Case 4 Flashcards
Why is endothelium significant in the clotting cascade?
Synthesis of von Willibrand factor (haemostasis) and PGI2 (antithrombotic, prevents aggregation of platelets)
Production of nitric oxide by endothelial cells
Ligand binds to GPCR. Activation of PLC which converts PIP2 to IP3 and DAG.
These molecules cause an increase in intracellular Ca2+.
Ca2+ binds to calmodulin and activates eNOS (endothelial NO synthase).
eNOS synthesises NO from L-arginine - BH4 is an essential cofactor.
How is NO production maintained when stimulus is prolonged?
Increased transcription of eNOS.
How do endothelial cells in the blood vessel walls respond to mechanical force?
Glycocalyces project into lumen of vessel and are attached to the cytoskeleton. Movement of glycocalyx activates Ca2+ channels. Increased Ca2+ intracellularly causing eNOS activation. NO production and vasodilation.
How does NO cause vasodilation?
Activation of cGMP and therefore PKG. PKG inhibits Ca2+ influx into sarcoplasm and promotes Ca2+ efflux out of sarcoplasm.
(PKG also inhibits IP3 mediated Ca2+ influx pathway)
Paracrine effects of Nitric Oxide
Decreased platelet aggregation + decreased monocyte and platelet adhesion
Decreased LDL oxidation - fewer atheromatous plaques formed.
Decreased expression of adhesion molecules
Decreased smooth muscle proliferation and contraction.
Changes in vascular endothelial cells with age
Older endothelial cells generate more reactive oxygen species.
ROS react with NO, reducing its bioavailability and producing peroxinitrites which have detrimental effects on cell functions.
Endothelial dysfunction - reduced vasodilation
Changes to blood vessels which occur as a result of endothelial dysfunction
Thickening of media and narrowing of lumen (due to vascular inflammation and remodelling)
Increased stiffness and potentially calcification.
Endothelium derived contracting factors
Usually prostanoids which cause contraction.
Has a greater effect when NO production is impaired.
Risk factors for atherosclerosis
Smoking Hyperlipidaemia Diabetes Hypertension Shear stress (occurs at sites where blood changes speed/direction)
Formation of an atheromatous plaque
Circulating LDL and monocytes cross the vascular endothelium into the intima.
LDLs become oxidised (oxidised LDL promotes increased permeability of endothelium)
Monocytes mature into macrophages.
Macrophages take up OxLDL and become foam cells.
Foam cells release inflammatory signals to recruit more leukocytes to site.
Foam cells accumulate and become apoptotic - releasing LDL and forming a lipid deposit. This also causes proinflammatory signal release, so further influx of inflammatory cells.
Finally, smooth muscle cells dedifferentiate, migrate and proliferate into intima. Secrete ECM forming a fibrous cap.
Factors responsible for monocyte adhesion to vascular endothelial cell membrane
P selections and E selectins
Factors responsible for monocyte migration across vascular endothelial cell membrane into intima
MCP-1 and OxLDL
Why does atheromatous plaque formation occur at regions where blood changes direction/speed?
Part of the wall will experience a decrease in shear stress - less eNOS activation.
Therefore, less endothelial repair.
More ROS generated, leukocyte adhesion, LDL entering intima and inflammation.
When the plaque is formed, the region of disturbed flow is amplified.
Eccentric plaque
Does not occupy the whole circumference
Concentric plaque
Occupies the whole circumference
Factors which affect stability of atheromatous plaques
Size - larger plaques contain more soft material and are therefore less stable.
Lipid content - higher ratio of lipid to fibrous cap is less stable
Bleeding inside the cap - increased pressure and therefore more susceptible to rupture.
Endothelial contracting factors
H2O2 Prostanoids Angiotensin II Endothelin - I Thromboxane A2 Superoxide anion
Endothelial relaxing factors
NO PGI2 H2O2 Adenosine Epoxyeicosatrienicacids (EETs)
Endothelium Derived Hyperpolarising Factor
Compensatory mechanism - cause vasodilation when NO bioavailability is compromised due to superoxide production.
Significant role in disease states e.g. hypertension
Left Anterior Descending coronary artery supplies…
Right and left ventricles and interventricular septum
Left Marginal coronary artery supplies…
Left ventricle
Left circumflex coronary artery supplies…
Left atrium and ventricle
Right Coronary artery supplies…
Right atrium and ventricle
Right Marginal Coronary artery supplies…
Right ventricle and apex
Posterior Interventricular coronary artery supplies…
Right and left ventricles and interventricular septum
RCA occlusion causing MI on an ECG
Inferior MI
ST elevation in II, III and aVF
LAD occlusion causing MI on an ECG
Septal MI - ST elevation in V1 and V2
Anterior MI - ST elevation in V3 and V4
LCx occlusion causing MI on an ECG
Lateral MI - ST elevation in I, aVL, V5 and V6
Composition of lipoproteins
Lipid core - Triglyceride and cholesteryl esters
Surface coat - phospholipid, unesterified cholesterol and apolipoproteins.
Function of HDL
Transport cholesterol back to liver
Apolipoprotein associated with HDL
ApoA1 (receptor ligand)
Apolipoprotein associated with LDL
ApoB100 (receptor ligand)
Function of LDL
Transport cholesterol from liver to tissues
Function of IDL
Transport cholesterol from liver to tissues
Apolipoprotein associated with IDL
ApoE (receptor ligand)
Function of VLDL
Transport cholesterol from liver to tissues
Apolipoprotein associated with VLDL
ApoCII (cofactor lipoprotein lipase)
Function of chylomicrons
Transport triglyceride from gut to liver
Apolipoprotein associated with chylomicrons
ApoB48 (Receptor ligand)
What are apolipoproteins?
Proteins that bind lipids to form lipoproteins - transport lipids through lymphatics and circulatory system.
Exogenous lipid transport pathway
Fat and cholesterol absorbed from GI tract assembled to form chylomicrons.
Chylomicrons carried in the bloodstream, deposit their fats when they meet tissues expressing Lipoprotein lipase (e.g. Adipose)
Remaining chylomicron remnant used to form empty HDL or are removed at the liver by binding of ApoE to their receptor.
Endogenous lipid transport pathway
Fatty acids in liver (transported here OR synthesised) packaged into VLDLs.
VLDLs carried in the bloodstream, deposit their fats when they meet tissues expressing Lipoprotein lipase (e.g. Adipose)
They are now called IDLs, which are absorbed into liver, broken down into LDLs by hepatic lipase.
Circulating LDLs are absorbed into various tissues on binding to their receptors.
HDL created as a biproduct.
Reverse cholesterol transport pathway
Too much cholesterol in peripheral tissue causes activation of ABCA1 receptor.
HDL interacts with this receptor causing LDL to be returned to the liver.
Antiatherogenic
When do patients with atherosclerosis become symptomatic?
Development of fibrous cap - increased risk of complications such as plaque rupture, thrombosis and haemorrhage
Familial Hypercholesterolaemia
Insufficient (heterozygote) or no (homozygote) ApoB100 receptor for LDL to bind to so that it is removed from circulation.
Autosomal dominant.
Causes development of cardiovascular disease 20yrs early.
Treatment of familial hypercholesterolaemia
Statins
Clinical signs for hypercholesterolaemia
Xanthelasma
Tendon Xanthoma
Corneal Arcus
PCSK9
Enzyme which binds to LDL receptor and breaks it down so that it is unable to remove LDLs.
Inhibited by certain drugs to lower serum cholesterol.
Cholesterol synthesis
Acetyl coA converted to HMG CoA.
HMG CoA converted to mevalonate by HMG CoA Reductase.
Mevalonate then converted to cholesterol
ADRs of statins
Nasopharyngitis Hyperglycaemia Headache Pharyngolaryngeal pain Epistaxis GI disorders Musculoskeletal and connective tissue disorders (Myositis in 2-3%)
Contraindications of statins
Active liver disease
Raised AST or ALT
Pregnancy or breastfeeding
Most commonly used statin
Atorvastatin
Statin used in children
Pravastatin
Indication for statins
Primary prevention - patients at high risk of CVD
Secondary prevention - patients who have had an MI already
Dicrotic notch
Sudden dip in pressure in aorta due to backflow of blood in artery as valve closes (AKA Incisura)
Effect of atherosclerosis on dicrotic notch
Larger - less compliant blood vessel, cannot compensate for pressure changes as quickly.
S1
Atrioventricular valve closure (“Lub”)
S2
Aortic/Pulmonary valve closure (“Dub”)
S3
“Ventricular gallop” - a large amount of blood striking a stiffened left ventricle
S4
Left atrium contracts against a stiffened ventricular wall due to reduced compliance (Hypertrophy or MI)
Area of pressure volume loop represents…
Net work done
Ejection fraction
Stroke volume/End Diastolic Volume (peak volume)
Heart sound which corresponds with end diastolic pressure/volume
S1
Heart sound which corresponds with end systolic pressure/volume
S2
At what point in the cardiac cycle is S4 heard?
Just before S1, at the end of diastole
Factors which increase preload
Increased blood volume
Increased skeletal muscle pump activity
Factors which increase afterload
Hypertension
Increased peripheral resistance (atherosclerosis and arteriosclerosis
Aortic stenosis
Changes to pressure-volume loop as a result of increased preload
Taller and shifted to the right
Increased pressures and volumes generated
Changes in pressure-volume loop as a result of increased afterload
Taller
Greater pressures generated by the same volume of fluid
Changes in pressure-volume loop as a result of increased inotropy
Taller and shifted to the left
ESPVR is steeper since more pressure can be generated by a smaller volume of fluid.
Orthostatic Hypotension
Pooling of blood in veins of legs when individual changes from supine to standing.
Decrease in venous return, therefore decreased stroke volume, cardiac output and arterial pressure.
Brief moment of cerebral ischaemia before autoregulation compensates for this.
Baroreceptors are expressed in…
Carotid sinus and aortic arch walls
How do baroreceptors detect blood pressure?
Express stretch sensitive TRP family channels which are non selectively permeable to cations (Ca2+, Na+_
Increased stretching, causes increased entry of cations into afferent neurons. Many action potentials generated
Information from baroceptors is carried to the brain via…
Glossopharyngeal nerve
Vagus nerve
Information from baroreceptors is carried to which structure in the CNS?
Nucleus Tractus Solitarii (NTS) in the medulla
High blood pressure detected by baroreceptors. What is the body’s response?
Inhibition of sympathetic activity
Increased vagal activity
Therefore, vasodilation
Right Vs Left sympathetic cardiac nerves
Right - more chronotropic (since SAN is on right)
Left - more inotropic (since muscle is thicker on left)
Right Vs Left Vagus Nerve
Right - affects SAN more
Left - affects AVN more
How does sympathetic nervous system exert its effects on blood vessels?
Causes vasoconstriction when noradrenaline binds to B1 receptors (Tonic constriction)
Causes vasodilation when adrenaline binds to its receptors (Preparation for fight or flight)
How does parasympathetic nervous system exert its effects on blood vessels?
ACh binds to M2 receptors on smooth muscle. Results in hyperpolarisation and therefore vasodilation.
Functional hyperaemia
Vasodilation in response to chemical byproducts of metabolism (CO2, K+, Lactic acid, ADP and Pi)
Facilitates removal of waste products .
Reactive hyperaemia
Blood pressure is greater than normal for a brief period once pressure is relieved from an artery.
Facilitates rapid removal or waste products and supply of nutrients.
Rate of action potential propagation in SAN
100bpm
Delay if ventricular excitation due to the AVN
0.1s
Bundle of His
Specialised large diameter cardiac myocytes arranged end to end. Excitation spreads via gap junctions.
Effect of sympathetic stimulation on AVN
Shortens delay by increased permeability to Na+ - steeper pacemaker potential.
How does sympathetic stimulation increase chronotropy?
Increases chance of Na+ channels opening - steeper pacemaker potential (phase 4), shorter distance between peaks
How does parasympathetic stimulation decrease chronotropy?
Increases chance of K+ channels opening - hyperpolarisation at the end of phase 3, takes longer for membrane potential to reach threshold level, longer distance between peaks.
Phase 4 of pacemaker potential
Na+ entry into pacemaker cell
Phase 0 of pacemaker potential
Rapid influx of Ca2+ into pacemaker cell
Phase 1 of pacemaker potential
Does not exist
Phase 2 of pacemaker potential
Does not exist
Phase 3 of pacemaker potential
K+ efflux from pacemaker cell
Phase 4 of myocyte action potential
Na+ and Cl+ leaking into myocyte - increasing membrane potential from -90 to -70mV
Phase 0 of myocyte action potential
At -70mV (threshold), Na+ channels open and flood into cell causing depolarisation up to 20mV
Phase 1 of myocyte action potential
At 20mV, Na+ channels close, membrane potential begins to fall since K+ is the dominant ion
Phase 2 of myocyte action potential
Membrane potential has reached 5mV due to outward movement of K+ in phase 1. At 5mV, Ca2+ channels open.
Membrane potential remains constant since outward K+ is balanced by Ca2+ in
Phase 3 of myocyte action potential
Spontaneous closure of Ca2+ channels. Membrane potential returns to -90mV since K+ is the dominant ion.
Effect of sympathetic stimulation on myocyte action potential
Activation of PKA (Binding of catecholamines to B1 adrenoceptors) which phosphorylates delayed rectifier K+ channels. Increases rate at which ventricular myocytes repolarise.
In a heart transplant patient, there is no autonomic innervation of the heart. How can heart rate be increased in response to exercise?
Increased venous return due to skeletal muscle pump.
Frank Starling mechanism states that the heart must pump out of the right atrium all the blood returned to it without letting any back up in the veins.
How do catecholamines cause an increased inotropy?
Noradrenaline/Adrenaline bind to B1 adrenoceptors.
Activates AC, increasing cAMP, activation of PKA.
PKA phosphorylates L-type Ca2+ channels, causing them to open.
Greater influx of Ca2+ therefore increased strength of contraction.
How do caffeine and theophylline cause an increase in chronotrophy and inotropy?
Inhibit phosphodiesterase which normally breaks down cAMP.
Therefore, increased [cAMP]
What is the difference between the effects of alpha and beta adrenoceptor activation on blood vessels?
Alpha - vasoconstriction (normally noradrenaline acts on this)
Beta - vasodilation (normally adrenaline acts on this)
Effect of vasopressin/ADH on blood vessels
Vasoconstriction in most tissues
Vasodilation in cerebral and coronary vessels
(Released in response to substantial haemorrhage)
Coronary blood flow throughout the cardiac cycle
Increased coronary blood flow during diastole due to extravascular compression during systole (endocardial vessels affected more than epicardial)
Thebesian Veins
Minute, valveless venous channels that open directly into the chambers of the heart from the capillary bed in the cardiac wall.
Enables collateral circulation (unique to the heart)
Compensatory mechanism which ensures adequate coronary blood flow during sympathetic stimulation
Sympathetic stimulation causes vasoconstriction of coronary vessels BUT accumulation of metabolites causes vasodilation (stronger effect than SNS)
Metabolic regulation of vasodilation/vasoconstriction
Low O2, high CO2 and H+ cause VASODILATION (inhibition of Ca2+ entry to smooth muscle cells)
High K+ causes VASODILATION (inhibition of Ca2+ entry into smooth muscle cells)
Effect of adenosine on blood vessels
Vasodilation
Why does cardiac ischaemia cause pain?
Oxygenated blood supply cannot meet myocardial demand. Anaerobic respiration by myocytes generates lactate.
Build up of lactic acid and low pH causes PAIN.
How does digoxin increase inotropy?
Inhibits Na+(out)/K+(in) ATPase
Increased [Na+] intracellularly
Na+(in)/Ca2+(out) exchange cannot occur.
Increased [Ca2+] intracellularly
Stimulates calcium induced calcium release from sarcoplasmic reticulum
Therefore, contraction is stronger
Effect of digoxin on chronotropy and dromotropy
Parasympathomimmetic - negative chronotrope and dromotrope
Stable Angina
Crushing, burning or tight pain in the chest precipitated by physical exertion or emotional stress.
Often accompanied by dyspnoea, nausea, sweating
Relieved by rest
AKA Classical/Exertional angina
Decubitus Angina
Occurs when patient lies down.
Usually associated with heart failure - due to increased central blood volume and consequent myocardial tensions.
Often have Coronary artery disease
Nocturnal angina
Wakes a person from sleep, triggered by vivid dreams.
Usually have critical coronary artery disease and may be associated with vasospasm
Variant angina
No provocation, occurs at rest, at night or early in the morning.
Prolonged and more severe pain.
Affects women more often than men
Caused by coronary artery spasm
Risk factors for angina
Obesity Family History Smoking Kidney disease Physical inactivity Hypercholesterolaemia HTN Diabetes Age (F >65, M>55) Psychosocial stress
ECG changes in angina
ST depression due to cardiac ischaemia
Imaging techniques used in diagnosis of angina
Coronary angiography - X ray based imaging, identifies narrowing of coronary arteries (injection of radio-opaque contrast dye into coronary arteries)
Echcardiography - Non invasive US imaging, identifies chamber wall abnormalities
First line treatment of Angina
Beta blocker or calcium channel blocker - depending on comorbidities
If ineffective, try the other option or both.
Second line treatment of Angina
If beta blocker and calcium channel blocker are not tolerated or both are contraindicated.
Try one of the following:
Long acting nitrate, ivabradine, nicorandil, ranolazine
Calcium channel blockers used to treat angina
Diltiazem
Verapamil
Important ADRs of CCBs
Heart block
Negative inotropy
Constipation
MOA of Nicorandil
Katp channel activation (hyperpolarisation, preventing Ca2+ entry) and NO donor
ADRs of nicorandil
Rectal bleeding and flushing
MOA of Ivabradine
Sinus node Kf channel blocker (Rate limiter)
ADRs of Ivabradine
Bradycardia
Heart failure
AF
MOA of Ranolazine
Uncertain
Na+ channel blocker and myocyte metabolic substrate utilisation
ADRs of Ranolazine
QT prolongation
Exogenous NO donors used in the treatment of Angina
Glyceryl trinatrate sublingual spray
Isosorbide trinitrate
ADRs of GTN spray
Headache
Postural hypotension
Rapid intolerance (4-12hrs nitrate-free period required daily to prevent loss of efficacy)
How does sympathetic stimulation increase lusitropy?
Activated PKA phosphorylates phospholamban.
Phosphorylated phospholamban has no inhibitory effect on RyR receptor therefore Ca2+ reuptake is faster.
Increased rate of relaxation.
Elastic arteries:
Aorta and pulmonary artery
Discontinuous capillaries are only found in…
The liver - between sinusoids and hepatocytes
Endothelium which lines the inner surface of blood vessels
Simple squamous (tunica intima)
Connective tissue which makes up the epicardium
Adventitia
Intercalated discs
Region where ends of cardiac myocytes are connected.
Contains gap junctions, adherens junctions and desmosomes.
Gap junctions allow for electrical coupling
Pericardium
2 layers connective tissue sac that encloses the heart.
Fibrous and a serous layer. Serous secretes serous fluid.
Endocardium
Lining of chambers and covering of heart valves.
Consists of endothelium, basement membrane and a small layer of loose connective tissue and some adipose tissue
Functions of pericardium
Protects against overfilling
Mechanical protection
Holds the heart in place
Protects heart from infection from other organs
Referred Pain
General visceral afferent (GVA) pain fibers follow sympathetic fibers back to the same spinal cord segments that gave rise to the preganglionic sympathetic fibers.
Symptoms of Pericarditis
Flu-like (night sweats, malaise, fever)
Dyspnoea
Chest pain (sharp, when lying down or bending, with deep inspiration and with pulsation of heart)
Pain sensation in pericarditis
Sensation comes from parietal layer due to afferent fibres which transmit sensation through the PHRENIC nerve (C3,4,5).
Caused by friction rub or effusion.
Pain may be visceral or referred (supraclavicular region).
Acute idiopathic pericarditis tends to occur in…
Young adults
Causes of pericarditis
Physical trauma/irradiation Haemorrhage (trauma/aortic rupture) Neoplasia Systemic disorders i.e. CT disease Infective Acute idiopathic
Pericarditis on an ECG
Stage I - ST elevation and PR depression in I, II, aVL, aVF, V2-6. Reciprocal ST depression and PR elevation in aVR.
Stage 2 - normalisation of ST. Generalised T wave flattening
Stage 3 - Inversion of T waves (3+ wks)
Stage 4 - Normal ECG (several wks)
Investigations in diagnosis of pericarditis
Pericardial paracentesis
Echocardiogram
Why is pain in pericardium relieved by sitting up and bending forward?
Pulls diaphragm down, creating more space between parietal and visceral pericardium. Reduced friction between them.
Symptoms of aortic dissection
Severe chest pain Sudden onset Radiation to neck and back Autonomic symptoms: N+V, sweating, fainting, hiccups Numbness in limbs
Type I DeBakey Classification
Aortic dissection involving the ascending aorta, aortic arch and descending aorta
Type II DeBakey Classification
Aortic dissection involving ascending aorta only
Type III Debakey Classification
Aortic dissection confined to descending aorta, distal to left subclavian.
Type A - Extending proximally and distally, mostly above diaphragm
Type B - Extending only distally, mostly below diaphragm
Symptoms specific to proximal aortic dissection
Anterior chest pain
Symptoms specific to distal aortic dissection
Interscapular and back pain
Factors which increase risk of Aortic Dissection
HTN Marfan's Syndrome Bicuspid aortic valve Coarctation (narrowing) of aorta Pregnancy Ehlers-Danlos Syndrome
Marfan’s Syndrome
Genetic connective tissue disorder.
Extremely tall, have long slender fingers and toes, partial dislocation of lens and heart defects.
Ehlers-Danlos Syndrome
Abnormal or deficient collagen Have elastic, fragile skin Easily bruised Scars poorly Hypermobility - joints easily dislocate Weaker heart valves
Management of Aortic Dissection
Emergency cardiac surgery
Treatment of risk factors (usually HTN)
Treat severe pain
Most effective treatment of nicotine dependence
Nicotine replacement therapy by patch and inhaler (31.5%)
How can pericardial effusion be differentiated from cardiac tamponade?
Both involve build up of fluid in pericardium.
Tamponade has more severe symptoms: dyspnoea, hypotension, distant heart sounds. Pericardial effusion may be asymptomatic or experience chest pain/pressure.
Site of auscultation of aortic valve
2nd intercostal space, right sternal border
Site of auscultation of pulmonary valve
2nd intercostal space, left sternal border
Site of auscultation of Tricuspid Valve
5th intercostal space, left sternal border
Site of auscultation of Mitral valve
5th intercostal space, left midclavicular line
Ligamentum arteriosum
Remnant of Ductus Arteriosum which connects pulmonary artery to proximal descending aorta in the foetus (allowing blood to bypass non functioning fluid filled lungs).
Surgical treatment for angina
Coronary artery bypass - improves blood supply to myocardium.
Why might a patient opt for a biological mitral valve replacement over a mechanical one?
Mechanical valves require lifelong treatment with warfarin which cannot be taken when pregnant or if patient is active and at risk of injury.
Therefore younger patients will opt for biological valve.
Biological valves will only last 12-15yrs, whereas mechanical valves are lifelong.
Troponin as a cardiac biomarker
Cardiac specific - released in myocardial injury (undetectable in health).
Not released instantly, therefore troponin must be taken 12 hrs later and compared with first sample.
Parenteral Anticoagulants
Heparin (IV)
LMWH - Enoxaparin (SC)
Fondaparinux (SC)
ADRs of parental anticoagulants
Bleeding
Purpura (purple toes)
Heparin induced thrombocytopenia.
MOA of warfarin
Vitamin K epoxide reductase shuttle inhibition.
Inhibition of synthesis of factors II, VII, IX and X
ADRs of oral anticoagulants
Haemorrhage
Purpura (purple toes)
Skin necrosis
Antiplatelet drugs
Aspirin
Clopidogrel
MOA of Aspirin
Irreversible inhibition of COX enzyme. Suppression of PG and thromboxane synthesis therefore reduced platelet aggregation
ADRs of Aspirin
GI irritation and ulceration Bleeding Nephrotoxicity HTN Reye's Syndrome (if given to under 16s, unless for Kawasaki Disease)
MOA of clopidogrel
Pro drug, its active metabolite reduces platelet aggregation through inhibition of ADP-dependent activation of the GPIIb/IIIa receptor (P2Y12 ADP receptor inhibitor)
ADRs of clopidogrel
Dyspepsia
Bleeding
Diarrhoea
Abdominal pain
Indication for aspirin
Secondary prevention in CVD
TIA
Acute stroke (for 14 days)
Acute coronary syndrome
Indication for clopidogrel
NSTEMI
Stroke (after 14 days of aspirin)
ADRs of warfarin
Haemorrhage
Hepatic Dysfunction
Jaundice
Nausea
Contraindications of warfarin
Harmorrhagic cardiovascular accident
Excessive bleeding
INR>4.5
Contraindications of Clopidogrel
Active bleeding
Prior to elective surgery
MOA of Tenectaplase
Fibrinolytic - a recombinant form of tPA which mediates conversion of plasminogen to plasmin.
More plasmin which rapidly dissolves clots by causing fibrinolysis
ADRs of Tenectaplase
Serious bleeds Reperfusion pathologies (cerebral oedema)
Contraindications of Tenectaplase
Recent haemorrhage On anticoagulant or antiplatelet drugs
Aneurysm
Aortic dissection
