Respiratory Pharmacology Flashcards
Where are cell bodies of the preganglionic fibres located?
Located in the brainstem
What is a sympathetic response triggered by?
External stimuli
Causes smooth muscle relaxation
What does a parasympathetic response do?
Resets everything
Act through cholingeric neurones to stimulate muscle contraction
Where are the cell bodies of postganglionic fibres located?
Embedded in the walls of the bronchi and bronchioles
What does stimulation of postganglionic cholingeric fibres cause?
- bronchial smooth muscle contraction (mediated by M3 muscarinic ACh receptors on ASM cells
- Increased mucus secretion mediated by M3 muscarinic ACh receptors on gland (goblet) cells
What does stimulation of postganglionic noncholingeric fibres cause?
- bronchial sooth muscle relaxation mediated by nitric oxide (NO) and vasoactive intestinal peptide (VIP)
Post ganglionic fibres supply what glands and muscle blood vessels?
- Submucosal glands
- Smooth muscle
What does stimulation of autonomic transmitters (sympathetic) cause?
- BRONCHIAL SMOOTH MUSCLE RELAXATION via Beta2-adrenoceptors on ASM cells activated by adrenaline released from adrenal gland
- DECREASED MUCUS SECRETION mediated by beta2-ADR on gland (goblet) cells
- INCREASED MUCOCILIARY SECRETION mediated by beta2-ADR on epithelial cells
- VASCULAR SMOOTH MUSCLE CONTRACTION, mediated by alpha1-ADR on vascular smooth muscle cells
Contraction of smooth muscle results from what?
Phosphorylation
of the regulatory mysoin light chain (MLC) in the presence of elevated intracellular Ca2+ (and ATP)
Relaxation of smooth muscle results from what?
Dephosphorylation
of MLC by myosin phosphatase which has constitutive activity
What do activities of myosin light chain kinase (MLCK) and myosin phosphatase do to each other?
Oppose each other
What happens to the rate of phosphorylation in the presence of elevated intracellular Ca2+?
The rate of phosphorylation exceeds the rate of dephosphorylation
If the rate of phophorylation exceeds the rate of dephosphoryltion in the presence of elevated intraceullar Ca2+ what does relaxation of smooth muscle require?
The return of intracellular Ca2+ concentration to basal level - achieved by primary and secondary active transport
What is asthma (in the short term)?
A recurrent and reversible obstruction to the airways in response to substances that…
- are not necessarily noxious
- normally do not affect non-asthmatic subjects
What are the causes of asthma attacks?
- Allergens (in atopic individuals)
- Exercise (cold, dry air)
- Respiratory Infections (e.g. viral)
- Smoke, dust, environmental pollutants etc.
What are the symptoms of asthma? (intermittent attacks of bronchoconstriction)
- tight chest
- wheezing
- difficulty in breathing
- cough
Chronic asthma involves pathological changes such as…
- increased mass of smooth muscle (hyperplasia and hypertrophy)
- accumulation of interstitial fluid (oedema)
- increased secretion of mucus
- epithelial damage (exposing sensory nerve endings)
- sub-epithelial fibrosis
Airway narrowing by inflammation and bronchoconstriction increase ______ decreasing ______ and ________
- airway resistance
- FEV1
- Peak expiratory flow rate (PEFR)
Epithelial damage, exposing sensory nerve endings (C-fibres, inrritant receptors) contributes to what?
Increased sensitivity of the airways to bronchoconstrictor influences (and may cause) neurogenic inflammation by the release of various peptides
What are the two components of neurogenic inflammation?
- Hypersensitivity
- Hyper-reactivity
Provocation tests for hypersensitivity and hyper-reactivity with inhaled bronchoconstrictors e.g. histamine or methacholine reveal what?
- hyper-responsiveness
In many individuals, an asthma attack comprises what phases?
- immediate (mainly bronchospasm)
- delayed (inflammatory reaction) phases
What is IgE associated with?
Severe asthma
What two general categories do drugs for treating asthma fall into?
- Relievers
- Controllers/ Preventors
