4.0 Cardiovascular and Renal Flashcards Preview

MedST IB: Mechanisms of Drug Action (MoDA) > 4.0 Cardiovascular and Renal > Flashcards

Flashcards in 4.0 Cardiovascular and Renal Deck (58)
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1

Acetazolamide

- 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

2

Alteplase

- 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

3

alpha-Methylnoradrenaline

- 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

4

Amiloride

- 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

5

Aminocaproic Acid

- 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

6

Amiodarone

- 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

7

Anistreplase

- 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

8

Bisoprolol

- 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

9

Captopril

- 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

10

Clonidine

- 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

11

Clopidogrel

- 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

12

Dabigatran

- 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

13

Digoxin

- 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

14

Diltiazem

- 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)

15

Enalapril

- 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

16

Eptifibatide

- 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

17

Furosemide

-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

18

Heparin

- 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

19

Hydrochlorothiazide

-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

20

Levosimendan

- 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)

21

Losartan

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

22

Mannitol

- 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

23

Milrinone

- 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

24

Minoxidil

- 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

25

Ouabain

- 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

26

Pimobendan

- 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

27

Propranolol

- 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

28

Reserpine

- 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)

29

Rivaroxaban

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

30

Saralasin

- 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