4.0 Cardiovascular and Renal Flashcards

Question 1

Q

Acetazolamide

Answer

A

Class = Carbonic anhydrase inhibitor - Target = Carbonic anhydrase - Mechanism = Inhibition (mainly in PT) - Steps: • Inhibition of carbonic anhydrase ⟶ ↓H⁺ availability in cell ⟶ ↑ HCO₃⁻ and Na⁺ in urine • Weak diuretic • Causes K⁺ loss - Info: Uses = • Glaucoma • Acclimatization to high altitudes • Can guard against mountain sickness • Help to alleviate sleep apnoea that can occur at high altitudes

Question 2

Q

Alteplase

Answer

A

Class = Anticlotting - Target = - - Mechanism = Recombinant human tissue plasminogen activator - Steps: Cleaves plasminogen to plasmin - Info: Preferentially targets plasminogen bound to fibrin clots (specificity) Single chain

Question 3

Q

alpha-Methylnoradrenaline

Answer

A

Class = False transmitter - Target = - - Mechanism = - Steps: alpha-methyldopa is converted to alpha-methyldopamine and alpha-methylnoradrenaline - Info: Functions as an anti-hypertensive by preferential competitive inhibition on alpha 1 receptors Less potent than NA on α1 but more potent on α2

Question 4

Q

Amiloride

Answer

A

Class = Potassium sparing diuretic - Target = Apical Na⁺ channels (ENaC) in Distal Tubule - Mechanism = Blocks - Steps: • Prevents Na⁺ reabsorption by blocking ENaC - Info: • Can be given with other diuretics to avoid hypokalaemia • Leads to a weak diuretic effect by spares potassium

Question 5

Q

Aminocaproic Acid

Answer

A

Class = Anti-clot lysis - Target = Plasminogen - Mechanism = Competitive inhibition - Steps: Chemically similar to lysine (which is a competitive inhibitor of plasminogen) - Info: Prevents severe bleeding caused by clot lysis

Question 6

Q

Amiodarone

Answer

A

Class = Type III antidysrhythmic - Target = - - Mechanism =Prolongs the action potential and refractory period - Steps: Exact mechanism = unkown ?inhibit K+ currents causing repolarisation? Inhibit both inward and outward currents - Info: Used in re-entry and circus dysrhythmias Inhibition of Ca²⁺ and Na⁺ currents is use-dependent + voltage dependent

Question 7

Q

Anistreplase

Answer

A

Class = Anticlotting - Target = Plasmin pathway - Mechanism = Combination drug containing plasminogen and streptokinase - Steps: Streptokinase binds to plasminogen activator → ↑ plasmin formation - Info: Streptokinase component is inactivated until the anisoyl group is removed (occurs in blood) Happens slowly (1/2 life = 2 hours) Has a prolonged activity than streptokinase alone

Question 8

Q

Bisoprolol

Answer

A

Class = Beta blocker (class II antidysrhythmic) - Target = B1 adrenoreceptor - Mechanism = blocker - Steps: - Info: Prevents damage caused by excessive catecholamine release in heart failure Used in heart failure and hypertension Reduces cardiac output and renin plasma concentration

Question 9

Q

Captopril

Answer

A

Class = ACE inhibitor - Target = ACE - Mechanism = Inhibitor - Steps: Provides antagonism for RAS by preventing production go Angiotensin II by blocking ACE activity - Info: Hypertension Heart failure Side effect = dry cough

Question 10

Q

Clonidine

Answer

A

Class = centrally-acting a2/I1 agonist - Target = presynaptic alpha2 adreno-autoreceptors and I1 in the brain - Mechanism = agonist - Steps: Stimulation of presynaptic alpha2 receptors reduces NA release (by downregulating PKA activity presynaptically) and thereby reduces blood pressure It also stimulates I1 receptors, which may have a more predominant role in clonidine’s ability to act as an anti-hyerpertensive - Info: Omitting a single dose of clonidine lead to rebound hypertension

Question 11

Q

Clopidogrel

Answer

A

Class = Anti-platelet - Target = ADP receptor on platelets - Mechanism = Blocker - Steps: Prevents ADP binding to its receptor on platelets - Info: Prevents platelet aggregation Used in combination with aspirin

Question 12

Q

Dabigatran

Answer

A

Class = Anticoagulant - Target = Thrombin - Mechanism = Inhibitor - Steps: - Info: Used in patients with AF + 1 other risk factor for stroke Also in prophy post ortho surgery

Question 13

Q

Digoxin

Answer

A

Class = Cardiac glycoside - Target = Na⁺/K⁺ ATPase - Mechanism = Inhibitor - Steps: Bind to K+ site Inhibition of sodium pump → ↑ [Na⁺]i → ↓ activity of NCX → Ca²⁺ accumulation in cells → ↑ contractility - Info: Used in heart failure and dysrhythmias

Question 14

Q

Diltiazem

Answer

A

Class = Ca²⁺ channel blocker - Target = L-type Ca²⁺ (preferentially blocks heart) - Mechanism = antagonist - Steps: - Info: Preferentially targets cardiac tissue because Ca²⁺ channels have highest opening frequency in these tissues Use dependent; Increases binding of DHPs Used as anti-dysrhythmic (class IV)

Question 15

Q

Enalapril

Answer

A

Class = ACE inhibitor - Target = ACE - Mechanism = Inhibitor - Steps: Enalapril = inactive. Converted into enalaprilat in liver Provides antagonism for RAS by preventing the production of Angiotensin II by blocking ACE activity - Info: Hypertension Heart Failure Side effect = dry cough

Question 16

Q

Eptifibatide

Answer

A

Class = Cyclic heptapeptide inhibitor - Target = IIb/IIIa receptor (aIIb/b3 integrin) - Mechanism = Inhibitor - Steps: Antagonism of this receptor → ↓ platelet aggregation by fibrinogen - Info: Used in patients with unstable angina/recently suffered MI

Question 17

Q

Furosemide

Answer

A

-Class = Loop diuretic - Target = NCCK2 in TAL of LoH -Mechanism = inhibition -Steps = • Loop diuretics are actively secreted in PT ∴ conc. in TAL is 10-30x plasma • Blocks Na⁺-K⁺-2Cl⁻ co-transport in luminal cells of TAL • Very weak inhibition of carbonic anhydrase • Causes venodilation that precedes diuresis (this ↑ renal plasma flow without an ↑ GFR and reduces the preload on the heart) • Impairs K⁺ reabsorption -Info = • Used in Heart failure (especially acute heart failure) -Side effects = • Hypokalaemia • Metabolic alkalosis (proton loss) • Ca²⁺ and Mg²⁺ loss (mechanism unknown) Uric acid excretion is reduced ⟶ deposition ⟶ gout

Question 18

Q

Heparin

Answer

A

Class = Anticlotting - Target = Antithrombin III (ATIII) - Mechanism = Activator - Steps: ATIII = enzyme inhibitor Heparin binds to ATIII → activational conformational change ATIII → inactivates thrombin, Xa and other proteases - Info: Used for unstable angina, after MI, DVT and prophylaxis Must be given by injection

Question 19

Q

Hydrochlorothiazide

Answer

A

-Class = Thiazide diuretic -Target = Na+/Cl- co-transporter (binds to Cl- site) -Mechanism = inhibition -Steps = • Partly inhibit formation of dilute urine (but not concentrated urine) • In DT - block Na+/Cl- cotransporter o This is achieved by binding to Cl- site • Vasodilator as well as diuretic actions (when given to treat hypertension, initially ↓ BP due to diuretic effects but in later phase they have direct action on blood vessels) o Vasodilator effect is due to K+ ATP channel opening • Some inhibition of carbonic anhydrase -Info = • Used in Hypertension • Can take 12 weeks for full effect -Side effects = • Hypokalaemia • Metabolic alkalosis • ↓ Ca2+ excretion • ↑ Mg2+ excretion • Uric acid excretion is reduced ⟶ deposition ⟶ gout

Question 20

Q

Levosimendan

Answer

A

Class = Inodilator - Target = phosphodiesterase III - Mechanism = Inhibits PDEIII + calcium sensitiser - Steps: Inhibits PDEIII Increases Ca²⁺ binding efficiency to cardiac troponin - Info: -used in heart failure (not in UK)

Question 21

Q

Losartan

Answer

A

Class = Angiotensin receptor blocker (ARB)/Angiotensin II antagonist - Target = AT1 - Mechanism = Antagonist - Steps: - Info: Used in HTN, CHF, people who cannot tolerate ACE inhibitors

Question 22

Q

Mannitol

Answer

A

Class = Osmotic diuretic - Target = - - Mechanism = Simple osmosis to increase urine volume (mainly in PT and descending limb) - Steps: • Mannitol = small molecular weight substance that is filtered at the glomerulus (not resorbed at all) • Retain osmotic equivalent of water ∴ ↑ urine volume • ↓ Na+ reabsorption in the PT as concentration is lowered - Info: • Promote loss of water very rapidly - e.g. in cerebral oedema • Maintains urine flow and can therefore be used in patients with low GFR • Does not cross the blood brain barrier

Question 23

Q

Milrinone

Answer

A

Class = Inodilator - Target = PDE III - Mechanism = Inhibitor - Steps: PDE inhibition → ↑cAMP→↑ chrono/ionotropy Also causes vasodilation (reducing afterload) - Info: Used in heart failure unresponsive to more conventional therapy Can cause dysrythmias

Question 24

Q

Minoxidil

Answer

A

Class = K⁺ channel opener - Target = ? K-ATP channel? - Mechanism = Opener - Steps: Exact mechanism unknown Opens K⁺ channel → K⁺ efflux → hyperpolarisation → relaxation of smooth muscle (e.g. that surrounding vasculature) - Info: Used in male baldness, hypertension, asthma, IBS - side effect: May cause hyperglycaemia by limiting insulin secretion by pancreatic β cells

Question 25

Q

Ouabain

Answer

A

Class = Cardiac glycoside - Target = Na⁺/K⁺ ATPase - Mechanism = Inhibitor - Steps: Bind to K+ site Inhibition of sodium pump → ↑ [Na⁺]i → ↓ activity of NCX → Ca²⁺ accumulation in cells → ↑ contractility - Info: Ouabain is too potent for clinical use

Question 26

Q

Pimobendan

Answer

A

Class = Inodilator/ calcium sensitiser - Target = Phosphodiesterase III - Mechanism = Inhibits PDEIII + ↑ Ca²⁺ binding affinity to cardiac troponin - Steps: ↑ Ca²⁺ binding efficiency → ↑ cardiac output without an increase in energy consumption - Info: Used in canine cardiomyopathy and mitral regurgitation

Question 27

Q

Propranolol

Answer

A

Class = Non-selective β antagonist (Class II antidysrhythmic) - Target = β1 and β2 antagonist - Mechanism = Antagonist - Steps: - Info: Was used for hypertension but replaced by β1 selective blockers class II antidysrhythmics are used where the abnormality increases excitation, such as after an MI, and in patients using drugs which sensitise to catecholamine (N.B sotalol, a class II, also has class III actions). used in the treatment of somatic anxiety Can unmask an alpha-1 mediated vasoconstriction of coronary blood vessels

Question 28

Q

Reserpine

Answer

A

Class = - - Target = VMAT2 - Mechanism = Blocks amine binding site on VMAT2 - Steps: • Blocks amine binding site ⟶ prevention of uptake of NA ⟶ depletion of stored NA (and 5-HT in brain) • Depletion occurs ∵ there is some leak and MAO in cytoplasm metabolises the neurotransmitters • Acts on periphery and CNS • Recovery requires synthesis of new vesicles - Info: Use as a hypertensive stopped ∵ lead to profound depression (5-HT depletion)

Question 29

Q

Rivaroxaban

Answer

A

Class = Anticoagulant - Target = Factor Xa - Mechanism = Inhibitor - Steps: - Info: Used in patients with AF + 1 other risk factor for stroke

Question 30

Q

Saralasin

Answer

A

Class = Angiotensin II agonist - Target = Angiotensin receptor (AT1) - Mechanism = Partial agonist - Steps: - Info: Not as effective as ACE inhibitors (not used anymore) Peptide, therefore is not suitable for oral administration

Question 31

Q

Sildenafil

Answer

A

Class = PDE inhibitor - Target = PDE V - Mechanism = Inhibition - Steps: - Info: • Inhibition of PDE V ⟶ persistence of cGMP in smooth muscle cells ⟶ smooth muscle relaxation, specifically of vascular smooth muscle in the penis • It is used in treating impotence and can also be used in pulmonary arterial hypertension

Question 32

Q

Streptokinase

Answer

A

Class = Anticlotting - Target = Plasminogen activator - Mechanism = ↑ plasmin generation - Steps: Bounds to plasminogen activator → ↑ generation of plasmin → ↑ breakdown of fibrin - Info: Also causes breakdown of factors II, V and VII Derives from bacterial protein

Question 33

Q

Tirofiban

Answer

A

Class = Non-peptide inhibitor - Target = IIb/IIIa receptor (aIIb/b3 integrin) - Mechanism = Inhibitor - Steps: Antagonism of this receptor → ↓ platelet aggregation by fibrinogen - Info: Used in patients with unstable angina/recently suffered MI

Question 34

Q

Tranexamic Acid

Answer

A

Class = Anti-clot lysis - Target = Plasminogen - Mechanism = Competitive inhibition - Steps: Analogue of aminocaproic acid. Chemically similar to lysine (which is a competitive inhibitor of plasminogen) - Info: Prevents severe bleeding caused by clot lysis

Question 35

Q

Triamterene

Answer

A

Class = Potassium sparing diuretic - Target = Apical Na⁺ channels (ENaC) in Distal Tubule - Mechanism = Blocks - Steps: • Prevents Na⁺ reabsorption by blocking ENaC - Info: • Can be given with other diuretics to avoid hypokalaemia • Leads to a weak diuretic effect by spares potassium

Question 36

Q

Warfarin

Answer

A

Class = Anticoagulant - Target = Factors II, VII, IX and X + regulatory factors protein C, S and Z - Mechanism = Inhibits synthesis - Steps: - Info: Used to prevent recurrence following MI/stroke, and in those with prosthetic heart valves INR monitoring needed Many interactions (food, drink and drugs)

Question 37

Q

Amyl Nitrite

Answer

A

Class = Nitrovasodialtor - Target = Soluble guanylyl cyclase - Mechanism = NO donor - Steps: Converted to NO in vascular smooth muscle via action of ecNOS causes actiation of sGC in vascular smooth muscle, leading to smooth muscle relaxation and vasular dilatation - Info: Not as much clinical use (acute attacks?) Taken recreationally to relax anal sphincter

Question 38

Q

Clofibrate

Answer

A

Class = Fibrate - Target = PPAR + lipoprotein lipase - Mechanism = Stimulates lipoprotein lipase - Steps: Causes the release of TAG from VLDL and chylomicrons These are then taken up for storage or metabolism, thereby reducing serum cholesterol and risk of atherosclerosis May also function by activating PPARs - Info:

Question 39

Q

Colestyramine

Answer

A

Class = Anion exchange resin - Target = - - Mechanism = Prevents reuptake of bile acids from intestine - Steps: ↓ reuptake → ↑ cholesterol metabolism to synthesise bile acids in liver - Info:

Question 40

Q

Doxazosin

Answer

A

Class = Alpha1 receptor antagonist - Target = Alpha1 receptor - Mechanism = Antagonist - Steps: - Info: Used in hypertension Dilates both resistance and capacitance vessels

Question 41

Q

Ezetimibe

Answer

A

Class = - Target = ¿Sterol transporter? Niemann-Pick C1 like 1 (NPC1L1) - Mechanism = ↓ intestinal bile absorption - Steps: Binds to and blocks sterol transporter NPC1L1 mediates sterol transport across the brush border - Info: Can be used in combination with a statin Circulates in enterohepatic circulation, therefore keeps getting redelivered to intestine to act again ↓ serum cholesterol → ↓ atheroma formation

Question 42

Q

Flecainide

Answer

A

Class = 1C antidysrhythmic agent - Target = voltage gated Na+ channel - Mechanism = Blocker - Steps: - Info: No effect on action potential in the myocardium; Very slow association and dissociation; slow kinetics make flecainide suitable for treated ectopic beats; however, these kinetics also means that almost everything else is suppressed as well, and so flecainide is actually pro-dysrhythmogenic Only used in unsual circumstances.

Question 43

Q

Glyceryl Trinitrate

Answer

A

Class = Nitrovasodialtor - Target = Soluble guanylyl cyclase - Mechanism = NO donor - Steps: Converted to NO in vascular smooth muscle via action of ecNOS causes activation of sGC in vascular smooth muscle, leading to smooth muscle relaxation and vasular dilatation - Info: Preferentially causes dilatation in collateral vessles. This reduces the amount of ischaemic myocardial tissue Used in acute angina Must be taken sublingually

Question 44

Q

Hydralazine

Answer

A

Class = Arteriolar vasodilator - Target = ? - Mechanism = Unknown - Steps: - Info: Direct acting vasodilator Can be used in HTN

Question 45

Q

Isosorbide Dinitrate

Answer

A

Class = Nitrovasodialtor - Target = Soluble guanylyl cyclase - Mechanism = NO donor - Steps: Needs to be metabolised in the liver to isosorbide mononitrate to work Converted to NO in vascular smooth muscle via action of ecNOS causes actiation of sGC in vascular smooth muscle, leading to smooth muscle relaxation and vasular dilatation - Info: Preferentially causes dilatation in collateral vessles. This reduces the amount of ischaemic myocardial tissue Used in acute angina

Question 46

Q

Ivabradine

Answer

A

Class = - Target = HCN in the SAN - Mechanism = Blocker - Steps: Blocking HCN channels → ↓ If This slows the heart rate, thereby increasing the proportion of the cardiac cycle in diastole This increases perfusion of the myocardium through coronary vessels - Info: Used in angina (mainly stable angina - they have high HR)

Question 47

Q

Labetalol

Answer

A

Class = Combined α and β blocker - Target = alpha1, beta1, beta2 adrenoreceptors - Mechanism = antagonist - Steps: Has 4 isomers with different actions: 1. R,R - β blocker + weak α1 blocker 2. R,S - no activity 3. S,R - α1 blocker + very weak β blocker 4. S,S - α1 blocker - Info: Used to treat hypertension in pregnancy

Question 48

Q

Moxonidine

Answer

A

-Class: imidazoline -Target: I1 receptors -Mechanism: agonist -Interest: -centrally acting antihypertensive -fewer side effects than alpha2 agonists (clonidine)

Question 49

Q

Nicotinic Acid

Answer

A

Class = - Target = - Mechanism = Inhibits Liver triglyceride production and VLDL secretion. Increases levels of tissue plasminogen activator - Steps: - Info: ↓ serum cholesterol and TAG Prevents clot formation by increasing endogenous tissue plasminogen activator (tPA)

Question 50

Q

Paclitaxel (Taxol)

Answer

A

Class = Taxane (drug eluting stents) - Target = Free microtubule dimers - Mechanism = Interferes with microtubule growth - Steps: Disrupts the equilibrium between free dimers and microtubules by shifting it in the direction of assembly rather than disassembly - leads to the stabilisation of ordinarily cytoplasmic microtubules and the formation of abnormal bundles of microtubules to inhibit mitosis - Info: Used in antiproliferative drug eluting stents in coranary angioplasty for the treatment of angina and ischaemic heart disease Used in treatment of lung, ovarian, breast, head and neck cancer, and in Kaposi’s sarcoma.

Question 51

Q

Phentolamine

Answer

A

Class = Alpha antagonist - Target = Non-selective α antagonist - Mechanism = Non-selective α antagonist - Steps: - Info: Obsolete in hypertensive treatment ∵ cause reflex tachycardia Can cause reflex hypotension

Question 52

Q

Pindolol

Answer

A

Class = Beta adrenoreceptor blocker - Target = B1 adrenoreceptor - Mechanism = Partial agonist - Steps: - Info: Little effect on CO or plasma renin levels

Question 53

Q

Ranolazine

Answer

A

Class = - - Target = Late phase of Na⁺ current in cardiac myocytes - Mechanism = inhibitor - Steps: Late inward Na⁺ current → Ca²⁺ accumulation because of ↓ Ca²⁺ extrusion via NCX Ca²⁺ overload leads to impaired relaxation and increases ventricular wall stiffness and end-diastolic pressure Stiffness causes compression of microcirculation in the ventricular walls, thereby impairing coronary bloodflow during diastole to worsen ischaemia Blocking the late Na⁺ current prevents Ca²⁺ overload to improve coronary blood flow - Info: Used in treatment of angina

Question 54

Q

Rosiglitazone

Answer

A

Class = PPARy agonist - Target = PPARy - Mechanism = Agonist - Steps: PPARy → ↑ LXR transcription ↑ LXR transcription → ↑ expression of ABCA1 ABCA1 controls the rate limiting step in cholesterol removal through HDL formation Therefore, rosiglitazone may reduce atherosclerosis - Info: Currently used in type II diabetes

Question 55

Q

Simvastatin

Answer

A

Class = Statin - Target = HMG-CoA reductase - Mechanism = Inhibitor - Steps: ↓ HMG-CoA reductase → ↓ cholesterol synthesis in the liver To maintain bile synthesis, the LDL receptor is upregulated to increase cholesterol uptake from the blood By doing this, statins reduce serum cholesterol, thereby reducing risk of atherosclerosis SCAP in hepatocytes contains a sterol-sensing domain capable of binding cholesterol In cholesterol-depleted cells, SCAP binds the SREBPs, and mediates their transportation to the golgi In the golgi, SREBPs are cleaved by SP1 and SP2, liberating them from the membrane They then translocate to the nucleus to upregulate LDL receptor expression Thus, by depleting hepatocellular cholesterol formation, statins activate the SREBP/SCAP pathway. - Info: Overall benefit > expected from changes in lipid alone MORE EFFECTIVE TAKEN AT NIGHT

Question 56

Q

Sirolimus

Answer

A

Class = Immunosuppressant (drug-eluting stents) - Target = FK-binding protein - Mechanism = Prevents cellular proliferation - Steps: Sirolimus binds the cytosolic protein FK-binding protein. The resulting complex inhibits mTOR, a serine/threonine kinase involved in cell cycle progression and protein synthesis. It thereby prevents cellular proliferation. - Info: Also known as rapamycin Used in antiproliferative drug-eluting stents in angioplast for the treatment of ischaemic heart disease/angina May also be used to decrease T cell proliferation in transplant rejection

Question 57

Q

Sodium Nitroprusside

Answer

A

Class = NO donor/directly acting vasodilator - Target = soluble guanylyl cyclase of smooth muscle - Mechanism = Activation - Steps: Activates sGC, leading to smooth muscle relaxation - Info: Used in hypertensive emergencies In solution, sodium nitroprusside is hydrolysed to cyanide

Question 58

Q

Trimetaphan

Answer

A

Class = - - Target = nAChR - Mechanism = Competitive antagonist - Steps: Targets (a₃)₂(B₄)₃ nAChR at autonomic ganglia - Info: Exclusive blockage at autonomic ganglia Old treatment for HTN Use dependent

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4.0 Cardiovascular and Renal Flashcards

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