Archive for the ‘ L3-Pharma Asthma ’ Category

L3- Pharmacology of Bronchial Asthma

Pharmacology of a Drug :

1.Source & chemistry

2.Absorption, Fate and Excretion

3.Pharmacological Actions and Effects

4.Preparation and Doses

5.Therapeutic Uses

6.Side Effects & Toxicity

7.Contraindications

CLINICAL  PRESENTATIONS of  Bronchial Asthma

1.ACUTE   ATTACK

2.STATUS  ASTHMATICUS

3.IN  BETWEEN  THE  ATTACKS

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PATHOPHYSIOLOGY  OF BRONCHIAL  ASTHMA

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HOW TO TREAT BRONCHIAL ASTHMA ?

[A]   BRONCHODILATORS

[B]   ANTI-INFLAMMATORY

[C]   PROPHYLACTIC

[D] OTHER DRUGS

[E]   PREVENTION

[F]   Anti-IgE monoclonal antibodies

[G]   Possible Future Therapies

[A]   BRONCHODILATORS

1. SYMPATHOMIMETICS ( Beta Agonists)

2.METHYLXANTHINES ( Theophyline )

3.MUSCARINIC  ANTAGONISTS ( Ibratopium )

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1- SYMPATHOMIMETICS (Beta- Agonists)

•INCREASE

  1. cAMP
  2. mucociliary function

•DECREASE

  1. mediators
  2. microvascular  permeability

1) NON-SELECTIVE B-Agonist.

  • EPINEPHRINE

2) SELECTIVE B- Agonist.

  • SALBUTAMOL
  • SALMETEROL

-LONGER DURATION

-COMPLETELY ABS. ORALLY

-MORE SELECTIVE FOR B2 OF RESP. T.

-DEVOID OF CVS EFFECTS

-CH. BR. ASTHMA

-ACUTE BR. ASTHMA (SALBUTAMOL INH.)

2- METHYLXANTHINES( Theophyline )

MECHANISM

1.  ADENOSINE  R. (A1) BLOCK

2.  cAMP (phosphodiesterase inh.)

3.  ANTI-INFLAMMATORY & IMMUNOMODULATING  EFFCTS (By inhibiting PDE &T lymphocyte proliferation &cytokine production)

•PH.  EFFECTS

  1. BRONCHODIL
  2. CNS    STIM.
  3. COP
  4. DIURESIS
  5. GASTRIC JUICE
  6. SK. M. POWER

•USES

  1. BRONCHIAL ASTHMA
  2. ANALEPTIC
  3. FATIGUE

•PH. KINETICS

  1. HEPATIC  METABOLISM
  2. GOOD INT.  ABSORPTION

•ADVERSE  EFFECTS

  1. GASTRIC  IRRITATION
  2. ARRHYTHMIAS
  3. HYPOTENSION, SYNCOPE  & CARDIAC ARREST With rapid i.v. injection
  4. IRRITABILITY, INSOMNIA  & CONVULSIONS
  5. TACHYPNEA &  RESPIRATORY  ARREST WITH LARGE DOSE

•INDICATIONS  &  DOSES

  1. ACUTE  ATTACK symptomatic relief slow iv loading dose infusion
  2. IN  BETWEEN    ATTACKS  &  CHRONIC ASTHMA
  3. CHRONIC  BRONCHITIS  WITH SPASM

PRECAUTIONS

  1. SEVERE  CARDIAC DISEASE
  2. SEVERE  HYPOXIA
  3. HEPATIC  DISEASE
  4. PEPTIC  ULCER
  5. DRUG INTERACTIONS
  6. RAPID  i.v. injection

3- MUSCARINIC  ANTAGONISTS  (Ibratopium )

i-IPRATROPIUM (inhalation)

•DERIVATIVE OF ATROPINE

•LESS EFFECT ON SPUTUM VISCOSITY

•QUATERNARY  AMINE

•LESS EFFECTIVE THAN  B2 AGONISTS

•+  B2 AGONISTS -INCREASES EFFECTIVENESS  & DURATION

[B] REDUCTION OF BRONCHIAL INFLAMATION & HYPERREACTIVITY

(1) STEROIDES

•Mechanism:

  1. ↑ STABILITY OF ENDOTHELIAL,SMOOTH M. & LYSOSOMES
  2. ↑ CATECHOLAMINE SENSITIVITY
  3. ↓ CAPILLARY PERMEABILITY
  4. ↓ IMMUNE REACTIONS
  5. ↓ THE INFLAMMATORY RESPONSE & HYPERREACTIVITY

USE

-OTHERS FAIL:

-for mild or moderate cases inhaled corticosteroids  are used chronically

•SIDE EFFECTS

  1. ADRENAL SUPPRESSION
  2. CUSHING      S.
  3. IMMUNOSUPPRESSION
  4. FLARE    UP     OF    INFECTION
  5. GROWTH    RETARDATION
  6. PEPTIC    ULCER
  7. OROPHARYNGEAL   CANDIDIASIS

PRECAUTIONS

-OF RAPID  WITHDRAWAL

-SODIUM  &    POTASSIUM  IN DIET

-FOLLOW UP FOR:

  1. GLUCOSURIA
  2. HYPERTENSION
  3. INFECTION

(2) LEUKOTRIENE INHIBITORS

i- RECEPTOR ANTAGONISTS:

Zafirlukast  & Montelukast

ii- SYNTHESIS  INHIBITOR:

Zileuton

[C] PROPHYLACTIC: MAST CELL STABILISERS

1- DISODIUM  CROMOGLYCATE

[D] OTHER DRUGS

1- TRANQUILIZERS

2- EXPECTORANTS  & MUCOLYTICS

3- MIXTUREE OF  O2  &  HELIUM

[E] PREVENTION OF EXPOSURE TO PRECIPITATING FACTORS

PRECIPITATING FACTORS

•ANTIGEN

•RESP.  INFECTION

•EMOTIONAL DISTURBANCE

•DRUGS :

  1. CHOLINOMIMETICS
  2. NON SELECTIVE   BB
  3. HISTAMINE LIBERATORS
  4. PENICILLINS
  5. PGF2œ
  6. NSAIDS

How To Make Proper Drug Choice ?

ACUTE ATTACK:

  1. B2- INHALATION
  2. ADRENALIN  SC
  3. THEOPHYLLINE SLOW  IV +  STEROID INHALATION

BETWEEN ATTACKS:

  1. MAST CELL STABILISER
  2. STEROID INHALATION

STATUS ASTHMATICUS:

  1. HOSPITALISATION

  2. HYDROCORTISONE 200MG IV

  3. SALBUTAMOL AEROSOL

  4. HUMIDIFIED O2 OR O2 + HELIUM

  5. ACIDOSIS & DEHYD. CORRECTION

  6. ANTIMICROBIA

  7. MUCOLYTIC & EXPECTORANT

CHRONIC ASTHMA:

  1. B2 AGONIST  SR

  2. THEOPHYLLINE SR

  3. B2 AGONIST  INH.

  4. + IPRATRPIUM BROMIDE

  5. + INHALED CROMOLYN

  6. + INHALED STEROID

  7. + ORAL STEROID

[F] Anti-IgE Monoclonal Antibodies (Omalizumab)

•Against the portion of IgE that binds to its receptors (FCe-R1 & Fce-R2) on mast cells

•Indicated with severe disease characterised by frequent exacerbations

[G] Possible Future Therapies

1. MC antibodies against:    1- IL-4, IL-5

2. Protease inhibitors

3. Immunomodulators aimed at shifting lymphocytes from the TH2 to the TH1 phenotype

4. Selective inhibitor against TH2 lymphocytes directed against particular antigens

5. Anti- Chlamydia pneumoniae or Mycoplasma pneumoniae