Autonomic Nervous System Pharmacology
How is ACH removed from the synapse and neuroeffector junction?
Acetylcholinesterase (AChE) hydrolyses ACh only.
What is the main advantage of inhaled delivery for asthma medication?
A) Faster renal clearance
B) Improved metabolic metabolism
C) Reduced systemic side effects
D) Increased cardiac stimulation
What type of disorder is asthma?
Obstructive lung disease
Visceral
Which neurotransmitter is released at post-ganglionic sympathetic synapses?
Noradrenaline
What class of drug provides rapid relief of acute bronchoconstriction in asthma?
Short acting B2-agonists
What are some of the risk factors for asthma?
Family history of asthma, parental smoking, major respiratory infection in the first 2 years of life, exposure to domestic allergens
What vertebral levels do the IVC, oesophagus and abdominal aorta pass through the diaphragm?
IVC: T8
Oesophagus: T10
Abdominal Aorta: T12
What is autonomic tone?
The resting balance between sympathetic and parasympathetic stimulation
What is the mechanism of montelukast? (just name the drug type)
Cysteinyl Leukotriene Receptor Antagonist
Outline 3 spirometry findings that indicate asthma
Decreased FEV1/FVC ratio, mildly reduced Peak Expiratory Flow, decreased FEV1, positive bronchodilator reversibility, late plateau but FVC preserved
Why is the T4 level significant?
Arch of aorta, bifurcation/carina of the trachea into the left and right primary bronchi, sternal angle, divider between the superior and inferior mediastinum
Describe the autonomic control of the heart, including the receptors involved
B1 receptors in SNS: increased rate in SA node, increased conduction in AV node, increased force in atrial and ventricular muscle
M2 receptors in PSNS: decreased rate in SA node, decreased conduction in AV node, decreased force in atrial muscle
List side effects of long term fluticasone use
Osteoporosis, hypokalaemia, mood swings, oral candidiasis, cushing's syndrome, growth retardation in children, glaucoma
List 4 findings during respiratory examination that support a diagnosis of asthma
Inhaler at bedside, increased work of breathing, peripheral cyanosis, cough, tremor, oral candidiasis, expiratory wheeze, hyperresonance to percussion
What are the anatomical layers that are pierced during intercostal catheter insertion?
1) Skin
2) Subcutaneous tissue
3) External intercostal muscle, internal intercostal muscle, innermost intercostal muscle
4) Endothoracic fascia
5) Parietal pleura
6) Intercostal neurovascular bundle
Compare ganglia and co-transmitters (give examples of co-transmitters).
Ganglia are clusters or neuronal cell bodies outside of the CNS. The site of synapse between the preganglionic and postganglionic fibers of the autonomic nervous system.
Co-transmitters are other transmitters aside from ACh and NaD such as NO, Dopamine, GABA,5-HTP, CGPR, substance P, GnRH, neuropeptide Y. The presence of these co-transmitters means that the autonomic nervous system cannot be completely blocked. There may still be autonomic effects if an autonomic antagonist drug is administered.
Contrast the different types of delivery systems for inhaled medications.
Metered-Dose Inhalers (MDIs): Small, handheld devices using a chemical propellant to push a measured puff of medicine out. Most commonly used for salbutamol and terbutaline.
Dry Powder Inhalers (DPIs): Breath-activated devices where you breathe in fast and deep to pull dry medicine powder out of the device into your lungs.
Soft Mist Inhalers (SMIs): Handheld devices that turn liquid medicine into a slow-moving, fine mist so it is easier to breathe in.
Nebulizers: Machines that turn liquid medicine into a continuous wet mist that you breathe through a face mask or mouthpiece
What is the pathophysiology of atopic asthma?
1. Sensitization to allergens: Triggers activate Th2 cells which secrete IL-3, IL-4 and IL-5. IL4 stimulates B cells to produce IgE antibodies and this causes an IgE dependent activation of mast cells. Th2 cells and mast cells also release IL-3 & IL-5 which recruits and activates eosinophils (note: eosinophils dominate the airway lumen and bronchial tissues compared to basophils which are in blood circulation)
2. Early phase (occurring within mins): inhaled antigens (aeroallergens) encounter pre-sensitised IgE coated mast cells on the airway mucusa causing them to release histamine and leukotrienes. This induces broncho-constriction (oedema and increased vascular permeability) and opens mucosal tight junctions so antigens can travel deeper to reach more mast cells.
3. Late phase (occurring over hours): the combination of mast cells and T helper cells secreting IL-3 and IL-5, vascular endothelium and airway epithelial cells recruits a new mix of neutrophils, monocytes, lymphocytes, basophils and eosinophils which causes epithelial damage and airway constriction
4. Airway remodelling (severe, chronic asthma): long term inflammation yields fibrosis of airway wall, blood vessel proliferation, dilation and basement membrane thickening. Leads to hypertrophy of smooth muscle and mucous glands with triggers mucuous hypersecretion, plugging and permanent smooth muscle cell constriction.
Note: mast cells are a type of WBC that settle in tissues exposed to the outside world like skin, airways and digestive tract. They open blood vessels for inflammation and help other immune cells reach the problem.
Distinguish between the right and left lobes of the lungs.
Right lung: 3 lobes, oblique and horizontal fissure, shorter and wider due to the upward compression by the liver, hilum contains 1 bronchial artery, contains the right main bronchus which splits into eparterial (superior lobar) bronchus and the hyparterial (bronchus intermedius)
Left lung: 2 lobes, oblique fissure, longer and narrower shape due to compression by the heart, cardiac notch, lingula (subsitute for the middle lobe), hilum contains 2 bronchial arteries, contains one bronchus only, cardiac notch