General Pharma Qs Flashcards
What is the difference between desensitisation and tolerance?
Desensitisation = effect of a drug gradually diminished when given continuously or repeatedly (minutes)
Tolerance = gradual decrease in responsiveness to a drug (hours-weeks)
What is drug potency?
The amount of drug required to produce an effect (of given intensity)
What is used to measure potency?
EC50 / ED50 - the concentration of a drug which induces a response halfway between baseline and maximum
What is the half-life of a drug?
Time for the plasma drug concentration of that drug to reduce by half.
What is the therapeutic window?
The range of concentrations between max efficacy and min toxicity in the majority of Ps.
How is the therapeutic index worked out?
TI / TD50 / ED50
What is the difference between pharmacodynamics and pharmacokinetics?
Pharmacodynamics (D = drug first) - what the drug does to the body
Pharmacokinetics = what the body does to the drug (ADME)W
What is bioavailability?
The fraction of the administered drug which reaches the systemic circulation as an intact drug
Worked out by Oral AUC / IV AUC (IV = 100%)
If a drug had an oral bioavailability of 20%, what dose would be needed to achieve the same effect as the corresponding IV dose?
x5 greater
What are the four compartments of the body?
Plasma
Interstitum
Intracellular
Fat
What is the volume of distribution?
A measure of how widely a drug is distributed between various body fluids and tissues
What is the difference between a water soluble drug and a lipid soluble drug in terms of distribution?
Water soluble is mainly confined to blood and body water compartments.
Lipid soluble - widely distributed to the tissues. Has a higher volume of distribution.
What effect does protein binding have on a drug?
It means it lasts longer in the blood than an unbound drug = longer therapeutic effect.
Which drugs are highly protein bound?
Warfarin
Aspirin
Ibuprofen
Heparin
Furosemide
What factors can increase the fraction of an unbound drug in the body?
Saturability
Displacement by another drug
Late pregnancy
Renal impairment
Low plasma albumin
What are the main sites of drug metabolism in the body?
Liver
Kidney
GI Tract
Lungs
Skin
What effect do all of the following have on CP450 enzymes?
Amiodarone
Ciprofloxacin
Erythromycin / Clarithromycin
Metronidazole
Flucozanole
Isoniazid
Grapefruit Juice
Inhibit CP450, therefore slower metabolism - means inc therapeutic effect and toxicity
What effect do the following have on CP450 enzymes?
Carbamazepine
Phenytoin
Rifampicin .
Alcohol
CARP
Induce CP450 - means faster metabolism, decreased therapeutic effect and decreased toxicity.
How can genetics affect drug metabolism?
Polymorphisms of drug metabolising enzymes can affect drug processing in the body:
Ultrarapid metaboliser = duplication of normal alleles
Extensive = normal
Intermediate = 1 normal + 1 abnormal
Poor metaboliser = 2 abnormal alleles
What are the two main sources of drug clearance?
Hepatic metabolism
Renal excretion
Hope does entero-hepatic circulation affect some drugs?
If the drug is excreted into the bile, it can be taken into entero-hepatic circulation - Enterohepatic circulation increases the elimination half-life of many drugs (thus prolonging their action) and causes multiple peaks in the plasma drug concentration-time profile.
What are the following determined by:
- Loading dose
- Maintenance dose
- Dose interval
Loading dose = determined by volume of distribution
Maintenance dose = determined by the clearance
Dose interval = determined by the half life of the drug
Why is formulation important for drugs?
Affects absorption of the drug - even the particle size of the same dose drug can affect therapeutic levels of the drug.
What are modified release preparations?
Contain a mixture of slow and fast release particles - allowing an increased dose interval and reduced adverse effects from high peak plasma concentrations.
How is warfarin affected by sulfonamides?
Warfarin is highly protein bound (95%) - it is displaced by sulfonamides - thus increasing the amount of free warfarin and increasing the patient’s INR.
Can bound drugs move between compartments?
Only free drugs can move between compartments.
What is metabolism of a drug?
Process by which a drug is chemically altered for facilitating therapeutic action or enhancing elimination.
What are the two phases of metabolism?
Phase 1 = modification to make drug more reactive (oxidation, reduction or hydrolysis) - by CYP450 enzymes.
Phase 2 = conjugation of the drug (glucuronidation, acetylation, salvation) - allows elimination from the body.
How does Rifampicin effect warfarin?
It is a CP450 inducer - which increases the metabolism of warfarin - meaning the anticoagulant affect decreases
What is drug clearance?
Theoretical volume of plasma from which a drug is completely removed in a given period of time.
By how many half-lives is steady state usually achieved?
3-5 half lives
What are the following called:
1 = A drug that activates its receptor upon binding
2 = A pharmacologic antagonist that can be overcome by increasing the concentration of the agonist
3 = A pharmacologic antagonist that cannot be overcome by increasing agonist concentration
4 = A drug that counters the effects of another by binding to a different receptor and causes opposite effects
5 = A drug that binds to and inactivates the agonist (not the receptor)
6 = A drug that binds to its receptor but produces a smaller effect (Emax) at full dosage than the full agonist
7 = The largest effect that can be achieved with a particular drug, regardless of dose
8 = The amount or concentration of a drug required to produce a specified effect
9 = A drug’s ability to bind to a particular receptor, type or subtypes
1 = Agonist
2 = Competitive antagonist
3 = Irreversible antagonist
4 = Physiologic antagonist
5 = Chemical antagonist
6 = Partial agonist
7 = Efficacy
8 = Potency
9 = Selectivity
What is responsible for desensitisation or tolerance to a drug?
Various things inc:
Change in receptors (conformational changes, phosphorylation or NMJ)
Translocation of receptors - up and down regulation
Exhaustion of mediators
Increased metabolic degradation
Active extrusion of drug from cells
What is a noxious and unintended response to a drug that occurs at normal therapeutic doses?
An adverse drug reaction
What are the four phases of clinical trials on humans?
Phase 1 - small number of healthy ppl - test for side effects and calculate right dose.
Phase 2 - larger group of ppl - look for effects in short term
Phase 3 - larger groups of sick ppl, compare to placebo or existing treatment
Phase 4 - now available widely - long term safety, SEs and effectiveness continue to be studied.
