Cardiovascular Block Flashcards
What are the actions of bradykinins?
Vascular
- Dilate arterioles and venules
- Increase vascular permeability
Neural
- Stimulate nerve endings = pain
Other
- Contract uterus, airways and gut
- Epithelial secretion in airways & gut
What are the targets, neurotransmitter, receptor and response of parasympathetic innervation of the heart?
Target: SA and AV node NT: ACh Receptor: Muscarinic Response: Bradycardia
What is an allosteric site?
A site of binding on a receptor other than where the endogenous ligand binds.
What is the different between a descriptive and analytical research question?
A descriptive eg how common is CHD
Analytical - does smoking increase the risk of CHD?
What are the steps of ACh production?
Choline is transported through the choline transporter into the cell cytosol. There it reacts with AcetylCoA (from mitochondria), catalysed by choline-acetyltransferase and becomes acetylcholine. It is packaged into synaptic vesicles through a ACh carrier.
What are the phases of SA pacemaker APs
4: Spontaneous depol to the threshold due to funny Na current and T type Ca++ channels (both into of the cell)
0: Depol - Ca into the cell via L type Ca++ channels - relatively slow
3: Repol due to K+ efflux
What is the early and end diastolic pressure in the LV?
Early: 5mmHg End: 15mmHg
Nitric Oxide is a potent…
Vasodilator
What are Nm type receptors?
Receptors that cause contraction of the skeletal muscle.
What are exosomes?
small membrane bound particle cells release. small, mini vesicles - can regulate organ tissue and function. contain mRNA and iRNA - therefore can be taken up and change transcriptional processes in that cell.
What is the name of the small area with a smooth surface adjacent to the pulmonary valve in the right ventricle?
Conus arteriosus
What is the mechanism of parasympathetic innervation slowing the heart?
ACh > muscarinic receptors > increase in G-protein > decrease in cAMP > increase opening of K+ channels > repolarisation is prolonged > longer to reach threshold > HR decreased
What affect does ACh have on endothelial cells?
It stimulates the release of a relaxing factor (NO).
What are the ridges in the right ventricle called?
Trabeculae carnae
What are the 4 classes of antidysrhythmias?
- Na channel blocker - slows Na depolarisation in ventricular APs
- Beta-adrenoceptor antagonist - blocks sympathetic innervation of SA and AV nodes
- K+ channel inhibitors - Slows phase 3 repolarisation of ventricular AP
- Ca2+ channel blockers - on SA and AV nodes, slows depolarisation til the threshold
What is the orthosteric site?
Where the endogenous ligand binds on a given receptor.
The downstream neurotransmitter in the sympathetic nervous system is noradrenaline is all cases except two, what are they?
Sympathetic innervation of sweat glands and adrenals where ACh is the post ganglionic neurotransmitter.
What receptor does smoking cessation drug nicotine act on?
The nicotinic receptors of the somatic and autonomic NS - it is a agonist.
What is the smooth aspect of the right atrium called?
Sinus venarum
What are the 7 points are which you can target neurotransmission at the synapse?
- Synthesis of the neurotransmitter 2. Storage of the neurotransmitter 3. Leakage of neurotransmitter out of vesicles 4. Release of neurotransmitter into the synapse 5. Degradation of the neurotransmitter in the synaptic cleft 6. Uptake of the neurotransmitter back into the pre-synaptic axon 7. Action of the neurotransmitter on its receptor
What are some effects of agonists of muscarinic receptors of the autonomic NS
Salivation, lacrimation (tears), urination, defecation
Sweating
Slowing of the heart
Bronchoconstriction Eg. Pilocarpine - glaucoma
What is the mean circulatory filling pressure?
The pressure of the blood in circulation if the heart was to stop.
What is the physiological role of NO?
Flow-dependent vasodilation - released in response to shear force
Inhibit platelet adhesion and aggregation
Neurotransmission
What is the name of the point at which the rough area of the right atrium abruptly stops?
Crista terminalis
What does “positively cooperative” refer to?
The bind of one O2 to Hb facilitates the binding of a further three O2’s. While the dissociation of one O2 makes dissociation of the remaining O2 easier.
What is the mechanism of sympathetic innervation increasing HR?
NA and adrenaline > beta1-adrenoceptors > G protein increases > cAMP increases > opening of Ca2+ channels > time for depolarisation to the threshold (phase 4) is shortened at SA and AV nodes > HR increased
What are the steps of receptor mediate NO synthesis in endothelial cells?
ACh or bradykinin, or mechanical stress are detected by receptors > increase in intracellular Ca2+ > NO synthase is activated > arginine is converted into NO and released into adjacent smooth muscle cells.
How does NO cause relaxation of vascular smooth muscle cells?
Enters the cells > activates guanylate cyclase > GTP is converted to cGMP > relaxation
Endothelin is a …
Vasocontrictor
What receptors does noradrenaline act on? And what type of receptor is it?
Alpha and beta adrenoceptors and they are GPCRs
What are the three phases of coagulation?
Initiation - blood is exposed to tissue factor
Amplification - small amounts of thrombin is made from prothrombin
Propagation - thrombin burst, thrombin converts fibrogen into fibrin and the fibrin net forms
What is the name of the structure of the heart that used to be the foramen ovale?
Fossa ovalis
What are the steps of pharmacokinetics?
Administration Absorption Distribution Elimination Metabolism Excretion ADME = absorption, distribution, metabolism and excretion.
What are the characteristics distinctive of thoracic vertebrae?
Articular areas for ribs - demi facets on the body - facets on the transverse process Long vertical spinous process
What are three factors that can reduce LV compliance?
Pericardial effusion
Fibrosis/scarring of the pericardium
Cancer
What are the steps of noradrenaline production?
Tyrosine is transported into the neurone. Tyrosine hydroxylase catalyses its conversion into L-DOPA. L-DOPA is converted into dopamine by DOPA decarboxylase. Dopamine is transported into synaptic vesicles where Dopamine beta-hydroxylase converts it into noradrenaline.
How is CO affected by changing venous pressure?
Increasing venous pressure results in increased CO as atrial refill is greater. The relationship is sigmoidal.
What causes the first heart sound?
The closure of the mitral and tricuspid valves
What are the factors affecting drug distribution?
Size of the molecule (eg large protein can’t get around BBB)
Lipid solubility
Ability to bind plasma proteins
What are coronets? How many are there? What is their function?
Coronets are loops in the heart’s fibrous skeleton There are two They are anchors to the aorta and pulmonary valve
What does Salbutamol do?
It is a agonist for beta2 adrenoceptors in the trachea - causes dilation.
What causes the second heart sound?
The closure of the aortic and pulmonary valve
What are two advantages of allosteric antagonists?
They can bind to non-conversed regions of receptors (the endogenous ligand binding site is conversed) that are individual to different subtypes. Incomplete antagonism is possible (toning down) so that physiological modulation can continue.
Activation of the sympathetic NS causes?
- increases HR - decreases atrioventricular conduction time - a response to less time between signals from SA node. - increases cardiac contractility - increases TPR - increase venous tone - transfer blood from veins to arteries.
What are the three board types of antagonists?
Competitive antagonists - act at the same site as the agonist
Non-competitive antagonist (at receptor) - Allosteric inhibitors (bind to different site on the receptor)
Non-competitive antagonist (not at the receptor) - pathway inhibitor or - functional (physiological) antagonist
What are the trigones?
Trigones are connective tissue that link the two coronets and the figure of eight of the heart skeleton
What type of drugs can cross into the CNS?
Lipid soluble drugs
What is the effect of reduced LV compliance on EDV and SV
EDV is decreased as the pressure in the LV is greater for a given volume of blood entering. Therefore, according the Frank-Starling law as EDV is reduced SV is also reduced.
What are three examples of drug reservoirs?
Plasma proteins Cells Fat
What do drug reservoirs do?
Where drug accumulates: - Can prolong action - Can quickly terminate action - Can lead to slow distribution
What end effect does cocaine, MAO inhibitors and sympathomimetics all share?
More noradrenaline in the synaptic cleft.
What are the phases of ventricular APs?
0: rapid depol: Na+ in 1: rapid repol: K+ out 2: plateau - Ca++ in and K+ out 3: Repol - K+ out 4: Stable membrane potential
What effect does cocaine have?
Blocks the reuptake of NA back into the pre-synapse.
What is the Bohr effect?
Active tissue is more acidic therefore stimulates Hb-O2 to yield more O2. Shift the curve to the right.
What are some effects of antagonists of the muscarinic receptors of the autonomic NS?
Reduce SLUD
Reduce sweating
Tachycardia
Bronchodilation
Eg. Atropine - reduces secretion and causes bronchodilation, used in anaesthetic
What are some stimuli that induce mast cells to degranulate and release histamine?
Cross linking of IgE on their surface
Complement C3a/C5a
Neuropeptides
Cytokines and chemokines
Bacterial components
Physical trauma
What is the role of thrombin?
Convert fibrinogen to fibrin - critical for plug formation Switch haemostasis on/off
What are the three factors that make up Virchow’s triad?
Vessel wall
Blood composition
Blood flow
What effect does increase contractility in the LV have on ESV and SV
SV increases ESV decreases
What is the name of the specialised muscles that attach the ventricle wall with the tricuspid valve? How many does each ventricle have?
Papillary muscle
Three in the RV due to three cusps in its valve
Two in the LV due to two cusps in its valve
What are the steps of adrenaline synthesis?
Dopamine is transported into a secretory vesicle where dopamine beta-hydroxylase catalyses it into noradrenaline. Then PNMT converts it into adrenaline.
What is the name of the structures that anchor the tricuspid valve to the ventricle wall muscles in the ventricles?
Chordae tendinae
What is Frank-Starling law?
Stroke volume will increase in response to an increase in volume of blood filling the heart (aka end diastolic volume). Also, more stretch = more tension
Activation of the parasympathetic NS causes?
- reduces HR by increasing atrioventricular conduction time
- not a big impact on contractility - parasympathetic NS doesn’t innervate vascular smooth muscle therefore not reduction in TPR. If you want to do that you can turn down the sympathetic NS - called the sympathetic tone (which produces the arterial tone)
When is are you likely to hear mitral murmurs?
Early diastole when blood is flowing turbulently from the LA to LV. Early systole when blood flows backwards due to a leaky mitral valve.
What is the difference between prevalence and incidence?
Prevalence is the number of existing cases, incidence is the no. of new cases.
Why do local mediators usually only act locally?
Often quite labile or rapidly metabolised or ‘diluted’ beyond their biologically active range close to their site of release.
What are the three steps of renal excretion?
- Glomerular filtration - passive (drugs out of the blood)
- Tubular secretion - active (drug out of blood)
- Tubular reabsorption - passive (drugs back into blood)
What do ganglia allow for in signal transduction in the autonomic nervous system?
Amplification, modulation and integration of signals.
Acidic drugs are more lipid soluble at … pH
Low
What receptors do ACh act on? And what type of receptor are they?
Nicotinic (ligand-gated ion-channel) Muscarinic (GPCR)
What is the rough aspect of the right atrium called?
Musculi pectinati
