1.2 Drug Interaction and Toxicology Flashcards

1
Q

Give the 4 general ways in which drugs may work

A
  • Inhibition
  • Activation
  • Destruction
  • Replacement
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2
Q

Most drugs interact with what?

A

endogenous proteins

(a few have unconventional mechanisms of action)

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3
Q

Compare an agonist with an antagonist

A

Agonists: activate endogenous proteins

Antagonists: block or inhibit endogenous proteins

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4
Q

Give the 6 main sites where drugs work

A
  1. Cell Surface Receptors
  2. Nuclear Receptors
  3. Enzyme Inhibitors
  4. Ion Channel Blockers
  5. Transport Inhibitors
  6. Inhibitors of Signal Transduction Proteins
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5
Q

Not all agonists elicit maximal responses in the same assay, what are the 2 types of agonist we can have?

Label each on the image below

A

Full and partial agonists

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6
Q

Full agonist

EC50 ___ Kd

+/- _________

A

Full agonist EC50 < Kd

+/- spare receptors

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7
Q

Is competitive antagonism surmountable or non-surmoutable and why?

A

Competes with agonist at receptor site thus Inhibition is SURMOUNTABLE

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8
Q

What would be seen on an agonist concentration-response curve for a reversible competitive antagonist

A

a parallel shift to the right

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9
Q

When does Non-Competitive antagonism occur?

Is it surmountable or non-surmountable and why?

A

Occurs when the antagonist dissociates slowly or not at all

NON-SURMOUNTABLE ➞ With increased [antagonist] or increased time more receptors are blocked by antagonist

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10
Q

Compare an ‘ideal drug’ vs a ‘real drug’

A

An ideal drug interacts at one site but not other sites preventing unwanted effects

A real drug acts at more than one binding site, may result in collateral effects ➞ adverse drug reactions

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11
Q

What is the advantage if a drug displays Selectivity?

A

The more selective a drug for its target, the less chance it will interact with different targets. Therefore it will have less undesirable side effects

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12
Q

What is the benefit of penicillan?

A

SELECTIVITY

The enzyme is involved in bacterial cell wall biosynthesis. As mammalian cells do not have a cell wall, penicillin has few side effects

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13
Q

What is the advantage of drug specificity?

The more specific a drug acts ___________

A

Targeting drugs against specific receptor subtypes often allows drugs to be targeted against specific organ.

The more specific a drug acts, the less action ther is on other organs

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14
Q

Give an example of drug targets for specific organs?

A

Adrenergic receptors:

  • heart β1 receptors
  • lungs β2 receptors
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15
Q
A
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16
Q

Define Therapeutic Window

A

The range of dosages that effectively treat a condition safely

Between the lowest dose that has a +ve effect, and the highest dose before the -ve effects outweigh the +ve effects

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17
Q

Label the Image

A
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18
Q

How do you calculate the Theraputic index?

A

Therapeutic index = Toxic Dose (TD50) / Effective dose (ED50)

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19
Q

Define Therapeutic index

A

Relationship between concentrations causing adverse effects and concentrations causing desirable effects

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20
Q

Compare drug version I and drug version II

**********

A
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21
Q

Define Affinity

A

The tendency of a drug to bind to a specific receptor type

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22
Q

The equilibrium dissociation constant is represented by _____, which is a measure of _____.

What is the relationship between the 2 blanks above?

A

Kd, affinity

Kd↓ then affinity↑

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23
Q

Define Efficacy and state what this tells us

A

Efficacy is the ability of a drug to produce a response as a result of the receptor or receptors being occupied

It describes the maximum effect of a drug

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24
Q

Define Potency and state what we are comparing

A

Potency is the dose required to produce the desired biologic response.

Potency compares doses of two drugs required to exact the same effect

25
Q
A
26
Q

What may increase the probability of drug interaction

A

Probability of drug interaction rises with the number of drugs patient uses

27
Q

What occurs in each phase of hepatic metabolism of a drug and why?

A

Phase 1

  • chemical changes
  • CYP 450 family
  • low substrate specificity

Phase 2

  • conjugation
  • ↑ solubility
  • allows elimination
28
Q

What is meant by low substrate specificity?

A

Can metabolise a range of substrates

29
Q

Inhibition of CYP 450 is related to what 2 factors?

Is it a fast or slow process?

A

Related to:

  1. Half life and clearance of affected drug
  2. Plasma concentration at time of interaction

Relatively quick onset (several hours to days)

30
Q

How can we induce enzymes?

Is this phase I or II and is it fast or slow?

A

By increasing the amount of enzyme present for a specific action

Normally a phase I processes and usually takes days to weeks to happen

31
Q

Rate of enzyme Induction depends on what?

A

Drug and enzyme

32
Q

Give 2 examples of enzyme induction and state how these function

Are these fast or slow onset and what is the implication of this?

A

Carbamazepine and warfarin (CYP 3A4)

  • CBZ induces CYP3A4
  • CYP 3A4 metabolises warfarin

So CBZ ⬆ metabolism of warfarin which ⬇ its effect.

Patient on both drugs will most likley be taking higher doses of Warfarin. However, as this process is slow onset (days-weeks), care must be taken when one drug is stopped to prevent over thinning of blood and risk of hemorrage

33
Q

Give 2 examples of drugs that may show drug-food interactions with grapefruit juice

Explain why and a possible danger of this

A

Simvastatin and Amiodarone (long QT)

Grapefruit Juice Inhibits several CYP450 isoenzymes which ↓ the clearance of many drugs. This may lead to ↑ exposures to drug of up to 16 fold!

34
Q

What is Cranberry Juice commonly use to treat and why?

A

Used therapeutically in UTI treatment by Inhibiting bacterial adherence to urothelium

35
Q

What is the drug-food relation between cranberry juice and Warfarin?

What MUST we advise patients?

A
  1. ↓ Clearance of warfarin
  2. Enhanced anticoagulant effect
  3. ↑ Risk of haemorrhage

because It inhibits CYP2C9 isoform

Advise patients not to drink cranberry juice if on warfarin

36
Q

Drug-Drug interactions either _____ or _____ therapeutic outcome through actions on the receptors

Drug interactions can occur via different _____ or different _____

A

enhance, reduce, receptors, tissues

37
Q

Give 2 examples of agonism/antagonism acting at same receptor

A

1) Opiate analgesics and Naloxone
2) Beta blockers and Beta2 agonists

38
Q

Give 2 examples of agonism/antagonism acting at different receptors

A

1) Amlodipine and Bendroflumethiazide
2) Warfarin and Aspirin

39
Q

What is the risk of amlodipine and bendroflumethiazide being used togther?

A

amlodipine = calcium channel blocker

bendroflumethiazide = thiazide diuretic

Both act to decrease BP which can result in hypotension

40
Q

What is a non-selective drug and give an example

A

They act on one or more receptors

Eg. Antidepressants interact with many receptor subtypes:

  • adrenergic, noradrenergic, serotoninergic, cholinergic, Na channels
41
Q

Give an example of how a drug may exhibit an enhanced effect

A

Digoxin toxicity enhanced by hypokalaemia caused by a loop diuretic (e.g. Furosemide)

42
Q

Give 5 drug classes which are likley to cause drug-drug interactions

(Hint: 5A’s)

A
  • Anticonvulsants
  • Antibiotics
  • Anticoagulants
  • Antidepressants/Antipsychotics
  • Antiarrhythmics
43
Q

Drug Disease Interactions are most common in which age groups and why?

A

More common at the extremes of age ➞ Children or Elderly

Due to altered PK profile (renal and hepatic) and/or Co morbidities

44
Q

Are drug disease interactions more common with chronic medical conditions or acute illness

A

Chronic medical conditions

45
Q

Give 4 reasons why Renal Disease affects drug function

Incl drug examples

A

1) A falling GFR (acute or chronic) results in reduced clearance of renally excreted drugs:
2) Disturbances of electrolytes (esp K+) may predispose to toxicity
3) Nephrotoxins will further damage kidney function
4) CKD can affect Vd of drugs

46
Q

Give 3 examples of renally excreted drugs

A

Digoxin, aminoglycoside, antibiotics

47
Q

Give 4 reasons why Hepatic disease affects drug function

A

1) Reduced clearance of hepatic metabolised drugs
2) Reduced CYP 450 Activity
3) Much longer half lives
4) Toxicity

48
Q

What ‘classic’ drug should NOT be given to patients with liver cirrhosis and why?

A

Opiates

Even small doses will accumulate which can lead to an coma. This is because metabolism of opiods in liver is not occuring normally.

49
Q

Give 3 ways in which cardiac disease can affect drug function?

A

Falling cardiac output will lead to:

1) Excessive response to hypotensive agents
2) Reduced organ perfusion leading to reduced hepatic blood flow and clearance
3) Reduced organ perfusion leading to reduced renal blood flow and clearance

50
Q

What is an adverse drug reaction? (ADR)

A

A noxious and unintended response to a medicine that occurs at normal therapeutic doses used in humans for prophylaxis, diagnosis, or therapy of disease, or for the modification of physiologic function.

51
Q

How do we classify ADR’s?

Explain each + example

A

A-F

52
Q

Give 3 reasons why ADRs are a serious problem

A

1) They increase morbidity, mortality and healthcare costs world wide.
2) They account for around 6-7% of admissions per year here in the UK
3) They cost the NHS £466,000,000

** ADRs are thought to occur in 10–20% of hospital in-patients AND they are avoidable!

53
Q

Give 4 factors that cause high risk for ADRs

A

1) Ignorant, inappropriate or reckless prescribing
2) Polypharmacy
3) Patients at the extremes of age
4) Multiple medical problems
5) Use of drugs with narrow therapeutic indexes (↑risk of toxicity)

54
Q

Why can use of drugs near their minimum effective concentration lead to ADRs

A

Increased risk of treatment failure if metabolism increased

55
Q

How is severity of ADR’s classified?

A

Major (permanent / life threatening)

Moderate (requiring additional treatment)

Mild (trivial or unnoticeable)

56
Q

Define Pharmacovigilance

A

The science and activities relating to the detection, evaluation, understanding and prevention of ADRs or any other drug related problem

57
Q

Give 4 ways in which we can improve pharmacovigilance

A

1) Early detection of unknown safety problems
2) Detection of increases in frequency
3) Identification of risk factors
4) Preventing patients from being affected unnecesarily

58
Q

What is the Yellow Card Scheme?

A

How adverse events regarding drugs or medical devices can be reported

59
Q

How can we prevent ADR’s?

A

1) Careful patient history
2) Avoiding treatments in cohorts who are at increased risk
3) Report ADR’s using the Yellow Card scheme