Drugs

Question 1

Explain difference classification of drug interactions and give example to each

Answer 1

Pharmacokinetics:

• Altered absorption in GI tract, e.g. metal chelate formation - metal-containing antacids or supplement decrease absorption of antibiotics; P-glycoprotein inhibition
• Induced drug metabolism, e.g. CYP450 perpetrator drug classes, aldehyde dehydrogenase for alcohol metabolism
• Altered elimination

Pharmacodynamics
- Both acting on same receptor, causing potentiation or antagonism

Question 2

Describe how to reduce harm from drug interaction

Answer 2

• Know the key concepts
• Know the perpetrator drugs most often involved: Azole antifungal, anticonvulsations, Macrolides
• Know about drugs with low therapeutic index: anticoagulants, antiarrhythmics, antiepileptics, antineoplasts, aminoglycosides, immunosuppressants
• Know the drugs you frequently prescribe
• Know drugs of low risk for common problems
• Know how to recognise high risk patients: extremes of age, number of medicine, organ impairment

Question 3

List the poisons you can detect from blood and urine test

Answer 3

Blood: salicylate (aspirin), paracetamol, ethanol, carbon monoxide, tricyclics, digoxin, theophylline
Urine: salicylate, opioids, tricyclics

Question 4

Describe the different physiological treatment of poisoning and give specific example

Answer 4

Activated charcoal - binds to drug in gut, decrease absorption, excreted in feces; in plasma, increase elimination by preventing drug from flowing back into gut
Fuller’s earth - paraquat poisoning
Haemoperfusion with charcoal - theophylline
Haemodialysis - for RF patients, methanol, ethylene glycol (antifreeze)

Question 5

Give examples of delayed response due to distribution (pharmacokinetics), binding to receptor (binding kinetics) and physiological intermetiates (physiokinetics)

Answer 5

Pharmacokinetics: thiopentone - limited binding to receptor (low effective compartment volume), high perfusion (high clearance), equilibrium half life short
Binding kinetics: digoxin - slow unbinding from Na/K ATPase, long equilibrium half life; errgotamine - slow unbinding
Physiokinetics: warfarin - inhibit vkorc1, anticoagulant, but response seen delayed due to long half life of prothrombin complex, low physiological turnover rate

Question 6

Give examples of schedule dependent cumulative response and non-schedule dependent cumulative response

Answer 6

Schedule dependent: frusemide - inhibit renal Na reabsorption, diuretics, greater overall effect if lower dose given in shorter interval
Non-schedule dependent: for irreversible drugs e.g. anticancer cisplatin, cyclophosphamide and busulfan - remove bone marrow before bone marrow transplant, total response depends only on total amount of drug not the dosing schedule, thus important to individulise dose according to plasma concentration of drug

Question 7

What is the chemotherapy specific for testicular cancer? What drugs are use? What is the mechanism and toxicity of each drug?

Answer 7

BEP combination chemotherapy:
Bleomycin - induces DNA breaks - toxicity to lungs
Etoposide - topoisomerase II poison - toxicity to bone marrow
Cisplatin - induces DNA crosslinks - toxicity to peripheral nerves

Question 8

What are the adverse effects of cancer chemotherapy?

Answer 8

Antiproliferating - myelosupression, mucositis, alopecia, sterility
Mutagenesis - second cancers, teratogenecity
Microtubule disturbance - peripheral neurotoxicity
Sex steroid deficiency - decreased libido, impotence, flushing

Question 9

List the phenotypic characteristics that make a cancer

Answer 9

• evading apoptosis
• sustained angiogenesis
• self-sufficiency in growth signal
• insensitivity to anti-growth signals
• ability to invade tissues and metastasis
• limitless replication potential