Drug used in asthma

Drug used in

Asthma

Drug used in Asthma

• Bronchodilator

• Corticosteroid

• Cromolyn&nedocromil

• Leukotriene pathway inhibitor

1. Bronchodilator

A. Sympathomimetic agents

B. Methylxanthines

C. Antimucarinic agents

Direct effect of autonomic nerve activity on bronchiolar smooth muscle

Sympathetic

• Receptor Beta-2

• Action ralaxation

Parasympathetic

• Receptor M3

• Action contraction


Beta-2- selective agent-Abuterol(Subutamol),Terbutaline,Metaproterenol,Mechanism of action• Relax airway smoothmuscle• release of mediators from inflammatory cells• Inhalation Onset(1-5 min) Maximum Bronchodilator(1hr) Duration of action (3-6hr)


Long-acting Beta-2- selective agonist

• Salmeterol and formoterol

• High lipid solubility

• Long duration of action(>12hr)


Clinical uses

• Acute bronchoconstriction

• Exercise-induced bronchoconstriction

• Nocturnal asthma(long-acting)


Adverse effects

• Skeletal muscle tremor

• Nervousness

• Trachycardia

• Arrhythmia

B. Methylxanthines

• Theophyline,theobromine,caffeine

Mechanism of action

1. Inhibit adenosine receptors Bronchodilation

Histamine release from mast cells

2. Inhibitor phosphodiesterase(PDE4 High dose

intracellular cAMP

Bronchodilation

B. Methylxanthines

Pharmacodynamics

• CNS

alertness,nervourness, insomnia, convulsion

Caffeine

• CVS

– positive chonotropic & inotropic effects

• GI tract

Secretion of gastric acid & digestive enzymes

B. Methylxanthines

Pharmacodynamics

• Kidney

Weak diuretics

• Smooth muscle

Bronchodilation

release of histamine

Theophyline

B. Methylxanthines

Pharmacodynamics

• Skeletal muscle

contractions

B. Methylxanthines

Pharmacokinetics

• Slightly soluble in water

• Sustained-release

Theraputic blood levels>12hr

• Metabolism(liver)

Liver disease=> metabolism

Smoking=> metabolism

Children=> metabolism

• Excretion(urine)

B. Methylxanthines

Clinical uses

• Pt. intalerant of inhaled beta-agonists

• Noctural asthma (sustained-release)

Adverse effects

• Narrow theraputic window(10-20mg/L)

• 15mg/L => anorexia, N/V, abd.discomfort, headache, anxiety

• 40mg/L => seizure or arrythmias

B. Methylxanthines

Drug interaction

• theophyline level Phemobarbital, phenytoin, rifampin

• theophyline level Clmetidine, ciprofloxacin, erythromycin

C.Antimucarinic agents

• Atropine, ipratropium(selective)

Mechanism of actions

• Competitively inhibit effects of Ach at mucarinic receptors

• Inhibit airway smooth muscle contraction

• Increased mucus secretion


Pharmacokinetics

• Quarternary ammonium derivative of atropine

• Poorly absorption

• Not enter CNS

• Inhalation

– Maximal bronchodilation(1-2hr)

– Duration of action (3-5hr)


Clinical uses

• Pt. intalerant of inhaled Beta-agonist

Adverse effects

• Dryness of mouth(inhalation)

2.Corticosteroids

• Belomethasone, budesonide, flunisolide, prednisolone

Mechanism of action

• Inhalation of production of inflammatory citokines

• Anti-inflammatory effect

• Decreased bronchail hyperresponsiveness

• Decreased frequency of asthma exacerbations

• Increased effects of Beta-agonists

2.Corticosteroids

Clinical uses

• Block late response(inhaled)

• Severe persistent asthma(Oral)

Adverse effects

• Oropharyngeal candidiasis, hoarseness

• Adrenal insufficiency

• Osteoporosis, cataracts

• Slow rate of growth(asthma)

3. Cromolyn & nedocromil

Mechanism of actions

• Inhibit mast cell degranulation

• Prevent inflammatory response

• Little inhibitory effect on mediator release form basophil

• Decreased bronchial hyperresponsiveness

(chronic use)


Pharmacokinetic

• Poorly absorbed from GI tract

• Maximal bronchodilate(15min)

• Excretion(urine,bile)


Clinical uses

• Children

• Protective effect

- antigen and exercise-induced asthma

Adverse effects

• Minor

• Throat irriation, cough, mouth dryness, chest tightness, wheezing

4. Leukotreine pathway inhibitor

Mechanism of action

• Zileuton

- 5-lipoxyginase inh.

- prevent leukotreine synthesis

• Zafirlukast, montelukast

- LTD4-receptor antagonist

- Inh. Binding of LTD4 to its receptor

4. Leukotreine pathway inhibitor

Pharmacodynamics

• Decreased airway response to antigen

• Decreased frequency of exacerbation

Clinical uses

• Pt. intolerant of inhaled beta-agonists

• Aspirin-induced asthma

Adverse effects

• Liver toxicity(Zileuton)

Imflammide MDI

Imflammide MDI• Budesenide alpha-17alpha-butylidene dioxypregna-1,4-dine-11bata-21-diol-3,20-dione

Budesenide inhaler corticosteroid airway hyper-responsiveness

IgE arachidonic acid metabolism leukotrimrte prostaglandins cytokine inflammatory cells -receptor

- g - mcg mcg - - g

- mcg - mcg -

-

cortisol neutrohilslymphocyte esinophiles hypercorticism hypothalamic-pituitary-adrenal

suppression HPA-Axis

budesonide asthma attack3. corticosteroid inhaler steroid hypothalamic-pituitary-adrenal axis Budesonide

corticosteroid corticosteroid Budesonide corticosteroid

corticosteroid corticosteroid

corticosteroid 4. corticosteroid steroid

eczema

glucocorticosteroid glucocorticosteroid

Budesonide blood placental barrier corticosteroid Budesonide rat

rat glucocorticosteroid

Budesonide Budesonidecorticosteroid Budesonide

candida candida oropharynx) Budesonide candida spacer

candida

• Budesenidealpha-17alpha-

butylidene dioxypregna-1,4-dine-11bata-21-diol-3,20-dione

•

Imflammide MDI

Imflammide MDI• Budesenide

inhaler corticosteroid

airway hyper-responsiveness

IgE arachidonic acid metabolism leukotrimrte prostaglandins

cytokine inflammatory cells

Imflammide MDI

•

- mcg

- mcg

mcg

- - g -

mcg - mcg

Imflammide MDI

•

-

-

Imflammide MDI

•

cortisolneutrohils

lymphocyte esinophiles

hypercorticism hypothalamic-pituitary-adrenal suppression

HPA-Axis

Imflammide MDI

•

• Drug interaction

corticosteroid Budesonide

Imflammide MDI

•

ipratropium bromide 500 mcg fenoterol 1250 mcg

Imflammide MDI

Berodual

Berodual

•

–4

ipratropium bromide 500 mcg fenoterol 1250 mcg

Berodual

•

2 ipratropium bromide fenoterol

hydrobromide

Berodual

•

ipratropium bromide vagus

cyclic GMP

ipratropium bromide

Berodual

•

fenoterol hydrobromideBeta-2 receptor

histamine , methacholine

Berodual

•

2

fenoterolipratropium bromide

fenoterol ipratropium bromide

Berodual

•

Berodual

•

, ,

fenoterol hydrobromide

Berodual

•

·

·

Berodual

•

· -2

(hypokalemia)

narrow-angle

Berodual

• S/E

-

Salbutamol(Ventolin)


• Pharmacology )

Salbutamol b - adrenergic agonist

· bronchodilater )

· vasodilater)

· uterine relaxation )

·

· tachycardia


• Administration )– > 12

· Inhaler for asthma : Metered-dose inhaler 90-180 mg ( 1-2 puff ) 4-6

Inhalation solution ( Nubulizar ) 2.5 mg 3-4

· Inhaler for severe bronchospasm : Nubulizer 2.5-5 mg ( 0.5-1 ml nubulizer

0.5% 2-3 ml ) 4-6 1-2


• Administration )

· PO for asthma 2-4 mg 6-8 32

mg/day

· Sustain-release tablet 4-8 mg 12 32 mg/day

Evohaler.JPG



< 12

· Inhaler for asthma : Metered-dose inhaler spacer 90-180 mg (1-2 puff ) 4-6 Inhalation solution 0.05-0.15 mg/kg 4-6

· 20 Nubulizer0.5% 0.25 ml

· 20 Nubulizer0.5% 0.5 ml 1ml 4-6

1-2 severe bronchospasm

· PO for asthma



2-6

· 100-200 mg/kg/dose 8 4 mg 8

6-12

· 2 mg 6-8 24 mg / day



· Inhaler for asthma

· PO : 2 mg 3-4 8 mg 3-4

spacer

· 4-5


·

· 1

· 10

· 1-2


• dosage form )Inhaler · Metered-dose 90 mg/puff 200 puff /inhaler · Metered-dose ( HFA ) 90 mg/puff 200 puff

/inhalerInhaler solution· 0.5% ( 5 mg/ml ) · 0.083% ( unit dose solution 3 ml )Tablet 2 mg 4 mgSyrup 0.4 mg/mlSustain-release tablet 4 mg 8 mg


• pharmacokinetic )onset )

Inhaler

· onset 15

· peak 60-90

Oral

· onset 30-60

· peak 2-3


• pharmacokinetic )duration )

· 4-6 Fate

Oral bioavailability 50% Peak serum level· inhaler 0.15 mg/kg peak 5.6 mg/L ( 23

nmol/L ) · tablet 4 mg peak 10 mg/L ( 42 nmol/L )

Hepatic first-pass metabolism 50% inactive

sulfate conjugate metabolized


•

Adverse reaction )

dose related tachycardia

peripheral vasodilation ) b - receptor ,

tremor ), palpitation ) nausea ) dose-related effect

aerosol b - agonist potassium


• precaution )

· pregnancy ) , cardiac disorder coronary insufficiency , hypertension )

Prednisolone

• is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant, and affects virtually all of the immune system

• Uses in

severe asthma,severe allergies, juvenile dermatomyositis

http://en.wikipedia.org/wiki/Corticosteroid

http://en.wikipedia.org/wiki/Immunosuppressive_drug

http://en.wikipedia.org/wiki/Allergies

http://en.wikipedia.org/wiki/Juvenile_dermatomyositis

http://en.wikipedia.org/wiki/Juvenile_dermatomyositis

Prednisolone

• Dose in asthma

1-2 mg/kg/day 2-3 3-5day

THE END

Drug used in asthma

Health & Medicine

Transcript of Drug used in asthma