Drugs used in asthma & COPD (Pharmacology)

In this section We describe drugs used in Asthma and COPD and Most of the slides are prescribed from Lippincott's Pharmacology. Other references include:
1. Kd triphati Pharmacology
2. Basic Pharmacology

1. Asst. Prof. Dr. Muhammad Haroon
MD, ECEA, MPH (JHSPH)

Head & Coordinator of MPH Program

Former Biochemistry Guest lecturer at SMS
medical college, India.
Email:[email protected]

2. Overview
e This chapter describes drugs used to treat:

— Asthma
- COPD

Respiratory Sys.
Pharmacology Part-1

3. Drugs used for Asthma

Respiratory Sys.
Pharmacology Part-1

4. Asthma

e Characterized clinically by recurrent bouts of:
- Shortness of breath
— Chest tightness
— Wheeze
- Cough (often associated)
e Other Characterizations:
- Physiologically
- Pathologically

Respiratory Sys.
Pharmacology Part-1

5. Characterization of Asthma

e Physiologically:
- Marked increase in bronchial responsiveness to inhaled
stimuli

e Pathologically:
- Lymphocytic, eosinophilic inflammation of the bronchial
mucosa
- Remodeling of the bronchial mucosa
- Hyperplasia of the cells & all structural elements of the

airway wall Respiratory Sys.
Pharmacology Part-1

6. Characterization of Asthma
Cont...........

© 2001 Encyelopaedia Britannica, Inc.

Anatomy of an Asthma Attack

larynx (voice box)
trachea (windpipe)

blood vessels
infitrated by inflarnanation
immune cells and sweling

decreased

contracted
smooth muscle

Respiratory Sys.
Pharmacology Part-1

normal airway obstructed airway

7. Characterization of Asthma
Cont...........

[A | Normal

Muscles of bronchi are
relaxed, allowing easy
airflow.

Respiratory Sys.
Pharmacology Part-1

8. Phases of Asthmatic Response

e Early phase:
- Onset and duration: 5-60 mins
- Mediated by: Histamine & Leukotrienes
- Pathology: Bronchial SM contraction, Edema, Thick
plugs of mucous
e Late phase:
- Onset and duration: 4-24 hrs
- Mediated by: Leukotrienes, Cytokines, Chemokines
- Pathology: Airflow obstruction $: Hyper responsiveness

Respiratory Sys.
Pharmacology Part-1

9. Goals of therapy in Asthma

e Reducing Impairment:
- Prevent Chronic and trouble some symptoms
- Require infrequent use
- Near Normal Pulmonary function
- Normal Activity level
- Expectations and satisfaction
e Reducing Risks:
— Prevent Recurrent Exacerbation
— Prevent progressive loss of lung function

Respiratory Sys.
— Less adverse effects Pharmacology Part-1

10. Classification of Asthma based on
Severity

Domains/Estimates Intermittent Persistent
Mild to ..
Moderate Severs
Daytime symptoms Monthly Weekly Daily
Nocturnal Less than Monthly to Nightly
awakening monthly weekly
Rescue ß, agonist Less than weekly | Weekly to daily | Several times a
use day
60 to 80 % of < 60 % of
*
PEF or FEVI > 80 % predicted predicted predicted
Treatment needed Occasional prn en + oe
to control asthma PB, only ADA
2 combination ocs
Respiratory Sys.

Pharmacology Part-1

11. Classification of Asthma based on
Severity Cont...........

BRONCHO- RESULTS OF PEAK LONG-TERMCONTROL | QUICK RELIEF OF
CLASSIFICATION | CONSTRICTIVE FLOW OR SYMPTOMS
EPISODES SPIROMETRY
Intermittent Cpe Me Near normal" No daily medication Short-acting B, agonist
More than 2
Mild persistent days per week, Near normal* Low-dose ICS Short-acting Pz agonist
not daily
Low-dose ICS + LABA Short-acting $, agonist
Moderate persistent Daily Certes of ol ICS/formoterolisan
pore Medium-dose ICS alternative
Medium-dose ICS +LABA Short-acting B, agonist
Severe persistent Continual Lese ion co OR ICS/formoterol is an
High-dose ICS + LABA alternative
Respiratory Sys.

Pharmacology Part-1

12. Characteristic

Nocturnal
symptoms /
awakening

Need for rescue /
“reliever”
treatment

Lung function
(PEF or FEV,)

Exacerbation

Controlled

(2 or less / week)

(2 or less / week)

Normal

Levels of Asthma Control

Partly controlled
(Any presentin any week)

More than
twice / week

More than
twice / week

< 80% predicted or
personal best (if known)
on any day

Uncontrolled

3 or more
features
of partly

controlled
asthma

present in
any week

‘One in any week
Respiratory Sys.
Pharmacology Part-1

13. Drugs used in Asthma

e Drugs used in asthma are:

P,-Adrenergic agonists
Corticosteroids
Leukotrienes modifiers
Cromolyn
Theophylline
Anti-muscarinic Agents
Monoclonal Antibodies

Respiratory Sys.
Pharmacology Part-1

14. Drugs used in Asthma Cont..

Box 15.4 Drugs use

Short-acting relievers
Inhaled ß, agonists (e.g. salbutamol (albuterol in USA),
terbutaline)

Long-acting relief/disease controllers
= Inhaled long-acting B. agonists (e.g. salmeterol,
formot

= Inhaled corticosteroids (e.g. beclometasone, budesonide,
fluticasone)

= Compound inhaled salmeterol and fluticasone

= Sodium lycate

= Leukotriene modifiers (e.g. montelukast, zafirlukast,
zileuton)

Other agents with bronchodilator activity

= Inhaled antimuscarinic agents (e.g. ipratropium,
‘oxitropium)

= Theophylline preparations

= Oral corticosteroids (e.g. prednisolone 40 mg daily)

Steroid-sparing agents

= Methotrexate

Ciclosporin
Intravenous immunoglobulin

= Anti-Ig& monoclonal antibody - omalizumab a

= er (p. 72), infliximab, jebrizumab Respiratory Sys.
Pharmacology Part-1

15. ß,-Adrenergic agonists

Respiratory Sys.
Pharmacology Part-1

16. Introduction

e These drugs selectively stimulate:
- P,- Receptor

e Classification:
— Short Acting
— Long Acting

e Short Acting:
— Terbutaline

— Salbutamol

e Long acting:
Respiratory Sys.
— Salmeterol & Formoterol Pharmacology Part-1

17. Classification

B, agonists

Long acting

3-4 hrs 12 hrs

Terbutaline Salmeterol
Salbutamol Formoterol

Respiratory Sys.
Pharmacology Part-1

18. Mechanism of action

e The ß, receptors are:
-G,

e These drugs are:
- Selective P, agonists

- Stimulate adenylyl cyclase
e Effect in asthma:

— Relax airway smooth muscle
- Inhibit microvascular leakage
- Increase mucoilliary transport

Respiratory Sys.
Pharmacology Part-1

19. ß, Receptors

e Location:
— Smooth muscle
e Vascular smooth muscle
e GI smooth muscle
e Uterine
e Bronchioles
- Glands
e Salivary glands
— Liver

e Function: .
Respiratory Sys.
- G-coupled (Gs) Pharmacology Part-1

20. ß, Receptors Cont...........

6, receptors

Smooth muscle

J 4
= ES

Eye Blood vessels supplying
Bronchioles * Skeletal muscle
Bladder

Uterus

Gl smooth muscle

Glycogenolysis

Mast cells V

Respiratory Sys.

Adrenergic neurons 4 Pharmacology Part-1

21. (+)

ß, Receptors Cont..

ATP
Ca?*- Calmodulin

MLCK" MLCK-PO,
(Active) (Inactive)

MLC MLC-PO,

|

— myosin
complex

y

( Contraction )

22. Quick Relief (Short Acting B,
Agonist)

e Drugs in this class include:
- Albuterol & Levalbuterol
— Terbutaline
e Onset of action:
- 5 to 30 minutes
- Provide relief for 4 to 6 hrs.
e Uses:

- Symptomatic treatment of bronchospasm

Respiratory Sys.
Pharmacology Part-1

23. Quick Relief (Short Acting B,
Agonist) Cont...........

e ß, agonists have no anti-inflammatory effects:

- Should not be used as monotherapy in persistent asthma

e SABAs as monotherapy can be used in:
- Mild, intermittent asthma

- Exercise-induced bronchospasm

e Contra-Indications:
— Cardiac dysrhythmias
— Angina pectoris
- Hypertension & Cerebrovascular disease

er Respiratory Sys.
- Hyperthyroidism Pharmacology Part-1

24. Quick Relief (Short Acting B,
Agonist) Cont...........

e Adverse effects:
- Tachycardia
— Hyperglycemia
- Hypokalemia
- Hypomagnesemia
— Skeletal muscle tremors

e These adverse effects are less common in:
- Inhaled delivery

Respiratory Sys.
Pharmacology Part-1

25. Albuterol (C)

e Dose:
- Oral: 2-4 mg
- IM/SC: 0.25 — 0.5 mg
— Inhalation: 100-200 ug

e Preparations:
- Tablet: ASTHALIN 2, 4 mg, 8 mg SR
- Syrup: ASTHALIN 2 mg/5 ml 100, VENTORLIN 2 mg/
5 ml
- Injection: CROYSAL 0.5 mg/ml
- MDI: DERIHALER 100 ug eer ed

26. Albuterol Preparations

? ES 10 X10 TABLETS
it y

N Ibutamol Tablets BP 4 mg

3 SAMOL-4

more Cipla

m
Salbutamol Inhalation IP
100 mcg/dose

asthalin

inhaler

Respiratory Sys.
Pharmacology Part-1

27. Ventolin’
Inhaler
Salbutamol
CFC Free

E PEER

Salbutamol BP 0.1 mg per dose

200 doses

Respiratory Sys.
Pharmacology Part-1

28. Terbutaline (C)

e It is mainly used for:
- Suppression of premature labor
- Rarely used now for asthma

e Dose:
- Oral: 5 mg
- IM/SC: 0.25 mg
- Inhalation: 250 ug

e Preparations:
- Tablet: BRICAREX 2.5, 5 mg
- Syrup: BRICAREX 3 mg/ ml; Injection 0.5/ml
Respiratory Sys.
- MDI: MISTHALER 250 ug Pharmacology Part-1

29. Terbutaline Preparations

Britany! tevie |
(Terbutaline sulphate)

A selective bronchodilator for
Asthma, Chronic Bronchitis, Emphysema

Respiratory Sys.
Pharmacology Part-1

30. Long Term Control (Long Acting ß;
Agonist)

e Drugs in this class include:
- Salmeterol
- Formoterol

e Onset of action:
- Provide relief for 12 hrs.

e Uses:
- Moderate to severe asthma
— In conjugation with Inhaled corticosteroids

Respiratory Sys.
Pharmacology Part-1

31. Long Term Control (Long Acting ß,
Agonist) Cont...........

e They shouldn’t be used as:
- Monotherapy
— Increase the risk of asthma related deaths
e Adverse effects:
- Similar to short acting B, Agonist

Respiratory Sys.
Pharmacology Part-1

32. Salmeterol (C)

e Dose:
- Inhalation: 2 Puffs BD; Severe cases 4 Puffs BD

e Preparations:
- Inhaler: SEROFLO- Salmeterol 25 ug + fluticasone 125

ug/250 ug per puff
- Inhaler: SEROFLO- Salmeterol 50 ug + fluticasone 100
ug/250 ug per puff
e Also available as:
- Rota Caps

Respiratory Sys.
Pharmacology Part-1

33. Salmeterol Preparations

Respiratory Sys.
Pharmacology Part-1

34. Formoterol (C)

e They have:
- Faster onset of action than Salmeterol
e Dose:
- Inhalation: 12-24 ug BD
e Preparations:
— Rota Caps: FORATEC 12 pg

Respiratory Sys.
Pharmacology Part-1

35. Formoterol Preparations

Mk: so copwies Cipla

foratec
rotacaps”
Rbanmacy 4NRXBR r macYA4NRX

Respiratory Sys.
Pharmacology Part-1

36. Adrenalin (C)

e This drugs stimulate:
- All adrenergic receptor
e Use:
- Status asthmatics
e Onset of action:
- 10-15 minutes
- Provide relief for 1-2 hrs.

Respiratory Sys.
Pharmacology Part-1

37. Adrenalin Cont...........

e Adverse effects:
- CNS disturbances
— Induce cerebral hemorrhage
— Cardiac arrhythmias
— Pulmonary edema
e Dose:
- IM: 0.2-0.5 mg
e Preparations:
— Injection: ADRENALINE Img/ml
— Injection: ADRENA 4mg/2ml a

38. Corticosteroids

Respiratory Sys.
Pharmacology Part-1

39. Introduction

e They are not:

- Bronchodilators

e They decrease:
- Inflammatory response to AG:AB
- Bronchial hyper reactivity
- Mucosal edema
e Administration:
- Inhalation

- Oral/Systemic Respiratory Sys.

Pharmacology Part-1

40. Mechanism of action

e Arachidonic acid is precursor of:

- Many inflammatory mediators

e These drugs:
- Inhibit phospholipase A,

- Decrease release of arachidonic acid

e Theses drugs must be used:
- Regularly (to be effective)

Respiratory Sys.
Pharmacology Part-1

41. Pharmacokinetic

e These drugs can be administrated by:
- Inhaled route
— Oral/Intravenous route

e Inhaled corticosteroids are used for:
- All cases of persistent asthma with B, Agonists

e Oral and Intravenous corticosteroids are used for:
— Severe chronic asthma
— Status Asthmatics
= COPD

Respiratory Sys.
Pharmacology Part-1

42. Pharmacokinetic Cont...........

~10-20% inhaled

Mouth and
pharynx

5 Systemic
Absorption circulation
from Gl tract

-80-90% swallowed
(y spacer/mouth wash)

Inactivation
in liver
“first pass”

espiratory Sys.
Pharmacology Part-1

43. Corticosteroids used for Asthma

e Systemic:
— Prednisolone (oral)
— Methyl Prednisolone (IV)

e Inhaled (ICS):
- Beclomethasone Dipropionate
- Budesonide
— Fluticasone

Respiratory Sys.
Pharmacology Part-1

44. Systemic Steroids

e Oral steroids
e Use:
— Patients not controlled with ICS
- Increasing severity of asthma
e Dose:
— Prednisolone (40-60 mg) (4-6 weeks)
— Maintenance dose: 10-15 mg/day
- Given as a single dose in morning
e Dose taper is:
. . . Respiratory Sys.
— Unnecessary prior to discontinuation Pharmacology Part-1

45. Systemic Steroids Cont...........

e Intravenous steroids

e Use:

— Status Asthmatics

- Acute Asthma Exacerbation
e Drug used:

— Hydro-cortisone
— Once control is achieved, Switch to oral prednisolone (5-7
days)
e Dose:

2 E Respiratory Sys.
- Hydrocortisone 200 mg/ divided dose Pharmacology Part-1

46. Adverse effects of Corticosteroids

e Local:
— Hoarseness
— Weakness of voice
— Oropharyngeal Candidiasis (5% Patients)
- Cough

e Systemic:

- Adrenal suppression

- Dermal thinning and bruising

— Osteoporosis

= Si Respiratory Sys.
— Metabolic abnormalities Pharmacology Part-1

47. Few Examples of Inhaled
Corticosteroids

Respiratory Sys.
Pharmacology Part-1

48. Beclomethasone Dipropionate
(NIA)

e Dose:
- 1-2 Puffs BD (Max 4 puffs QID)

e Preparations:
- MDI: BECLATE 50, 100, 200 ug (200 doses)
- Puff Inhaler: BECORIDE 50, 100, 250 ug per puff
- Rota Caps: BECLATE ROTACAPS 100, 200, 400 ug
- MDI: AEROCORT 50 ug/with salbutamol 100 ug
Rota Caps: AEROCORT 100 ug/with salbutamol 200 ug

Respiratory Sys.
Pharmacology Part-1

49. Beclomethasone Dipropionate
Preparations

Respiratory Sys.
Pharmacology Part-1

50. Budesonide (D)

e Dose:
- 2-4 Puffs BD-QID

e Preparations:
- MDI: PULMICORT 100, 200, 600 ug

- Rota Caps: FORACORT: Formoterol 6 ug + Budesonide
100 ug (200 doses)

Respiratory Sys.
Pharmacology Part-1

51. Budesonide Preparations

Respiratory Sys.
Pharmacology Part-1

52. Budesonide Preparations
Cont...........

120 metered Cipla

R Fomotel Fumarate
and Budesonide Inhaler

Respiratory Sys.
Pharmacology Part-1

53. Fluticasone Propionate (D)

e High Potency:
- Double of Beclomethasone
e Dose:
- Inhalation: 100-250 ug BD (max 1000 ug/day)
e Preparations:
- Inhaler: FLOHALE 25, 50, 125 pg
— Rota Caps: FLOHALE 50, 100, 250 ug

Respiratory Sys.
Pharmacology Part-1

54. Fluticasone Propionate
Preparations

30 copsules ‚cap
Fie open |
Formotesl Fumarate Rtacps

maxiflo

> | rotocas" EE]

rotahaler
I

Respiratory Sys.
Pharmacology Part-1

55. Leukotrienes Modifier

Respiratory Sys.
Pharmacology Part-1

56. Introduction

e Leukotrienes are involved in:
- Many inflammatory diseases
— Anaphylaxis
e Important Leukotrienes include:
- LTB,
- Cysteinyl leukotrienes (LTC,, LTD, & LTE,)
e They are products of:
- 5-lipoxygenase pathway of arachidonic acid metabolism

- Part of the inflammatory cascade A
Respiratory Sys.

Pharmacology Part-1

57. Introduction Cont...........

e 5-Lipoxygenase is found in cells of:
- Myeloid origin, such as:
- Mast cells, basophils, eosinophils, and neutrophils
e LTB4:

- Potent chemoattractant for neutrophils and eosinophils

e Cysteinyl leukotrienes:
— Constrict bronchiolar smooth muscle
— Increase endothelial permeability

- Promote mucus secretion á
Respiratory Sys.
Pharmacology Part-1

58. Mechanism of Action

e Zileuton:
- Selective and specific inhibitor of 5-lipoxygenase
— It is use is limited due:
— Short duration of action
- Hepatitis
e Zafirlukast and Montelukast are selective
antagonists of:
- Cysteinyl leukotriene-1 receptor

Respiratory Sys.
Pharmacology Part-1

59. pay
Extracellular rs
>»

space s

ya

>

7
BLT Ll
receptor.

=

Pitt
Traismembrane 666454)

transporter +
Leukotriene A
(Leukotriene Ca } | | Leukotriene Es |

e
Montelukast =

Leukotriene As Pranlukast
Zafirlukast

Eosinophil migration
Edema

60. Pharmacokinetics

e Administration:
- Oral
- Food impairs the absorption of Zafirlukast

e Distribution:
— Highly protein bound

e Metabolism:
- Liver

e Elimination:
— Kidney: Zileuton .

Respiratory Sys.

- Bile: Zafirlukast , Montelukast Pharmacology Part-1

61. Clinical Usage & Contra-Indications

e Clinical usage:
- Prevention of asthma symptoms
— Not used when immediate bronchodilation required
- Prevention of exercise induced bronchospasm
e Contra Indications:
- Liver Failure
- Montelukast: Age > 2 years
- Zafirlukast: Age > 5 year
— Zileuton: Age > 12 years

Respiratory Sys.
Pharmacology Part-1

62. Adverse effects & Drug Interaction

e Adverse Effects:

— Hepatitis

— Headache

- Dyspepsia

- Hypersensitivity reactions

- Upper respiratory tract infection
e Drug Interaction:

- Inhibit metabolism of other drugs

Respiratory Sys.
Pharmacology Part-1

63. Montelukast (B)

e Dose:

- Oral: Adults10 mg OD; children 2-5 yr. 4 mg OD, 6-14
yr. 5 mg OD; in the evening

e Preparations:
— Tablet: EMLUKAST, MONTAIR, VENTAIR 4, 5, 10 mg

Respiratory Sys.
Pharmacology Part-1

64. Montelukast Preparations

msD
en gulair®
MONTELUKAST.

10 mg

Respiratory Sys.
Pharmacology Part-1

65. Zafirlukast (B)

e Dose:
- Oral: 20 mg BD; children 5-11 yr. 10 mg BD
e Preparations:
- Tablet: ZUVAIR 10, 20 mg ACCOLATE

zafirlukast

Respiratory Sys.
Pharmacology Part-1

66. Anti-muscarinic Agents

Respiratory Sys.
Pharmacology Part-1

67. Introduction

e The anticholinergic agents block vagally mediated:
- Contraction of airway smooth muscle
— Mucus secretion
e Drug in this class include:
- Inhaled Ipratropium Bromide
- Oxitropium bromide
- Inhaled Tiotropium Bromide
e Not recommended for routine asthma:

- Slow onset A
Respiratory Sys.
Pharmacology Part-1

68. Mechanism of action

e These drugs block:
- M; Muscarinic receptor
- Competitively inhibit the effect of acetylcholine
e M, Receptor:
- Location: Smooth muscles & exocrine gland
- Function: (G,) Excitatory
e End result of M; block:

— M; mediated contraction is inhibited

— Airway smooth muscle relax
a 3 Respiratory Sys.
- Bronchi are dilated Pharmacology Part-1

69. Mechanism of action Cont...........

CNS Smooth muscle
Parietal cells
Salivary glands Exocrine glands

Respiratory Sys.
Pharmacology Part-1

70. Clinical usage & Contra-Indications

e Clinical usage:
- Patients unable to tolerate SABA
— Patients with Asthma & COPD overlap
— Asthma exacerbations (Combined with a SABA)
- COPD (Drug of Choice)
e Contra Indications:
- Glaucoma
- Pyloric Stenosis
— Prostatic Hypertrophy

Respiratory Sys.
Pharmacology Part-1

71. Adverse effects

e Most common are:

- Dry mouth
- Headache

- Constipation & Urinary retention

- lurred vision
Side effects “onstipation

BCDU Y mouth
rinary retention

72. Ipratropium Bromide (B) &
Tiotropium Bromide (B)

e Half-lives:
- Ipratropium Bromide (4-6 hrs.)
— Tiotropium Bromide (24 hrs.)

e Dose:
- Inhaler: ipratropium 2-4 puffs 6 hourly
- Rota Cap: Tiotropium 1 OD

e Preparations:

- MDI: DUOLIN INHALER 100 pg Salbutamol + 20 ug

Ipratropium
Respiratory Sys.
Pharmacology Part-1

73. Ipratropium Bromide & Tiotropium
Bromide Preparations

Respiratory Sys.
Pharmacology Part-1

74. Theophylline
(C)

75. Introduction

e In the past:
- Main stay of asthma treatment
e Mechanism of Action:
- Exact: Unclear
— May inhibit phosphodiesterase
— May also possess anti-inflammatory activity
e Use:
- Bronchodilator in chronic asthma
- Replaced by ß2 agonists and corticosteroids

N Respiratory Sys.
- COPD (More effective) Pharmacology Part-1

76. Mechanism of Action

Respiratory Sys.
Pharmacology Part-1

77. Pharmacokinetic

e Administration:

- Oral

— Well tolerated
e Metabolism:

- Liver

- Numerous drug interactions
e Elimination:

- Kidney

Respiratory Sys.
Pharmacology Part-1

78. Adverse effects & Dose

e Adverse effects:
- Narrow therapeutic window
— Arrhythmias
— Drug Interaction
- Seizure (High dose)
e Dose:
- Oral: 100-300 mg TDS (15 mg/kg/ day)

Respiratory Sys.
Pharmacology Part-1

79. Preparations

Respiratory Sys.
Pharmacology Part-1

80. Mast cells Stabilizers

Respiratory Sys.
Pharmacology Part-1

81. Introduction

e This drug inhibits:
— Mast cell degranulation and release of histamine
— Not bronchodilators

e Drug in this class include:
- Cromolyn (B)

e Use:
- Prophylaxis of mild to moderate asthma
— Therapeutic effects occur in 2-4 weeks

- Rarely, used now SR,

Pharmacology Part-1

82. Pharmacokinetic

e Administration:
- Inhalation

e Absorption:

- Small fraction of the inhaled drug is absorbed
systemically

e Elimination:
- Unchanged Kidney

Respiratory Sys.
Pharmacology Part-1

83. Adverse effects & Dose

e Adverse effects:
— Throat irritation
— Cough
- Bad Taste
e Dose:
- MDI: 2 puffs 4 times a day (1 mg per dose)

Respiratory Sys.
Pharmacology Part-1

84. Anti-Ig E monoclonal
Antibodies

Respiratory Sys.
Pharmacology Part-1

85. Introduction

e This drug inhibits:
- Binding of Ig E to mast cells
— Effective for 10 weeks
e Drug in this class include:
- Omalizumab
e Use:
— Severe extrinsic Asthma
— Its use is limited due to:
- High cost (1 150mg vial: $600)
Respiratory Sys.

- Adverse effects Pharmacology Part-1

86. Adverse effects of Omalizumab

e It include:
- Serious anaphylactic reactions (rare)
— Arthralgia
- Fever
— Rash
- Increased risk of infections
- New malignancies have been reported

Respiratory Sys.
Pharmacology Part-1

87. Persistent Asthma: Daily Medication
Intermittent
Ratna Consult with asthma specialist if step 3 care or higher is required.
Consider consultation at step 2.
Step 6 = ;
tep up i
Step 5 Preferred: needed
Step 4 High-dose ics+ | MUR ag
Preferred: High-dose ICS+ | | either adherence,
Step 3 2 either LABA or inhaler
à Medium-dose | | LABAor EIA technique, and
Step 2 1 ICS + either RE Grp environmental
| [Pio corticosteroids control)
Step 1 Preferred: Ics Montelukast
à TRES
Preferred: Alternative: control
SEEN Cromolyn or Step down if
Montelukast possible
(and asthma is

well controlled
at least
3 months)

Patient Education and Environmental Control at Each Step

Quick-Relief Medication for All Patients

+ SABA as needed for symptoms. intensity of treatment depends on severity of symptoms

+ With viral respiratory infection: SABA q 4-6 hours up to 24 hours (longer with physician consult) Bann
systemic corticosteroids if exacerbation is severe or patient has history of previous severe

+ Caution: Frequent use of SABA may indicate the need to step up treatment. See ex fr recormendalions on ing daly
long-term-control therapy.

Key: Alphabetical order is used when more than one treatment option is listed within either preferred or
alternative therapy. ICS, inhaled corticosteroid; LABA, inhaled long-acting beta,-agonist; SABA, inhaled short- Sys.
acting betaz-agonist 'art-1

88. ® Box 15.3 The s ise management of asthma

1. Occasional symptoms; 100% predicted As-required short-acting ß, agonists
less frequent than daily If used more than once daily, move to step 2
2. Daily symptoms <80% predicted Regular inhaled preventer therapy:
Anti-inflammatory drugs: inhaled low-dose corticosteroids up to
800 yg daily

Leukotriene receptor antagonists (LTRA), theophylline and
‘sodium cromoglycate are less effective
If not controlled, move to step 3
3. Severe symptoms 50-80% Inhaled corticosteroids and long-acting inhaled B, agonist
predicted Continue inhaled corticosteroid
‘Add regular inhaled long-acting B, agonist (LABA)
Still not controlled, add either LTRA, modified release oral

theophylline or B, agonist
If not controlled, move to step 4
4, Severe symptoms 50-80% High-dose inhaled corticosteroid and regular
uncontrolled with predicted bronchodilators
high-dose inhaled Increase high-dose inhaled corticosteroids up to 2000 yg daily
corticosteroids Plus regular long-acting B, agonists
Plus either LTRA or modified release theophylline or B, agonist
5. Severe symptoms <50% predicted Regular oral corticosteroids
deteriorating Add prednisolone 40 mg daily to step 4
6. Severe symptoms <30% predicted Hospital admission
deteriorating in spite of
prednisolone

Short-acting bronchodilator treatment taken at any step on an as-required basis.

89. Drugs used for COPD

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90. Introduction

e Definition:
- Chronic, irreversible, usually progressive obstruction of
airflow and characterized by persistent symptoms
e Symptoms are:
- Cough
- Excess mucus production
- Chest tightness
— Breathlessness
- Fatigue

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91. Introduction Cont...........

e Characteristic difference with Asthma:
- Airflow obstruction is irreversible & Progressive
e Greatest risk factor:
- Smoking
e Smoking is directly linked to:
- Progressive decline of lung function
e Smoking should be stopped regardless of:
- Stage & Severity

- Age of patient Respiratory Sys.
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92. Goal of Drug therapy & Drugs used

e Goal is to:
- Relief of symptoms
- Prevention of disease progression
e Drugs used are:
- Inhaled Bronchodilators
- Corticosteroids

- Theophylline

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93. Inhaled Bronchodilators

e Inhaled bronchodilators used in COPD are:
- ß, -adrenergic agonists

- Anticholinergic agents (muscarinic antagonists)

e Benefits of Bronchodilators:
- Increase airflow
- Alleviate symptoms
- Decrease exacerbations

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94. Inhaled Bronchodilators
Cont...........

e Long Acting Beta agonist include (LABAs):
- Once daily: Indacaterol, Olodaterol, and Vilanterol
- Twice daily: Formoterol, and Salmeterol

e Long Acting Muscarinic Antagonist include:
- Aclidinium, Tiotropium, Glycopyrolate and
Umeclidinium

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95. Inhaled Bronchodilators
Cont...........

e Use:
- They are first line all COPD patients
— They are alternative to each other
- Anti-cholinergic (Mostly recommended)
e Combined use:
- Inadequate response to a single inhaled bronchodilator

— Risk of exacerbations

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96. Corticosteroids

e Inhaled corticosteroids combined with a long-acting
bronchodilator may improve:
— Symptoms
— Lung function
- Quality of life
e Inhaled corticosteroids along with bronchodilators
are used in:
- Severe COPD cases (FEV1 of less than 60%)
- COPD-Asthma syndrome

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97. Corticosteroids Cont...........

e Oral corticosteroids are used in:
— Acute exacerbations

e They are not recommended for:
— Long term treatment of COPD

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98. Other drugs used

e These drugs include:
- Roflumilast
— Theophylline
e Mechanism of action:
- Phosphodiesterase-4 inhibitor
e Use:
— Severe chronic bronchitis
- Replaced by bronchodilators

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99. Summary of COPD treatment

PATIENT GROUP RECOMMENDED FIRST CHOICE RECOMMENDED ESCALATION

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100. Inhaler Techniques

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101. Additional Images (Inhaler)

Ventolin”
Inhaler

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102. Additional Images (MDI)

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103. Additional Images (Rota Cap)

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104. Additional Images (Rota Cap)
COM...
cc |

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105. Additional Images (Nebulizer)

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106. Additional Images (Nebulizer)

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107. Additional Images (Spacer)

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108. References

e Katzung, B. G., Masters, S. B., & Trevor, A. J. (2015). Basic & clinical
pharmacology. New York: McGraw-Hill Medical

e Whalen, K., Finkel, R., & Panavelil, T. A. (2017). Pharmacology
(Seventh Edition.). Philadelphia: Wolters Kluwer

e Tripathi, K. (2008). Essentials of medical pharmacology (6th ed.). New
Delhi: Jaypee Brothers

e The images are retrieved from: www.google.com/images

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109. Thank You

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