Cardiovascular pharmacology

Question 1

ACEIs

Answer 1

Examples: captopril, ramipril, enalapril, lisinopril, perindopril
Hypertension and angina treatment
Inhibit Ang II formation, inhibiting vasoconstriction and water retention.
Potentiate bradykinin
May cause hypotension, hyperkalemia and angiodema

Question 2

AT1 antagonists (sartans)

Answer 2

Examples: losartan, candesartan, valsartan
Hypertension
Block the action of Ang II at the AT1 receptor, no bradykinin effects

Question 3

Aliskiren

Answer 3

Hypertension
Inhibits renin in the RAAS system

Question 4

Spironolactone

Answer 4

Resistant hypertension and heart failure
Aldosterone receptor antagonist, preventing fluid retention

Question 5

Dihydropyridines

Answer 5

Examples: nifedipine, felodipine, amlodipine
Hypertension and angina
Inhibit VGCC on smooth muscle cells, causing vasodilation and reducing BP

Question 6

Non-DHP calcium channel blockers

Answer 6

Verapamil - blocks cardiac L-type calcium channels (CaV1.2) to decrease heart rate and so cardiac output.
Diltiazem - affects the heart and smooth muscle
Hypertension and angina

Question 7

Diuretics

Answer 7

For hypertension, thiazides, such as bendroflumethiazide, and thiazide-like drugs, such as chlorthalidone and indapamide, are used.
Inhibit reabsorption of Na and Cl in DCT, leading to diuresis and a decrease in BP.
Vasodilation occurs after the diuretic effect
Cause hypokalemia and postural hypotension.

Question 8

Beta-blockers

Answer 8

Examples: propranolol, atenolol
Used for hypertension and angina
When β1 adrenal receptors in the SA node are blocked, the rate of contraction decreases.
When β1 adrenal receptors in the atria and ventricle muscles are blocked, force of contraction decreases
β-adrenoceptors normally increase K+ channel closing, which increases the rate of depolarisation and reduces the time between contractions.
Limited as β-adrenoceptors on vascular smooth muscle causes vasodilatation → blocking these causes vasoconstriction

Question 9

α-adrenoceptor antagonists

Answer 9

Examples: prazosin and doxazosin
Inhibit α1-mediated vasoconstriction
Last choice antihypertensives

Question 10

Statins

Answer 10

Examples: simvastatin, lovastatin, pravastatin, atorvastatin, fluvastatin
Hypercholesterolaemia
Inhibit HMG-CoA reductase, involved in the synthesis of mevalonate and eventually cholesterol.
Reduce plasma cholesterol, which upregulates LDL receptors.
Need to be used with care in liver disease
May cause myopathy leading to Rhabdomyolysis
Metabolised by CYP3A4, which is inhibited by the DHP amlodipine → DDI

Question 11

Ezetimibe

Answer 11

Cholesterol absorption inhibitor - inhibits the intestinal steroid transporter Niemann–Pick C1-Like 1 (NPC1L1)
Vytorin is a combination of simvastatin and ezetimibe

Question 12

Cholestyramine

Answer 12

Bile acid binding resin - binds bile salts in the intestine and prevents reabsorption and recycling of cholesterol.

Question 13

PCSK9 inhibitors

Answer 13

Examples: alirocumab and evolocumab (monoclonal antibodies) and inclisiran (siRNA)
PCSK9 breaks down the LDL receptor in hepatocytes → inhibiting it promotes LDL uptake.
Long-term effects, given as a monthly injection.

Question 14

Fibrates

Answer 14

Examples: bezafibrate, clofibrate and gemfibrozil
Activate α-PPAR, which alter gene transcription - increases peripheral lipoprotein lipases, promoting the breakdown of VLDL and LDL and increasing HDL.
Also decrease glucose levels so can be used in diabetes.
May cause increased biliary excretion of cholesterol, which predisposes the patient to gallstones

Question 15

Nitrates

Answer 15

Angina treatment
Glyceryl trinitrate (GTN) is converted to NO by aldehyde dehydrogenase.
Enhances NO action on guanylyl cyclase activation, leading to PKC production. MLCP stimulation and so vasodilation.

Question 16

Nicorandil

Answer 16

Combined NO donor and activator of K-ATP channels.
It increases pumping out of K+ leading to hyperpolarization and vasodilatation.
Used in angina

Question 17

Ivabradine

Answer 17

inhibits If channels responsible for pacemaker Na/K currents in the sinoatrial node.
Inhibits channels in their open state from the inside.
Decreases HR in the treatment of angina

Question 18

Aspirin

Answer 18

Ischemia treatment
Irreversible COX inhibitor
Inhibits production of thromboxane A2, but also prostacyclin (PGI2). Prostacyclin inhibition can be overcame at low doses.

Question 19

Clopidogrel

Answer 19

ADP forms in the aggregating platelet. This binds to the receptor P2Y12, which leads to expression of glycoprotein IIb/IIIa, involved in linking fibrinogen and platelets.
Clopidogrel antagonises the P2Y12 receptor.
Used in ischemia.

Question 20

Streptokinase

Answer 20

Fibrinolytic/thrombolytic
An enzyme that converts plasminogen to plasmin, dissolving the clot as plasmin digests fibrin and clotting factors.
Protein, so antibodies can develop against it.

Question 21

Alteplase

Answer 21

Alternative to streptokinase.
Recombinant human tissue-type plasminogen activator.

Question 22

Heparins

Answer 22

Include heparin and LMW fractions like enoxaparin.
Activates the natural protein antithrombin III, which inactivates some clotting factors and thrombin.
Immediate action, used to prevent DVT.

Question 23

DOACs

Answer 23

Used when anticoagulants are needed long-term
Dabigatran is an oral thrombin inhibitor, acting in the same way as heparin.
Apixaban and Rivaroxaban are oral inhibitors of activated factor X.

Question 24

Warfarin

Answer 24

Vitamin K reductase inhibitor
Reduced vitamin K is essential for the production of prothrombin and some clotting factors.
As warfarin inhibits the last stage of clotting factor synthesis, it takes a long time to have an effect - only works once all existing clotting factors have been used up.
Narrow therapeutic window and many drug interactions.

Question 25

Non-depolarising skeletal muscle blockers

Answer 25

Competitive nAChR antagonist - e.g. atracurium, vecuronium
Derived from tubocurarine
These block neuromuscular transmission, leading to paralysis.
It also used to be used as adjunct to anaesthesia to relax muscles.
The block is not preceded by stimulation, i.e. no contraction of muscle with stimulation.
The block is antagonised by agents that depolarizes the muscle membrane or an increase in ACh release.
The block is reversed by acetylcholinesterase inhibitors, e.g. neostigmine, as this increases the ACh concentration and allows the antagonist to be overcome.

Question 27

Depolarising skeletal muscle blockers

Answer 27

nAChR agonists, e.g. suxamethonium and decamethonium.
Cause persistent receptor activation, causing the muscle to become over-stimulated and fatigue. This causes inactivation of voltage-gated Na+ channels.
Cannot be reversed, have to wait for the agonist to be metabolised.
The block is preceded by muscle twitches.