CHD / STROKE Drugs

Question 1

Nitrates (Nitrovasodilators) affect what most?

• Systemic Arteries
• Narrow Coronary Arteries
• Large Veins
• Cerebral Arteries

Answer 1

LARGE VEINS

As there will be less blood returning to the heart because there’s more in the venuos system.
So, heart fills less due to less workload and less O2 demand…

Question 2

What is the most common Nitrate? (Nitrovasodilator)

Answer 2

Glycerin Trinitrate (GTN)

Either- spray, sub lingual tablet, or transdermal patch.

Question 3

Name common side effects of Nitrovasodilators (Nitrates)?

Answer 3

Dizziness (due to lowered BP)
Throbbing Headache (due to cerebral vasodilation)

Question 4

What things need to be cautioned when people are on GTN and other Nitrates?

Answer 4

That they’re not on anyother BP medication as it can get too low causing fainting and dizziness.

Caution with other drugs acting on same pathway such as:
Viagra (Sildenafil)

Question 5

What are STATINS in the most basic sence

Answer 5

They’re lipid lowering drugs.

Question 6

What side effect is a big concern if people are on STATINS?

Answer 6

Muscle problems such as ‘strange muscle pains’

As this can be a serious sign of myopathy (muscle disease)

Question 7

Examples of statins…

Answer 7

Fluvastatin
Lovastatin
Pravastatin
Simvastatin

Question 8

Some side effects of STATINS…

Answer 8

GI upset (usually wears off)
Anbormal Liver Tests (usually mild)
Muscle Problems (Myopathy - RARE BUT SERIOUS)

Question 9

How do STATINS work?

Answer 9

They are inhibitors of ‘HMG0Co-A reductase’ a rate-limiting step in cholestral synthesis

So by inhibiting them, you inhibit cholestral synthesis.

Question 10

True or false:

STATINS can’t work in diabetes

Answer 10

FALSE

Statins CAN work in diabetes and also in people at any age and gender.

Question 11

What’s an MI

Answer 11

Myocardial infarction – coronary artery completely blocked, typically by blood clot on ruptured plaque

Question 12

How do Nitrates work (Nitrovasodilators)?

Answer 12

They Produce Nitric Oxide (NO) which increases the production of cGMP in muscle cells. Therefore relaxing muscles and vessles dilate (because there’s a smooth muscle layer in vessles)

Question 13

Who’s at risk of a stroke?

Answer 13

56 yr old ♂  
smoker  
High BP - 170/110 (Heart overworked)
Total chol - HDL  ratio 5
Ischemic heart pain on exertion

Question 14

What constitutes a “Cerebrovascular Accident”

Answer 14

• A Blockage; Thromboembolic infarction (~85%) (embolism breaking off from somewhere else in body and travels to the brain)
• Damage/Bleed; Intracranial Haemorrhage
• Cerebral, cerebellar and subarachnoid haemorrhage (~15%) - blood leaks into the brain
• Cerebral Infarction - blood clot stops blood flow to an area of the brain

Question 15

What drug is an example of Fibrinolysis (Thrombolysis)

Answer 15

‘recombinant tissue plasminogen activators’ or ‘r-tPAs’

They activate PLASMIN which is the body’s natural clot busting drug. Turning plasminogen into plasmin!
e.g.
Alteplase® (& other r-tPAs): recombinant HUMAN proteins, so non-antigenic.
Given IVin in stroke units (bleeding risk)
Short-acting.

Question 16

What is Plasmin

Answer 16

It’s the body’s natural clot busting agent. It degrades Fibrin (clots) .

It’s inactivated form is Plasminogen which requires Plasminogen activators to convert it to Plasmin in order to dissolve clots.

Question 17

What are

‘recombinant tissue plasminogen activators’ or ‘r-tPAs’

Answer 17

They’re clot busting drugs:

‘Fibrinolysis/ Thrombolysis’ Drugs

eg ALTEPASE

Question 18

Give examples of Anti-platelet drugs

Answer 18

Aspirin (Ihnibit COX1 from turning aracadonic acid to thromboxane)
Clopidogrel (Antagonizer on platelett the cell surface)
Dipyridamole (Prevent the conversion of prostaglandin H2 into Thromboxane
Abciximab (Inhibit Fibrinogen)

Question 19

What antiplatelett drugs:

PREVENT AGGREGATION &; CLOT FORMATION by preventing GPIIa/IIIb receptor expression?

Answer 19

Aspirin® (acetylsalicylic acid): non steroidal anti-inflammatory drug (NSAIDS)
→ Inhibits cyclo-oxygenase (COX1).
→ Prevents thromboxane formation Dipyridamole
→ Inhibits thromboxane synthase
→ Prevents thromboxane formation Dipyridamole often used in conjunction with Aspirin & Clopidogrel
→antagonize actions of ADP at purinergic (ADP) receptors

Question 20

Which antiplatelett Drugs:

prevent GPIIa/IIIb receptor interaction and Inhibits Fibrinogen

Answer 20

Abciximab: Ab to GPIIb/IIIa receptors: prevents linking of platelets to fibres

And inhibits Fibrinogen

Question 21

What triggers the clotting cascade?

Answer 21

When blood contacts:

Damaged Tissue and exposed collagen

Question 22

What does Thrombin do?

Answer 22

It converts

Fibrinogen –> into Fibrin (an insoluble clot)

Question 23

What is the mechanism of action for Anti- coag drug HEPARIN

Answer 23

Heparin (intravenous administration), activates (one of) body’s own anti-clotting molecules, antithrombin III.

Works IMMEDIATELY

Question 24

What is the mechanism of action for Anti-coag drug WARFERIN

Answer 24

It is similar to the structure of Vitamin K

Works on the liver to reduce the enzyme:
‘vitamin K reductase’
Which uses vit k to ‘final assemble’ clotting factors.
Which diminished the body’s ability to make clotting factors and therefore the ability to make fibrin.

Question 25

If a patient is on Warferin, what certain things can effect the drug and clotting?

Answer 25

diet, drinking, acute illness etc

Question 26

What anticoag/clotting cascade drug is derived from the saliva of the medicinal leech

Answer 26

Direct (selective) Inhibition
of steps of clotting cascade

So direct inhibitors of THROMBIN

People on these drugs need less monitoring, less side effects and can be used if warferin isn’t tolerated.

Question 27

What are the 2 types of Heparin?

Answer 27

1. unfractionated heparin.

2. low molecular-weight heparins.

Question 28

True or false…

In haemorrhagic stroke, anticoagulants should be continued.

Answer 28

FALSE

• If haemorrhage confirmed, stop anticoagulating / reverse to establish ‘normal’ clotting (INR!) To prevent the bleed getting worse. Unless good reason to keep on- AF

Question 29

True or false…

There is no evidence to suggest that anticoagulants are effective in the treatment of Acute Ischemic Stroke.

Answer 29

TRUE

Meta-analysis of 6 randomized trials (22,000 patients) found: no evidence the use of anticoagulants (unfractionated heparin, low molecular-weight heparins, heparinoids, thrombin inhibitors, or oral anticoagulants) in the acute phase of stroke improves functional outcomes

Question 30

How can you reverse Anti-Coagulant action (like you would in haemorrhagic stroke?

Answer 30

If not in hurry, can stop anticoagulant drugs & wait

Vitamin K to reverse warfarin action (still takes a while – why?)

URGENT: give clotting factors

Question 31

How do you treat a long term Ischemic Stroke?

Answer 31

1. Antiplatelet therapy:

Long-term anti-platelet therapy reduces substantially the incidence of further infarction.

Secondary Prevention
e.g. combined aspirin (75 mg day) and dipyridamole (200 mg 2x day)