Session 2 Flashcards
List the factors affecting drug absorption
First pass metabolism: Gut lumen - gastric acid, enzymes Gut wall - P-glycoprotein efflux Liver Drug formulation Food (lipid soluble > water soluble) Vomiting Malabsorption (Coeliac's disease)
List the factors affecting drug distribution
Protein binding: Albumin - acidic drugs Globulins - hormones Lipoproteins - basic drugs Hypoalbuminaemia Pregnancy Renal failure Displacement by other drugs
Explain the terms ‘bioavailability’ and ‘volume of distribution’
Bioavailability - fraction of an administered dose of unchanged drug that reaches the systemic circulation, IV = 100%
Volume of distribution - measure of how widely a drug is distributed in body tissues
Vd = dose/[drug]t0
List the factors affecting drug metabolism
Metabolism dependent on CYP enzymes
Can be influenced by drugs (inducers/inhibitors)
List some common CYP450 inducers
Phenytoin Carbamazepine Barbiturates Rifamiicin Alcohol (chronic) Sulphonylureas, St John's Wort
List some common CYP450 inhibitors
Omeprazole Disulfiram Erythromycin Valproate Isoniazid Cimetidine, Ciproflaxin Ethanol (acute) Sulphonamides Grapefruit juice
List the factors affecting drug excretion
Unbound/bound drugs
Urine flow rate
Recognise the equations used for clearance and drug half life
Clearance = urine conc x urine flow rate/plasma conc
Half life is indirectly proportional to clearance
It takes 4-5 half lives to reach a drug’s steady state
Understand the difference between linear and non-linear kinetics
Linear (1st order) - rate of elimination is proportional to drug level
Non-linear (0 order) - rate of elimination is constant and does not vary with drug concentration, no half life calculable therefore drug monitoring essential
List some common zero order drugs
Alcohol Phenytoin Warfarin Heparin Aspirin (high dosage) Theophylline, tolbutamide Salicylates
Appreciate how steady stage therapeutic levels in plasma (CpSS) are reached and how loading doses are employed to reach CpSS more rapidly
4-5 doses = steady state
Loading dose = Vd x [drug]target
Understand the basic concepts relevant to pharmacodynamics
How do drugs work - interact with endogenous proteins (agonise/antagonise/unconventional mechanisms)
Where do drugs work - receptors ion channel, transporter enzymes
Define the terms ‘specificity’ and ‘selectivity’
Specificity - target drugs against specific receptor subtitles and specific organs
Selectivity - less chance of interaction with different targets therefore fewer undesirable side effects
Define ‘affinity’, ‘efficacy’ and ‘potency’ and appreciate the idea of a therapeutic window
Affinity - tendency of a drug to bind to a specific receptor type
Efficacy - ability of a drug to produce a response when the receptor is occupied
Potency - dose required to produce the desired biological response
Therapeutic index - relationship between concentrations causing adverse and desirable effects (TD50/ED50)
Therapeutic window = treatment while still safe
Describe, with examples, pharmacokinetic and pharmacodynamic drug interactions
CYP450 inducers/inhibitors
Understand induction and inhibition of the cytochrome P450 system
Induction - enzymes become more active causing drug to be processed quicker –> drug ineffective at treatment
Inhibition - enzymes inhibit activity causing drug to remain in body for longer –> drug has a larger effect (toxic?)
Outline how cardiac, renal and hepatic disease cause disease-drug interactions
Cardiac - decreased cardiac output, low perfusion of organs
Renal - low GFR= decreased clearance of drugs
Hepatic - decreased CYP enzyme activity
Recognise circumstances in which drug interactions are most likely to occur
Polypharmacy Extremes of age Co-morbidities Drugs with a narrow therapeutic index Drugs used near their minimum/maximum effective concentration
List some important drug-food interactions
Grapefruit juice (CYP450 inhibitor) - decreased clearance of simvastatin, amiodarone Cranberry juice (CYP2C9 isoform inhibitor) - decreased clearance of warfarin, increased risk of haemorrhage *used as a UTI treatment as inhibits bacterial adherence to urothelium
Recognise the main routes of drug administration into the body
Oral IV SC IM Parenteral PR Transdermal
