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Drug Treatment For Asthma, Side effect and toxicity - Coggle Diagram
Drug Treatment For Asthma
Class of drug
Reduce symptoms
B-adrenoceptor stimulants
Methylxanthine
Histamine receptor antoagonist
NSAIDS
Anticholinergic agents
Anti-inflammatory drugs
Corticosteroid
Reduce symptoms and anti-inflammatory
Sodium cromoglycate
Nedocromil sodium
Leukotriene antagonist
5-lipoxygenase inhibitors
Reduce asthmatic symptoms
B-adrenoceptor stimulants
Main effect
Bronchodilator
Inhibit mast cell secretion
Revive circulatory system -effect on blood vessels and renin-angiotensin system
Adrenaline
ACT on
mast cell
Inhibit of secretion ,B2
Bronchial
smooth muscle
Relax,B2
Kidney
Increase renin secretion ,B2
Heart
Increase rate and force ,B1
GI tract
Decrease motility ,alpha and B2
Liver
glycogenolysis (cause diabetes ,alpha and B2)
Eye
Mydriasis ,alpha
Piloerector muscle
Constriction alpha 1
Blood vessel of skin
Constriction ,alpha 1
Blood vessel of skeletal ms
dilatation ,B2
Chemical modification of adrenaline
First objective : receptor selectivity
Isoprenaline- B-selective
Salbutamol ,terbutaline and procaterol -B2>B1
Second objective :Increase duration of action of bronchodilator action thru inhibition of AD inactivator
By monoamine oxidase and catechol-O-methyltransferase
Duration is lengthen to 4-5 hours by inhalation and 4-8 hrs orally
Newer
B-adrenoceptor stimulants
Bambuterol
Isoetharine
Bitolterol
Metaproterenol
Levalbuterol
Reproterol
Mechanism of action of B-adrenoceptor stimulant
B-adrenoceptor stimulant binds to receptor
Encourage GTP binding to alpha subunit on G-protein
alpha cleavage from G-protein
alpha formed a complex with adenylate cyclase
cAMP is formed from ATP
cAMP activate protein kinase
1 more item...
OTHER mechanism
Inhibit histamine ,tryptase ,eicosanoids production by mast cell
Inhibit TNF alpha production from monocyte
Methyxanthine
Major drug -
theophylline
Mechanism
of action
Inhibit
cAMP phosphodiesterase leading to increase in cAMP conc
Inhibit bronchoconstriction
Increase
breathing capacity
Increase
adrenaline
(bronchodilator) and
cortisol
(anti-inflam) conc
:star:
Increase
diaphragm contractility
-ease breathing
Reduce activation of inflam cell
Pharmacokinetic
Narrow therapeutic index
-monitor carefully
10-20 -therapeutic effect
more than 20 -toxic
Side effects
Drug interaction (major)
Conc. reduced by drug that increase CYP450
- rifampicin, phenobarbital, phenytoin , carbamazepine
Conc. increased by drugs that inhibit CYP450
- oral contraceptive, erythromycin ,ciproflocaxin ,CCB, fluconazole and cimetidine
Histamine receptor antagonist
Two classes
Older agent
Mepyramind ,diphenhydramine ,chlorpeniramine and ketotifen
Coss CNS and cause sedative effect
Beneficial in nocturnal asthama
Limit use :warning:
Increase alcohol effect
Atropine-like effect
Inhibit alpha -adrenergic and 5HT receptors
Newer agent
Astemizole ,terfenadine,cetirizine, mequitazine, loratadine and acrivastin
Free from sedative and atropine-like effect
Anticholinergic agents
M3 muscarinic receptor involved in bronchial smooth ms contraction
Mediated by cAMP
EXP :Atropine
Anti-cholinergic bronchodilator
Inhibit parasympathetic nervous system
in heart - LIMIT IN USE
EXP :Ipratropium bromide and oxitropium bromide
Potent anticholinergic agents
TOPICALLLLLL
WEAK systemic absorption - less systemic side effects
Little bronchodilator effect
Anti-inflammatory drug
Corticosteroid
Treat chronic severe asthma
Reduce bronchial inflammation and control development of mild asthma
Hydrocortisone
Natural glucocorticoid (GC)
secreted by zona fascicularis in adrenal cortex
Potent anti-inflammatory agent
Side effects-influence glucose metabolism and mineral absorption by kidney
Mechanism
Stimulate lipomodulin synthesis
Lipomodulin is an anti-inflammatory drug by inhibiting phospholipase A
Reduce the secretion of inflammatory cytokines ,eosinophils and mast cell
Pharmacokinetic
Oral
Chronic severe asthma
IV
Acute severe asthma
Beclomethasone and dexamethasone
Rapid absorption and distribution
High affinity towards receptors
Slow metabolism and free from mineralocorticoid reaction
Other drug:prednisolone and prednisone
Less severe chronic asthma
Inhalation
Beclomethasone dipropionate ,budesonide and fluticasone
Rapid metabolism and less systemic side effects
New corticosteroid
Flunisolide, ciclesonide, triamnicolone ,mometasone
Drug that reduce symptoms and anti-inflammatory
Sodium chromoglycate (SC) and nedocromil sodium (NS)
Anti-allergic drug
Inhibit early phase of asthma, chronic allergic inflammation
SCG-mast cell stabilizer
NS-treat pulmonary inflammation
Mechanism
SCG
Reduce histamine, PGD2 ,LTC4 secretion
Reduce bronchoconstriction
caused by allergen ,exercise an cold air
NS
Reduce bronchoconstriction caused by bradykinin and capsaicin
Protect from
early phase of asthma
and
bronchial hyperresponsiveness
Pharmacokinetics and side effects
Treat mild asthma
Free from systemic toxicity
Side effect
Temporary coughing
Mild wheezing
SCG
Weak action
Not effective in 30% of patient
Leukotriene antagonist (LT) and 5-lipoxygenase
Involved in
bronchoconstriction and proinflammation
:warning:
Mechanism
Competitive antagonist at LP receptor
Inhibit LT synthesis (by inhibit 5-lipoxygenase)
Cystheinyl LT -LTC4, LTD4 and LTE4 ,all are potent bronchoconstrictor at bronchial smooth ms
receptor - cys-LT, LT1 (bronchoconstrictive effect)
LT antagonist
Zafirlukast ,montelukast ,pranlukast
Potent LTD4 inhibitor :lock:
Selective and high affinity towards LT1 receptor :!!:
Inhibit early and late phase of asthma :!:
Inhibit bronchial hyperresponsiveness by allergen
Mechanism - inhibit bronchial smooth ms contraction by cys-LT
LT synthesis inhibitor
Action thru 5-LPX inhibition -arachidonic acid lipoxygenation formed LT ,catalyzed by 5-LPX
Zileuton
Potent selective inhibitor of 5-LPX
Inhibit all 5-LPX products
Inhibit LTB4
Therapeutic effect
Effect similar to cys-LT1 antagonist
Inhibitory effect of LTB4
Inhibitory effect of 5-LPX product
TOXICITY
Very little
Factor - LT production is confined at inflammatory site only
Newer agent
Immunomodulator
Omalizumab
Recombinant DNA - derived humanized IgG monoclonal antibody
Specific bind to IgE therefore reducing IgE binding to mast cell
Reduce sensitivity to allergen
Control sever allergic asthma (that does not respond to high dose of corticosteroid)
Side effect and toxicity
EXCESSIVE use
Skeletal ms tremur
Hyperglycemia
Cardiovascular effect
Hypertension
ORAL administration cause
Systemic effect
Parenteral administration
Severe case (status asthmaticus)