GPCR II Flashcards
main physiologocal eggects of adrenergic agonists of the α sub types
smooth muscle contraction from α1 and α2
except the gastrointenstinal tract
predominantly in the vascular
increase in systolic and diastolic blood pressure
increase in peripheral resistance, the resistance in teh body of that blood pressure
increases a reflex bradycardia via baroreceptors
icrease smooth muscel proliferation, cardaic hyperthropy which means incease in heart size
decrease in noradrealine release, stimulated on the α2 presynaptic nerves
main physilogiclal effects of adrenergic agonists of teh beta subtypes
smooth muscle relaxation β2 and GIT
bronchial tissue and uterous strongle dilates β2
powerful chronotropic and inotrpoic effect on the heart
effects on glycogenolysis β2 and lipolysis β3
skeletal muscle , peripheal vasodilation β2
histamine relase from mast cells β2
tremort in the hands β2
aqueous homour production, a water like fluid that is secreted to support the lens of the eye β2
what does chronotropic and inotropic mean
chronotropic is the rate at which the heart beats and iontropy is the force at which the heart beats
stimulation β receptors on the heart
postiive inotropy which is increased force of the heart
postive chronotropy which is increase rate of the heart
cardiac efficiency is reduced which increases cardiac output and increase oxygen consumption
clinical use of adrenorecpetor agonists
selective β2 agonists for asthma
vasoconstriction to relieve nasal decongension
oxymetazoline via α1 rhintis medicamentosa which is runny nose
ephedrine be basal drops
psuedoephedrine stsemic decongestants
mast cells, where are they found and what do they do
mast cells are embedded within the smooth muscele fibres
mast cell degranulation causes the release of histamnines
the histamines act a ligand for the Gqα g protein coupled receptor pathway
which results in bronchoconstriction
short acting β2 agonits
salbutamol and terbutaline
the maximum effect occurs within 30 minutes to last 3 to 5 hours
used on an as needed basis to control symptoms when they are feeling a little breathless
long acting β2 agonists
they are used in addition to inhaled corticostreroird in pateins requiring prophylatic treatments (“controllers”)
exmaples are salmeterol and formoterol
givenregulartlt as adjunctive therapty in pateints whose asthma is inawquately controllefd by glucocorticoids ~(same as corticosteriods)
side effects of adereceptors from receptors
β2 agonists can cause tremor in the hands, headaches. peropheal dilation and palpitations also inculde tachycardia and arrhythmias
β2 hypokalaemia decrease in the blood concentration od potassium Na+/K+ ATPase
β1 agonits - tachycardai and rise in blood pressure
hypertension and as a esults headache, bradycardia, arrhythmias and urinary retention - treatment in bed wetting
what are phosphodiesterases and how does PDE4 inhibtors acts as bronchodilators
phosphodiesterases break down cyclic AMP
\inhibtors of PDE4 stops the break donw of cAMP and upregulates cAMP
cAMP binds to tritamer protein kinase a regulatory units which allows the release of the catalytic units
catalytic units phosphorlates and resulats in opening in calcium activated potassium channels
cause downregulation is myosin light chain kinase and upregulation in myspin light chain phosphotase
results in smooth muscle relaxation
main physiological effects of adrenoreceptor α adrenergic antagonists
non selective antagonists cuase fall in aterial blood pressure, postual hypertension where sitting for long times can increase blood pressure and relflex tachycardia
increase in gastrointestinal activity causes diarrhoea
α1 selctive cause vasofilation, decrease in blodpressure and an inhibtion effect on tachycardia
relaxation of smooth muscle for example the bladder neck and prostate
α2 increase noradrenaline release due to inhibition of negative feedback loop therofre therefore sympathomimetic effets occur
clinical use for α adrenoceptor antagonirs
treatmnet for α1 selective hyperenstion is prazosin, doxazosin and terazosin
this is also the case for prostatic hyperthrophy for those with enlarged prostates due to urine retentantion
tamsulosin causes relaxation and increase urination
no clincal use for α2 blockers
side effects of α adrenoceptor antagonists
side effects for non-selective is tachycardia. dysrhythmias, increased GI activity and idarrhoea
slective α1 is postural HYPOtension
increased urinary frequency, incontinence, priapism which is uncontrolled erections in males and nasl congestion
main physiological effects of β-adrenergic antagonists
little effect onthe heart rate, cardiac output or aterial pressure at rest
exercise tolerance is reduced due to the blocking effect of β2 receptor in skeletal muscle
coronary flow reduced
reduction in force of contraction on exercise
clinical uses of β-adrenergic receptor antagonists
used to treat cardiovascular effects
hypertension
angina pectoris
following heart attack for secondary protection
cardiac dysrhythmias
outside of the heart
glucoma
anxiety
migraine prophylaxis
benign tremor (antagonist blocks it β receptors)
thyrotoxicosis
cardiac failure
t
β-blockers used to treat angina
reduce oxygen consumption
slow the heart down (negative chronotropy)
depress the myocardium (negative inotropy)
anti-ischaemic action
no effect on the coronary atery
slow withdrawl from not taking beta blockers becuase beta receptor channels have been upregulated therfore taking a patient off beta blockers too quickly will cause them to go into overdrive
side effects og β-blockers/antagonists
severe bronchoconstriction in asthmatic patients
bradycardia
cardiac failure
cramps
hypoglycaemia
fatigue- reduced cardiac output and muscle perfusion
ocold extremities β2
erectile dyfunction( any drugs to treat high blood pressure)
impaired glucose tolerance β2
what are the muscarinic receptors
they a gprotien coupled receptors they are linked to Gq or Gi
m1, 3 and 5 are Gq and m2 and 4 are
embedded in the cell membrane
five are muscarinic receptor subtypes
how do m3-muscarinic acetylcholine receptors cause smooth muscle contraction
nictonic receptoes causes release the releaseof acetylcholine
acetlycholine binds to m3- muscarinic receptors on smooth mucle airways
binding causes a cascade of the Gq pathway
which results in the contraction of smooth muscle
clinical use muscarininc receptor antagonists
anticholinergics are predominantly inhaled by paitents with asthma and copd
angiotensin converting enzyme (ACE) inhibtors and angiotensin II receptor antagonists
used in heart faulure
hypertension
diabeteic nephropathy kidney disease
reduces the preload and afterload of the heart by bloacking the fomration of angiotensin II (ACE inhibtors) or blocking angiotensin receptors using angtiontensin II receptros antagonists
describe the angiotensin pathway
angiotensinogen is converted by renin producced by the kidneys into agiontensin I
ACE (angiotensinconveting enzyme) converts angiotensin I into angiotension II
ANgiotensin II binds to the angiotensin receptor, a g-protein coupled receptor, which goes on to cause vascontrication and increase blood pressure
descibe what happens with ACE inhibtors and Angiotensin II receptor antagonists
ACEi blocks ACE causes the decreased production of angiotenisn II and decreased effect on the blood pressure
ACEi inhibits the break down of bradykinin which is a vasodilator and that cause an addiotnal effect on the blood pressure
angiotensin receptor antagonists decrease the amount of angiotensin II binds to angiotensin receptor I therefore decreased effect on blood pressure
side effects of ACE inhibits and ARA
hypotensin
dry cough as a results of accumulation of brdaykinin
renal function needs to be monitored as it can change
hyperkalemia (high levels of potassium in the blood)
foetal toxicity in 2nd and 3rd trimesters
