General Pharma Qs Flashcards

1
Q

What is the difference between desensitisation and tolerance?

A

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

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

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1
Q

What is drug potency?

A

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

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2
Q

What is used to measure potency?

A

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

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3
Q

What is the half-life of a drug?

A

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

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4
Q

What is the therapeutic window?

A

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

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5
Q

How is the therapeutic index worked out?

A

TI / TD50 / ED50

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6
Q

What is the difference between pharmacodynamics and pharmacokinetics?

A

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

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

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7
Q

What is bioavailability?

A

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

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

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8
Q

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

A

x5 greater

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9
Q

What are the four compartments of the body?

A

Plasma
Interstitum
Intracellular
Fat

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10
Q

What is the volume of distribution?

A

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

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11
Q

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

A

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

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

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12
Q

What effect does protein binding have on a drug?

A

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

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13
Q

Which drugs are highly protein bound?

A

Warfarin
Aspirin
Ibuprofen
Heparin
Furosemide

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14
Q

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

A

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

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15
Q

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

A

Liver
Kidney
GI Tract
Lungs
Skin

16
Q

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

A

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

17
Q

What effect do the following have on CP450 enzymes?

Carbamazepine
Phenytoin
Rifampicin .
Alcohol

CARP

A

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

18
Q

How can genetics affect drug metabolism?

A

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

19
Q

What are the two main sources of drug clearance?

A

Hepatic metabolism
Renal excretion

20
Q

Hope does entero-hepatic circulation affect some drugs?

A

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.

21
Q

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

A

Loading dose = determined by volume of distribution

Maintenance dose = determined by the clearance

Dose interval = determined by the half life of the drug

22
Q

Why is formulation important for drugs?

A

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

23
Q

What are modified release preparations?

A

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

24
Q

How is warfarin affected by sulfonamides?

A

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

25
Q

Can bound drugs move between compartments?

A

Only free drugs can move between compartments.

26
Q

What is metabolism of a drug?

A

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

27
Q

What are the two phases of metabolism?

A

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.

28
Q

How does Rifampicin effect warfarin?

A

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

29
Q

What is drug clearance?

A

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

30
Q

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

A

3-5 half lives

31
Q

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

A

1 = Agonist

2 = Competitive antagonist

3 = Irreversible antagonist

4 = Physiologic antagonist

5 = Chemical antagonist

6 = Partial agonist

7 = Efficacy

8 = Potency

9 = Selectivity

32
Q

What is responsible for desensitisation or tolerance to a drug?

A

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

33
Q

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

A

An adverse drug reaction

34
Q

What are the four phases of clinical trials on humans?

A

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.

35
Q
A