nice guidelines, agonists and treatment options

what is given if patient has < 3 asthma attacks a week

• SABA inhaler as reliever

what is given if >3 asthma attacks a week or uncontrolled

• SABA

• and inhaled corticosteroid ICS as preventer

is SABA reliever of preventer

reliever

is ICS preventer or reliever

preventer

what is given if SABA + ICS does not work

luekotriene receptor antagonist on top of it

what happens if leukotriene receptor antagonist LTRA doesnt relieve asthma

long acting beta agonist LABA used with or without the LTRA

what happens if long acting beta agonist is ineffective

• maintenace and reliever therapy is given

• combined preventer and reliever in single inhaler

what is given if asthma is not controlled by MART inhaler

• increase steroid dose from low to moderate

• further increase to high may be considered

what is the most common treatment strategy in the UK

• MART

what are the target tissues for beta 1 adrenoreceptors

• SA node

• ventricular muscle

• gut smooth muscle

• renal juxtaglomerular

• adipocytes

• hepatocytes

what are the target tissues for beta 2 adrenoreceptors

• airway smooth muscle

• uterus

• blood vessels

• skeletal muscle

how is relaxation of smooth muscle achieved in airway via beta 2 adrenoreceptors

• gs protein binds

• gtp replaces gdp

• alpha subunit binds to adenylyl cyclase so inc cAMP

• protein kinase a activated

• myosin light chain kinase neg modulated

• calcium levels fall

what prevents mast cells from degranulating

• activation of beta 2 receptors in mast cells

what increases selectivity of beta adrenoreceptors

• increasing size of amine substituent

salbutamol function and selectivity

• commonly used as SABAs and reliever drugs

• rapid onset

• effect of up to 6 hours

• 21x more selective for beta 2 vs beta 1

terbutaline function and selectivity

• commonly used as SABAs and reliever drugs

• rapid onset

• effect of up to 6 hours

• 41x more selective for beta 2 vs beta 1

• more selective than salbutamol

which is the best short acting bronchodilator SABA

• terbutaline

long acting beta agonist examples

• salmeterol

• formoterol

short acting beta agonists examples

• salbutamol

• terbutaline

salmeterol

• LABA

• used as preventer drug to slow onset

• used in conjunction with inhaled corticosteroid

formoterol

• LABA

• rapid onset

• used in combination with corticosteroids as part of MART

which LABA has a rapid onset

• formoterol

factors which affect duration of salmeterol and formoterol

• lipophilicity

• high affinity binding to the agonist site

• binding to exosite

lipophilicity of LABAs

• salmeterol is much more lipophilic than formoterol

• dissolves extensively in biological membrane

which LABA has high binding affinity for duration

formoterol

• so can bind and rebind over extended period of time

which LABA binds to exosite

• salmoterol

• has long alkylamine chain which can anchor the drug to receptor outside of agonist binding site

side effect of beta 2 adrenoreceptor agonists

• muscle tremors

• muscle cramps

• flushed skin

• headaches

side effects of beta 1 adrenoreceptor agonists

• tachycardia

• palpitations

metered dose inhalers colours

• reliever inhalers are blue

• preventer or mart are red, orange or brown

function of spacer device

improves drug delivery

glucocorticoids

• group of endogenous and synthetic steroids that act on glucocorticoid receptor, which is a nuclear receptor

• mimic cortisol

• used as preventers

anti inflammatory effects of glucocorticoids

• Decreased activation, proliferation and migration of immune system cells

• Decreased expression of pro-inflammatory cytokines

• Decreased expression of cyclo-oxygenase 2 (therefore decreased prostaglandin production)

• Increased expression of anti-inflammatory mediators (some interleukins, annexin A1)

glucocorticoids/corticosteroids examples

• beclometasone

• fluticasone

• prednisolone (tablet)

• budesonide

• beautiful fat people burp

advantages of MART

• convenience of one inhaler

• better control

• lower dose of glucocorticoids needed

what do leukotriene receptor antagonists end in

• lukast

when are leukotriene receptor antagonists (LTRAs) effective

• effective in exercise induced asthma

• have an effect on aspirin induced asthma

• effect is not as great as SABA so used as an add on in preventer context

phospholipase a2 function

• enzyme which releases arachidonic acid from membrane phospholipids

aspirin induced asthma attacks

• inhibitor to cyclo-oxygenase 1

• inc production of leukotrienes

• reduced production of anti inflammatory prostaglandin

side effects of lukasts (leukotriene receptor antagonists)

• abdominal pain

• gi tract pain

• headaches

• rare - psychiatric effects hallucinations and depression

tiotropium

• long acting muscarinic acetylcholine receptor antagonists (LAMA)

• blocks effects of acetylcholine released by parasympathetic neurons

• atropine derivative

• selective to m3 muscarinic receptors found in airway smooth muscle

theophylline

• alkyl xanthine class of drugs

• closely related to caffeine

• inhibits phosphodiesterases that breakdown cAMP and blocks adenosine receptors

• has narrow therapeutic window