The document discusses drugs related to the respiratory system. It covers several classes of drugs including bronchodilators, corticosteroids, antihistamines, and cough preparations. Bronchodilators such as beta-2 agonists, antimuscarinic agents, and xanthine derivatives are used to relieve bronchospasm. Corticosteroids are used to reduce inflammation and include inhaled and systemic formulations. The document provides examples of drugs in each class, their mechanisms of action, dosages, and adverse effects.

1. Drugs related to Respiratory
System
1
SPEAKER: Dr. Vamshidhar
MODERATOR: Dr.Dilip sir
Department of anaesthesiology
Esic medical college
hyderabad

2. Introduction
• The respiratory system is subjected to many disorders that interfere
with respiration and other lung functions, including
• Respiratory tract infections
• Allergic disorders
• Inflammatory disorders
• Conditions that obstruct airflow (e.g. asthma and chronic
obstructive pulmonary disease, COPD)
2

3. • Drugs that act on the respiratory system include
• Bronchodilators
• Corticosteroids
• Cromoglycates
• Leukotriene receptor antagonists
• Antihistamines
• Cough preparations
• Nasal decongestants
3

4. Bronchodilators
• Drugs used to relieve bronchospasms associated with
respiratory disorders
• Includes:
• Adrenoceptor agonists
• Selective β2-agonists & other adrenoceptor agonists
• Antimuscarinic bronchodilators
• Xanthine derivatives
4

5. Adrenoceptor agonists
• (i) Selective beta2 agonists
• Stimulate beta2 receptors in smooth muscle of the lung, promoting
bronchodilation, and thereby relieving bronchospasms
• They are divided into short-acting & long acting types
• MOA
• causes a stimulatory G protein to activate adenylate cyclase
converting adenosine triphosphate (ATP) into cyclic adenosine
monophosphate (cAMP). It causes smooth muscle relaxation
5

6. • Longer acting β2 agonists have unique properties that allow for a longer
duration of action.
• For example, salmeterol has a longer duration of action because a side
chain binds to the β2-receptor and prolongs the activation of the receptor.
• The lipophilic side chain of formoterol allows for interaction with the lipid
bilayer of the plasma membrane and a slow, steady release prolonging its
duration of action.
• Short-acting β2 agonist therapy is effective for the rapid relief of wheezing,
bronchospasm, and airflow obstruction.
• Longer acting β2 agonists are used as maintenance therapy providing
improvement in lung function and reduction in symptoms and exacerbations
6

7. 7

8. DOSAGES
Drug Formulation Dosage
Adult Child
Salbutamol Oral tablet (C.R) 8 mg twice daily 4 mg twice daily
Inhaler (MDI), 100mcg/dose 100-200mcg up to three to
four times daily
Same as adult
Syrup, 2mg/5ml 4 mg three to four times
daily
1-2 mg three to four times
daily (≥2 yr)
Terbutaline Oral tablet (S.R) 5-7.5 mg two times daily -
Inhaler 500mg / dose
( Turbuhaler)
500 mcg up to four times
daily
-
Inhaler 250mg / dose (MDI) 250-500mcg up to 3-4 times
daily
Same as adult
8
Short-acting β-2 agonists

9. Formoterol Inhaler 4.5mcg / dose
(Turbuhaer)
4.5-9 mcg once or twice
daily
Same as adult
Inhaler 9mcg / dose
(Turbuhaer)
Salmeterol Inhaler 25mcg / dose
(MDI)
50-100 mcg twice daily Same as adult
50 mcg / dose (Accuhaler) 50 mcg twice Same as adult
9
Long-acting β-2 agonists
Adverse effects
Tachycardia and palpitations
Headache
Tremor

10. Bronchodilators
• (ii) Other adrenoceptor agonists
• Less suitable & less safe for use as bronchodilators because they are more likely to cause arrhythmias & other
side effects
• Ephedrine
• MOA: Activates alpha and beta receptors and by inhibiting nor adrenaline reuptake
• Adults: 15-60 mg tid po
• Child: 7.5-30 mg tid po
• Adrenaline (epinephrine) injection is used in the emergency treatment of acute allergic and anaphylactic
reactions.
• I.V administration for anaphylaxis requires the use of a 1:10000 adrenaline solution.
• IM injection of Adrenaline 1/1000 (1mg/ml) may be administered
• In acute severe asthma: 0.01 mg/kg divided into 3 doses of approximately 0.3 -0.5 mg every 20 minutes
10

11. Antimuscarinic bronchodilators
• Blocks the action of acetylcholine in bronchial smooth muscle
mediated by M3 receptor, this reduces intracellularGMP, a
bronchoconstrictive substance
• Used for maintenance therapy of bronchoconstriction associated
with chronic bronchitis & emphysema
11

12. Inhaled Cholinergic Antagonists
• There are two inhaled anticholinergics specifically approved for the treatment of obstructive airway diseases.
• Adverse effects:
• Dry mouth
• Nausea
• Constipation
• Headache
12
Ipratropium
as therapy for COPD and
as rescue therapy for
both COPD and asthmatic
exacerbations.
Inhaler 20 mcg / dose
(MDI)
Inhaler 18 mcg /dose
Tiotropium
Long acting
reduce COPD exacerbations, respiratory failure
Inhaler 18 mcg /dose
18 mcg daily

13. Systemic Cholinergic Antagonists
• The systemically administered anticholinergics atropine and glycopyrrolate act via the
same mechanisms as inhaled anticholinergics.
• While these anticholinergics can be administered by IV or inhalation, significant
systemic absorption occurs and their use is generally limited by side effects.
• Atropine, in particular, is limited in use because of its tertiary ammonium structure.
• It has a tendency to cause tachycardia, gastrointestinal upset, blurred vision, dry
mouth, and central nervous system effects secondary to its ability to cross the blood–
brain barrier.
• Glycopyrrolate has a quaternary ammonium structure and is insoluble in lipids, similar
to ipratropium and tiotropium, and has fewer systemic side effects than atropine.
• IV glycopyrrolate is also clinically limited in use secondary to side effects.
• Glycopyrrolate as inhaled therapy, however, an effective bronchodilator with an
intermediate duration of action.
13

14. • The ANS also influences bronchomotor tone through the nonadrenergic
noncholinergic (NANC) system.
• It has excitatory and inhibitory neuropeptides that influence
inflammation and smooth muscle tone, respectively.
• Vasoactive intestinal peptide (VIP) and nitric oxide (NO) are the main
inhibitory transmitters thought to be responsible for airway smooth
muscle relaxation.
• Substance P (SP) and neurokinin A (NKA) are the main excitatory
transmitters and have been shown to cause neurogenic inflammation,
including bronchoconstriction.
14

15. Xanthine Derivatives
• Xanthine used clinically is theophylline
• Theophylline is a bronchodilator which relaxes smooth muscle of the
bronchi, it is used for reversible airway obstruction
• Mechanism of action:
• Theophylline is a weak non-selective inhibitor of PDEs, which break
down cyclic nucleotides in the cell, thereby leading to an increase in
intracellular cyclic 3'5' adenosine monophosphate (AMP) and cyclic
3',5' guanosine monophosphate (GMP) concentrations
• It leads to bronchodilation
15

16. Drug Formulation Dosage
Adult Child
Theophylline Tablet 200 / 300 mg
(S.R.)
200 – 300 mg twice daily 10 mg / kg ((≥2yrs) twice
daily
Aminophylline Injection 25 mg / ml
10 ml
500 mcg / kg / hr IV infusion,
adjust when necessary
1 mg / kg /hr (6 months – 9
years)
800 mcg / kg /hr (10 – 16 yrs)
IV infusion, adjust when
necessary
16
ACUTE BRONCHOSPASM: loading dose of 4.6mg/kg via infusion over 30 mins
F/B 0.4 mg/kg/hr maintenance dose
Adverse effects:
Toxicity is related to theophyline levels (usually 5-15 µg/ml)
20-25 µg/ml : Nausea, vomiting, diarrhea, insomnia, restlessness
>30 µg/ml : Serious adverse effects including dysrhythmias, convulsions,
cardiovascular collapse which may result in death

17. Corticosteroids
• Used for prophylaxis of chronic asthma
• Suppressing inflammation
• Decrease synthesis & release of inflammatory mediators
• Decrease infiltration & activity of inflammatory cells
• Decrease edema of the airway mucosa
• Decrease airway mucus production
• Increase the number of bronchial beta2 receptors & their responsiveness to beta2 agonists
• Mechanism of action:
• The glucocorticoid receptor alpha (GRα) located in the cytoplasm of airway epithelial
cells is the primary target .
• activation or suppression of gene products at a transcriptional level and alteration of
chromatin structure
17

18. Inhaled Corticosteroids
• In the treatment of asthma, the use of inhaled corticosteroids (ICS)
reduces the inflammatory changes associated with the disease,
thereby improving lung function
• In COPD, ICS are used as a part of combination therapy along with
long-acting β-adrenergic agonists (LABA) reduces inflammation.
• Currently, combination therapy of ICS and LABA is recommended for
use in severe to very severe COPD.
• Adverse effects:oropharyngeal candidiasis, pharyngitis, easy bruising,
osteoporosis, cataracts, elevated intraocular pressure, dysphonia,
cough, and growth retardation in children
18

19. Systemic Corticosteroids
• Systemic corticosteroids given in IV or oral form are used for treatment of
asthma and COPD exacerbations.
• Patients that are hospitalized with a COPD exacerbation will typically
receive IV corticosteroids to suppress any inflammatory component that
may be contributing to the flare up.
• In asthma, corticosteroids are recommended for exacerbations that are
either severe, with a peak expiratory flow of less than 40% of baseline, or
a mild to moderate exacerbation with no immediate response to short-
acting β- adrenergic agonists.
• Side effects :
• Hypertension, hyperglycemia, adrenal suppression, increased infections,
cataracts, dermal thinning, psychosis, and peptic ulcers
19

20. DOSAGE
Drug Formulation Dosage
Adult Child
Beclomethason
e
Inhaler 50 mcg / dose
(MDI)
200 mcg twice daily /
100mcg three to fours
times daily
Up to 800 mcg daily
50 – 100 mcg two to four
times daily
Inhaler 250 mcg / dose
(MDI)
500 mcg twice daily / 250
mcg four times daily
Not recommended
20
Budesonide Inhaler 50 mcg / dose (MDI) 200 mcg twice daily
Up to 1.6 mg daily
50 – 400 mcg twice daily
Up to 800 mcg daily
Inhaler 200mcg / dose (MDI)
Inhaler 100 mcg / dose
(Turbuhaler)
200-800 mcg once daily in
evening
Up to 1.6 mg daily in two
divided doses
200-800 mcg daily in two
divided doses / 200-400
mcg once daily in
evening
(<12 yrs)
Inhaler 200 mcg / dose
(Turbuhaler)
Inhaler 400 mcg / dose
(Turbuhaler)

21. Corticosteroids
Drug (Cont’d) Formulation Dosage
Adult Child
Fluticasone Inhaler 25mcg / dose (MDI) 100 – 1000 mcg
twice daily
50-100 mcg twice daily
(4-16 yrs)
Inhaler 50 mcg / dose (MDI)
Inhaler 125 mcg / dose (MDI)
Inhaler 250 mcg / dose (MDI)
Inhaler 50 mcg / dose (Accuhaler)
Inhaler 100 mcg / dose (Accuhaler)
Inhaler 250 mcg / dose (Accuhaler)
21
Acute attacks of asthma should be treated with short courses of oral
corticosteroids, starting with a high dose for a few days

22. Intranasal Corticosteroids
• Most effective for treatment of seasonal and perennial rhinitis
• Have anti inflammatory actions and can prevent or suppress all
major symptoms of allergic rhinitis including congestion,
rhinorrhea, sneezing, nasal itching and erythema
22

23. Intranasal Corticosteroids
Drug Formulation Dosage
Adult Child
Beclomethasone
Dipropionate
Nasal Spray 50 mcg /
dose
1 spray in each nostril
four times daily
Max. 10 sprays / day
4-6 sprays / day
Nasal Spray 50 mcg
dose (Aqueous)
2 applications into
each nostril twice to
four times daily
Max. 400 mcg daily
Same as adult (>6 yrs)
Not recommended in
children <6yrs
23

24. Intranasal Corticosteroids
Drug (Cont’d) Formulation Dosage
Adult Child
Budesonide Nasal Spray 50 mcg /
dose (Aqueous)
1-2 sprays into each
nostril twice daily; after
2-3days: 1 spray into
each nostril twice daily
Not recommended for
age 12 yrs or below
Turbuhaler 100mcg /
dose
400 mcg in the morning
given as 2 applications
into each nostril; then
reduce to the smallest
amount necessary
-
24
Fluticasone Nasal Spray 50 mcg /
dose (Aqueous)
2 sprays into each
nostril in the morning
Max: 8 sprays/day
1 spray into each nostril
in the morning (4-11yrs)
Max: 4 sprays/day
Adverse effects:
Most common effects are drying of nasal mucosa & sensations of burning or
itching

25. Combination Products
• May be appropriate for patients stabilised on individual
components in the same proportion
• Muscarinic antagonist+β2 agonist
• Combivent (20mcg Ipratropium & 100mcg salbutamol
/dose, MDI)
• Corticosteroid+β2 agonist
• Symbicort (160mcg Budesonide+4.5mcg Formoterol /
dose, Turbuhaler)
• Seretide (Salmeterol+Fluticasone: MDi in Lite, Medium,
Forte preparation & Accuhaler)
25

26. Mast Cell Stabilizers
• Cromolyn sodium and nedocromil are the two agents in this category
• They stabilize submucosal and intraluminal mast cells.
• MECHANISM OF ACTION: acts by inhibiting the release of histamine and
leukotrienes from the mast cell , that cause bronchoconstriction, mucosal
edema, and increased mucus secretion
• These agents are delivered by powder inhaler and are not first-line
therapy for asthma.
• Cromolyn sodium and nedocromil may be used as preventative
treatment before exercise or known allergen exposure causing
symptoms of asthma.
• Side Effects: gastrointestinal upset and coughing or irritation of the
throat.
26

27. Drug Formulation Dosage
Adult Child
Cromoglycate Na Inhaler (1 mg
& 5mg/dose)
10 mg four times daily, may be
increased to six to eight times
daily
Same as adult
Nebuliser
solution 10 mg
/ ml
20 mg four times daily, may be
increased six times daily
Same as adult
Nedocromil
Sodium
Inhaler 2 mg /
dose (MDI)
4 mg two to four times daily Sames as adult (>6
yrs)
27

28. Leukotriene receptor antagonists
• MECHANISM OF ACTION :Act by suppressing the effects
of leukotrienes, compounds that promote
bronchoconstriction as well as eosinophil infiltration,
mucus productions, & airway edema
• Help to prevent acute asthma attacks induced by
allergens & other stimuli
• Indicated for long-term treatment of asthma
28

29. • Dosage:
• Montelukast (5 & 10 mg tablets)
• Adult: 10 mg daily at bedtime
• Adverse effects:
• GI disturbances
• Hypersensitivity reactions
• Restlessness & headache
• Upper respiratory tract infection
29

30. Antihistamines
• H1 receptor antagonists
• Inhibit smooth muscle constriction in blood vessels & respiratory & GI tracts
• Decrease capillary permeability
• Decrease salivation & tear formation
• Used for variety of allergic disorders to prevent or reverse target organ
inflammation
• Non-selective/sedating
• Bind to both central & peripheral H1 receptors
• Usually causeCNS depression (drowsiness, sedation)
• Also have substantial anticholinergic effects
30

31. Antihistamines
Drug Dosage
Adult Child
Chorpheniramine (4
mg tablet, 2mg/ml
Elixir & expectorant)
4 mg q4-6hr, max: 24 mg daily 1-2yrs: 1 mg twice daily
2-12yrs: 1- 2 mg q4-6h, Max:12 mg daily
Hydroxyzine (25 mg
tablet)
25 mg at night; 25mg three to
four times daily when necessary
6 months-6yrs: 5-15 mg daily; 50 mg daily in
divided dose if needed
>6yrs: 15-25 mg daily; 50-100 mg daily in
divided dose if needed
Diphendramine (10
mg/5ml Elixir)
25-50 mg q4-6h 6.25-25 mg q4-8 hr ( >1 yr)
31
Promethazine (10 &
25 mg tablets,
5mg/5ml Elixir)
25 mg at night; 25 mg twice
daily if needed
2-10yrs: 5-25 mg daily in 1 to 2 divided dose
Azatadine (1 mg
tablet)
1 mg twice daily 1-12 yrs: 0.25-1 mg twice daily

32. Antihistamines
• Adverse effects:
• Sedation
• Dry mouth
• Blurred vision
• GI disturbances
• Headache
• Urinary retention
• Hydroxyzine is not recommended for pregnancy & breast-
feeding
32

33. Antihistamines
• Second-generation H1 receptor antagonists
• Selective/non-sedating
• Cause less CNS depression because they are selective for
peripheral H1 receptors & do not cross blood-brain barrier
• Longer-acting compared to first-generation antihistamines
33

34. Antihistamines
Drug Dosage
Adult Child
Acrivastine 8 mg three times daily Not recommended
Cetirizine 10 mg daily 5 mg daily / 2.5 mg twice daily (2-6 yrs)
Desloratadine 5 mg daily 1.25 mg daily (2-5 yrs)
2.5 mg daily (6-11yrs)
Fexofenadine 120-180 mg daily Not recommended
Loratadine 10 mg daily` 5 mg daily (2-5 yrs)
34
Adverse effects:
 May cause slight sedation
 Some antihistamines may interact with antifungal, e.g. ketoconazole; antibiotics,
e.g. erythromycin; prokinetic drug-- cisapride, leading to potentially serious ECG
changes e.g. Terfenadine

35. Cough preparations
• There are three classes of cough preparations:
• Antitussives
• Expectorants
• Mucolytics
35

36. • Antitussives
• Drugs that suppress cough
• Some act within the CNS, some act peripherally
• Indicated in dry, hacking, nonproductive cough that interfere with
rest & sleep
36
Drug Dosage
Codeine phosphate 25mg/5ml syrup 15-30 mg three to four times daily
Pholcodine 5mg/5ml Elixir 5-10 mg three to four times daily
Dextromethorphan 10mg/5ml in Promethazine
Compound Linctus
10-30 mg q4-8h
Diphenhydramine 10 mg/ 5ml 25 mg q4h, Max:150 mg daily

37. Cough preparations
• Adverse effects:
• Drowsiness
• Respiratory depression (for opioid antitussives)
• Constipation (for opioid antitussives)
• Preparations containing codeine or similar analgesics are
not generally recommended in children & should be
avoided altogether in those under 1 year of age
37

38. Cough preparations
• Expectorants
• Render the cough more productive by stimulating the flow of respiratory tract secretions
• Guaifenesin is most commonly used
• Available alone & as an ingredient in many combination cough & cold remedies
• Dosage
• Guaifenesin
• 100-400 mg q4h po
• Ammonia & Ipecacuaha Mixture
• 10-20 ml three to four times daily po
38

39. • Mucolytics
• Reacts directly with mucus to make it more watery.This should
help make the cough more productive
• Dosage
• Acetylcysteine
• 100 mg two to four times daily
• Bromhexine
• 8-16 mg three times daily po
• Carbocisteine
• 750 mg three times daily, then 1.5 g daily in divided doses
39

40. Nasal Decongestants
• Sympathomimetics are used to reduce nasal congestion
• Stimulate alpha1-adrenergic receptors on nasal blood
vessels, which causes vasoconstriction & hence shrinkage
of swollen membranes
• Topical administration:
• Response is rapid & intense
• Oral administration:
• Response are delayed, moderate & prolonged
40

41. Nasal Decongestants (Cont’d)
Drug Formulation Dosage
Adult Child
Oxymetazoline Nasal Drops 0.025% 20 ml - 2-3 drops q12h (2-5 yrs)
Nasal Spray 0.05% 15 ml 2-3 sprays q12h Same as adults for
children >6 yrs
Phenylephrine Nasal Drops 0.5% 10 ml 5 -7 drops q2-4h -
Xylometazoline Nasal Drops 0.05% / 0.1% 2-3 drops q8-10h (0.1%) 2-3 drops q8-10h (2-12
yrs) (0.05%)
41

42. • Adverse effects:
• Rebound congestion develops with topical agents when
used for more than a few days
42

43. Influence of Anesthetics on the
Airways
• Volatile Anesthetics
• Volatile anesthetics reduce bronchomotor tone and all commonly used
volatile anesthetics except desflurane, produce a degree of
bronchodilatation that may be helpful in patients with obstructive lung
disease or in patients that experience any degree of
bronchoconstriction.
• Volatile anesthetics likely induce bronchodilation by decreasing
intracellular calcium, partly mediated by an increase in intracellular
cAMP and by decreasing the sensitivity of calcium mediated by protein
kinase C.
• The effect is seen to a greater degree in distal airway smooth muscle
secondary to the T-type voltage-dependent calcium channel, which is
sensitive to volatile anesthetics.
43

44. Intravenous Anesthetics
• IV anesthetics can decrease bronchomotor tone when used for induction
• Ketamine, propofol, and midazolam have relaxant effects on airway smooth muscle.
• Etomidate and thiobarbiturates do not affect bronchomotor tone to the same extent.
• Ketamine is thought to have a direct relaxant effect on smooth muscle.
• Propofol is thought to reduce vagal tone and have a direct effect on muscarinic receptors by
interfering with cellular signaling and inhibiting calcium mobilization.
• The preservative metabisulfite in propofol prevents the inhibition of vagal-mediated
bronchoconstriction.
• The use of these IV agents for induction or maintenance of anesthesia over other agents
can be useful in minimizing the intraoperative effects of bronchospasm.
• The use of ketamine is associated with increased salivation and coadministration of a small
dose of anticholinergic can attenuate secretion production.
• Propofol is associated with hypotension that usually is easily corrected with vasopressors.
44

45. Local Anesthetics
• Local anesthetics are primarily used to blunt the hemodynamic
response to tracheal intubation.
• The use of local anesthetics as pure bronchodilators is limited by
toxicity and the ready availability of more potent bronchodilators such
as short-acting β-adrenergic agonists
45

46. 46
Influence of Adjunctive Agents on the Airway
Helium-oxygen mixtures
 It is useful as short-term temporizing therapy to decrease the work of breathing
in patients with upper airway obstruction.
 The use of helium-oxygen mixtures is limited by a progressive reduction in
efficacy at higher inspired oxygen concentrations.
Magnesium sulfate.
 Magnesium sulfate produces additional bronchodilation when given in
conjunction with standard therapy for asthma exacerbations.
 The combination of nebulized magnesium sulfate and β- adrenergic agonists
have shown benefit in asthma exacerbations.
 Overall, magnesium sulfate, IV or nebulized, is not a first-line therapy for
asthma exacerbations and should be reserved for situations when the patient is
not responding to conventional therapy.

47. Pulmonary Hypertension
• They have poor cardiorespiratory reserve and are at risk of having
perioperative complications including pulmonary hypertensive crises
with resultant heart failure, respiratory failure, and dysrhythmias.
• Reducing the consequences of an elevated pulmonary vascular
resistance and the resulting right ventricular dysfunction should be
considered as the primary goal of therapy with pulmonary vasodilators.
47

48. • ETOMIDATE: In patients with cardiac disease, an induction dose of
etomidate increases mean arterial pressure (MAP), decreases SVR,
and decreases PAP.
• OPIODS : Opioids seem to have little to no deleterious effects on the
pulmonary vascular system.
• Under anaesthesia, administration of morphine, fentanyl, remifentanil,
and sufentanil causes a vasodilatory response
• The mechanism seems to involve histamine and opioid-mediated
receptor pathways.
48

49. Volatile anaesthetic agents
• Volatile anesthetics have little to no direct vasodilating effect on the pulmonary
vasculature.
• Nitrous oxide is typically avoided in patients with PHTN as it is believed to cause
pulmonary vasoconstriction, perhaps via release of catecholamines from sympathetic
nerves supplying the pulmonary vasculature.
• MAGNESIUM:
• Magnesium is a vasodilator in both the systemic and pulmonary circulations.
• The mechanism of action of magnesium’s effects on vasodilation is likely through its
effects on membrane channels involved in calcium flux and through its action in the
synthesis of cAMP.
• It would appear to be an important cofactor for endothelial-dependent pulmonary
vasodilation..
49

50. Regional Analgesia
• Pain can increase PVR.
• Perioperative thoracic epidural analgesia (TEA) is commonly used in
abdominal and thoracic surgery. TEA may decrease PAP through
decreases in CO or via attenuation of the pulmonary sympathetic
outflow.
• The potential benefits of regional anesthesia in thoracoabdominal
surgery typically outweigh the risks of hypotension and right ventricular
dysfunction.
50

51. Pulmonary Vasodilators
• The ideal pulmonary vasodilator should have a rapid onset of action, a
short half-life, and produce regional pulmonary vasodilation.
• This would avoid systemic hypotension and the potential adverse effects on
ventilation-perfusion matching.
• In this regard, inhaled vasodilators are attractive as they preferentially
dilate ventilated alveoli and have less systemic effects.
• Nitric Oxide
• Inhaled nitric oxide (iNO) is preferentially delivered to ventilated lung units
leading to improved perfusion to alveoli that are able to participate in gas
exchange
51

52. Prostaglandins
• Prostanoids induce relaxation of vascular smooth muscle, inhibit
growth of smooth muscle cells
• Inhaled prostanoids involve an aerosol delivery mechanism that is
attached by a nebulizer to the ventilator circuit.
• Owing to the short half-life of epoprostenol, the drug must also be
continuously nebulized.
• As a result, changes of dose delivery with alterations in ventilator
volumes, FIO2, airway pressures.
• The synthetic prostanoids, treprostinil and iloprost require intermittent
administration.
52

53. Phosphodiesterase Inhibitors
• Phosphodiesterase inhibitors prevent the degradation of cGMP and
cAMP.
• cAMP and cGMP are activated by NO and are intermediaries in a
pathway that leads to vasodilation via the activation of protein kinases
and reduction in cytosolic calcium.
• Milrinone is an adenosine-3′, 5′-cAMP–selective phosphodiesterase
enzyme (PDE) inhibitor.
• When nebulized, it has been shown to produce relative reduction in
PVR compared to SVR.
• When milrinone is combined with inhaled prostacyclin, potentiation and
prolongation of the pulmonary vasodilatory effect occurs.
53

54. • Oral sildenafil and tadalafil is used in chronic PAH.
• Sildenafil: Dosage: 2.5mg or 10 mg TID administered as an iv bolus
inection
• 5mg BD PO
• Tadalafil: Dosage:40 mg OD PO
• In the acute setting, sildenafil has been demonstrated to enhance the
effects of inhaled NO
• The benefits of sildenafil in acute pulmonary embolism, cardiac
transplantation, and in patients with PHTN being considered for
pulmonary thromboendarterectomy have also been described.
54

55. 55
THANK YOU