Pharmacology Flashcards
where are cell bodies of preganglionic fibres located?
The brainstem
Where are cell bodies of postganglionic fibres located?
The walls of the bronchi and bronchioles
What is the result of parasympathetic stimulation of postganglionic CHOLINERGIC fibres?
Bronchial smooth muscle contraction
Mediated by M3 muscarinic ACh receptors on ASM cells
What is the result of parasympathetic stimulation of postganglionic NONCHOLINERGIC fibres?
Bronchial smooth muscle relaxation
Mediated by NO and VIP
What is the result of sympathetic stimulation?
Bronchial smooth muscle relaxation via B2-ADRon ASM cells (activated by adrenaline released from the adrenal gland)
Decreased mucus secretion mediated by B2-ADR on goblet cells
Increased mucociliary clearance mediated by B2-ADR on epithelial cells
Vascular smooth muscle contraction mesiated by a1 adrenoceptors on vascular smooth muscle cells
what is the General mechanism of contraction in smooth muscle cells mediated by M3 ACh receptors activated by parasympathetic stimulation?
Contraction caused by Ca2+ exiting the SARCOPLASMIC RETICULUM
(via Ca2+ activated Ca2+ channel/ IP3 receptor)
*Voltage activated Ca2+ channels bring calcium ions into ASM cell
*GCPRs produce IP3 via
Gq -> PLC -> IP3
How does calcium initiate contraction?
- binds to calmodulin (makes Ca2+ - calmodulin)
- this activates MLCK
- active MLCK Dephosphorylises ATP and the Pi goes on to phosphorylate MYOSIN CROSS BRIDGE
- This permits binding of myosin with actin- causing contraction
What causes reaxation in ASM cells?
Dephosphorylation of MLCK by myosin phosphatase
Increase of intracellular calcium leads to…
constriction
Decrease of intracellular calcium leads to…
Relaxation
How does adrenaline promote ASM relaxation?
- activates B2-ADR
- activates Gs
- actvates AC
- activates cAMP (If converted to 5’AMP then pathway switched off)
- activates PKA
- Phosphortlates & stimulates myosin phosphatase- which dephosphorylates MLCK- which promotes relaxation
Causes of asthma attacks?
allergens, exercise, respiratory infections, smoke, dust, environmental pollutants
What are the airway problems associated with asthma?
- increase in SM mass
- Accumulation of fluid in tissue (oedema)
- increased mucus secretion
- epithelium damage (exposed sensory & parasymp. nerves- causes contraction)
- sub-epithelial fibrosis
What are the two “Hyper”s associated with asthma?
Hypersensitivity- decrease in conc. inhaled from bronchoconstrictor
Hyper-reactivity- larger fall in FEV1
What are the two main types of hypersensitivity?
I: Immediate bronchospasm
IV: delayed bronchospasm
What TH response is associated with a nonatopic individual?
TH1
- low level response
- IgG and macrophages
What TH response is associated with atopic individuals?
TH2
- strong response
- IgE
What makes up the induction phase of allergic asthma?
APCs CD4+ TH cells TH2 (IL-4 production) B cells plasma cells
what makes up the effector phase of allergic asthma?
plasma cells
antibodies (IgE)
IL-5 / IL-4 and IL-13
eosinophils / mast cells
What are the two categories of asthma treating drugs?
Relievers & controllers/preventers
What are three types of asthma relieving drugs?
Short acting B2 agonists
long acting B2 agonists
CysLT1 receptor antagonists
what are some examples of asthma controllers/ preventors?
Corticosteroids
chromoglicate
humanised monoclonal IgE antibodies
what do methylxanthine drugs do?
can be used to relieve and control/ prevent asthma symptoms
what is the preferred route of administration for asthma drugs?
aerosol or nebulised
when might an oral asthma drug be used?
In children or people unable to sufficiently use an inhaler
what are the advantages of using aerosol asthma drugs?
low dose required effective distribution effective for bronchodilators effective in mild/moderate disease little risk of adverse affects as drug rapidly clears systemic circulation
what are the advantages of using oral asthma drugs?
easy to administer, as unaffected by airway diseae
easy to administer
effective in severe disease
what is the mechanism of a B2- Adrenoceptor agonist?
B2-ADR activated
Gs protein activates AC
AC is phosphorylised by ATP to produce cAMP
(If converted to 5’AMP then pathway stopped)
cAMP activates PKA
phosphorylation of MLCK and myosin phosphatase
ASM Relaxation
which drug type act as physiological antagonists of all spasmogens?
B2- adrenoceptor agonists
what does SABA stand for?
short acting B2-ADR agonists
what does LABA stand for?
long acting B2-ADR agonists
salbutamol is an example of which type of B2-ADR agonist?
SABA
what is the usual route of administration for salbutamol?
inhaler
how might salbutamol be administered in more severe cases?
nebulised
oral (in children)
IV
How long does it take for salbutamol to act and how long for maximal effect?
5 mins
30 mins
what is the effect of salbutamol?
Bronchodilation (ASM cell relaxaation)
Increased mucus clearance
decreased mediator release from mast cells and monocytes
what are some potential adverse effects of salbutamol?
fine tremor (can be observed in a general examination)
tachycardia
cardiac dysrythmia
hypokalaemia (low blood potassium levels)
salmeterol and formoterol are examples of which type of B2-ADR agonist?
LABA
What should LABAs be used for?
Nocturnal asthma
Add on therapy in astma inadequately controlled by corticosteroids
what kind of drug is isoprenaline?
a non-selective B2-ADR agonist
what adverse side effect could using a non-selective B2-ADR agonist potentially cause?
stimulation of cardiac B1-ADR
propranolol is an example of which kind of drug?
non-selective B-ADR antagonist
why should using a B-ADR antagonist for asthma be carefully considered?
risk of causing bronchospasm
LTC4, LTD4 and LTE4 are examples of what? and where are they derived from?
CysLTs (cysteinly leukotrienes)
derived from mast cells & infiltrating inflammatory cells
what do CysLT1 receptor antagonists prevent?
ASM contraction
mucus secretion
oedema
montelukast and zafirlukst are example of what type of drug?
CysLT1 receptor antagonists
when should CysLT1 receptor antagonists be used?
As an add on therapyagainst early and late bronchospasm in mild persistent asthma
Should be used with corticosteroids in more severe conditions
which bronchosmasms are CysLT1 receptor antagonists effective against?
antigen induced
exercise induced
how are CysLT1 receptor antagonists administered?
Oral route
Theophylline and aminophylline are example of which asthma drug?
Methylxanthines
what is the mechanism of action for methylxantines?
uncertain
might inhibit isoforms of phosphodiesterases, which inactivate cAMP and cGMP
how are methylxanthines administered?
oral route
which asthma drug has a very narrow therapeutic window?
methylxanthines
which asthma drug combines bronchodilatory and anti-inflammatory responses?
methylxanthines
which major classes of steroids are synthesised in the adrenal cortex and released into the circulation?
glucocorticoids
mineralocorticoids
what are the main essential processes glucocorticoids regulate?
decrease inflammatory responses
decrease immunological responses
mineralocorticoids (eg. aldosteone) regulate what?
retention of salt and water by the kidney
what are the main synthetic derivatives of cortisol used in asthma?
Beclometasone
Budesonide
Fluticasone
What are glucocorticoids for?
for the prophylaxis of asthma (prevention)
How are glucocorticoids administered?
inhalational route
How do glucocorticoids signal?
via nuclear receptors- specifically GRa
What are glucocorticoid effects on gene transcription?
increase transcription of genes encoding anti-inflammatory proteins
Decrease transcription of genes encoding inflammatory proteins
What do glucocorticoids do to inflammatory response?
decrease Th2 formation
cause apoptosis
prevent antibody production
prevent allergen-induced influx into lung
reduced number of mast cells, eosinophils, macrophages and dendritic cells
what are cromones?
second line drug used prophylactically in childhood asthma (mast cell stabilizers)
has no direct effect on ASM
what is omalizumab?
a monoclonal antibody directed against IgE
what is mepolizumab?
a monoclonal antibody directed against IL-5
What is chronic bronchitis?
Inflammation of bronchi and bronchioles Cough Clear mucoid sputum Infections with purulent sputum Increasing breathlessness
What is emphysema?
Distension and damage to alveoli
Destruction of acinial pouching in alveolar sacs
Loss of elastic recoil
What do muscarinic receptor antagonists do?
Reduce parasympathetic neuroeffector transmission
Act as pharmacological antagonists of bronchocontriction caused by ASM M3 receptor activation in response to ACh released from postganglionic parasympathetic fibres
What receptor responds to ACh released from postganglionic parasympathetic fibres?
M3 receptors
where are M1 receptors located?
Ganglia
where are M2 receptors located?
postganglionic neurone terminals
where are M3 receptors located?
ASM
what is the function of M1 receptors?
facilitate fast neurotrasmission mediated by ACh acting on nicotinic receptors reducing ACh release
what is the function of M2 receptors?
act as inhibitory autoreceptors reducu
what is the function of M3 receptors?
Mediate contraction to ACh
which SAMAs are used for COPD treatment?
Ipratropium
which LAMAs are used for COPD treatment?
Tiotropium
Glycopyrronium
Aclidinium
Umeclidinium
how are SAMA and LAMA COPD treatments administered?
By inhalation
Quaternary ammonium group reduces absorption and systematic exposure
what weak anti-inflammatory drug is used in allergic asthma? particularly in children/young people?
Inhaled sodium chroglycate
