4.0 Cardiovascular and Renal Flashcards

Question

Ouabain

Answer 1

- 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

Answer 2

- 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

Answer 3

- 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

Answer 4

- 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)

Answer 5

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

Answer 6

- 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

Answer 7

- 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

Answer 8

- 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

Answer 9

- 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

Answer 10

- 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

Answer 11

- 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

Answer 12

- 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)

Answer 13

- 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

Answer 14

- 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:

Answer 15

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

Answer 16

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

Answer 17

- 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

Answer 18

- 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.

Answer 19

- 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

Answer 20

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

Answer 21

- 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

Answer 22

- 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)

Answer 23

- 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

Answer 24

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

Answer 25

- 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)

Answer 26

- 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.

Answer 27

- 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

Answer 28

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

Answer 29

- 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

Answer 30

- 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

Answer 31

- 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

Answer 32

- 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

Answer 33

- 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

Answer 34

- 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