General Pharma Qs

Question 1

What is the difference between desensitisation and tolerance?

Answer 1

Desensitisation = effect of a drug gradually diminished when given continuously or repeatedly (minutes)

Tolerance = gradual decrease in responsiveness to a drug (hours-weeks)

Question 1

What is drug potency?

Answer 1

The amount of drug required to produce an effect (of given intensity)

Question 2

What is used to measure potency?

Answer 2

EC50 / ED50 - the concentration of a drug which induces a response halfway between baseline and maximum

Question 3

What is the half-life of a drug?

Answer 3

Time for the plasma drug concentration of that drug to reduce by half.

Question 4

What is the therapeutic window?

Answer 4

The range of concentrations between max efficacy and min toxicity in the majority of Ps.

Question 5

How is the therapeutic index worked out?

Answer 5

TI / TD50 / ED50

Question 6

What is the difference between pharmacodynamics and pharmacokinetics?

Answer 6

Pharmacodynamics (D = drug first) - what the drug does to the body

Pharmacokinetics = what the body does to the drug (ADME)W

Question 7

What is bioavailability?

Answer 7

The fraction of the administered drug which reaches the systemic circulation as an intact drug

Worked out by Oral AUC / IV AUC (IV = 100%)

Question 8

If a drug had an oral bioavailability of 20%, what dose would be needed to achieve the same effect as the corresponding IV dose?

Answer 8

x5 greater

Question 9

What are the four compartments of the body?

Answer 9

Plasma
Interstitum
Intracellular
Fat

Question 10

What is the volume of distribution?

Answer 10

A measure of how widely a drug is distributed between various body fluids and tissues

Question 11

What is the difference between a water soluble drug and a lipid soluble drug in terms of distribution?

Answer 11

Water soluble is mainly confined to blood and body water compartments.

Lipid soluble - widely distributed to the tissues. Has a higher volume of distribution.

Question 12

What effect does protein binding have on a drug?

Answer 12

It means it lasts longer in the blood than an unbound drug = longer therapeutic effect.

Question 13

Which drugs are highly protein bound?

Answer 13

Warfarin
Aspirin
Ibuprofen
Heparin
Furosemide

Question 14

What factors can increase the fraction of an unbound drug in the body?

Answer 14

Saturability
Displacement by another drug
Late pregnancy
Renal impairment
Low plasma albumin

Question 15

What are the main sites of drug metabolism in the body?

Answer 15

Liver
Kidney
GI Tract
Lungs
Skin

Question 16

What effect do all of the following have on CP450 enzymes?
Amiodarone
Ciprofloxacin
Erythromycin / Clarithromycin
Metronidazole
Flucozanole
Isoniazid
Grapefruit Juice

Answer 16

Inhibit CP450, therefore slower metabolism - means inc therapeutic effect and toxicity

Question 17

What effect do the following have on CP450 enzymes?

Carbamazepine
Phenytoin
Rifampicin .
Alcohol

CARP

Answer 17

Induce CP450 - means faster metabolism, decreased therapeutic effect and decreased toxicity.

Question 18

How can genetics affect drug metabolism?

Answer 18

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

Question 19

What are the two main sources of drug clearance?

Answer 19

Hepatic metabolism
Renal excretion

Question 20

Hope does entero-hepatic circulation affect some drugs?

Answer 20

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.

Question 21

What are the following determined by:
- Loading dose
- Maintenance dose
- Dose interval

Answer 21

Loading dose = determined by volume of distribution

Maintenance dose = determined by the clearance

Dose interval = determined by the half life of the drug

Question 22

Why is formulation important for drugs?

Answer 22

Affects absorption of the drug - even the particle size of the same dose drug can affect therapeutic levels of the drug.

Question 23

What are modified release preparations?

Answer 23

Contain a mixture of slow and fast release particles - allowing an increased dose interval and reduced adverse effects from high peak plasma concentrations.

Question 24

How is warfarin affected by sulfonamides?

Answer 24

Warfarin is highly protein bound (95%) - it is displaced by sulfonamides - thus increasing the amount of free warfarin and increasing the patient's INR.

Question 25

Can bound drugs move between compartments?

Answer 25

Only free drugs can move between compartments.

Question 26

What is metabolism of a drug?

Answer 26

Process by which a drug is chemically altered for facilitating therapeutic action or enhancing elimination.

Question 27

What are the two phases of metabolism?

Answer 27

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.

Question 28

How does Rifampicin effect warfarin?

Answer 28

It is a CP450 inducer - which increases the metabolism of warfarin - meaning the anticoagulant affect decreases

Question 29

What is drug clearance?

Answer 29

Theoretical volume of plasma from which a drug is completely removed in a given period of time.

Question 30

By how many half-lives is steady state usually achieved?

Answer 30

3-5 half lives

Question 31

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

Answer 31

1 = Agonist 2 = Competitive antagonist 3 = Irreversible antagonist 4 = Physiologic antagonist 5 = Chemical antagonist 6 = Partial agonist 7 = Efficacy 8 = Potency 9 = Selectivity

Question 32

What is responsible for desensitisation or tolerance to a drug?

Answer 32

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

Question 33

What is a noxious and unintended response to a drug that occurs at normal therapeutic doses?

Answer 33

An adverse drug reaction

Question 34

What are the four phases of clinical trials on humans?

Answer 34

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.