24- Respiratory Medicines Flashcards
What are the 5 main categories of bronchodilators
LA,SA anti cholinergic
LA,SA B2 agonists
Theophylline (derivatives of xanthine)
Why isn’t a large dose needed
Inhalation and not systemic meaning directly flows to the lungs
Which property are LA
Lipophilic
What 3 things happen in asthmatic airways
Sm contraction, inflammation and mucus secretion
What is the immediate phase
Where igE bind and present allergens to the fcr on mast cells which causes degranulation of arachidonic products causing permeability (leukotrienes also release mucus and bronchoconstrict)
And histamine also contraction = bronchospasm
How does the immediate phase relate to late phase
Th2 cytokines from mart cells eg il4 and il6 then allow th2 response and attraction of eosinophils etc which cause inflammation and hyper reactivity of airways
Which drugs target the late phase
Glucocorticoids
What are th2 responsible for
Ige release, eosinophilia attraction, mast cell stimulation = airway sensitivity
Which article discusses eosinophils in asthma
Mcbrien et al 2017
Which protein in eosinophils granules you increases histamine release from mast cells
Mbp major basic protein
Which th2 cytokines do eosinophils release
Il4 and il13
What apc do they attract for more T cell responses
Dc
How does mbp cause tissue/ epithelial damage
It’s toxic to them
How does ach from PNS cause smooth muscle contraction and mucus secretion from goblet cells/submucosal glands
Binds to M3 receptors on smooth muscle cells in airways and submucosal glands to cause secretion
What type of receptor is it
Gpcr
How does it cause sr calcium release for constriction
Activates Phospholipase c and then production of ip3 and dag. Ip3 binds ryr and allows ca release
How does calcium then cause contraction
Binds troponin releasing tropomyosin from myosin bs allowing cross bridging
How do anticholinergics work
Competitive antagonists of the muscarinic receptors stopping constriction and mucus release from vagal stimulation
What is the short acting one to relieve symptoms
Ipratropium bromide (lasts around 1-6 hours)
What is the LA one for prevention
Tiotropium bromide (up to 18 hours)
Why isn’t it first choice for asthma but good for copd
Doesn’t stop mast cell stimulated constriction eg via histamine
Why does copd need it
They have cholinergic hypersensitivity eg causing cb
What are some side effects of blocking PNS
Dry mouth, urinary retention, constipation (lack of bladder contraction)
Why do they have poor penetration and interaction
Only 1-2% of ipratropium is absorbed systemically. They are inhaled and stay in lungs mostly
Why isn’t it advised for pregnant yet
Not enough studies
Why is ipratropium not given with cromolyn sodium drugs
Because can form a precipitate which stops nast cell stabilisation
Which article discusses how cromolyn works and how
Puzzovio et Al 2022
Suggested by secreting il10 cromolyn reduces the stimulation of mast cells via igE and there’s a shift to igg4. Means no mast cell degranulation
B2 agonists bind to B2 gpcr and help it reduce ic calcium. What does gpcr activate and what does this do
Activates adenylyl cyclase which increases atp to cyclic amp transition. Camp then activates pka
Which 2 channels are activated by pka which help reduce ic calcium or help hyperpolarisation
Ca2 activated k channel activation
Na/k activation which helps ncx exchanger as sodium gradient
Hydrolysis of what is reduced in pka which stops ca release
Phosphoinositol which forms ip3
Which kinase needed for contraction is blocked by pka
Myosin light chain kinase MLCK
Which article says how this works and how
Schaub 2017
It is a ca/calmodulin dependant kinase which phosphorylates the regulatory light chain RLC on myosin 2 , This causes the contraction through cross linking
What is the ca activated k channel called
Maxi K
Give an example of SA and how it’s given how long it lasts
Salbutamol
Given as powder, aerosol or nebulised inhalation
Or iv
Lasts up to 4 hours
Give an example of a long acting
Salmeterol
Inhaled or iv
Lasts up to 12 hours
What cardiac effects can they have
Tachycardia
Why are selective B2 preferred
No tachycardia, tremors, headaches which are common in non specific
Interaction with what with sabutamol causes hypokalemia as non specific
Corticoids, diuretics, theophylline
Which antidepressants induce salmeterol action and risk of hypokalenia and tachy
Maoi/ tricyclic
Monoamine oxidase inhibit
Which article discusses side effects of non specific B2 agonists
Abosamak et al 2021
What do they do to ensure ac activation
Stabilise the gs-gtp complex
What does systemic exposure to B2 agonists cause
Systemic dilation causing headaches
Hypokalemia presents as what with non specific
Tachycardia, tremors, hallucinations, hypotension, hallucinations
How does theophylline work
Blocks pde which increases camp and therefore pka effects occur
They are last resorts if B2 agonists don’t work. Why
Very small therapeutic window. Can have adverse effects
Where are they metabolised and what reduces this
Liver. Reduced eg in hepatic failure, taking drugs which block enzymes eg cimetidine
What can increase clearance from liver
Drugs inducing metabolism eg alcohol or smoking
Which drug is most important anti asthmatic and taken at each step of severity (all 6)
Glucocorticosteroids/ anti inflammatory/antimucosal
What is step 1 of the asthma treatment (for intermittent asthma
Saba and gc
What is the last for severe asthma
Both oral and inhaled gc and also laba
Which receptor do they bind which then translocates to the nucleus for gene modulation
A glucocorticoid ic receptor
What sorts of genes are downreg
Pro inflam cytokines and modulators
Why isn’t it taken for symptom relief
Takes days to work
Why are oral avoided where possible
Bad side effects like reducing bone density causing osteoporosis ,
Also diabetes, weight gain
What minor side effects do inhaled have
Hoarseness and oral candidiasis as inhaled and so immunosuppressive
Which type are used as preventative inhalers
Inhaled gc eg beclomethasone
Which article discusses gc effects
Van der velden 1998
Which tf can gr bind to after nucleus translocation
Ap-1
What does ap1 binding stop
Reg genes of cytokines and chemokines
How does gr also block nfkb and therefore inflammation
Binds to the p65 subunit
Which enzyme do glucocorticoids directly block
Cox2 and Phospholipase a2
What does H1 histamine binding do
Increase calcium
Increase bronchoconstriction, vasodilation, mucus secretion, sensory pain nerve endings stimuated, increased permeability eg nasal secretions
Why are first generation not ideal
Lipophulkuc so cross the bbb and cause cns detession like drowsiness, loss of cognition, psychomotor ability and hallucinations
What other receptor can it bind to and block causing things like dry mouth and blurred vision
It is anticholinergic
Second generation can’t cross bbb so better. Give example
Terfenadine
What are mucoactice medications
Ones which increase ability to expel sputum with mucus
or reduce mucus
What type of muco actives increase salinity of mucus making it easier to expel
Expectorants
What do mucoregulstors do
Type of anticholinergics which blocks mucus release
What do mucolytics do
They break ss bonds in mucins so easy to clear
Which type of mucoactives are bronchodilators whcih increase cough peak flow
Mucokinetics
How does a cough work after vagal stimulation
Glottis closes first then abdominals and intercostals contract to increase positive pressure
The air expelled out when vocal cords/larynx opens again and loud as tight airway
What are the meds called which suppress cough (not efficient)
Anti tussives
Give an example of a non narcotic which is anti tussive but was approved 60 years ago
Dextromethorphan
Codeine can be used as an anti tussive but why not
Sedative effects and affects gi too
Which drugs can be used to treat infection which can excacerbste asthma
Antibiotics/antivirals
How does pirfenidone work for ipf but not good enough so need transplant
Tgf b inhibitors which blocks profibrotic effects
Which 2 therapies excacerbsted ipf
Triple therapy and the mab simtuzimab
What does simtuzimab block
Lysyl oxidase like 2.
Enzyme which cross links collagen
