathetic system (muscarinic receptors, increase in cGMP)

-Histamine (mild impact)

-can be induced by stimulation of irritant receptors

-reduced airway diameter (smooth muscle contraction), impaired gas exchange

Bronchoconstriction

-sympathetic system (beta 2 - receptor stimulation, increase in cAMP)

-increases airway diameter, improved gas exchange

Bronchodilation

Blocking B2receptors allows parasympathetic to dominate →

constriction

Blocking cholinergic receptors allow sympathetic domination →

dilation

-Other inflammatory mediators cause bronchoconstriction: prostaglandins, leukotrienes,

Serotonin plays a role in cat asthma but little in dog bronchoconstriction

Histamine plays a minor role (less effect than what we used to think)

Pathophysiology of Bronchoconstriction

The cells lining the trachea, bronchi, and the larger bronchioles have ciliated epithelium

-mucus glands excrete sticky mucus onto the surface of the epithelial cells to form a sheet covering the cilia

-particles inhaled land on the sticky mucus (like fly paper)

-the cilia sweep the mucus up to the larynx where the mucus is expelled or swallowed

-the mucus sheet + the ciliated epithelium = mucociliary apparatus or mucociliary elevator

Mucociliary Apparatus

Mucociliary system:

-secretory action and mechanical action

-ciliary action (secretory and mechanical) increased by beta-receptor agonists

-Secretory action also induced by muscarinic stimulation

Defense Mechanism

-protects against infection

-comprised of monocytes, macrophages and dendritic cells

-releases mediators of inflammation → decrease in airway diameter

Respiratory mononuclear phagocyte system

four types: synergistic approach

1.Modify airway resistance

2.Increase respiratory secretions

3.Suppress the cough reflex

4.Stimulate respiration

treatment

-to improve delivery of air to the terminal portions of the respiratory tree

-to eliminate obstruction due to excessive and secretions, edema of the mucosa and spasms

treatment: modification of airway resistance

what are the most effect bronchodilator, regardless of stimulus?

Beta-adrenergic agonists and anticholinergic agents

-act on smooth muscle (reverse contraction) and decrease mucosal edema

-anti-inflammatory action (decrease release of inflammatory)

Beta-adrenergic agonists

Bronchodilators also act on:

Bronchodilation, increase watery secretion (less viscous) and rate of ciliary movement. Only beta2-receptors in airways!

Beta 2 receptors

Bronchodilators also act on:

inotropic and chronotropic effect, relaxation of GI tract (results in the side effects of this drug class)

Beta 1 receptors

Decongestants:

• induce vascular smooth muscle constriction

• Decrease capillary blood flow in the bronchial mucosa = decreased edema

alpha-adrenergic agonists