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57 Cards in this Set
- Front
- Back
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name calcium antagonists
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veraprimili
nifedipine amlodipine |
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how do calcium antagonits work
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inhibit Ca2+ channels
less ca2+ enteres cells less ca2+ release from sarcplasmic reticulum less ca2+ means less activation of myosin light chain kinase, less activation of troponin = less sarcomere activation = less contraction = vasodilation of coronayr and peripheral arteries = better bloodflow = -ve iono- and chronotropic effect = less 02 demand = less angina |
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name beta1-adreonreceptors antagonists
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propanolol
atenolol |
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how do beta1-adrenoreceptors antagonists work
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less Beta1 activation = less GPCR activation = less Gs subunits = less ATP to cAMP = less phosphorylation of Ca2+ channels= less ca2+ entry
less ca2+ entry and less myosin light chain kinase = less contraction= -ve ionotropic and chronotropic effect = reduced 02 demand = less angina |
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goals of angina treatment
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reduce 02 demand, reduce metabolic needs, increases coronayr bloow glod
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B1 receptors side-effects
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postural hypotension
bradycardia |
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Calcium antagonists side-effects
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BP drop causes reflex tachycardia due to baroreceptor reflex
hypotension reduced intestinal motiligy |
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name organic nitrates
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isobordide mononitrate
glyceryl trinitrate |
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how do organic nitrates works
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nitrates break down in to N02- ions, these become NO. NO activates guanylate cyclase, this convertes GTP to cGMP. cGMP activates protein kinase G, this increases Ca2+ extrusion, and increases K+ passage out of the cell. less Ca2+ and hyperpolarisation decreases myocytre firing rate and contractility
this causes vasodilation. this decreases afterload and increases bloow flow to heart |
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organic nitrate side-effects
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postural hypotension
headaches due to cerebral vasodilation |
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what are the characteristics of coronoary blood flow
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1. most blood flow during diastole
2. so blood flow only during 2/3 of all cardiac cycle |
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descirble cardiac cycle
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1. rate of contraction dependent on sinoatrial node. Sinoatrial node has an intrinsic rate of depolarisation
2. when the cell depolarises membrane voltage increases from -90 to + 40 3. depolarisation triggers opening of Na+ channels, Na+ floods in and cell depolarises to reach +20mv 4. At peak of depolarisation the Na+ shut and enter refracotry period. at the same time Ca2+ channels open and Ca2+ floods in creates the plateau phase 5. at the end of the plateau phase the Ca2+ channels shut and the k+ channels open the k+ floods in and respolarises the cell the inward flood of Ca2+ binds to myosin light chain kinase and tropinin, this causes muscle contractiion |
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define cardiac output?
How is output calculated? what are the other equations of the cardiovascular system |
cardiac output is whole heart output in a minute in litres
CO= HR x SV MAP= CO x TPR MAP = ( a third of systolic pressure) + ( two thirds of diastolic pressure) |
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How does the sympathic and parasympathetic nervous system redulate cardiac output
What other laws dictate CO |
3 ways:
beta1 receptors M2 receptors beta1 receptors - GPCR, Gs subunit, activates adenylate cyclase, increases cAMP, activates protein kinase A, phosphorylates Ca2+ channels and activates myosin light chain kinase. More Ca2+ + myosin light chain kinase increases contractility and heart rate - positive ionotropic and chronotropic effect - increases HR M2 receptors - GPCR, Gi subunit, activation by ACh from vagus, activation increases Gi, Gi opens K+ channels and inhibits adenylate cyclase, K+ hyperpolarisation and reduced adenylate cyclase activity results in a -ve ionotropic ad chronotropic effect Starling's laws - more CVP = more pre-load = greater EDV = greater EDV means more ventricular filling = more filling results in greater SV due to larger contractility due to the greater stretch of the ventricular muscle |
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causes and characteristics of cardiac failure
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cardiac failure is the result of cardiac damage or insufficiency that results in inability of the heart to keep tissue perfused
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describe the cycle of cardiac failure
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cardiac failure results in less blood flow
reduced blood is detected by the juxtaglomerular apparatus, reduced blood flow causes increased salt and water retention and renin release renin release catalyses the conversion of aniotensinogen into angiotensin 1 angiotensin converting enzymes convert angiotensin 1 into angiotensin 2 angiotensin 2 increase aldosterone release from the adrenal gland. angiotensin 2 is also a vasoconstrictor the vasoconstriction increases TPR, increased TPR increases afterload, increased afterload puts more strain on the heart aldosterone inserts Na+ channels into the collecting duct of the nephrons these channels cause the reasorption of more Na+ and more water more Na+ and water results in a greater plasma volume greater plasma volume results in a greater CVP, a greater CVP increased filling pressure A greater filling pressure increased pre-load and this increases strain on the heart |
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The role and action of diuratecs in CHF? what are they
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done in 2 ways:
diuretics aldosteron reduction 2 diuretics thiazide diuretics - bendroflumethiazide loops diuretics - furosemide furosemide - knocks out Na+/K+/2Cl- transporteringin the membrane of the cells in the ascending limb of the loops of henle. This reduces salt and H20 reabsorption, this reduces plasma volume and therefore decreases pre-load side-effect: hypokalaemia, hypotension, metabolic alkalosis bendroflumethiazide - knocks out Na+/Cl- co-transporter in the membrane of the cells of the distal convoluted tubules, reduces salt and H20 reabsoprtion. this reduces plasma volume and therefore reduces pre-load side-effects: hypokalaemia, hypotension, metabolic alkalosis |
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The role of ACE inhibitors in CHF? what are they?
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ACE inhibitors :
captopril enalopril Action: the inhibition of ACE means there is less conversion of angiotensin 1 to angiotensin 2. Less angiotensin 2 means less vasoconstriction and therefore less afterload less angiotensin 2 means less aldoersteron release. less aldosteron means less water and salt retention. this reduces pre-load less pro-load and less afterload means less cardiac strain and better cardiac health Side-effects: cough |
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The rolse of angiotensin 2 antagonists
in CHF? what are they |
Angiotensin 2 antagonists reduce the action of angiotensin 2, so:
Less vasoncstrinction less aldosteron release |
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role of B1 adrenoreceptors in CHF?
What are they? |
drugs:
atenolol propanolol initirally, B1 adrenoreceptors acivity is compensatory and helps to maintain cardiac output. However, parasympathic activity quikly becomes excessive and pathological. B1 adrenoreceptors antagonise the receptors, so less Gs subunit, so less ATP to cAMP, less cAMP means less protein kinase A activation, less phopshorylation of Ca2+ channels, less Ca2+ channels means less Ca2+ movement into the cell = less contraction = -ve ionotropic and chronotropic effect this reduces cardiac strain |
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role of digital glycosides in CHF? what are they?
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digoxin
these inhibit the Na+/K+ transporter in the membrane of the myocytes. this reduces Na+ movement out of the cell and reduces k+ into the cell less Na+ means less acivity of the Na+/Ca+ counter-transporter = less Ca2+ movement out of the cell = less Na+ movement into the cell This means higher intracellular Ca2+ levels, these high levels result in an increased contracility for no increase in 02 demand Higher contracility = higher CO side-effects: vomting confusion dysryhythmias |
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role of organic nitrates in CHF? what are they
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isobordide mononitrate
glyceryl nononitrate Side-effets headaches postural hypotension Nitrates becomes NO2- NO2- becomes NO NO activates guanylate cyclase guanylate cyclase makes cGMP cGMP activates protein kinase G Protein kinase G increases Ca2+ sequestering, opens K+ channels and inhibits myosin light chain kinase less k+ causes hyperpolarisation, less Ca2+ and myosin light chain kinase means that there is less smooth contraction less contraction = vasodilation vasodilation = reduced preload reduced preload = greater CO |
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what are the 3 receptors of sympathetic control of blood pressure?
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beta1 receptors
beta2 receptors alpha1 receptors beta1 receptors =GPCR =Gs subunit =cardiac function mode of action =Gs subunit activates adenylate cyclase =adenylate cyclase converts ATP to cAMP =cAMP activates protein kinase A =protein kinase A phopshoryaltes Ca2+ channels =phosphrylation of Ca2+ channels casuing them to open for longer =longer opening, more Ca2+ =more Ca2+ means a +ve ionotropic and chronotropic effect =this increases blood pressure beta2 adrenoreceptors =GPCR =use Gs subunit =on blood vessels =cause vasodilation =this decreases BP alpha1 receptors =GPCR =Uses Gq subunit =vascular function mode of action =receptor activation increases levels of Gq subunits =Gq subunit activates phospholipase C =Phospholipase C splits IP2 into PIP3 and DAG =PIP3 increases Ca2+ levels =DAG activates protein kinase C =Increased Ca2+ activates myosin light chain kinase and troponin =this increases smooth muscle contraction of blood vessels =this causes vasoconstriction and increases BP |
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what are the alpha subunits of:
M1 receptors M2 receptors M3 receptors Beta1 receptors Beta2 receptors Alpha1 receptors Alpha2 receptors |
M1 receptors
=Gq M2 receptors =Gs M3 receptors =Gq Beta1 receptors =Gs Beta2 receptors =Gs Alpha1 receptors =Gq Alpha2 receptors =Gi |
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Describe the renin-angiotensin system
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=Redcued renal blood flow is detected by the juxta-glomerular apparatus
=this causes renin release =renin causes the conversion of angiotensinogen into angiotensin 1 =angiotensin 1 is converted into angiotensin 2 by angiotensin-onverting enzymes =angiotensin 2 is a vasonconstrictor so increases BP but also causes aldosteron release =aldosterone causes the insertion of Na+ channel into the cells of the collecting duct =this increases Na+ reabsorption and water reabsorption =this increases blood volume and increases BP |
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What are the major treatments of hypertension? how do they work
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1.calcium antagonists
2. diuretics 3.ACE inhibitiors 4. Beta1 antagonists calcium antagonsits -veraprimil mode of action =the calcium antagonists block the calcium channels in the myocyte membranes =this reduces calcium input =less calcium means less calcium mediated release from the sarcoplasmic reticulum =less calcium means that there is less action of myosin light chain kinase and troponin =this decreases muscle contraction effects vasodilation =lowers BP reduced HR =lower BP Reduced contractility =lower BP Side-effects constipation hypotension reflex tachycardia diuretics -bendroflumethiazide mode of action =these thiazide diuretics knock out Na+/K+ co-transporters in the distal convoluted tubule =this decreases Na+ and Cl- reabsoprtion =less ion reabsorption means less water reabsorption =less water reabsorption means less plasma volume and therefore less BP side-effects =hypovolaemia =hypokalaemia =metabolic alkalosis ACE inhibitors -captopril mode of action =ACE inhibitors inhibt ACE, these reduce convesion of angiotensin 1 to angiotensin 2. =less angiotensin 2 means less vasoconstriction and less aldosteron release =this decreaes BP Side-effects =hypotension =dry cough Beta-antagonsits =propanolol =atenolol mode of action =beta1 antagonism reduces activation of adenylate cyclase by the Gs subunit =less adenylate cyclase means less cAMP =less cAMP means less activation of protein kinase A =less protein kinase A means less Ca2+ phosphorylation =this results in less channel opening and therefore less Ca2+ channels =less Ca2+ means less contraction =this reduces contractility and HR so has a negative ionotropic and chronotropic effect =this reduces BP side-effects =postural hypotension |
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What is the principle excitatory neurotransmitter of the CNS?
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glutamate
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what is the principle inhibitory NTS of the CNS?
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GABA
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What are the glutamate receptors? what are there structures?
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2 receptors:
NMDA receptors AMPA receptors NMDA receptors: =these are made from 4 subunits =these are blocked by Mg2+ receptors =Glutamate, with glycine co-binding, causes a conformational change that results in the expulsion of the Mg2+ ion =expulsion of these ions result in Na+ or Ca2+ passage AMPA receptors =these are ligand-gated ion channels =binding of glutamate results in the free passage of Na+ and K+ |
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What are the GABA receptors
What are there strucutres? |
There are 2 GABA receptors
=GABAa =GABAb GABAa =GABA is a ligang-gated ion channel =binding of GABA causes the opening of a Cl- channel =the free movement of Cl- causes hyperpolarisation of the cell =this is an inhibitory function GABAb =these are GPCRs =these use a Gi subunit Mode of action =Gi subunit =Gi subunit opens K+ channels =Gi subunit inhibits adenylate cyclase =this inhibition reduces Ca2+ entry =less Ca2+ and less K+ means the cell is hyperpolarised =this inhibits the cell |
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What are the NTS of the autonomic nervous system? and on what receptors do they act?
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ganglia use ACh on nicotinic receptors
Sympahetic system uses noradrenaline on Alpha and Beta adrenoreceptors. It aslo causes adrenaline release from the adrenal medulla Parasympathetic system uses ACh on muscarinic receptors |
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What enzyme makes ACh?
What enzyme(s) breaks ACh down? |
made by Choline Acetyl-transferase
Broken down by cholinesterases |
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What inhibits ACh release?
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Botulinum toxin
Aminoglycosides - antibiotics |
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Describe the structure and action of nicotinic receptors
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4 subunits
Open Na+ channels Causes cell depolarisation |
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Name a nicotinic antagonists? what side-effects would it cause
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trimetephan
hypotension tachycardia - due to inhibition of Vagal ganglia - so reduces vagus activity Dry mouth - due to vagal block of M3 activity |
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Describe the stucture and action of neuromuscular junctions
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motorneurons releases ACh from presynaptic knob in response to cell depolarisation
ACh crosses synaptic cleft to synapse on nicotinic receptors in the T-tubules of the motor endplate Receptors open Na+ channels Na+ moves in, depolarises cells and open Ca2+ channels Ca2+ binds to rynadine receptors on the terminal cisternae sarcoplasmic reticulum. Causes more Ca2+ release Ca2+ increase causes muscle contraction |
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What are the blockers of the NMJ? how are they different? what are there side-effects
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Depolarising blockers - succinycholine
binds to ACh receptors, causes them to open, long term opening causes sustained depolarisation, sustained depolarisation causes surrounding area to enter refractory period. this desentises motor end plate and prevents muscle contraction Side-effects: Bradycardia Inreased intraocular pressure Non-depolarising blockers Tubocurarine vecuronium pancuronium These competitively antagonise the nicotinic receptors to prevents channel opening and so prevent muscle contraction side-effects: tachycardia hypotension |
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What are the types of muscarinic antagonists? what is there structure?
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They are all GPCRs
M1 - uses Gq subunit M2 - uses Gi subunit M3 - uses Gq subunit When Ach binds the receptor undergoes a conformational change, this activates the alpha-subunit which then has a cellular effect. Gq - activates phospholipase C, this splits IP2 into PIP3 and DAG. DAG activates protein kinase C, PIP3 causes Ca2+ release from the sarcoplasmic reticulum. Gi - this opens K+ channels in the cell's membrane and inhibits adenylate cyclase. This reduces intracellular cAMP levels which in turn reduces Ca2+ channel psohproylation. So overall there is less intracellular Ca2+ and K+ |
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Where are the three types of muscarinic receptors found?
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M1 - neural - ganglia, parietal cells,
M2 - Cardiac function M3 - vascular function |
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What are the effects of the three muscarinic receptors?
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M1 - increased NTS release, Increases HCL secretion
M2 - decreases HR, decreases Contractility M3 - vasodilation |
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Name a antagonist for each muscarininc receptor. Cite there functions and side-effects
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M1 - prienzipine - reduce HC2 secretion
M2 - Atropine SE: tachycardia, hypertension M3 - scopolamine, atropine - pupil dilation SE: hypertension, constipation |
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What are the normal physiological cholinesterases? what are there substrates? what are there locations
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Acetylcholinersterase - ACh specific, found in synpases and neuromuscular junction
Butyrylcholinesterases - fairly non-specific in action, found in plasma |
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Name two anti-cholinersterases. What are there side-effects
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ephodrium, neostigmine
SE: hypotension, bradycardia, blurred vision, bronchoconstriction |
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What drugs affect the proximal convoluted tubule? what are there actions?
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Probenecide - inhibit the organic ion transporter:
increases urate excretion decreases penicillin excretion Acetazolamide inhibits carbonic anydrase: results in less H+ being free to be pumped into the lumen of the nephron, so less H+ reacting with HCO3-. Less H+ and more HCO3- means that the filtrate is more alkali More alkali urine increases aspirin excretion. this is because aspirin is salicylic acid, so in the filtrate it reacts with HCO3- , the result of the reaction means that the aspirin cannot be reabsorbed, so more is excreted |
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How is urinary pH modified?
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Through:
potassium citrate ammonium chloride Potassium citrate: -dissociates into K+ and HCO3- -increased HCO3- means less H+ as the two react -this increase pH Ammonium chloride: -this dissociates into NH3 and HCl -The HCl enters the filtrate and dissociates to form H+ and Cl- -More H+ = lower pH |
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What affect does aspirin have on blood pH? What affect does it have as a result?
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aspirin is salicylic acid = large aspirin does causes metabolic acidosis
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What drugs on the loop of Henle? what do they do? What are there side-effects
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Loop diuretics act on the ascending limb of the loop of Henle
-Furosemide These knock out the Na+/k+/Cl- co-transporter. This results in less ion reabsoprtion, less ions means a lower cellular osmolarity so less water is reabsorbed. less water reabsorption = more water loss = diuresis But K+ channels are still open = K+ loss Side effects: Hypotension Hypokalaemia matbolic alkalosis |
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What drugs act on the distal convoluted tubule? what do they do? What are there side-effects?
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Thiazide diuretics - bendrogflumethiazide
These inhibit the N+/Cl- co-transporter = less ion rabsorption = less osmolarity of interstitium = less water reabsorption = diuresis Side-effects: -hypokalaemia -metabolic alkalosis -hypotension |
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What drugs act on the collecting duct? what doe they do? what are the side-effects?
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Potassium sparing diuretics:
Spironolactone Aclimoride Spironolactone -this is an aldosterone antagonist -This is used in Conn's syndrome , AKA primary mineralocorticoid excess and in secondery hyperaldosteronism -reduced aldosteron effect = reduced Na+ channel insertion = less Na+ reabsorption = less water reabsorption = diuresis and potassium retention, as less intracellular K+ means less activting of the Na+/k+ ATPase counter-transporter Side-effects: -hyperkalaemia Amiloride -this is used to treat hypertension -this inhibits Na+ channel insertion into the basolateral membrane on the collecting duct = same effect as spinoloctone Side-effects: hypokalaemia, acidosis |
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What does aldosterone do?
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Causes the insertion of Na+ channels into the basolateral membrane of the collecting duct. This increases Na+ reabsorption and as a result increases water rebasorption
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Name a osmotic diuretic
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mannitol
-this compound is an osmotic diuretic and works by increasing the osmolarity of the nephron's filtrate. This reduces water rebasorption and increases water loss |
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What is angina? what are the types of angina?
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Angina is pain as a result of the heart not being able to be supplied with enough oxygen to meet its metabolic needs
3 types of angina: stable - pain upon exertion, pain relieved upon resting Unstable - pain upon increasingly low levels of exertion, eventually pain is present eve on resting Variant - due to coronary artery spasm |
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What causes Angina?
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Angina is commonly due to atherosclerosis causing a reduced blood flow to the myocardium
Atherosclerosis: -endothelial damage occurs -this causes macrophage migration -macrophages release cytokines that increase smooth muscle proliferation and free radicals -these free radicals reacting with LDL creats oxidised LDL -oxidised LDL is enguled by the macrophages to become foam cells -these foam cells die to deposit the LDL underneath the endothelium -the buildup of endotheliam and foam cells cause them to occlude the blood vessel -this reduces blood flow |
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What are the goals of angina treatment?
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the goals of angina are to:
-increase perfusion of the heart -decreased oxygen demand by decreased metabolic need by decreasing work |
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What is the treatment of angina? what are there side-effects
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organic nitrates
Beta1-adnreoreceptor antagonists calcium antagonists Organic nitrates: -glyceryl trinitrate -isobordide mononitrates -These break down in nitrite ions NO2- -NO2- becomes NO -NO activates guanylate cyclase -this convert GTP in cGMP -cGMP activates protein kinase G -Protein kinase G causes =inhibition of myosin light chain kinase =Increased Ca2+ sequestering =Increased K+ channel opening -this means there is less motor activity, less contractility and relaxtion of smooth muscle -this causes vasodilation SE: headaches, postural hypotension Calcium antagonists -veraprimil -nifedipine -these competitively antagonists Ca2+ channel -this decreases intracellular levels of Ca2+ -less Ca2+ means less activation of mysoin light chain kinase (Via protein kinase C) -there is therefore less contraction and vasodilation as a result -less vasodilation increases cardiac perfusiion and reduces after-load which reduces cardiac work so reduced oxygen demand Beta1-adrenoreceptor antagonists -propanolol -atenolol action: -these antagonise the action of noradrenaline on beta1 receptors -this means less action of Gs subunit -this means less activation of adenylate cyclase -less adenylate cyclase means less conversion of ATP to cAMP -less cAMP means less activation of protein kinase A -Less protein kinase A means less phosphorylation of Ca2+ channels -this reduces Ca2+ channel opening -less opening means less Ca2+ -this reduces contractililty -this results in a negative ionotropc and chronotropic effect -This reduces metabolic demand so reduces angina |
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What is the cardiac action of beta1-adrenoreceptors? what are there antagonists?
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antagonists:
-atenolol -propanolol Action -Beta1 receptor activation results in activation of Gs subunits -Gs subunits activated adenylate cyclase -adenylate cyclase causes conversion of ATP of cAMP -cAMP activates protein kinase A -protein kinase A phosphorylates Ca2+ channels -this increases channel opening so increases intracellular Ca2+ levels -this has a positive ionotropc and chronotropic |
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How does calcium levels effect smooth muscle contractililty? What doesnt it act through? and why does this differ from myocardiam and skeletal muscle
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Calcium causes the activation of myosin light chain kinase by phosphorylating it.
It does NOT act through troponin as only skeletal and myocardium have troponin |
