Pharmacology Pharmacology departmentdepartment
FACULTY OF MEDICINES LAMPUNG UNIVERSITY
DRUGS USED IN ASTHMA
BRONCHODILATORS ANTI-INFLAMMATORY LEUKOTRIENE AGENTS ANTAGONISTS
β RELEASE LIPOXYGENASE RECEPTORAGONISTS INHIBITORS INHIBITORS INHIBITORS
MUSCARINIC STEROIDS ANTIBODIES ANTAGONISTS
METHLYXANTHINES SLOW ANTI- INFLAMMATORY DRUGS
BRONCHIAL ASTHMA
Airway inflammationEpisodic, reversible bronchospasmChronic inflammation that leads to
marked bronchial hyperreactivity
BRONCHIAL ASTHMA
BRO
NCH
IAL
ASTH
MA
Bronchial ToneBronchial Tone
ConstrictionConstriction
Leukotrienes
Adenosine
Acetylcholine
CAMP
ATP
PDEPDE
AMP
DilataDilatationtionACAC
BRONCHIAL ASTHMARelease of several mediators from IgE-
sensitized mast cells and other cells involved in immunologic responses
Mediators include LeukotrienesChemoattractantsCytokinesEnzymes
DRUGS USED IN ASTHMASTRATEGIES OF ASTHMA THERAPYACUTE ASTHMATIC ATTACKS
Treated promptly and effectively with bronchodilatorsβ2 agonistMuscarinic antagonistsTheophylline and its derivatives
DRUGS USED IN ASTHMASTRATEGIES OF ASTHMA THERAPYCHRONIC ASTHMA
Long term preventive treatment Requires control of inflammatory process in
the airwaysCorticosteroidsCromolyn
DRUGS USED IN ASTHMA BRONCHODILATORS ANTI-INFLAMMATORY LEUKOTRIENE
AGENTS ANTAGONISTS
β RELEASE LIPOXYGENASE RECEPTORAGONISTS INHIBITORS INHIBITORS INHIBITORS
MUSCARINIC STEROIDS ANTIBODIES ANTAGONISTS
METHLYXANTHINES SLOW ANTI- INFLAMMATORY DRUGS
DRUGS USED IN ASTHMABETA-ADRENOCEPTOR AGONISTSMechanism of action
Stimulate adenyl cyclase and increasing cAMP in smooth muscle cells bronchodilatation
Relaxation
Bronchial ToneBronchial Tone
ConstrictionConstriction
Leukotrienes
Adenosine
Acetylcholine
CAMP
ATP
PDEPDE
AMP
DRUGS USED IN ASTHMABETA-ADRENOCEPTOR AGONISTSMost important sympathomimetic used
to reverse asthmatic bronchoconstrictionAlmost given exclusively by inhalation
Decreases the systemic dose and adverse effects
Occasionally by nebulizer
DRUGS USED IN ASTHMABETA-ADRENOCEPTOR AGONISTSAlbuterol, terbutaline, metaproterenol
Short-actingDrug of choice for acute asthma
DRUGS USED IN ASTHMA
BETA-ADRENOCEPTOR AGONISTSSalmeterol and formoterol
Long-acting12 h or moreUsed for prophylaxis
DRUGS USED IN ASTHMA
BETA-ADRENOCEPTOR AGONISTSEpinephrine and isoproterenol
Still used occasionally Used for chronic obstructive pulmonary
disease (COPD) patients
DRUGS USED IN ASTHMABETA-ADRENOCEPTOR AGONISTSTOXICITY
Skeletal muscle tremorSignificant β1 effects (tachycardia) at high
clinical dosageArrhythmias may occur when used
excessively
DRUGS USED IN ASTHMABETA-ADRENOCEPTOR AGONISTSTOXICITY
Tolerance, tachyphylaxis (loss of responsiveness) is an unwanted effect
COPD patients often with concurrent cardiac disease may have arrhythmias at normal dosage
DRUGS USED IN ASTHMAMETHYLXANTHINESPurinePurine derivativesMOA
Inhibit phosphodiesterase (PDE), the enzyme that degrades cAMP to AMP, thus increases cAMP
Anti-PDE effect requires high concentration of the drug
Relaxation
Bronchial ToneBronchial Tone
ConstrictionConstriction
Leukotrienes
Adenosine
Acetylcholine
CAMP
ATP
PDEPDE
AMP
DRUGS USED IN ASTHMAMETHYLXANTHINESFound in plants and provide the stimulant
effect of 3 common beveragesCaffeine (coffee)Theophylline (tea)Theobromine (cocoa)
DRUGS USED IN ASTHMAMETHYLXANTHINESTheophylline and several analogs
Orally active Available as salts and base
Slow-release theophylline For control of nocturnal asthmaMost important in clinical use
DRUGS USED IN ASTHMAMETHYLXANTHINESClearance varies
Highest in young adolescentsHigher in smokersConcurrent use of other drugs that inhibit or
induce hepatic enzyme
DRUGS USED IN ASTHMAMETHYLXANTHINESBronchodilation is the most important
therapeutic effectCNS stimulation, cardiac stimulation,
vasodilation and slight increase in BP (due to release of NE from adrenergic nerves
DRUGS USED IN ASTHMA
METHYLXANTHINESEliminated by Cytochrome P450-drug
metabolizing enzyme in the liverPentoxifylline
Used for treatment of intermittent claudication
DRUGS USED IN ASTHMAMETHYLXANTHINESTOXICITY
Common adverse effectsGI distressTremorInsomnia
DRUGS USED IN ASTHMAMETHYLXANTHINESTOXICITY
OverdosageSevere nausea and vomitingHypotensionCardiac arrhythmiasConvulsion
DRUGS USED IN ASTHMAMUSCARINIC ANTAGONISTSMOA
Competitively blocks muscarinic receptors in the airways
Prevents bronchoconstriction mediated by vagal discharge
Relaxation
Bronchial ToneBronchial Tone
ConstrictionConstriction
Leukotrienes
Adenosine
Acetylcholine
CAMP
ATP
PDEPDE
AMP
DRUGS USED IN ASTHMAMUSCARINIC ANTAGONISTSReverses bronchoconstrictionReverses bronchoconstriction
Useful in 1/3 to 2/3 of asthmatic patients (especially children)
No effect on the inflammatory aspects of asthma
Useful in many COPD patients More effective and less toxic than β
agonists
DRUGS USED IN ASTHMAMUSCARINIC ANTAGONISTSAtropineAtropine and other naturally-occurring
belladona alkaloids were used for asthma
DRUGS USED IN ASTHMAMUSCARINIC ANTAGONISTSIpatropiumIpatropium
Quaternary antimuscarinic drugDelivered to the airways by pressurized aerosol Have little systemic action
TiotropiumTiotropiumNewer longer-acting analog
DRUGS USED IN ASTHMAMUSCARINIC ANTAGONISTSTOXICITY
Delivered directly to the airway, minimally absorbed
Systemic effects are smallIn excessive dosage, minor atropine-like toxic
effects may occurDoes not cause tremor or arrhythmias
DRUGS USED IN ASTHMA
CROMOLYN AND NEDOCROMILNo bronchodilator action but can prevent
bronchoconstriction caused by a challenge with antigen to which the patient is allergic
DRUGS USED IN ASTHMACROMOLYN AND NEDOCROMILMOA
Decrease in the release of mediators (leukotrienes and histamine) from mast cells
Prevents both early and late responses to challenge
DRUGS USED IN ASTHMACROMOLYN AND NEDOCROMILCromolynCromolyn – prototype drug – prototype drugUnusual chemicalsExtremely insolubleMassive doses given orally or by
aerosol result in minimal systemic levels (local effects)
Given by aerosol for asthma
DRUGS USED IN ASTHMACROMOLYN AND NEDOCROMILFood allergy
Given orallyAsthma in childrenAsthma in children
Most important useHay feverHay fever
Nasal and eyedrop formulations
DRUGS USED IN ASTHMACROMOLYN AND NECRODOMILTOXICITY
Cough and irritation of the airway when given by aerosol
Drug allergy is rare
DRUGS USED IN ASTHMA BRONCHODILATORS ANTI-INFLAMMATORY
LEUKOTRIENE AGENTS ANTAGONISTS
β RELEASE LIPOXYGENASE RECEPTORAGONISTS INHIBITORS INHIBITORS INHIBITORS
MUSCARINIC STEROIDS ANTIBODIES ANTAGONISTS
METHLYXANTHINES SLOW ANTI- INFLAMMATORY DRUGS
DRUGS USED IN ASTHMACORTICOSTEROIDSMOA
Reduces the synthesis of arachidonic acid by phospholipase A2
Inhibit the expression of COX-2 (anti-anflammatory action)
Postulated that: this drugs increases the responsiveness of beta agonists in the airway
DRUGS USED IN ASTHMAArachidonic acidArachidonic acid
LipooxygenaseLipooxygenase CyclooxygenaseCyclooxygenase
HydroxypeptidaseHydroxypeptidase EndoperoxidaseEndoperoxidase
LeukotrienesLeukotrienes ProstacyclineProstacycline
Thromboxane A2Thromboxane A2
ProstaglandinProstaglandin
Membrane Lipid
Phospholipase Phospholipase A2A2
DRUGS USED IN ASTHMA
CORTICOSTEROIDSAll are potentially beneficial in severe
asthmaSystemic (oral corticosteroids)
Used chronically only if other therapies fail
DRUGS USED IN ASTHMACORTICOSTEROIDSLocal aerosol administration of surface
active corticosteroids are relatively safeBeclomethasoneBudesonideDexamethasoneFlunisolideFluticasoneMometasone
DRUGS USED IN ASTHMACORTICOSTEROIDSInhaled corticosteroids
Common first-line therapy for moderate to severe asthma
Appropriate (even in children) in cases of moderate asthma that does not fully respond to aerosol β agonist
DRUGS USED IN ASTHMACORTICOSTEROIDSPrednisolone and hydrocortisone
Intravenous For status asthmaticus
DRUGS USED IN ASTHMACORTICOSTEROIDSReduced activity of phospholipase
A2 Leukotrienes that result from the
synthesis of prostaglandins are potent bronchoconstrictors
DRUGS USED IN ASTHMACORTICOSTEROIDSEarly use may prevent the severe,
progressive inflammatory changes of long-standing asthma
DRUGS USED IN ASTHMACORTICOSTEROIDSTOXICITY
Changes on oropharyngeal flora result to candidiasis
For oral therapyAdrenal suppression can be reduced by
using alternate day therapy (give the drug in slightly higher dosage every other day)
DRUGS USED IN ASTHMACORTICOSTEROIDSTOXICITY
Systemic toxicitiesOccur if treatment is required for more
than 2 weeksRegular use of inhaled steroids cause
mild growth retardation in children
DRUGS USED IN ASTHMA
BRONCHODILATORS ANTI-INFLAMMATORY LEUKOTRIENE AGENTS ANTAGONISTS
β RELEASE LIPOXYGENASE RECEPTORAGONISTS INHIBITORS INHIBITORS INHIBITORS
MUSCARINIC STEROIDS ANTIBODIES ANTAGONISTS
METHLYXANTHINES SLOW ANTI- INFLAMMATORY DRUGS
DRUGS USED IN ASTHMALEUKOTRIENE ANTAGONISTSInterfere with the synthesis or action synthesis or action
of leukotrienesof leukotrienesNot as effective as corticosteroids in
severe asthma Not recommended for acute asthmaLow toxicity
DRUGS USED IN ASTHMAArachidonic acidArachidonic acid
LipooxygenaseLipooxygenase CyclooxygenaseCyclooxygenase
HydroxypeptidaseHydroxypeptidase EndoperoxidaseEndoperoxidase
LeukotrienesLeukotrienes ProstacyclineProstacycline
Thromboxane A2Thromboxane A2
ProstaglandinProstaglandin
DRUGS USED IN ASTHMALEUKOTRIENE ANTAGONISTSZileutonZileuton
Orally activeSelectively inhibits 5-lipoxygenase,
a key enzyme in the conversion of arachidonic acid to leukotrienes
DRUGS USED IN ASTHMALEUKOTRIENE ANTAGONISTSZileuton
Effective in Exercise- and antigen-induced
bronchospasmAspirin allergyToxicity include occasional elevation of
liver enzymes
DRUGS USED IN ASTHMALEUKOTRIENE ANTAGONISTSZafirlukast and montelukastZafirlukast and montelukast
Antagonist at the LTD4 leukotriene receptorOrally active
DRUGS USED IN ASTHMALEUKOTRIENE ANTAGONISTSEffective in preventing exercise-,
antigen-and aspirin-induced bronchospastic attacks
DRUGS USED IN ASTHMAAnti-IgE antibody
OmalizumabHumanized murine monoclonal
antibody to human IgEProphylactic management of asthmaGiven parenterally
DRUGS USED IN ASTHMAAnti-IgE antibody
Binds to IgE on sensitized mast cellsPrevents activation by asthma triggers Subsequent release of inflammatory
mediators
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