Bronchial Asthma, COPD, Antitussive & Expectorants Flashcards
Describe Bronchial Asthma; symptoms, pathophysiology and goals of therapy.
Bronchial Asthma is a chronic inflammatory disease of the bronchial airways.
Symptoms due to;
= episodes of Acute Bronchoconstriction
- Wheezing,
- Paroxysmal dyspnoea,
- Chest tightness
- Dry cough
Pathophysiology;
- Airflow Obstruction - resulting from;
- contraction of bronchial smooth muscle,
- chronic inflammation of the bronchial wall
- increased secretion of mucus
- Bronchial hyper-responsiveness
- due to histamine release from mast cells
- Inflammation
- due to Th2 cells = Eosinophils and Neutrophils
- Th2 = B cells = IgE production
— if left untreated, it may cause airway remodelling
Triggered by; Exposure to Allergens, Exercise, Stress, Respiratory infections.
Therapeutic Goals;
- Decreas the intensity and frequency of symptoms
- Quick relief medication
- Long term drugs designed to reverse and prevent airway inflammation.
What are the stages of Bronchial Asthma?
Mild Intermittent
- max 1x /week symptoms
- <2x /month night symptoms
- FEV1 >80% PEF < 20%
Mild Persistent
- min 2x / week symptoms
- > 2x /month night symptoms
- FEV1 >80% PEF 20-30%
Moderate Persistent
- daily symptoms can impair physical activity
- > 1x /week night symptoms
- FEV1 60-80% PEF >30%
Severe Persistent
- daily symptoms, reduced activity, exacerbations.
- frequent night symptoms
- FEV1 <60% PEF >30%
List types of Asthmatic drugs
ß2 Agonists (SABA)/(LABA)
Antimuscarinic drugs
Leukotrine Antagonists
Xanthines
Glucocorticoids
Anti- IgE antibodies
Degranulation Inhibitors
What is the main difference between asthma and COPD and the goal of therapy
Asthma is Reversible
- goal is to relieve symptoms and reverse and prevent airway inflammation.
COPD is Irreversible- chronic inflammatory damage
- goal is to prevent complete closure of the airways
Describe SABA medication
** Short Acting ß2 Agonists ***
Onset : 5 mins
Duration : 4-6 hrs
Dosage : Inhalation, *oral (Albuterol) *injection(terbutaline)
Used in Acute asthmatic attacks
Terbutaline - only one with injection form
Salbutamol (Albuterol) - fastest acting agent
Metaproterenol
Levosalbutamol (Levalbuterol)
Fenoterol
- **Actions***
- Bronchodilation
- Increased mucociliary transport
- Decrease release of inflammatory mediators
Describe LABA medication
** Long Acting ß2 Agonists **
Duration : >12 hrs
Dosage : Inhalation
High Lipid Solubility!!
Used to prevent symptoms not to relieve them
Used in combination with antiinflammatory drugs
SALMETEROL
FORMOTEROL (fastest onset)
***disadvantage = increased risk of death from an asthma attack
Describe VLABA
*** Ultra Long Acting ß2 Agonists ***
Duration: >24 hrs
Dosage: Inhalation
Used in COPD patients
Indacaterol Carmoterol Clenbuterol *oral Bambuterol *oral Procaterol *oral
List Adverse effects of ß2 Agonists
Heart - due to ß1 stimulation = ^HR & contractility
Vessels in Skeletal.m = Vasodilation
Tocolytic activity
Hyperglycemia
Hyperlipidemia
Hypokalemia (due to insulin release)
Sleeping problems
Tolerance
Describe other non-selective ß2 Agonists
Epinephrine - higher activity on ß than a receptors
Isoproterenol - Equally potent to ß1 & ß2 receptors
Ephedrine - very weak sympathetic stimulator
- Indirect release of NE
- Directly binds and stimulates ß2 receptor
Describe and list Xanthenes
**Theophylline*****
(used for asthma orally)
**Aminophllyine*****
(a more water soluble form administered parenterally)
*other Xanthines not used for asthma
= Caffeine, Theobromine
*** Mechanisms of action ****
- PDE Inhibition
PDE 3 & 4 inhibition leads to relaxation of smooth muscle which results in vasodilation and bronchodilation due to the elevated levels of cAMP
- Adenosine 1 receptor antagonists
Results in increased cAMP.
(A1receptors are coupled to inhibition ofadenylate cyclaseand their effects are opposite to those ofß-receptoragonists.)
Effects of Xanthenes
- Bronchodilation
- Enhancement of movement of cilia
- Inhibit release of inflammatory mediators
- Heart = increased contractility
- Kidney = dilated vessels
- CNS = Caffeine like actions, **tremors, **seizures
Describe Theophylline
It is a Xanthene
Inhibits PDE & Adenosine 1 receptor
Administered orally for severe asthma prophylaxis
Inactivated by CYP1A2
** interaction with fluoroquinones & macrolides
May saturate Hepatic metabolism
Has a narrow Therapeutic window.
Zero kinetic metabolism enhances the risk of too high plasma concentration
Effects
= Bronchodilation, cilia movement, inhibit release of inflammatory mediators, increased contractility in heart, vasodilation in kidney and caffeine like effects in CNS
Adverse Effects;
- Arrhythmia, decreased respiratory rate
- GI symptoms; diarrhea,
- Hypokalemia, Hyperglycemia (* increased ß2 )
- Restlessness, insomnia, seizures
- increased Diuresis
Describe Antimuscarinic agents used for asthma and list of drugs
M3 receptors are in the bronchial smooth muscle cells = causing Contraction.
** We only use drugs having Quaternary nitrogen because plasma concentration remains low and the drugs do not enter the brain **
** not recommended for routine treatment
** less effective than ß2 agonists
Dosage: Inhalation
Ipratropium (non selective) : 4-6 hrs Tiotropium (M3 selective) : 24 hrs Glycopyrronium (M3 selective): 24 hrs Aclidinium Br (M3 selective) : 12 hrs
Actions
- Bronchodilation
- Inhibition of bronchial secretion
- used as adjuncts to ß2 agonists
- replace ß2 agonists if they are contraindicated
- in patients with concomitant COPD
Adverse effects
*** Dry mouth!!
Describe Glucocorticoids and give drug examples
They are Controllers from the 2nd stage of Asthma
Small doses are used (reduced to min needed)
Usually administered in the morning (less influence on HPA axis)
Onset of effects needs hours due to intracellular nuclear receptors
Discontinuation leads to loss of control within a few weeks intermittent vs continuous taking
All Glucocorticoids are Lipophylic (absorbed in GI)
*** Effects *****
- Inflammation decreases
(decrease inflammatory cascade, reverse mucosal edema, decrease capillary permeability and inhibit release of leukotrienes)
- decreased Hyperactivity of airways
- expression of ß2 receptors increases
**Mechanism of action**
- Inhibit the release of arachidonic acid through Phospholipase A2 Inhibition
= direct antiinflammatory action
\_\_\_\_\_\_\_Inhalation\_\_\_\_\_\_ Beclomethasone Fluticasone Budesonide ***used only for local indication not systemic
________Oral___________
Prednisolone
Methylprednisolone
_________IV____________
Dexamethasone
Methylprednisolone
- **Adverse effects*******
- local oropharyngeal Candidiasis
- Hoarseness (due to atrophy)
- systemic long term effects
****Inhalation drugs are part of therapy from the 2nd stage of asthma. Systemic drugs are only given in case of severe chronic asthma or acute attack.
Describe function of Cysteinyl leukotrienes and LTB4
LTC4, LTD4, LTE4
bind to CysLT1 Receptors
= Bronchoconstriction and hyper-responsiveness
= increase capillary permeability = mucosal edema
= promotes mucus secretion
LTB4 is a potent chemoattractant for neutrophils and eosinophils.
Describe and list drugs influencing leukotriene pathway
Used in severe asthma or when steroids need to be replaced.
- *** CysLT1 Receptor Antagonists ****
- Zafirlukast (2× / day)
- Montelukast (1× / day)
- *** 5 - Lipoxygenase inhibitor ****
- Zileuton (not used today)
** Effects *****
= Antiinflammation
= Bronchodilation
Onset : in about 3 hrs
Dosage : Oral
Metabolised by CYP enzymes
Food impairs the absorption of Zafirlukast
Zafirlukast and Montelukast undergo biliary excretion
Zileuton is eliminated in urine
*** Adverse effects **
Zileuton might be Hepatotoxic
Zileuton inhibits CYP1A2
Headache and dyspepsia
Zafirlukast is an inhibitor of cytochrome P450 Isoenzymes
** Aspirin cannot be given to asthmatic patients because it results in increased conversion of AA to LT due to COX inhibition.
