Treatment in Respiratory Diseases

Question 1

Which branch of the autonomic nervous system secretes noradrenaline?

Answer 1

Which branch of the autonomic nervous system secretes noradrenaline:
sympathetic

n.b. sympathetic nervous system secretes noradrenaline at the effector organ site;
the parasympathetic nervous system secretes Ach at the effector organ site

Question 2

If u activate the parasympathetic nervous system the airways…..

If u activate the sympathetic nervous system the airways ….

Answer 2

If u activate the parasympathetic nervous system the airways CONSTRICT

If u activate the sympathetic nervous system the airways …. DO NOTHING no evidence that sympathetic nervous system innervates airway smooth muscle cells

Question 3

innervation of mucosal glands and airway smooth muscle cells by _____ nerve; when these SMOOTH MUSCLE cells contract airway diameter _____ , when they relax the airway diameter ______

Answer 3

innervation of mucosal glands and airway smooth muscle cells by VAGUS nerve– when these muscle cells contracts airway diameter constricts, when they relax the airway diameter dilates

Question 4

*what does stimulation of postganglionic cholinergic fibres cause?

*what does stimulation of the postganglionic noncholinergic fibres cause?

Answer 4

stimulation of postganglionic cholinergic fibres causes:
*bronchial smooth muscle contraction mediated by M3 muscarinic ACh receptors on ASM (airway smooth muscle) cells
*increased mucus secretion mediated by M3 muscarinic ACh receptors on goblet cells

stimulation of postganglionic noncholinergic fibres causes:
*bronchial smooth muscle relaxation mediated by nitric oxide (NO) and vasoactive intestinal peptide (VIP)

Question 5

explain mechanism behind bronchoconstriction

Answer 5

Ach via the stimulation of the parasympathetic branch of the autonomic nervous sytem at the neuromuscular junction will act on M3 (muscarinic) ACh receptors that leads to airway bronchoconstriction:

detail:
Acetylcholine (ACh), binds to G-protein (Gq)-coupled muscarinic M3 receptors on the neuromuscular junction of the effector organ site( of airway smooth muscle cells) =
↑ phospholipase C (PLC) = ↑ inositol 1,4,5-trisphosphate (IP3)
IP3 binds to ligand-gated IP3 receptors (IP3Rs) on the endoplasmic reticulum (ER) =
Ca2+ release into the cytoplasm
↑ intracellular Ca2+ = Ca2+ binding to calmodulin (CaM) & subsequently
myosin light chain kinase (MLCK) = catalytically active (Ca2+)4-CaM-MLCK complex
= which then phosphorylates (P) light chain of myosin (MLC20) =
actin–myosin cross-linking causes smooth muscle contraction= bronchoconstriction

Question 6

define isoenzyme/isozyme

Answer 6

isozymes/isoenzymes are defined as enzymes that catalyze the same type of reaction but are created by different genes and have different molecular shapes.

Question 7

what is the mechanism of bronchodilation

Answer 7

Bronchodilator effect
* The bronchodilator nerves in human airways are
nonadrenergic noncholinergic (NANC)
* Major neurotransmitter is nitric oxide (NO)
* NOS {nitric oxide synthase isoenzymes} expressed in epithelial and nerve cells

Question 8

what is asthma

Answer 8

chronic inflammation of the lungs that over time will lead to airway remodelling when uncontrolled

common triggers: Indoor allergens, such as dust mites, mold, and pet dander or fur. Outdoor allergens, such as pollens and mold. Emotional stress, such as intense anger, crying, or laughing

Question 9

describe the effect on M3 muscarinic effectors when we give patient a
* Short- or Long-acting muscarinic antagonists (SAMA & LAMA)
* Short- or Long-acting Beta2-adrenergic receptor agonists (SABA/LABA)

Answer 9

Short- or Long-acting muscarinic antagonists (SAMA & LAMA) block the binding of acetilcholine (ACh) to M3 muscarinic receptor
= inhibit smooth muscle cell contraction=bronchodilation
i.e. these meds are for asmathics

Short- or Long-acting Beta2-adrenergic receptor agonists (SABA/LABA) bind to beta2-adrenergic receptor & induce a cascade of signal transduction events
= inhibits smooth muscle relaxation= bronchocontriction

Question 10

how does a beta-2 agonist work?

Answer 10

So ACh binds to the G-protein coupled receptor on the cell surface. Adenyl cyclase converts ATP to cAMP (cyclic AMP). The cAMP converts protein kinase (PK) to it’s active form (PKA) which leads to airway smooth muscle relaxation.=major pharmalogical target!!

ANTICHOLINERGIC Short- or Long-acting muscarinic antagonists (SAMA & LAMA) block the binding of acetylcholine (ACh) to M3 muscarinic receptor
= inhibit smooth muscle cell contraction= KEEP AIRWAY OPEN

BRONCHODILATORS AKA Short- or Long-acting Beta2-adrenergic receptor agonists (SABA/LABA) bind to beta2-adrenergic receptor & induce a cascade of signal transduction events
= increase smooth muscle relaxation= KEEPS AIRWAY OPEN

Question 11

what is the first-line therapy for COPD

Answer 11

LABA/LAMA: first-line therapy for COPD

LABA=bronchodilator
LAMA= anticholinergic

Question 12

what do inhaled corticosteroids

Answer 12

inhaled corticosteroids suppress the cytokines {e.g. CXCL8, IL-6, TNF-alpha} produces which cause the inflammation in the lungs

inhaled cotricosteroids reduce underlying inflammation

Question 13

how does allergic asthma work

Answer 13

IgE- mediated allergy (immune response)

APC (antigen presenting cell) process antigen{the body has picked up the allergen and decided its harmful making an APC out of it}-> major histocompatibility complex II molecules present antigen to naive T cells (Th0)-> promotes development of Th2 cells (IL-4 promotes this differentiation)->Th2 cells produce IL-4 + IL-13-> B cells produce IgE-> IgE binds to mast cells-> sensitised mast cells-> exposure to allergen-> IgE crosslinking + mast cell degranulation-> release of mast cell mediators{e.g. histamine, nitric oxide}= causes the allergy; hay fever, asthma, dermatitis

n.b. these cell mediators lead to chronic inflammation + overtime airway remodelling