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MVST1B MODA > cardio renal L5 > Flashcards

cardio renal L5 Flashcards

1
Q

what drugs may be given soon after an MI?

A

Fibrinolytic (‘clot-busting’) drugs given soon after myocardial infarctions limits myocardial damage and improves survival

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2
Q

how do msot anticlotting drugs work?

A

Most anti-clotting drugs work by catalysing the production of the serum protease, plasmin from its precursor plasminogen.

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3
Q
A
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4
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5
Q

describe streptokinase?

A

streptokinase binds plasminogen activator and causes generation of plasmin

This leads to degradation of the fibrin in clots

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6
Q

what does plasmin hydrolyse?

A

plasmin (a protease hydrolysing Arg-Lys bonds)

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7
Q

what is alteplase

A
  • Anistreplase is a combination of plasminogen and anisoylated streptokinase.
  • Streptokinase is inactive until the anisoyl group is removed in the blood
  • Alteplase is a recombinant human tissue plasminogen activator.
  • It has greater activity on plasminogen bound to fibrin in clots, thus localising their action
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8
Q

Oral low-dose ______ is used alongside these therapies to prevent further thrombosis.

A

Oral low-dose aspirin is used alongside these therapies to prevent further thrombosis.

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9
Q

aspirin is often combined with what

A

clopidogrel

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10
Q

how does clopidogrel act?

A

inhibits platelet aggregation by inhibiting the binding of ADP to its receptor on platelets

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11
Q

aspirin + clopidogrel is given for what reason?

A

Oral low-dose aspirin is used alongside these therapies to prevent further thrombosis. Low- dose aspirin combined with clopidogrel (which inhibits platelet aggregation by inhibiting the binding of ADP to its receptor on platelets) can improve morbidity and mortality in patients over a wide range of heart disease

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12
Q

when might the metabolism of clopidogrel be compromised?

A

The metabolism of clopidogrel is compromised in some people who carry two non-functioning copies of the gene for CYP2C19, a cytochrome P450 enzyme (it is a prodrug and has to be metabolised in the liver to become active), so another ADP inhibitor, ticagrelor, is starting to predominate.

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13
Q

Glycoprotein IIb/IIIa Receptor - whats it do?

A

Receptor required for the fibrinogen bridging between platelets (and between platelets and foreign surfaces) that causes aggregation

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14
Q

give some Inhibitors of the Glycoprotein IIb/IIIa Receptor

A
  • Eptifibatide is a cyclic heptapeptide inhibitor
  • Tirofiban is a non-peptide inhibitor that can be used for prevention of myocardial infarction in patients with unstable angina or in patients who have recently suffered certain types of myocardial infarction
  • Abciximab is a monoclonal antibody against the receptor which also binds to the vitronectin receptor on platelets (vitronectin is involved in cell adhesion and haemostasis), endothelial cells and vascular smooth muscle cells.
  • It is used with coronary angioplasty for coronary artery thrombosis
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15
Q

describe heparin

A

Heparin is a naturally occurring anticoagulant produced by basophils and mast cells.

It binds to the enzyme inhibitor antithrombin III (AT-III) causing a conformational change which results in exposure of its active site.

The activated AT-III then inactivates thrombin and other proteases involved in blood clotting, most notably factor Xa.

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16
Q

Like tirofiban, heparin can be used for unstable angina, and after myocardial infarction, but heparin also has uses for treatment of deep vein thrombosis and as a prophylactic drug to ……..

A

Like tirofiban, heparin can be used for unstable angina, and after myocardial infarction, but heparin also has uses for treatment of deep vein thrombosis and as a prophylactic drug to prevent clots formin during and as a result of surgery.

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17
Q

T or F

Heparin binds to the enzyme inhibitor antithrombin III causing a conformational change which results in exposure of its active site

A

T

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18
Q

how is heparin given?

A

injection

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19
Q

describe low molecular weight heparins?

+ give an example?

A

wider application, subcutaneous route of admininstration and more predictable pharmacokinetics - easier use.

Dalteparin is the commonest example, being the mainstay of venous thromboemblism prophylaxis as well as being used for other anticoagulant indications.

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20
Q

give a complication of heparin?

A

Heparin can lead to heparin-induced thrombocytopenia (HIT), which is the development of a low platelet count. This is undesirable.

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21
Q

is warfarin injected?

A

no - given orally

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22
Q

what are the actions of warfarin?

A

It inhibits the synthesis of clotting factors II, VII, IX and X,

and regulatory factors protein C, protein S and protein Z

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23
Q

uses for warfarin?

A
  • Warfarin is used by people who have an increased tendency for thrombosis or can be used as prophylaxis for individuals who have already formed a blood clot which required earlier treatment (to guard against reoccurrence)
  • A further use for warfarin is to prevent clot formation on prosthetic heart valves
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24
Q

describe why dosing for warfarin is complicated?

A

Dosing of warfarin is complicated by the fact that it interacts with many commonly used drugs and other chemicals that may be present various foods and drinks

These interactions may enhance or reduce warfarin’s anticoagulation effect As a result, patients taking warfarin over a long period need to have their blood levels of the drug carefully and continuously monitored.

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25
Q

describe Dabigatran

and give its uses

A
  • Dabigatran is a thrombin inhibitor
  • Introduced in 2012 for use in patients with atrial fibrillation and one additional risk factor for stroke
  • Based upon evidence that it could reduce risk by up to 40% compared with warfarin
  • Further use prophylactically in the short term, to prevent thromboembolism following recent knee or hip replacement surgery
26
Q

There is a class of drugs which directly inhibit factor Xa.

what are they?

A

The first was rivaroXaban, but now apiXaban and edoXaban are available as well

27
Q

describe rivaroXaban, apiXaban and edoXaban

A

It is increasingly common to see patients to be started on one of these instead of warfarin

factor Xa inhibitors

new

28
Q

Fondaparinux - what does it do?

A

ondaparinux is an indirect inhibitor of activated Xa. It is common, as it is the mainstay of treatment in acute coronary syndromes

29
Q

give some other new drugs in use (3)

A

Also in use are

argatroban (a synthetic direct thrombin inhibitor - this is used if patients suffer from HIT),

bivalirudin, which is a hirudin analogue,

danaparoid (an indirect inactivator of Factor Xa and a direct inhibitor of thrombin activation of Factor IX)

30
Q

Excessive clot lysis can lead to severe bleeding. This can be inhibited with…..

A

Excessive clot lysis can lead to severe bleeding. This can be inhibited with tranexamic acid (TXA), which competitively inhibits plasminogen activation. TXA is also used to suppress bleeding seen in traumatic injury, postpartum etc.

31
Q

The amount of plasma filtered at the glomerulus is measured by the….

A

The amount of plasma filtered at the glomerulus is measured by the glomerular filtration rate (GFR)

32
Q

what regulates the GFR of the kidney

A

The amount of plasma filtered at the glomerulus is measured by the glomerular filtration rate (GFR). This is kept constant by each nephron, which regulates its own filtration rate (autoregulation).

33
Q

The blood supply of the glomerulus operates at _____ pressure

A

The blood supply of the glomerulus operates at high pressure

34
Q

Blood enters Bowman’s capsule via…..

A

Blood enters Bowman’s capsule via the afferent arteriole and leaves via

the efferent arteriole

35
Q

how do we measure GFR?

A

Filtration is measured by the glomerular filtration rate (GFR -measured by inulin clearance)

36
Q

problms with a GFR thats too low?

A

Too low a GFR leads to excessive reabsorption of solutes and the concentration of toxic solutes in a low volume of urine

37
Q

problems if GFR is too high?

A

Too high a GFR results in inadequate reabsorption of solutes

38
Q

Autoregulation is produced by the activity of the …

A

Autoregulation is produced by the activity of the juxtaglomerular apparatus which is closely associated with the afferent and efferent arterioles and the early distal tubule

39
Q

The macula densa monitors levels …. of?

A

The macula densa monitors levels of Na+ and Cl-

40
Q

what secretes renin?

A

The juxtaglomerular apparatus secretes renin

41
Q

The capillary bed of the glomerulus operates at ___ pressure (at around ___ mm Hg).

A

The capillary bed of the glomerulus operates at high pressure (at around 40 mm Hg).

42
Q

The capillary bed of the glomerulus operates at high pressure (at around 40 mm Hg).

This allows control of GFR by …..

A

The capillary bed of the glomerulus operates at high pressure (at around 40 mm Hg). This allows control of GFR by actions constricting or dilating the afferent and/or efferent arterioles.

43
Q

role of the vasa recta?

A

The glomerular efferent arteriole also gives rise to the vasa recta which supply oxygen to medullary regions. The vasa recta accounts only for 1-2% of total renal blood flow.

44
Q

Anatomy of the glomerulus and the juxtaglomerular apparatus.

A
45
Q

the_____ _____ detects levels of Na+ and Cl- in the filtrate and secretes local hormones that influence the calibre of the vessels to maintain a constant GFR and thus achieve autoregulation.

A

the macula densa detects levels of Na+ and Cl- in the filtrate and secretes local hormones that influence the calibre of the vessels to maintain a constant GFR and thus achieve autoregulation.

46
Q

which cells secrete renin?

A

Juxtaglomerular cells around the afferent vessels secrete renin.

47
Q

Renin secretion leads ultimately to the production of what?

A

Renin secretion leads ultimately to the production of angiotensin II (and angiotensin III)

48
Q
A
49
Q

At the afferent arteriole a fall in GFR leads to:

A
  • Increased reabsorption of salt in the proximal tubule →
  • Decreased Na+ and Cl- detected at the macula densa →
  • Release of a local vasodilator →
  • Dilatation of afferent arteriole →
  • Increased GFR
50
Q

At the efferent arteriole a fall in GFR leads to:

A
  • Decreased Na+ and Cl- detected at the macula densa →
  • Prostaglandin I2 (PGI2) release and stimulation of renin release from juxtaglomerular cells →
  • Increased angiotensin II production →
  • Constriction of efferent arteriole →
  • Increased filtration pressure →
  • Increased GFR
51
Q

An increase in GFR leads to:

A
  • Increased Na+ at the macula densa →
  • Adenosine release →
  • A1 receptor stimulation at afferent arteriole and juxtaglomerular cells →
  • Decreased cAMP →
  • Constriction of afferent arteriole and inhibition of renin release
52
Q

Approximately __% of the filtered Na+, K+ and Cl- are reabsorbed in the proximal tubule.

A

Approximately 80% of the filtered Na+, K+ and Cl- are reabsorbed in the proximal tubule.

53
Q

The driving force for reabsorption or excretion of ions in all parts of nephron is the ……in the basolateral membrane of the cells of the tubule

A

The driving force for reabsorption or excretion of ions in all parts of nephron is the Na+/K+ ATPase in the basolateral membrane of the cells of the tubule

54
Q

describe the loop of henle water permeability wise

A
  • The descending limb of the loop of Henle is permeable to water, which moves out into the hypertonic interstitium.
  • The thick ascending limb of the loop is impermeable to water. Na+ is actively pumped into the medullary interstitium to provide a driving force creating an osmotic gradient from the cortex to the inner medulla (300 milliosmolar at the top of the loop (isotonic to plasma) up to 1200 mOsm at the bottom
55
Q

Na+ enters thick ascending limb cells from the lumen via a ……… cotransporter.

A

Na+ enters thick ascending limb cells from the lumen via a Na+-K+-2Cl- cotransporter.

56
Q

In the distal tubule there is:

what?

A
  • In the distal tubule there is: HCO3- absorption
  • Active reabsorption of Na+ (which enters distal tubule cells via Na+-Cl- cotransport)
57
Q

In the later distal tubule Na+ is absorbed ______ (modulated by _______)

A

In the later distal tubule Na+ is absorbed actively (modulated by aldosterone)

58
Q

Tnor F

K+ or H+ move into the filtrate down the potential gradient created thus providing a route for the excretion of potassium

A

K+ or H+ move into the filtrate down the potential gradient created thus providing a route for the excretion of potassium

True

59
Q

fat

A

mamba

60
Q
A

MVST1B MODA (22 decks)

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