W3 ICS- CVS

Question 1

Patient A attends his GP practice with intermittent chest pain when walking the dog and playing golf with his friends. Taking the patient’s history into account, what condition do you think the patient is likely to be diagnosed with? Please justify your answer.

PMHx Hypertension Hyperlipidaemia
FHx * Father passed away of a heart attack at the age of 58
SHx * Retired IT manager
* Smoker – previously 10 cigarettes a day but now approximately 5 (is
cutting down with the aim of stopping)
* Alcohol – 2 large glasses of wine most evenings with his evening
meal, 7-8 pints on a Friday night down the rugby club
* Hobbies – playing golf with his friends

• Predictable CP on exertion (walking the dog, playing golf) which improves at rest and has
  now subsided since altering exacerbating factors
• Risk factors for IHD:
  o Hyperlipidaemia
  o Hypertension – currently controlled
  o Obesity (110kg)
  o Age
  o Male
  o FHx of ACS

Answer 1

Stable Angina

Why not unstable angina?
o Relieved at rest
o Predictable – occurs on exertion and has now resolved since avoiding triggers
o First time presenting

Question 2

The patient information leaflet of amlodipine reads “Each tablet contains 10 mg of amlodipine (as besilate)”. Why is amlodipine given as amlodipine besilate?

Answer 2

• The besilate salt of amlodipine has higher water solubility than amlodipine alone
• Increasing solubility helps to improve the bioavailability of the drug

Question 3

Why is GTN spray given under the tongue (sublingually)?

Answer 3

The drug is absorbed into the body very quickly this way
o The sublingual region holds a rich source of blood vessels
o Thin epithelium (100 – 200 mm) on the underside of the tongue and on the floor of the mouth
o The sublingual mucosa contains high amounts of polar lipids, and nitroglycerin is lipophilic
o Avoids first-pass metabolism by the liver
- Therefore, useful for fast relief of chest pain caused by angina

Question 4

GTN Spray Counselling points:

Answer 4

• Dose: 1 – 2 sprays under the tongue when chest pain experienced
• Can repeat after 5 mins if the pain hasn’t resolved
• If pain hasn’t resolved 5 mins after 2nd dose → 999
• Always carry your GTN spray on you at all times
• Check your GTN spray regularly to ensure it is working
• Check the expiry date on your GTN frequently

HOW TO USE GTN SPRAY:
- Sit down
- Hold the canister upright and near your mouth
- Hold your breath
- Aim the spray under your tongue
- Press down on the button firmly, once only
- Close your mouth immediately
- Do not inhale the spray
GTN S/E
- Headache
- Low BP – can cause dizziness which is why you
should sit down when using
- Flushing

Question 5

What should you do if a patient is intolerant (experiences) SE with a CCB?

Answer 5

Switch to a BB
Before starting treatment, check patients HR and BP

Question 6

What diagnostic tests would you expect to be carried out with an ACS diagnosis?

Answer 6

• Troponin: elevated troponin >100 indicative of MI
  o NOT diagnostic
  o Troponin can be elevated as a result of HF and PE
• 12 lead ECG to determine if ST or Non-ST elevated MI
• Thorough patient history and identification of risk factors

Question 7

Indicate the most important structural features required for Losartan (structure below) to interact with
its biological target and explain for each of them why they are essenti

Answer 7

• tetrazole acidic group mimics either Tyr4 phenol or Asp1 COO of angiotensin II. Tetrazole: superior metabolic stability, lipophilicity, and oral bioavailability
• Tetrazole in the biphenyl group must be in the ortho position for optimal activity.
• n-butyl group: hydrophobic binding. mimics side chain Ile5
• Imidazole ring required to mimic His6
• CH2OH (hydroxy-methyl group). Mimic the interaction between COOH C-terminal angiotensin II and AT1 receptor

Question 8

Aspirin and Atorvastatin are two drugs from different classes with different biological targets and mechanisms of action BUT with the same main absorption site for OD.
Briefly indicate the biological target, the mechanism of action and the class for these two drugs and explain where they are mainly absorbed and why. Draw the correct protonation state of the two
absorbed drugs.

Answer 8

Aspirin: antiplatelet drug. Inhibits biosynthesis of Thromboxane A2 (TXA2), a potent vasoconstrictor and
inducer of platelet aggregation, in the platelets by
irreversibly and permanently inactivating cyclooxygenase (COX)-1, the enzyme that converts arachidonic acid
(AA) to prostaglandin H2 (PGH2) which is further converted to TXA2. Acylation of Serine530.
Atorvastatin: Statins family. Lower the plasma cholesterol levels by disrupting cholesterol biosynthesis by
inhibiting the HMG-CoA reductase enzyme, which is responsible for the conversion of HMG-CoA in
Mevalonic acid. Statins block access of HMG-CoA to the active site.
Both drugs are mainly absorbed in the stomach because the carboxylic acid group present in both drugs is
mainly unionised at the stomach pH, so the drugs can be easily absorbed. Once they reach a physiological pH
or a pH above their pKa value, they will be ionised.
The protonation form is the same of the picture above

Question 9

Why Prasugrel is considered an irreversible antagonist of P2Y12 receptor?

Answer 9

Prasugrel, after been activated, forms a covalent di-sulfide bond with critical cysteine residues (Cys97,
Cys175) in the ADP site of P2Y12. This prevents the binding of endogenous agonist blocking platelets
aggregation. The covalent bond with P2Y12 is irreversible, so Prasugrel cannot be displaced by the ADP, and
the receptor remains inactive.