Cardiovascular 3 Flashcards
how to control vascular smooth muscle tone
vascular smooth muscle cells are bathed in microenvironment rich in vaso-active substances
tone is determined by balance of vasoconstrictive and vasodilatory influences
Where are voltage operated calcium channels found and the types
are found in : - Nerves - Vascular smooth muscle - Cardiac cells Types 1) L type • Vascular smooth muscle • Cardiac muscle (won't effect nerves or skeletal muscle - nodal tissue - Myocardium 2) N-type • Effect nerves
What are the 2 main classes of drugs used as vasodilators and classes within
1) Venous dilators
- Nitrates
2) Arterial dilators
- Hydralazine
- Calcium channel blockers
- Alpha blockers
- Beta blockers
- Angiotensin converting enzyme inhibitors
Nitrates what class of drug what does it breakdown into, what does it do and how used in veterinary medicine and how given
venous dilator (venodilator)
- reduces venous return, reduce EDV, reduce workload as reduce SV and CO
- increases NO which increases cGMP inactivating myosin resulting in vasodilation
- used in acute decompensated heart failure (animal collapsed)
- not tablet as fist pass effect but onto the skin
Hydralazine what class of drug, how work, how strong, what problems and when used
arteriodilator
- mechanism unknown
- very potent
- reflex tachycardia - problem as quick reduction in blood pressure but then restore of pressure
- used in retinal detachment
calcium channel blocker what class of drug, what does it block, mechanism of action, what tissues and affect at those tissues
direct vasodilator
- block L type calcium channels (heart and vas smooth muscle)
- bind to channel from inside so requires a open channel to block - use dependence (vascular beds with higher resting tone will dilate more)
What tissues do they effect
• Nodal /conducting tissue–> decreased heart rate, & AV conduction
• Myocardium –> decreased force of contraction
• Vascular smooth muscle –> relaxation
vascular:myocardial selectivity for 3 different drugs of calcium channel blockers
– Verapamil 1:1 - equal effect on both
– Diltiazem 7:1
– Amlodipine 14:1 - 14 times more selective for vascular smooth muscle than myocardial
alpha blocker what class of drug, where does it act and machanism and what is benefit
indirect vasodilator acts on arteriolar and venous mechanism - less NA binding - less IP3 and DAG - decreased intracellular Ca2+ - relaxation - less contraction - less tachycardia then hydralazine
beta blocker what class of drug and what is it cardiac and renal effects
indirect vasodilator
Cardiac effect:
- Decrease HR (SA node)
- Decrease SV (contractility)
- Decrease cardiac output
- Reduce blood volume so reduce blood pressure
Renal effect
- Block B1 receptors on JG (juxtaglomerular) cells
- Decreased renin release
- Decreased angiotensin formation - most potent vasoconstrictor
- Decreased TPR
what are the 3 main side effects of beta blockers and what is the mechanism behind them
1) cold extremities
- alpha dominance without beta receptor activation more vasoconstriction
2) Fatigue - reduced cardiac output baroreflex cannot occur as blocking beta so cannot get increase in HR
3) bronchoconstriction - beta 2 antagonist effect causing bronchodilation - now blocked
what does chronic activation of the RAAS system result in
• Persistent vasoconstriction –> increased pre load and afterload (consistent)
• Increased blood volume–> increased preload
• Increased angiotensin–> decreased baroreceptor sensitivity and myocardial toxicity
- Baroreceptors get reset at a higher pressure
Myocardial toxin as damage blood vessels
what are the 2 drugs used that affect RAAS and what is used most commonly
1) Angiotensin converting enzyme inhibitors (ACE inhibitors) - most widely used
2) Angiotensin II receptor blockers - bind on receptors and prevent binding of angiotensin II
what are the main cardiorenal effects of ACE inhibitors
• Vasodilation (arterial & venous)
- reduce arterial & venous pressure - TPR
- reduce ventricular afterload & preload
• Decrease blood volume as decrease fluid retention
- natriuretic
- diuretic
• Depress sympathetic activity
Inhibit cardiac and vascular hypertrophy
how are ACE inhibitors administered and when used
- as a prodrug - metabolised in liver to active form and dependent on kidney for clearnace therefore TEST RENAL FUNCTION FIRST
used in congestive heart failure as reduce pre and afterload - generally lifelong drug
also used in chronic renal insufficiency in cats where systemic hypertension leads to increased glomerular filtration pressure and glomerular damage (still requires clearnace through kidney need to be considered)
what are the 2 main effects of ACE inhibitors and why
1) ACE converts angiotensin to active form - ACE I to ACE II
therefore ACHEI decrease vasoconstriction and water retention as prevents ACE II being produced
2) ACE also breaks down bradykinin which causes vasodilation
ACHEI increases vasodilation and increase vascular permeability - generally occurs more in lungs resulting in dry cough (doesn’t occur as much in animals)
angiotensin II receptor antagonists
- More selective than ACE inhibitors (no effect on BK metabolism)
- More complete inhibition of Angiotensin
- Drugs of the future
maximal oxygen consumption what is it, how relate to athletes
comes a point where you can run faster but oxygen consumption plateaus out
Above this point relying on anaerobic respiration
- better the athlete - thoroughbred racehorses higher then maximal oxygen consumption
what determine oxygen delivery
VO2 = Q X (Ca - Cv)
- VO2 is rate of oxygen consumption (mls/min)
- Q is the cardiac output (L/min)
- Ca is the content of oxygen in the arterial blood (into the muscles/tissue)
- Cv is the content of oxygen in the venous blood (out of the muscle/tissue)
What are the 3 ways in which you can increase oxygen delivery
1) increase cardiac output
2) increase Ca - content of oxygen within arterial blood
3) decrease Cv - content of oxygen in the venous blood
What are the ways in which you can increase cardiac output
1) increase HR - decrease parasymapthetic and increase sympathetic tone
2) increase SV - increase EDV - larger heart
increase ESV - increase contractility or decrease afterliad
what are the ways in which you can increase Ca and decrease Cv
Increase Ca
- increase Hb concentration in the blood, horse uses splenic contraction - increase RBCs
decrease Cv
- increase oxygen extraction, Bohr Effect
does heart size matter and what can affect this
heart size in terms of percetnage body weight does matter for elite athletes - athletic animals have relatively larger hearts
- excercise training can increase heart size - increase ventricular size increase EDV
steps in formation of sigmoid heart
establish ventricle and atrium sac via
1) elongation of pericardial sac
2) elongation folds up on itself and forms S shape
3) creation of inflow and outflow trunks
what are the 4 steps in the formation of the four-chambered heart
1) 2 projections
2) the interventircular spetum
3) formation of valves
4) formation of the inter-atrial septa