24- Respiratory Medicines Flashcards by Anna Safrankova

What are the 5 main categories of bronchodilators

LA,SA anti cholinergic
LA,SA B2 agonists
Theophylline (derivatives of xanthine)

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Why isn’t a large dose needed

Inhalation and not systemic meaning directly flows to the lungs

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Which property are LA

Lipophilic

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What 3 things happen in asthmatic airways

Sm contraction, inflammation and mucus secretion

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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

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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

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Which drugs target the late phase

Glucocorticoids

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What are th2 responsible for

Ige release, eosinophilia attraction, mast cell stimulation = airway sensitivity

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Which article discusses eosinophils in asthma

Mcbrien et al 2017

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Which protein in eosinophils granules you increases histamine release from mast cells

Mbp major basic protein

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Which th2 cytokines do eosinophils release

Il4 and il13

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What apc do they attract for more T cell responses

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How does mbp cause tissue/ epithelial damage

It’s toxic to them

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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

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What type of receptor is it

Gpcr

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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

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How does calcium then cause contraction

Binds troponin releasing tropomyosin from myosin bs allowing cross bridging

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How do anticholinergics work

Competitive antagonists of the muscarinic receptors stopping constriction and mucus release from vagal stimulation

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What is the short acting one to relieve symptoms

Ipratropium bromide (lasts around 1-6 hours)

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What is the LA one for prevention

Tiotropium bromide (up to 18 hours)

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Why isn’t it first choice for asthma but good for copd

Doesn’t stop mast cell stimulated constriction eg via histamine

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Why does copd need it

They have cholinergic hypersensitivity eg causing cb

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What are some side effects of blocking PNS

Dry mouth, urinary retention, constipation (lack of bladder contraction)

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Why do they have poor penetration and interaction

Only 1-2% of ipratropium is absorbed systemically. They are inhaled and stay in lungs mostly

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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