Anti-inflammatory Drugs & Cough Flashcards
Use of Anti-inflammatory Drugs
- Reduce severity and frequency of asthma attacks
- Limit progression of disease by inhibiting remodelling
- Reduce night-time asthma attacks by preventing late-phase
Glucocorticoids
- Mainly used anti-inflammatory
properties in asthma - Not a bronchodialator not relieving early phase
- Prevents progression of chronic asthma
- Effective in acute severe asthma
- Add-on inhalational therapy in asthma when bronchodilator is used more than once daily
Glucocorticoid mechanism
- Glucicorticoids drugs bind to the glucocorticoid receptors in the cytoplasm
- Complex migrates into nucleaus and binds to glucocorticoid response elements
- effects inhibit glucocorticoid response element - decrease pro inflammatory COX-2
- effect stimulatory glucocorticoid response element increase anti-inflammatory gene products IL-10
Immunosupression response of Glucocorticoids
- IL-10 Decreases cytokine formation
decreases recruitment and activation of inflammatory T cells - Inhibit esponses responsible for production of IgE and its receptors and for recruiting eosinophils
- Effect early phase and causes late phase of asthma
Anti-inflammatory response of Glucocorticoids
- inhibits phospholipase A2
- decreased inflammatory mediators
also suppress COX-2 induction ↓inflammatory prostanoid production - Reduce severity of early phase response and prevent late phase response
Glucocorticoids impact on inflammatory cascade
- Upregulate Beta 2 adrenoreceptors - regular use of beta 2 adenorecptor agonist (LABA) use with ICS
- Eventually reduce number of mast cells
– May have some effect on early phase
Formulation of corticosteroids: Inhaled
Examples
- Beclometasone dipropionate (BDP)
- Budesonide
- Fluticasone propionate (2 x potent as BDP)
- Mometasone
Formulation of corticosteroids: oral
Examples
- Prednisolone
- Given as a single dose in the morning to mimic the body’s
cortisol secretion
Formulation of corticosteroids: IV
Example
- Hydrocortisone
Glucocorticoids Unwanted effects that are uncommon with inhaled
- Systemic effects only in high doses
– Spacers minimise
Glucocorticoids unwanted side effects: Oropharyngeal candidiasis
- Suppress T-lymphocytes important
against fungal infection
– Spacer devices reduce
Glucocorticoids unwanted side effects: Regular high doses
- Adrenal suppression esp in
children
Other unwanted side effects of Glucocorticoids
- Iatrogenic Cushings
- Osteoporosis
- Increased risk of pneumonia in elderly with COPD
- Poor absorption from GI tract
– Fluticasone / mometasone unwanted effects less likely
Steroid card
Mast cell stabilisers
- Variable efficacy shown in antigen, exercise and irritant induced asthma - not a bronchodialator
- Weak anti-inflammatory effects
- Reduce immediate & late-phase responses
– Reduce bronchial hyper-reactivity
How is the mast cell stablisation mechanism unclear
- Mast cell stablisation plays no part in oral anti-histamines
- Drepresses signal from irritant receptors
- May inhibit cytokine release
Immunotherapies: Omalizumab
- Monoclonal antibody
- Anti-IgE antibody –
- Once binds to IgE these are
removed from circulation - IgE receptors also reduced
- Reduces mediator release from
mast cells - Gradually reduces inflammation
- prophylaxis severe and persisitant
- Risk of anaphylaxis with injection
Reflex cough action
- Afferent sensory stimulus to an efferent motor response
- A forceful movement of respiratory muscles to affect the reflex
- essential reflex response of the airways under both physiological and pathophysiological conditions
Two roles of a cough
- The final pathway of mucociliary clearance
- Part of the defence mechanisms against inhaled particles and
noxious substances
Causes of a cough
- Irritants-smokes, fumes, dusts, etc.
- Diseased conditions like COPD, tumors of thorax, etc.
- Pressure on respiratory tracts
- Infections
Components of cough reflex
- Cough receptors
- Afferent nerves
- Cough center (medulla)
- Efferent nerves
- Effector muscles
Irritation
A stimulus irritates the upper
airways and results in a reflex action leading to cough
Inspiration
Occurs to achieve optimum
thoracic gas volume thus allowing the
most efficient use of the expiratory muscles
Compression
With the glottis closed, the
abdominal muscles and the thoracic cage actively contracts, leading to high
intrathoracic pressures
Expulsion
The glottis opens and a high airflow results. The force of expression is increased by collapsing the airways following the explosive decompression caused by glottic opening
Relaxation
At the end of the cough,
the intrathoracic pressure decreases
as the expiratory muscles relax and a
transient bronchodilatation occurs
Mechanism of ACE
- ACE metabolises bradykinin which is potent vasodialator peptide that exerts its vasodialatory action via B2 receptors
- Aterioles dilate due to the release of prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor
ACE inhibitor effect on bradykinin
- Increase in bradykinin levels contributing to vasodilator action
What is bradykinin
- Chemical irritation of c fibres of
respiratory tract – through release of proinflammatory peptides - Substance p and histamine – these stimulate hyper stimulate
the cough reflex
Classification of cough
- Dry or chesty
- Classified as acute, subacute or chronic
Acute cough
- Been present for less than three weeks and can be divided into infectious and non-infectious causes
Subacute cough
Resolves over three to eight weeks
Chronic Cough
- Coughs are those present for more than eight
weeks
Chronic Cough cause
- Environmental irritants
- Conditions within the lungs
- Conditions in the upper airways
- Conditions within the chest cavity
- Digestive causes
- Asthma and COPD common
Antitussives
- Cough suppressants
- All in clinical use are opioid analgesics
- Suppress cough in doses below those required
for pain relief - Action is poorly defined
- Suppress cough centre
What do dry cough drugs do
- Increase bronchial secretion or reduce its viscosity to facilitate removal
Secretion enhancers
Sodium citrate, potassium iodide, guaiacol, tolu
balsam, ammonium salts
Mucolytics: Acteylcysteine
- Actively breaking down sulphide bonds thinning mucus
- Useful in cystic fibrosis and COPD
COPD treatment efficacy: ICS
- Very effective in asthma but may only reduce exacebations in COPD
Side effects of ICS
- Adrenocortical suppression
- Bone mineral density reduced – osteoporosis
- Candidiasis of mouth and throat
- Resistance in certain individuals
Phosphodiesterase type 4 inhibitors
- Inhibition of PDE results in cAMP accumulation e.g. Roflumilast
- found in airways smooth muscle and inflammatory cells in COPD
- Reduced cytokines released from neutrophils
– Reduced accumulation of T-cells in lungs
– Reduced cell death of airway cells
Treatment of acute exacerbations of oxygen
- use low strength O2 in COPD 24%
- Become tolerant to prolonged CO2 retention & respiratory drive is maintained by low levels of O2
- High strength O2 will cause respiratory arrest
