Cardiology Non-Clinical Pharmacology Flashcards
Electrical activity yin the heart spreads via?
Gap junctions
The P wave on ECG represents?
AP upstroke through atrial muscle (0.08-0.10)
The QRS complex on ECG represents?
AP upstroke through ventricular muscle (<0.10)
What does the T wave on ECG represent?
Ventricular depolarisation
What does the PR interval on ECG represent?
Largely AV node delay (0.12-0.20)
What does the ST segment on ECG represent?
maintained ventricular depolarisation (systole)
What does the TP interval on ECG represent?
Diastole
What does the S wave on ECG represent?
Depolarisation of the ventricles at base of hear moving away from recording electrode
What does the R wave on ECG represent?
Depolarisation of the main ventricular mass moving towards the recording electrode
A large box on ECG paper represents?
0.2 seconds
A small box on ECG paper represents?
0.04 seconds
How can the HR be calculated from ECG paper?
300 / Number of large boxes between beats
In the heart, sympathetic (noradrenalin + adrenaline) activate beta-1-adrenoceptors in nodal and myocardial cells causing…?
Activation of adenylyl cyclase to increase cAMP
Sympathetic influences increases contractility (positive inotropic response) due to?
Increase in plateau phase in ventricular/atrial myocytes + enhanced calcium influx and sensitisation of contractile proteins to Ca
Sympathetic influences increases HR (positive chronotropic response) due to?
Increase in pacemaker potential caused by enhanced funny and calcium current + reduction in threshold for Ap initiation caused by enhanced calcium
Mediated by SA node
Why may sympathetic influence cause arrhythmia in atria?
Decreased AP duration and refractory period predispose to re-entrant arrhythmias
Vagal manoeuvres increase parasympathetic output may be used in ________ to suppress impulse conduction via AVN?
atrial tachycardia
Vagal manoeuvres like carotid artery bifurcation massage activate?
baroreceptors (aorta or carotid sinus)
Hyper-polarisation activates cation selective HCN channels in SA node facilitation?
Slow phase 4 depolarisation
Block of HCN channels decreases the slope of _______ and reduce _____?
pacemaker potential
Reduce heart rate
What is an example of a HCN channel blocker?
Ivabradine
Outline the mechanism of cardiac muscle contraction.
Ventricular AP
Open voltage-gated Ca-channels
Ca influx into cytoplasm
CICR from SR (via ryanodine Type 2 channel)
C binds to troponin C & shift tropomyosin out of the actin cleft
Cross-bridge between actin & myosin
Contraction via sliding filament mechanism
Outline the mechanism of cardiac muscle relaxation.
Depolarisation
Ca channels close
Ca influxx stops and calcium efflux occurs via NCX1
Ca release from SR stops and active sequestration via Ca-ATPase from cytoplasm beings
Ca dissociates from troponin C
Cross bridges between actin and myosin break
Relaxation
What is the mechanism of Levosimendan? (calcium sensitiser)
Binds to troponin C in cardiac muscle sensitising it to Ca-action
Opens K-ATP channels in vascular smooth muscle causing vasodilation (decrease after load and cardiac work)
Levosimendan is used in the treatment of?
Acute decompensated heart failure
What are functions of lipids?
Membrane biogenesis
Integrity and energy source
Precursor for hormones
Signalling molecules
Non-polar lipids are transported within?
Lipoproteins
What are lipoproteins?
Spherical particle consisting of a hydrophobic core and hydrophilic coat
What determines the target/pathway of the lipoprotein and stabilises the outer shell?
Apoproteins
Apo-B-containing lipoproteins deliver _____ to _____ for ATP synthesis and _____ for storage
Triglycerides
Muscle
Adipocytes
Where are chylomicrons formed?
Intestinal cells
Chylomicrons transport?
Dietary triglycerides via exogenous pathway) to muscle and adipocytes
VLDL are synthesised in?
Hepatocytes
VLDL transport _____ synthesised de-novo in that organ via the ______ pathway
triglycerides
endogenous
What are the (3) stages of the life cycle of App-B-containing Lipoproteins?
Assembly
Intravascular Metabolism (involves metabolism of triglyceride core)
Receptor-mediated clearance
How do triglyceride enter the systemic circulation?
Absorbed Coalesce into triglyceride droplets Apo-B protein produced by ribosomes Mature chylomicron formed Add 2nd apoprotein (Apo-A1) Enters lymphatic system Enters systemic circulation via thoracic duct
VLDL is assembled in hepatocytes using ____ from adipose tissue and de-novo synthesis
fatty acids
MTP lipidases apoB100 forming new VLDL coalesce with?
Triglyceride droplets
How does chylomicron and VLDL activation occur?
Transfer of apo-C2 from HDL particles
How does intravascular metabolism of ApoB-containing Lipoproteins occur?
Bind to chylomicrons and VLDL (facilitated by Apo-C2) and the core triglycerides are hydrolysed
Free fatty acids and glycerol enter tissues
How are Apo-B-Containing Lipoproteins cleared?
LPL causes VLDL and chylomicrons to become relatively enriched with cholesterol due to triglyceride metbaolism
Chylomicrons and LDL dissociate from LPL
ApoC2 transferred to HDL particles in exchange for ApoE
VLDL & Chylomyicrons now remnants
Return to liver and further metabolised by hepatic lipase
Lipoprotein clearance is highly dependent on?
LDL receptors expressed by liver (main) and other tissues
How is LDL take up by cells?
Receptor-mediated endocytosis
What is the rate-limiting enzyme in de-novo cholesterol synthesis?
HMG-CoA-reductase
In the cell cholesterol is released from cholesteryl ester by?
Hydrolysis
Released cholesterol causes _________ inhibition causing down regulation of LDL receptors and esterification of stored cholesterol
HMG-CoA reductase
HDL accepts excess cholesterol from the plasma membrane of cells and removes it by transporting it to the?
Liver
Where is HDL mainly formed?
In the liver
The precursor of HDL is?
Pre-beta-HDL
Apo-A1 in association with small amount of surface phospholipid and unesterified cholesterol
Where des pre-beta HDL mature into spherical alpha-HDL?
Meanwhile cholesterol is converted to?
In the plasma
cholesterol ester that migrates into the core of the particles
In the liver, HDL interacts with _____- receptor which allow cholesterol and cholesterol ester transport into hepatocytes
Scavenger
In lasma cholesterol ester transfer protein (CETP) mediates cholesteryl ester transfer from _____-to _____-
HDL
VLDL and LDL
Fibrates (lipid lowering drug) such as bezafibrate or gemfibrozil act as an agonist of ______ to enhance gene transcription including LPL
nuclear receptor
Adverse effects of fibres?
Rarely myositis (don't combine with statin) Avoid in alcoholics
Bile salt resins like colestyraminase, colestipol and colsevelam cause _______ resulting in more cholesterol being converted to ___ via enterohepatic recycling
Bile salt
Bile salts
Bile salt resins cause?
Decreased triglyceride absorption
Increased LDL receptor expression
What are adverse effects of bile salt resins?
Gi tract irritation
Fibrates act to?
Decrease triglycerides and LDL
Increase HDL
Ezetimibe reduces absorption of cholesterol by inhibiting?
Niemann-Pick-C1 like 1 transport protein in enterocytes of the duodenum
Ezetimibe is used if?
Statin doesn’t give sufficient result
Ezetimibes and Bile acid resins are administered?
PO
Ezetimibe undergoes what kind of metabolism?
Enterohepatic recycling
What are adverse effects of ezetimibe?
Diarrhoea
Abdominal pain
Headache
Ezetimibe is contraindicated in?
Breast feeding females because neonates need cholesterol for normal development
In normal sinus rhythm the origin of electrical signal is the _______ and the major point of delay is the _______
SA node
AV node
Physiological electrical dysfunction results in modulation of the _______ by the ___
SA node
ANS
Pathological electrical dysfunction results when a __________ subverts the SA node’s function
latent pacemaker
Pathologically low SA firing rate (or impaired conduction) results in?
Escaped beats
A series of escaped beats is known as an?
Escape rhythm
If the latent pacemaker beats faster than the SA node it results in?
Ectopic beats
A series of ectopic beats is known as an?
Ectopic rhythm
What are causes of an ectopic rhythm?
Ischaemia
Hypokalaemia
Increased sympathetic activity
Fibre stretch
Early afterdepolarisation occurs during which phase(s) of the action potential?
Phase II (mediated by calcium channels) Phase II (mediated by sodium channels)
EAD is associated with?
Prolonged APs and drugs that prolong the QT interval
Which drugs are known to prolong the QT interval?
Sotalol
CCB
B-blocker
How is reentrant (aka ‘circus’) circuit established?
Self-sustaining circuit stimulates an area of the myocardium repeatedly allowing retrograde conduction
In some patients, there are pathways (like the pathway of Kent) that bypass the AV node. These are known as?
Accessory pathways
In the pathway of Kent impulses are sent faster than via the AV node - the ventricles impulses from both the normal and accessory pathways
This can set up a condition for a ________ predisposing to?
Re-entrant loop
tachyarrythmias
What mediates gamma-carboxylation of factor II, VII, IX and X (required for subsequent prodcutio not active forms)
Vitamin K
What are the sources of Vitamin K?
Diet
Intestinal flora
Which enzyme allow the conversion of reduced vitamin K (hydroquinone) to oxidised vitamin K (exposed)?
Vitamin K reductase
Outline the mechanism of vascular smooth muscle contraction.
Calcium induced calcium release
Ca binds to Calmodulin (caM)
Ca-CaM phosphorylates myosin light chain leading to contraction
Outline the mechanism of vascular smooth muscle relaxation?
Myosin-LC-phosphate is activated by protein kinase G and then dephosphorylated to Myosin-LC leading to relaxation
How do vasodilation substances cause relaxation of vascular smooth muscle?
Simulate guanylase cyclase which converts GTP to cGMP increasing protein kinase G
Also stimulate Ca-dependent-K-channels causing hyperpolarising K-efflux
How do adrenaline, angiotensin II, ADH, etc lead to contraction?
Increase gene expression to produce endothelium I via precursor in endothelial cells via ET-A-Receptor in smooth muscle cells causing increased Ca leading to contraction
What are antagonist of ET-A-receptor that can be used to treat pulmonary hypertension?
Basentan
Ambrisetan
Renin inhibitors should not be combined with?
ARBS or Ace inhibitors
