VIVA: Pharmacology - Miscellaneous Flashcards
During clinical drug trials, what factors might confound the results?
Variable natural history of most disease
Presence of other diseases and risk factors
Subject and observer bias*
- needed to pass
What can be done to minimise confounders in drug trials?
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
What is erythropoietin?
Glycoprotein hormone produced by the kidney
What are the clinical applications of erythropoietin?
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
What toxic effects may occur with the use of erythropoietin?
Toxicity is mainly related to rapid haemoglobin rise and includes (1/2 needed to pass):
- Hypertension
- Thrombosis
Allergic reactions are infrequent and mild
Name some of the ingredients in over-the-counter preparations that may cause toxicity
3/7 needed to pass:
- Ethanol
- Antihistamines
- Salicylates
- Caffeine
- Local anaesthetics
- Sodium
- Sympathomimetics
Give an example of toxicity which may be caused by an over-the-counter preparation
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
What are the therapeutic uses of penicillamine?
Wilsons disease
Copper poisoning
Cystinuria
Severe rheumatoid arthritis
List the adverse effects of D-penicillamine
2 needed to pass:
- Nausea and vomiting
- Nephrotic syndrome
- Hypersensitivity (avoid if history of penicillin allergy)
- Pancytopaenia
- Pemphigus
- Myaesthenia
- Optic atrophy
- Athropathy
Describe the phases of testing of new drugs
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)
Describe ways in which new drugs might be discovered or produced
2 needed to pass:
- Chemical modification
- Random screening
- Rational design
- Gene methods
- New drug target identification
What are the medical uses for St John’s Wort?
Mild to moderate depression
What are the important drug interactions of St John’s Wort?
Kinetic: acts as CYP P450 inducer (decreases effect of drugs metabolised by CYP P450 enzymes)
Dynamic: inhibits catecholamine reuptake (potentiates some drug effects)
List the advantages of eye ointments over eye drops
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
List by action the types of drugs used topically in the eye
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)
List the ideal properties of an ocular local anaesthetic
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
What is vitamin K?
Fat-soluble vitamin* found in leafy vegetables (vitamin K1) and usually synthesised by gut bacteria* (vitamin K2)
- needed to pass
Describe the mechanism of action of vitamin K in reversal of warfarin anticoagulation
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
What methods are available to reverse warfarin-induced anticoagulation?
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
How long does it take for vitamin K to work?
6-24hrs (onset at 6hrs, complete by 24hrs)
What are the preferred administration routes for vitamin K?
Oral, IM, IV
Oral absorption is inconsistent
Rapid IV infusion may produce flushing, cyanosis, dizziness, hypotension and bronchoconstriction
Subcutaneous is erratic
What are the clinical indications for prescribing vitamin K?
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)
