VIVA: Pharmacology - Miscellaneous

Question 1

During clinical drug trials, what factors might confound the results?

Answer 1

Variable natural history of most disease
Presence of other diseases and risk factors
Subject and observer bias*

• needed to pass

Question 2

What can be done to minimise confounders in drug trials?

Answer 2

To minimise the variability of the natural history of most diseases as a confounder:
- Conducting trials in large populations over sufficient time
- Cross-over trials

To minimise the presence of other diseases and risk factors as a confounder:
- Exclusion criteria
- Randomisation
- Cross-over trials

To minimise subject and observer bias as a confounder:
- Placebo controls
- Blinding
- Cross-over trials

Question 3

What is erythropoietin?

Answer 3

Glycoprotein hormone produced by the kidney

Question 4

What are the clinical applications of erythropoietin?

Answer 4

Stimulates red cell precursors to proliferate and differentiate*
Stimulates release of reticulocytes from bone marrow
Main use is for anaemia of chronic renal failure* (where EPO production is impaired)
Helps some marrow failure* states (e.g. aplastic anaemia, myeloproliferative/myelodysplastic disorders, multiple myeloma, AIDS, cancer)

• 1/3 needed to pass

Question 5

What toxic effects may occur with the use of erythropoietin?

Answer 5

Toxicity is mainly related to rapid haemoglobin rise and includes (1/2 needed to pass):
- Hypertension
- Thrombosis

Allergic reactions are infrequent and mild

Question 6

Name some of the ingredients in over-the-counter preparations that may cause toxicity

Answer 6

3/7 needed to pass:
- Ethanol
- Antihistamines
- Salicylates
- Caffeine
- Local anaesthetics
- Sodium
- Sympathomimetics

Question 7

Give an example of toxicity which may be caused by an over-the-counter preparation

Answer 7

Sympathomimetics: hyperglycaemia (type 1 DM), HTN, asthma, hypothyroidism
Salicylates: Reye’s syndrome in children, PUD, coagulopathies
Antihistamines and ethanol: drowsiness
Sympathomimetics and caffeine: agitation, headaches, interstitial nephritis
Drug interactions

Question 8

What are the therapeutic uses of penicillamine?

Answer 8

Wilsons disease
Copper poisoning
Cystinuria
Severe rheumatoid arthritis

Question 9

List the adverse effects of D-penicillamine

Answer 9

2 needed to pass:
- Nausea and vomiting
- Nephrotic syndrome
- Hypersensitivity (avoid if history of penicillin allergy)
- Pancytopaenia
- Pemphigus
- Myaesthenia
- Optic atrophy
- Athropathy

Question 10

Describe the phases of testing of new drugs

Answer 10

In vitro/animal
Human phases:
- Phase 1: effects of a drug as a function of dosage established in a small number of healthy volunteers
- Phase 2: drug studied in patients with target disease to determine efficacy (“proof of concept”) and doses to be used in subsequent trials, has the highest rate of failure
- Phase 3: drug evaluated in large numbers of patients with target disease
- Phase 4: after-market monitoring for safety under actual conditions of use in large numbers of patients (to detect rare adverse events)

Question 11

Describe ways in which new drugs might be discovered or produced

Answer 11

2 needed to pass:
- Chemical modification
- Random screening
- Rational design
- Gene methods
- New drug target identification

Question 12

What are the medical uses for St John’s Wort?

Answer 12

Mild to moderate depression

Question 13

What are the important drug interactions of St John’s Wort?

Answer 13

Kinetic: acts as CYP P450 inducer (decreases effect of drugs metabolised by CYP P450 enzymes)
Dynamic: inhibits catecholamine reuptake (potentiates some drug effects)

Question 14

List the advantages of eye ointments over eye drops

Answer 14

2 needed to pass:
- More stable
- Less absorption into lacrimal ducts
- Longer retention time on conjunctival surface
- Safer with potent drugs
- Ointment bases provide protection and comfort at night

Question 15

List by action the types of drugs used topically in the eye

Answer 15

4 needed to pass:
- Mydriatics (e.g. tropicamide)
- Miotics (e.g. pilocarpine)
- Cycloplegics (e.g. cyclopentolate)
- Decongestants (e.g. phenylephrine)
- Antibiotics (e.g. chloramphenicol)
- Antivirals (e.g. acyclovir)
- Antiseptics (e.g. chlorhexidine)
- Corticosteroids (e.g. dexamethasone)
- Local anaesthetics (e.g. oxybupracaine)
- Stains (e.g. fluorescein)

Question 16

List the ideal properties of an ocular local anaesthetic

Answer 16

Quick onset of action (10-20 secs)*
Useful duration of action (10-20 mins)*
No obvious effects on function or healing
No interactions with drugs used concurrently

• needed to pass

Question 17

What is vitamin K?

Answer 17

Fat-soluble vitamin* found in leafy vegetables (vitamin K1) and usually synthesised by gut bacteria* (vitamin K2)

• needed to pass

Question 18

Describe the mechanism of action of vitamin K in reversal of warfarin anticoagulation

Answer 18

Pharmacodynamic interaction with warfarin to reduce INR
Warfarin is a coumadin anticoagulant which prevents reductive metabolism of inactive vitamin K to active form, and in doing so produces biologically inactive* factors II (prothrombin), VII, IX and X and protein C and S
Vitamin K1 confers biological activity* upon prothrombin and factors VII, IX and X by participating in their post-ribosomal modification
Onset of action 6hrs*, complete by 24hrs

• need concept of warfarin producing biologically inactive factors, vitamin K overcoming this, and delayed onset of action

Question 19

What methods are available to reverse warfarin-induced anticoagulation?

Answer 19

Cease warfarin
Vitamin K (oral or IV 1-10mg)*
+/- FFP, prothrombinex (contains factors II, VII, IX and X) or NovoSeven (recombinant factors VIIa)
Note single dose may not be sufficient due to warfarin’s long half-life

• needed to pass + one other

Question 20

How long does it take for vitamin K to work?

Answer 20

6-24hrs (onset at 6hrs, complete by 24hrs)

Question 21

What are the preferred administration routes for vitamin K?

Answer 21

Oral, IM, IV
Oral absorption is inconsistent
Rapid IV infusion may produce flushing, cyanosis, dizziness, hypotension and bronchoconstriction
Subcutaneous is erratic

Question 22

What are the clinical indications for prescribing vitamin K?

Answer 22

Reversal of oral anticoagulant effect*
Management of warfarin toxicity or superwarfarin toxicity (brodifacoum)*
Vitamin K deficiency*
Prevention and treatment of haemorrhagic disease of the newborn

Indications for oral vitamin K:
- In small ingestions or when amount is uncertain but presumed to be small

Indication for IV vitamin K:
- Severe cases where rapid correction is required (in adults minimum of 10mg IV diluted in saline or glucose at a rate not exceeding 5% of total dose per minute; in maximally anticoagulated individuals, repeat doses at 6-8hr intervals)