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Unit 3 > Quantitative pharmacology lecture > Flashcards

Quantitative pharmacology lecture Flashcards

1
Q

What is the drug classification of flucloxacillin?

A

A beta-lactam antibiotic.

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2
Q

Explain the pharmacology and physiology of flucloxacillin.

A

Binds to bacterial transpeptidase enzymes (a type of penicillin binding protein).
Acts as an irreversible inhibitor or a suicide substrate.
This prevents crosslinks from forming between D-ala-D-ala and other amino acids in the polyglycan cell wall.
This inhibits bacterial cell wall synthesis, hence the bacteria loses rigidity, often dies due to bursting from osmosis.

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3
Q

What is the clinical use of flucloxacillin?

A

Used as a narrow spectrum (gram-positive only) antibiotic.

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4
Q

When might the concentration of a drug be measured for medicinal purposes and what units may be used?

A

Concentration in the plasma - micrograms per ml
Concentration at the target - micromolar.
Note these concentrations are not always the same.

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5
Q

What is the difference between pharmacokinetics and pharmacodynamics?

A

PK - what the body does to the drug
PD - what the drug does to the body.

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6
Q

What are the four elements of pharmacokinetics?
(what happens to the drug within the body)

A

Absorption
Distribution
Metabolism
Excretion/Elimination.

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7
Q

What factors affect all four elements of pharmacokinetics?

A

Drug properties
Biological properties of patients - age, sex etc.

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8
Q

What affects the absorption of a drug?

A

Route of adminstration
Bioavailability

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9
Q

What affects the distribution of a drug?

A

Blood flow
Volume of distribution.

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10
Q

What affects the metabolism of a drug?

A

Biotransformation
Transforming enzymes e.g in the liver.

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11
Q

What affects the excretion/elimination of a drug?

A

The clearance
Removal mechanisms.

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12
Q

What are the different routes of administration?

A

Parenteral - avoiding the digestive sytem
- intravenous, intramuscular, sub-cutaneous, epidural, trans-dermal, sublingual, inhaltion

Enteral - through the digestive system
- oral or rectum (suppositories)

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13
Q

What is the difference between systemic and topical?

A

Systemic affects whole body systems, travels everywhere
Topical affects a localised area e.g local anaesthetic.

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14
Q

What is oral bioavailability?
Why is it useful clinically?
What factors influence it?

A

Also known as fractional availability (F)
The proportion of a drug that gets into systemic circulation (plasma).
The higher F the more useful the drug as an oral systemic.
Affected by stability within the gut, absorption across the gut wall into plasma and metabolism in the liver.
These factors are all influenced by drug properties, the patient biological factors and the pharmaceutical formulation that the drug is given in.

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15
Q

What affects drug stability within the gut?

A

Chemical properties of the drug e.g acid/base stability
Biological stability - exposed to enzymes in the gut.

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16
Q

What affects drugs absorption across the gut wall?

A

Must travel across the gut epithelium, extracellular matrix and capillary endothelium.
size, solubility and pKa of drug.

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17
Q

What is pKa?
How does it realte to pKb?

A

An indication of acid strength.
pKa = -log10(ka)
A lower pKa shows a stronger acid.
pKa + pKb = 14

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18
Q

How does acid/base strength affect solubility of drugs?

A

unionised drugs cross membranes more easily.
This means acids are more soluble when the equilibrium of HA —> H+ + A- is to the left.
Similarly, bases are more soluble when the equilibrium B + H+ —-> HB+ lies to the left.

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19
Q

What is an xenobiotic?

A

A substance found within an organism that is not normally present or produced by that organism.

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20
Q

What is the link between liver metabolism and oral bioavailability?

A

Drugs that enter the digestive system pass through the liver, the liver screen and metabolites xenobiotics.
Drugs that undergo substantial hepatic metabolism have poor oral bioavailability.

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21
Q

What is considered within the distribution of a drug?

A

How much drug is needed?
Where does the drug go?
Hence how often should the drug be given?

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22
Q

What is the proportion constant relating the amount of a drug and its concentration?

A

The volume that it is injected into.
E.g injecting twice the amount into the same volume will double the concentration.

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23
Q

What is the volume of ditribution?
What does the value suggest about the drug?

A

A conversion factor relating the concentrayion of drug in the plasma and the total amount of drug.
Calculated by the amount divided by plasma concentration.
A larger value shows the drug has spread further about of the plasma, into ECF, cells and fat etc.

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24
Q

What is the effect of blood flow in drug distribution?
Intravenous administration

A

A higher blood flow often means the drug has a faster effect, this is seen in areas such as the brain.
Areas with low blood flow need longer for the drug to take effect for example bone and joints. This makes it harder to achieve adequate concentrations of the drug in these areas before it is eliminated.

25
Q

What is meant by drug metabolism and what are the different stages of this?

A

When the chemical structure of a drug is altered within the body.
Phase 1- synthetic - small changes in structure/chemical group e.g oxidation, reduction, hydrolysis, deamination

Phase 2 - conjugation - Adding a larger chemical group to the drug often by covalent modification.

26
Q

What are the potential outcomes of drug metabolism?
(by phase)

A

Synthetic stage - makes drugs more polar and soluble, is able to make an active drug into an active metabolite, inactive metabolite or toxic metabolite.
Conjugation stage - makes drugs more soluble, polar and larger. Increases so more likely to be excreted by the kidney. Typically drugs become inactive.

27
Q

What is the difference between excretion and elimination?

A

Excretion = is the physical removal of the drug/metabolite from the body.

Elimination is the disappearance of drug (not necessarily the metabolite) from the blood plasma.

28
Q

What factors promote renal elimination?

A

Increased polarity
Increased solubility
Increased size, up to 6nm

29
Q

What are the different ways that elimination can be quantified?
What are the suitable units?

A

Rate of elimination - mass of drug removed from plasma over time mg.min-1
Clearance - the volume of plasma cleared of drug over time ml.min-1
Rate constant of elimination - the proportion of drug (unitless) eliminated in a unit to time min-1
Half life - the time taken for plasma concentration to half minutes or hours.

30
Q

How would you calculate the does required to reach a certain plasma concentration of a drug?

A

Volume dilution x desired plasma concentration.

31
Q

How is the rate of elimination related to the concentration?

A

As the concentration increases (in a set volume) the rate of elimination increases.
This is due to the fixed proportionality constant of the clearance ml.min-1.

32
Q

How do I calculate the dosage rate to reach a desired plasma concentration?

A

Clearance (ml.min-1) x desired plasma concentration (mg.ml-1)

Replacing what has been lost, by calculating the amount of drug lost in a set time period.

33
Q

How can the rate constant of elimination be calculated?

A

Clearance/ the volume of distribution.

34
Q

How is the half life of a drug calculated?

A

ln(2) / rate constant of elimination

35
Q

What is the difference between a linear and a log scale?

A

In a linear scale you increase by addition along the axis, e.g 1,2,3,4,8
In a log scale the axis increases by multiplication e.g 1,2,4,8,16

36
Q

What values are often used for the rate of elimination constant?

A

1 to 0 min-1
where 0.1 would be ten percent of the drug is removed in one minute

37
Q

How does elimination affect half life?

A

A higher rate of elimination constant a shorter half life.

38
Q

What is meant by first-order elimination?

A

A constant rate of clearance but a variable amount of drug eliminated.
This means the same amount of plasma is cleared of a drug within a set time period but as the plasma concentration decreases as drug removed a smaller amount of actual drug will be removed.

39
Q

What is meant by zero order elimination?

A

A constant amount of drug is eliminated, this means the amount of plasma cleared will change,
As the concentration of plasma decreases more plasma will needed to be cleared in order to eliminate the same amount of drug.

40
Q

What is meant by occupancy when talking about drugs?

A

The proportion of receptors occupied by the drug.

41
Q

Why might the effect of a drug appear to plateau even as concentration continues to increase?

A

All the receptors become saturated.

42
Q

Why might the affect of a drug appear to consistently increase with concentration?

A

Drugs have a selectivity for receptors, meaning they prefer to bind to certain receptors.
When a drug concentration increases too high the drug will occupy all of its most favourable receptors and occupy its less favourable receptor causing an additional effect (potentially toxic)

43
Q

What is meant by the dissociation constant of a drug?

A

Kd (d in subscript), the concentration of the drug at which 50% of receptors are occupied.

44
Q

Why is Kd (d in subscript) used rather than amount of drug to occupy 100% of receptors?

A

Measuring the amount of drug needed to occupy 50% of receptors is easier.

45
Q

What is meant by affinity of a drug?
Why is this important in relation to concentration?

A

Affinity is the tendency of a drug to bind to a receptor, undermined by the drugs shape and chemical structure.
This is important clinically as drugs of a higher affinity are often needed in lower concentrations, than if that make drug had a lower affinity.

46
Q

What is meant by an exponent?

A

The reverse of a log.
Or a number that a power is raised to.

47
Q

What is meant by structure activity relationships?

A

A part of pharmacodynamics.
Recognised that small alterations to a drug structure can have large implications for the function of that drug.

48
Q

Explain the difference between selectivity and specificity in relation to drugs?

A

Selectivity means drugs have a preference for which of the receptors they bind to out of all the receptors they are able to bind to.
Specificity is the ability for more than one drug or receptor to be involved in a reaction, e.g if a drug will only bind to one receptor is it highly specific.

49
Q

What is the therapeutic index?
How is it calculated?

A

A measure of how far apart a drugs safe therapeutic dose is from its dangerous toxic dose.
A low TI means that there is only a small gap between the toxic and safe dosage.
It is calculated by dividing the toxic dose by the therapeutic dose (ensure units are the same).

50
Q

What is meant by efficacy?

A

The actual molecular impact that a drug has after binding to a receptor, does it cause any cellular changes?

51
Q

What is the difference between an agonist and an antagonist drug?

A

Agonist binds to a drug that has an affect so has efficacy.
An antagonist binds to the drug and then has no affect, has no efficacy.

52
Q

What is potency in relation to drugs?

A

An expression of the activity of a drug, in the terms of what dosage is needed to have an effect.
A higher potency drug will have a greater effect at the same dosage as a lower potency drug.

53
Q

What is meant by EC50?

A

The concentration of an agonist that produces 50% of the maximum effect of the agonist.

54
Q

What is the difference between EC50 and kd (d in subscript)?

A

Kd is relating to 50% of receptors hence affinity.
EC50 is relating to effect hence potency.

55
Q

What is meant by spare receptors in relation to drugs?

A

Refers to the proportion of receptors that need not be occupied in order to elicit a maximal response.

56
Q

What are the different types of agonists?

A

A full agonist - elicits a maximum response without binding to all the receptors.
A partial agonist - cannot elicit a full response despite 100% efficacy.

57
Q

What are the different types of antagonists?

A

Competitive - mutually exclusive binding to receptor alongside natural ligand, binds to the orthosteric site.
Non competitive - the endogenous ligans may or ma not bind alongside the drug, drug binds to the allosteric site.

58
Q

What type of drug are channel blockers?

A

A non-competitive antagonist.
Bind to the channel when it is open or closed.

59
Q

What are the differences between a reversible and an irreversible drug?

A

Reversible - an equilibrium of binding and unbinding
Irreversible - binds by covalent modification, does not unbind, high very 100% affinity.

Unit 3 (18 decks)

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