Pharmacology- Blood Pressure Flashcards
what cause contraction of vascular smooth muscle
increase of intercellular calcium done by either l type channels or through the release of calcium from the SR by the activation of Gg/11 proteins
and
myosin light chain kinase
what is responsible for the relaxation of vascular smooth muscle
myosin light chain phosphatase
what does Nitric oxide cause when arriving at vascular smooth muscle and how
relaxation
by activating calcium activated K channels which removes k from cell hyperpolarisaing it taking it away from threshold and causing relaxation
what mechanisms do organic nitrate drugs activate and how
relaxation mechanisms by donating NO which diffuse to smooth muscle cells
what types of muscle do organic nitrates relax
all smooth muscle types
what do organic nitrates do to the vasculature
venorelaxation (small doses), arteriolar dilatation (higher doses), increased coronary blood flow
what are the effects of venorelaxation
decreases pressure in right atrium (CVP) (preload)
reduces SV
CO maintained by increased HR
no change in arterial blood pressure
what are the effects of arteriolar dilatation
decreases arteriolar pressure reducing afterload
why are organic nitrates good at treating angina
TREATS PAIN ONLY NOT CAUSE
as blood is redirected towards the ischaemic zone
-decreases myocardial oxygen requirement (via decreased preload, afterload and increased perfusion of the ischaemic zone
what are organic nitrates used to treat
stable angina and acute coronary syndrome
give three examples of organic nitrates
glyceryltrinitrate (GTN)
isosorbide mononitrate (ISMN)
isosorbide dinitrate
what is first pass metabolism
when oral drug goes through the liver before getting into systemic system
what are the side effects of organic nitrates
tolerance, postural hypotension, headaches
what is endothelin 1 and its receptor
potent vasoconstrictors
ETA receptors
what leads to the expression of endothelin 1
decreased nitric oxide, shear stress and natriuretic peptides (hormones from chambers of heart)
increased adrenaline, angiotensin II and ADH
what are antagonists of the ETA receptor used in
the treatment of pulmonary hypotension
what does the renin-angiotensin-aldosterone system play a major role in the regulation of
sodium secretion and vascular tone
what two types of drugs act on the renin-angiotensin-aldosterone system
ACE inhibitors and angiotensin receptor antagonists
what three factors lead to increased renin release
decrease renal perfusion pressure
increase symp activity
decreased glomerular function
what is contraction of vascular smooth muscles the result of (2)
Activation of smooth muscle AT1 receptors
Increased release of noradrenaline from sympathetic nerves
what does renin turn into
angiotensin I
what is the receptor for angiotensin II
AT1 receptor (GPCR)
what does the contraction of vascular smooth muscle do to mean arterial blood pressure
increases it
what part of renin process leads to increased blood volume and MABP
aldosterone secretion from adrenal cortex leads to tubular Na+ reasbsorption and salt retention
what is an ARB
agiotensin 1 (AT1) receptor blocker
what two types of drugs stop the renin cycle
agiotensin converting enzyme inhibitors (ACE inhibitors)
angiotensin 1 (AT1) receptor blockers (ARBs)
what does ACE inhibit
bradykinin (vasodilator)
name an ACE inhibitor and what they ALL have in common
lisinopril (opril)
give an example of a ARB and what they all have in common
losartan (sartan at end of name)
what do ACE inhibitors cause
vasodilatation (decreased preload), arterial dilatation (decreased afterload and TPR)
what affect do ace inhibitors have on cardiac contractility
none (CO may decrease as a result of decreased TPR)
what do ACE inhibitors reduce the release of
aldosterone (decrease in Na+ ans H20)
what are the side affects of ACE inhibitors
hypotension and dry cough
do ARBs affect the metabolism of bradykinin
no
when would you switch from an ACE inhibitor to an ARG
to get rid of dry cough
what can ACE inhibitors and RGB not be used in
pregnancy and bilateral renal artery stenosis
what are the clincal uses of ACE inhibitors and AT1 receptor agonists
hypertension
cardiac failure
following myocardial infarction
what are adrenoceptors
G-protein-coupled receptors (GPCRs) that are activated by the sympathetic transmitter noradrenaline (norepinephrine) and the hormone adrenaline (epinephrine)
what does the activation of alpha 1 adrenoceptor lead to
constriction of vasculature
what does activation of Beta 1 adrenoceptor lead to
increase heart rate, force, av conduction
what does the activation of beta 2 adrenoceptors lead to
relax of airway smooth muscle and vascular SM
what are the clinical uses of beta adrenoceptor agonists
treatment of angina pectoris, hypertension, heart failure
what do beta 1 selective agents do
decrease myocardial O2 requirement (descrease HR and SV), counter elevated sympathetic activity, increase amount of time spent in diastole (improving perfusion) of the left ventricle)
what must happen in order for blood to perfuse the myocardium
aortic pressure must exceed ventricle pressure
how do beta blocker treat hypertension
reduce cardiac output (and therefore MABP), reduce renin release from the kidneys, CNS action that reduces sympathetic activity
how do beta blockers reduce renin release from the kidneys
renal adrenoceptors
what is RAAS
renin–angiotensin–aldosterone system
how are beta blockers administered when used to treat failure
in combination with other drugs to suppress adverse effects associated with elevated activity of the symp system and RAAS
what do calcium antagonists do
prevent the opening of L-type channels in excitable tissues in response to depolarisation
what parts of the AP in SA and AV nodes do the L channels mediate
the upstroke, Ca2+ antagonist can reduce rate and conduction through the AV node
what parts of the AP in ventricles do the L channels mediate
phase 2 (plateau phase), Ca2+ antagonists can reduce force of contraction
what is the role of L type channels in vascular smooth muscles
provide pathway for entry of Ca2+
what are the three main types of calcium antagonist
verapamil, amlodipine, diltiazem
what is opening of L-type channels caused by
activation of a G protein on membrane cells (adrenoceptors coupled to G proteins)
how do calcium antagonists treat hypertension
reduced Ca2+ entry in to vascular smooth muscles causing arteriolar dilatation (reducing TPR and MABP)
cause coronary dilatiation (treats hypertension and angina)
what are the adverse effects of calcium antagonists
excessive vasodilatation= hypotension, dizziness, swollen oedema
name three calcium antagonists
amlodipine, diltiazem and verapamil
how can calcium antagonists treat dysrhythmias
suppress conduction through the AV node
what do potassium channel opener drugs do
Open ATP-modulated K+ channels (KATP) channels in vascular smooth muscle
cause hyperpolarisation which switches of L type channels
acts primarily on arterial smooth muscle
give two example of potassium channel openers
minoxidil and nicorandil
what do alpha 1 adrenoceptor receptor agonist
cause vasodilatation by blocking vascular alpha 1 adrenoceptor
name 2 alpha 1 adrenoceptor antagonists
prazosin and doxazosin
how does reduced sympathetic output affect MABP
decreases it
what is the main adverse effect of a1 adrenoceptor receptor antagonists
postural hypotension
what do diruetics do
act on kidney to increase the excretion of Na, Cl and H2O and excert indirect relaxant effects on the vasculature
what are the two main types of diuretics
thiazides and loop diuretics
what is the undesirable effect cause by both types of diuretics
loss of K+ (corrected by co-administration of K sparring diuretic/ K+ supplements
how can diuretics help in cardiovascular disease
dilate vasculature so help in mild heart failure, hypertension, oedema, heart failure
