Pharmacology Flashcards
What does stimulation of postganglionic cholinergic fibres cause? (2) (parasymp)
Bronchial smooth muscle contraction
Increased mucous secretion
What does stimulation of postganglionic noncholinergic fibres cause? (parasymp)
Bronchial smooth muscle relaxation
In the sympathetic division, what brings about bronchial smooth muscle relaxation via β2-adrenoceptors on ASM cells?
Activation by adrenaline from adrenal gland
In the sympathetic division, what is the result of stimulated B2-adrenoreceptors? (3)
Bronchial smooth muscle relaxation
Decreased mucous secretion
Increased mucociliary clearance
In the sympathetic division, what is the result of stimulated a1-adrenoreceptors?
Vascular smooth muscle contraction
Effect of PKA on activity of MLC
Phosphorylates and inhibits MLCK
Phosphorylates and stimulates myosin phosphatase
–>Dephosphorylates MLC
–>Causes relaxation of bronchial smooth muscle
Asthma
A recurrent and reversible obstruction to the airways in response to stimuli that are not necessarily noxious
Causes of asthma attacks (4)
Allergens (in atopic individuals)
Exercise (cold, dry air)
Respiratory Infections (e.g.viral)
Smoke, dust, environmental pollutants
Intermittent attacks of bronchoconstriction can cause (4)
Tight chest
Wheezing
Cough
Difficult breathing
Chronic Asthma
Involves pathological changes to the bronchioles that result from long-standing inflammation
Pathological changes from chronic asthma (5)
Increased mass of smooth muscle (hypertrophy, hyperplasia)
Accumulation of interstitial fluid (oedema)
Increased secretion of mucus
Epithelial damage (exposing sensory nerve endings)
Sub-epithelial fibrosis
FEV1
Forced expiratory volume in 1 second
PEFR
Peak expiratory flow rate
What is bronchial hyper-responsiveness in asthma?
Exposed sensory nerve endings leads to increased sensitivity of the airways to bronchoconstrictor influences (hyper-reactivity and hypersensitivity)
Type I Hypersensitivity reaction
Immediate/ early phase
Bronchospasm and acute inflammation
Fall in FEV1
Type IV Hypersensitivity reaction
Late phase
Bronchospasm and delayed inflammation
More prolonged and more severe fall in FEV1 than with type 1
Low level TH1 response to allergen in non atopic individual
Phagocytosis by antigen presenting (dendritic) cell
Cell-mediated immune response involving IgG and macrophages
Strong TH2 response to allergen in atopic individual
Phagocytosis by antigen presenting (dendritic) cell
Antibody-mediated immune response involving IgE
Cysteinyl leukotriene (CysLTs) receptors
Derived from mast cells and infiltrating inflammatory cells
Cause smooth muscle contraction, mucus secretion and oedema
Short acting B2-adrenoceptor agonists
SABAs
e.g. salbutamol
Are first line treatment for mild, intermittent, asthma
Are relievers taken as needed
Act rapidly to relax bronchial smooth muscle, increase mucous clearance and decrease mediator release from mast cells and monocytes
Long-acting B2-adrenoceptor agonists
LABAs
e.g.salmeterol, formoterol
Used for treatment of nocturnal asthma
LABAs must always be co-administered with a glucocorticoid.
Relievers in treatment of asthma
Act as bronchodilators
Relief of acute bronchal spasms
SABAs and LABAs
CysLT1 receptor antagonists
Preventors/ Controllers in treatment of asthma
Act as anti-inflammatory agents that reduce airway inflammation
Reduce frequency and severity of asthma attack
Glucocorticoids
Cromoglicate
Humanises monoclonal IgE antibodies
CysLT1 receptor antagonists
e.g. montelukast, zafirlukast
Relax bronchial smooth muscle in response to cysLTs,
Effective as add on therapy against early and late bronchospasm in mild persistent asthma
Effective in combination with other medications, including inhaled corticosteriods in more severe conditions
Methylxanthines
e.g. theophylline and aminophylline
Inhibit mediator release from mast cells, increase mucus clearance
Increase diaphragmatic contractility and reduce fatigue
Are second line drugs used in combination with B2-adrenoceptor agonists and glucocorticoids
Have a very narrow therapeutic window
Glucocorticoids
E.g.hydrocortisone/cortisol Decreases Inflammatory responses Decreases Immunological responses Increase translation of anti-inflammatory genes Used in prevention of asthma attacks
Chromones
Second line drugs used preventatively in treatment of allergic asthma
Decrease sensitivity of irritant receptors and stabilise mast cells
Short acting muscarinic antagonists used for treatment of COPD
Ipatropium
Long acting muscarinic antagonists used for treatment of COPD
Tiotropium
Glycopyrronium
Aclidinium
Umeclidinium
Which part of muscarinic receptor antagonists’ chemical structure reduces absorption and systemic exposure?
Quaternary ammonium group
M1 muscarinic receptors
Increase frequency of action potential resulting from nicotinic receptor stimulation
M2 muscarinic receptors
Reduce release of ACh
M3 muscarinic receptors
Mediate contraction to ACh
What muscarinic antagonist is the most useful in treatment of COPD
M3 muscarinic receptor antagonist
What is the drawback of using ipatropium? (SAMA)
Non-selective blocker of M1, M2 and M3 receptors
How is functional selectivity of M3 receptors achieved?
Differences in rates of association and dissociation- Drugs act on M3 receptors longer than M1 and M2 receptors
Short acting B2 adrenoreceptor agonists used in treatment of COPD
Salbutamol
Long-acting B2 adrenoreceptor agonists used in treatment of COPD
Formoterol
Salmeterol
Ultra-LABA’s used in maintenance treatment for COPD
Indacaterol
Olodaterol
Rofumilast
Selective PDE4 inhibitor
Suppresses inflammation and emphysema in COPD
Drawbacks of rofumilast
Adverse gastrointestinal effects
Benefits/ limitations of administering glucocorticoids in combination with LABAs in COPD
Of benefit in patients who develop frequent and severe exacerbations when given with a LABA
Do not in themselves suppress inflammation
Reason for glucocorticoid unresponsiveness in COPD patients
Oxidative/nitrative stress
Reduced HDAC2
Drugs used in triple inhalers as one daily treatment for COPD
Fluticasone
Umeclidinum
Vilanterol
Rhinitis
Inflammation of the nasal mucosa
Symptoms of rhinitis
Rhinorrhoea
Sneezing
Itching
Nasal congestion and obstruction
Types of rhinitis
Allergic
Non-allergic
Mixed
Anti-inflammatory treatment of rhinitis
Glucocorticoids
Mediator receptor blockade in treatment of rhinitis
CysLT1 receptor antagonist
H1 receptor antagonists
Treatment to target nasal blood flow in rhinitis
Vasoconstrictors
Anti-allergic treatment for rhinitis
Sodium cromoglicate
Mechanism of glucocorticoids
Suppress recruitment of cytokines and mediators, eosinophils, basophils into nasal mucosa
Reduce vascular permeability
Examples of glucocorticoids
beclometasone
fluticasone
prednisolone
Mechanism of anti-histamines
Antagonists that block effects of histamine
Examples of second generation anti-histamines
Loratidine
Fexofenadine
Cetirizine
Mechanism of anti-cholinergic drugs
Antagonists which block muscarinic receptors on nasal glands that stimulate watery secretions when activated by ACh
Possible side effects of anti-cholinergic drugs
Dryness of nasal membrane
Example of anti-cholinergic drug
Ipatropium
Mechanism of sodium cromoglicate
Mast cell stabilization
Mechanism of cysteinyl leukotriene receptor antagonists
Reduce effects of CysLTs upon nasal mucosa
Example of CysTL receptor antagonist
Montelukast
Mechanism of vasoconstrictor
Mimic effects of noradrenaline
Act on a1-adrenoreceptors to decrease swelling in vascular mucosa
Example of vasconstrictor
Oxymetazoline
Classifications of allergic rhinitis
Seasonal allergic rhinitis (SAR)
Perennial allergic rhinitis (PAR)
Episodic allergic rhinitis (EAR)
Classifications of non-allergic rhinitis
Infectious rhinitis Hormonal rhinitis Vasomotor rhinitis Nonallergic rhinitis with eosinophila syndrome (NARES) Drug induced rhinitis
Types of rhinitis in which glucocorticoids are used
SAR
PAR
NARES
Vasomotor rhinitis
Types of rhinitis in which anti-histamines are used
SAR
PAR
EAR
Types of rhinitis in which anti-cholinergic drugs are used
Reduce rhinorrhoea in SAR and PAR
Types of rhinitis in which CysTL receptor antagonists are used
SAR
PAR