WEEK 1 - Pharmacokinetics Flashcards
What are the 4 pharmacokinetic properties that determine speed of onset of drug action, intensity of drugs effects and duration of drug action?
ADME
Absorption
Distribution
Metabolism
Elimination
What is bioavailability ?
Fraction of administered dose of unchanged drug that reaches systemic circulation
IV bonus = 100% bioavailability
What factors affect bioavailability?
Drug formulation Age Food : lipid soluble> water soluble Vomiting/malabsorption 1st pass metabolism = any metabolism occuring before drug reaches system circulation. Occurs in gut lumen, gut wall, liver
What is the equation for bioavailability?
Amount of drug reaching systemic circulation / total amount of drug administered (IV)
Or
AUC oral/ AUC IV
What factors affect drug distribution?
- PROTEIN BINDING - most drugs bound to protein but must be unbound to be active normally. Competing for binging sites = DDIs. Changes in distribution are only important when : high protein binding, low Vd, narrow therapeutic range
- VOLUME OF DISTRIBUTION -
What is volume of distribution (Vd)
A theoretical volume.
Vd = fluid volume that is required to contain the entire drug at the same concentration measured in the plasma. I.e. How widely distributed in body tissues
Drug taken up into muscle and fat has a much larger Vd than a drug that just remains in circulation
Vd = amount of drug in body i.e dose / plasma conc. at time zero
E.g. A 100mg dose of gentacmin, peak plasma conc of 5mg/L; Vd = 20L.
HALF LIFE (t1/2) = proportional to Vd (and clearance).
How does Vd affect the half life of a drug?
If Vd is very high then longer half life and longer to eliminate
Approximately how many half lives does it normally take a drug to reach a steady state?
4-5 half life’s
And if Vd is large –> this could be longer
Compare the properties of a drug with a high Vd cf a low Vd?
High Vd - low protein binding, high free drug, hydrophilic drugs i.e. High lipid solubility,and thus move into fat and muscle compartments
Low Vd - mainly confined to intravascular fluid and therefore plasma. May be a large molecule, high protein binding, low lipid solubility.
What is the difference between phase 1 metabolism and phase 2 metabolism?
Phase I : oxidation , hydrolysis or reduction commonly. Make drug into an active metabolite. To make drug more polar. Converts lipophilic drugs. Dependent on CYP450 enzymes.
Phase II : glucuronidation or sulfation. .These are conjugation reactions that increase water solubility . Convert drugs to inactive metabolites –> renally excreted.
What are the common CYP450 inducers
Inducers:
CRAP GPS
Carbamazepine
Rifampicin
Alcohol - Chronic
Phenytoin
G
Phenobarbital
Sulphonylureas + St Johns Wort
What are the common CYP450 inhibitors?
SICK FACES.COM
Sodium Valproate Isoniazid Cimetidine (H2 receptor blocker) Ketoconazole & Fluconazole Fluoxetine Alcohol - Acute consumption Cardiac Failure and liver failure Erytrhomycin and clarithromycin (macrolides) Sulphonamides
Ciprofloxacin (quinolone)
Omeprazole
Metronidazole (against anaerobes)
Man suffering from constipation for few months. Which of the medications is least likely to cause this? A Ferrous Sulphate B Ranitidine C Co-codamol D Ondansteron E Amitryptilline
Ranitidine - unlikely to cause constipation. More likely to cause diarrhoea.
45 year old, recently had a course of Co-amoxiclav tablets. Since taking them has had severe diarrohea. Admitted to hospital and diagnosed with C. Difficle. Which antibiotic is most appropriate for treating his infection?
Oral Vancomycin. 125mg every 6 hours for 10-14d.
Which of the following is the least appropriate treatment choice for nausea and vomiting in a patient with Parkinson's? A Metoclopramide B Cyclizine D Domperidone C Ondansetron E Promethazine
Metoclopramide - may exhibit extrapyramidal side effects and is cautioned in PD
Domperidone is similar to metoclopramide (both are D2 antagonists) but has less CNS ADRs
As CTZ is outside BBB, both have antiemetic effects. But as metoclopramide crosses BBB it has adverse SEs like extrapyramidal side effects including dyskinesia. Also galactorrhea.
