Dr. Jibachha Sah,M.V.Sc( Veterinary pharmacology, TU,Nepal),posted lecturer notes on AUTONOMIC AND SYSTEMIC PHARMACOLOGY for B.V.Sc & A.H. 6 th semester veterinary students of College of veterinary science,Nepal Polytechnique Institute, Bharatpur, Bhojard, Chitwan, Nepal.I hope this lecture notes may be beneficial for other Nepalese veterinary students. Please send your comment and suggestion .Email:jibachhashah@gmail.com,moble,00977-9845024121

1. Respiratory stimulants, bronchial
dilators
Dr. Jibachha Sah
M.V.Sc (Pharmacology)
College of veterinary science, NPI,
Bhojard, Chitwan

2. Respiratory stimulants
DEFINITION
It is defined as "the drug or chemical agent which
is used to stimulate the respiratory system or restore the normal
respiration when lungs are unable to eliminate sufficient amount
of carbon dioxide and unable to take sufficient amount of oxygen
molecule are collectively known as respiratory stimulant.

3. • It include the class of those drug which is used to
stimulate the CNS i.e Central nervous system of the body,
hence it is known as CNS stimulator
•It Also stimulate the chemo receptor and vasomotor
center (regulates blood vessel diameter ) of the body
•As the drug act as a irritating agent therefore it irritate
the epithelial layer of the air passage such as bronchi,
trachea and lungs which leads to respiratory stimulation

4. Mechanism of Action
Produces respiratory stimulation in medulla (which propagates
stimulation to other parts of brain & spinal cord) through peripheral
carotid chemoreceptors.
Pharmacokinetics
Onset: 20-40 sec
Duration: 5-12 min (single IV injection)
Peak Plasma Time: 1-2 min
Half-life: 3.4 hr (2.4-4.1 hr)
1. Doxapram
Example of Respiratory Stimulant Drugs

5. Dosages:
1–5 mg/kg, IV, in dogs and cats, or 1–2 drops under the tongue of
apneic neonates.
In adult horses, the dosage is 0.5–1 mg/kg, IV, while foals are
dosed carefully at 0.02–0.05 mg/kg/min, IV.

6. BRAND FORM.
Dopram
20 mg/mL
solution
doxapram
20 mg/mL
solution

7. Caffeine
Mechanism of Action
Methylxanthine; promotes cAMP (Cyclic adenosine monophosphate )accumulation
by inhibiting phosphodiesterase; increases medullary respiratory center sensitivity
to carbon dioxide; may prevent apnea by acting as an adenosine receptor
antagonist.
The CNS stimulant action of these drugs also contributes to improved respiratory
function, as also the improvement in circulatory and renal function in cardiac
asthma of dogs.
·

8. Pharmacokinetics
●Half-Life: 72-96hr
●Peak plasma time: 30-120 min
●Peak plasma concentration: 1.5-1.8 mcg/mL
●Protein Bound: 17-36%
●Vd: 0.6-0.9 L/kg
●Metabolism: hepatic CYP1A2
●Excretion: Urine

9. Dose:
Respiratory Failure
Caffeine and sodium benzoate: 250 mg IV/IM once

10. Bronchial dilators
A bronchodilator is a substance that dilates the bronchi and bronchioles, decreasing
resistance in the respiratory airway and increasing airflow to the lungs.
They make breathing easier for people with asthma or other lung conditions.
Bronchodilators include
(i) short acting beta2-agonists such as albuterol,
(ii) long-acting beta2-agonists (such as salmeterol, formoterol),
(iii) anticholinergic agents (eg, ipratropium) and theophylline.

11. The 3 most widely used bronchodilators are:
(i) beta-2 agonists, such as salbutamol, salmeterol, formoterol and vilanterol.
(ii) anticholinergics, such as ipratropium, tiotropium, aclidinium and glycopyrronium.
(iii) theophylline.

12. (i) Beta-2 agonists
Example: epinephrine, salbutamol, levosalbutamol, isoprenaline
●Beta-2 agonists are available in short-acting and long-acting varieties, and are
usually taken through an inhaler.
● They relax the muscles in the lungs, which allows the airways to widen. Long-
acting beta-2 agonists can also reduce the amount of mucus in the lungs by
speeding up the motion of cilia. Cilia are tiny hairs that line the walls of airways
and help 'sweep' mucus out of the airways.
● Beta-2 agonists tend to be more effective in treating asthma than in treating
chronic obstructive pulmonary disease (COPD)

13. Mechanism of action
●Activation of β adrenergic receptors leads to relaxation of smooth muscle in the
lung, and dilation and opening of the airways.
● β adrenergic receptors are coupled to a stimulatory G protein of adenylyl
cyclase. This enzyme produces the second messenger cyclic adenosine
monophosphate(cAMP).
● In the lung, cAMP decreases calcium concentrations within cells and
activates protein kinase A. Both of these changes inactivate myosin light-chain
kinaseand activate myosin light-chain phosphatase.
● In addition, β2 agonists open large conductance calcium-activated potassium
channels and thereby tend to hyperpolarize airway smooth muscle cells.
● The combination of decreased intracellular calcium, increased membrane
potassium conductance, and decreased myosin light chain kinase activity leads to
smooth muscle relaxation and bronchodilation.

14. Dose
Albuterol for Dogs and Cats
●In dogs and cats, a conservative oral dose is 0.025 mg per pound (0.05 mg/kg)
given up to 4 times a day, as tolerated.
● The common method of use of albuterol in cats is by aerosol. The aerosolized
form in cats, with feline asthma, a pediatric spacer and a standard albuterol
inhaler are used; the typical dose is two “puffs” of albuterol into the spacer,
then allowing the cat to breathe through the mask for 10 to 15 seconds. The
does is repeated every four to six hours, as necessary and as tolerated.

15. Adverse effects
β2 stimulants, especially in parenteral administration such as inhalation or injection, can
induce adverse effects:
●Tachycardia secondary to peripheral vasodilation and cardiac stimulation; tachycardia can
be accompanied by palpitations
● Tremor, excessive sweating, anxiety, insomnia, and agitation
● More severe effects, such as pulmonary edema, myocardial ischemia, and cardiac
arrhythmia, are exceptional.

16. (ii) Anticholinergic drugs
Anticholinergic drugs block the action of a neurotransmitter called acetylcholine
This inhibits nerve impulses responsible for involuntary muscle movements and
various bodily functions. Examples of these drugs include
◘Atropine (Atropen) ◘ Belladonna alkaloids
◘ Benztropine mesylat ◘ Glycopyrrolate
◘ Homatropine hydrobromide ◘ Hyoscyamine
◘ Ipratropium ◘ Mmethscopolamine
Anticholinergics can treat a variety of conditions, including:
● urinary incontinence
● overactive bladder (OAB)
● chronic obstructive pulmonary disorder (COPD)
● certain types of poisoning

17. Mechanism of action
Anticholinergics block acetylcholine from binding to its receptors on certain nerve
cells. They inhibit actions called parasympathetic nerve impulses.
These nerve impulses are responsible for involuntary muscle movements in the:
●gastrointestinal tract
● lungs
● urinary tract
● other parts of your body
The nerve impulses help control functions such as:
● salivation
● digestion
● urination
● mucus secretion

18. Dosage Information
i) Dogs & Cats
(1) 0.02 to 0.04 mg/kg (0.01 to 0.02 mg/lb) IV, IM, SC
(a) This works out to 1 cc per 10 to 20 kg (20 to 40 lb)

19. Blocking acetylcholine signals can decrease:
●involuntary muscle movement
● digestion
● mucus secretion
Side effects :
● dry mouth ● blurry vision
● Constipation ● drowsiness
● Sedation ● hallucinations
● memory problems ● trouble urinating
● Confusion ● delirium
● decreased sweating ● decreased saliva

20. (iii) Theophylline.
Theophylline is a long-acting bronchodilator that is usually used in the treatment
of COPD. Exactly how theophylline works is unclear, but it seems to relax the
muscles in the lungs, while reducing any possible inflammation (swelling) in the
airways.
Theophylline is also used to treat both dogs and cats with collapsing trachea, intrathoracic
airway collapse and pulmonary edema.

21. ● Derivatives of theophylline with superior pharmacokinetic properties are now
preferred.
● Aminophylline, diprophylline and etamiphylline given by slow intravenous,
intramuscular or subcutaneous injection are effective in reducing airway
resistance in acute bronchoconstriction.
● Aminophylline is more soluble than theophylline and is better absorbed.

22. CORTICOSTEROIDS
●The reduction of mucosal edema in bronchi and bronchioles can be achieved by
use of glucocorticoids to suppress the inflammatory response.
● In man the corticosteroids are used for severe, disabling, bronchodilator-
resistant asthma.
● These may be administered orally, parenterally or as an aerosol.
● Corticosteroids can be used with advantage to control chronic allergic-type
summer coughs in dogs either by the oral administration of prednisolone or by
the use of injectable depot preparations.

23. NSAIDS
●The introduction of NSAIDs with high antiinflammatory potency has made this
group beneficial as adjuncts along with antimicrobials.
● They lack the suppression of the immune response seen with the corticosteroids
.
● Their ability to suppress the production of the chemical mediators of the
inflammatory response underlies their ability to reduce structural damage and
functional impairment in the pneumonic lung.
● Ventilation, gaseous exchange and pulmonary haemodynamics can all be
improved by NSAID administration.
● Flunixin is especially recommended for this purpose.