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Personalised Medicine - Cardiovascular > L1 - Personalised Medicine > Flashcards

L1 - Personalised Medicine Flashcards

1
Q

What is personalised medicine?

A

Aims to customise healthcare with decisions and treatments tailored to each patient

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2
Q

How many patients do not benefit from the first drug they receive?

A

43% of diabetic patients

50% arthritis patient

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3
Q

What are the benefits of personalised medicine?

A 
Reduce trial and error prescribing
Avoid adverse reactions
Increase patient compliance
Reveal additional uses
Control costs of health care
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4
Q

What is personalised medicine currently useful for?

A

Guiding cancer therapy

Choosing cardiovascular drugs

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5
Q

What is pharmacogenomics?

A

The study of how a persons genes influence their response to medication
It is the newer term for pharmacogenetics

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6
Q

What is the common genetic polymorphism in a drug metabolising enzyme?

A

CYP450

Variations in this account for metabolism of 25% of all drugs

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7
Q

What is pharmacoepidemiology?

A

Drug effects at a population level or between populations

Increasingly important for health economic decisions

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8
Q

What % of hospital admission are due to adverse drug reactions?

A

5%

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9
Q

What 3 diseases/drugs are panel tests used for?

A

Warfarin
Heart transplant –> allomap multi gene expression
Familial hypercholesterolaemia

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10
Q

What is Warfarin used for?

A

Used to prevent clots
Metabolized by CYP2C9 enzyme
Usually dose is adjusted by trial and error –> FDA have recommended genotyping

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11
Q

What is allomap multi gene expression test used for?

A

Used in end-myocardial biopsies after heart transplant

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12
Q

What is an example of personalised medicine in cardiology?

A

Clopidogrel –> drug called Plavix

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13
Q

What does Plavix do?

A

Anti-platelet medication – stop clot formation
Blocks P2Y12 receptor
Particularly effected by SNPs

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14
Q

What is the guide to taking Plavix?

A

Clopidogrel bisulfate tablets
Plavix may not work as well in people who
- Have certain genetic factors that affect how the body breaks down Plavix
– May do genetic tests to make sure Plavix is right for you
– Take certain medicines - especially omeprazole

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15
Q

What metabolises Plavix?

A

Liver enzymes CYP2C9 metabolises Plavix to its active form

Reduced enzyme activity leads to reduced drug effectiveness

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16
Q

What is inter-individual variation?

A

Variations in concentrations of the drug at the site of action
Different responses to the same concentration of drug

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17
Q

What is pharmacokinetics?

A

Drug concentrations change with time in different regions of the body in relation to dosing

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18
Q

What is pharmacokinetics dependent on?

A

Metabolism
Excretion
Absorption `
Distribution in compartments

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19
Q

What is pharmacodynamic variation?

A

Individualised response (anti-hypertensives, anticoagulants) are adjusted by monitoring physiological endpoints

  • Blood pressure
  • Platelet function
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20
Q

In results why is it important to look at individual data?

A

Bar graph suggests no difference but actually there are hidden differences in individuals
May be attributable to age or some other factor

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21
Q

What are the main causes of variability in drug responses?

A 
Age 
Ethnicity 
Genomics 
Immunological factors 
Concomitant disease 
Drug interactions 
Body composition
22
Q

What is the drug response different in young and old people?

A

Drug elimination less efficient
GFR in newborns is 20% of the adult value
Drug metabolising enzymes are altered in newborns
More drugs in the elderly so more interactions

23
Q

How does body composition affect drug response?

A

Body composition changes with age
- Older and after mostly leading to changes in volume and distribution
GFR is normalised to body surface area

24
Q

Why is morphine not given in labour?

A

As transferred to the baby via the placenta –> causes respiratory depression

25
Q

Why is it risky to give old people heart failure drugs?

A

Cause postural hypertension more commonly in elderly patients even if plasma concentration is the same as in a younger person

26
Q

Digoxin half line in young vs old people?

A

Increases force of heart contraction
½ life in neonate = 200h
½ life in adult = 40h

27
Q

Why does ethnicity affect the drug response?

A

Variation in genetics between ethnicities

28
Q

How does hydrazine differ between different ethnicities?

A

Hydralazine (vasodilator) used for HF

Hydralazine + nitrate –> prolongs life in African Americans but not in white Americans

29
Q

The metabolism of what is different in the Chinese population?

A

Metabolise ethanol to produce a higher concentration of acetaldehyde
- Adverse effects - palpitations and flushing
Propranolol metabolism is also different

30
Q

What are the two types of genetic mutation?

A

Heritable change in DNA

Polymorphism

31
Q

What is an example of a heritable change in DNA?

A

Slow/fast acetylators - hepatic acetyl transferase

Acetylations important in some drugs but these are not used frequently

32
Q

What is an example of a polymorphism?

A

Inherited thrombophilia – SNP in Factor V Leiden (a coagulation factor)

  • Increased blood clots
  • When they travel  deep vein thrombosis
33
Q

What is a polymorphism?

A

Alternative sequence at loci within the DNA strand (allele)

SNPs are very common –> C-T most common

34
Q

What is the possible explanation for difference in propanalol metabolism?

A

Differences in beta receptors

35
Q

What is an example of an immunological factor?

A

Some people form anti-drug antibodies or allergic reaction

36
Q

What are some examples of concomitant disease?

A

Disease in kidney or liver
Pregnancy
Some diseases cause gastric stasis
Diseases that influence receptors

37
Q

How do diseases in the liver to kidney affect drug response?

A

Metabolise drugs and diseases can affect elimination profiles
Can cause prolonged or intense drug effects

38
Q

How do some diseases that cause gastric stasis affect drug response?

A

Stasis in migraine, diabetic neuropathy

Can lead to differences in how we metabolise drugs

39
Q

How do some diseases influence receptor affect drug response?

A

Familial hypercholesterolaemia –> lack of function of LDLR receptor
Homozygous form relatively resistant to statins
- Heterozygous form responds well
- New PCSK9 inhibitors useful

40
Q

What % of ADR are due to drug interaction?

A

5-20%

41
Q

What do drugs interact with?

A

Other drugs
Chemicals - grapefruit juice or herbal remedies
- Grapefruit juice regulate sCYP3A4 in the gut
Pharmacodynamic interactions – usually predictable
- E.g. diuretics (heart failure) lower plasma K+ and predispose to digoxin toxicity
- E.g. Sildenafil (vasodilator) mechanism of action potentiates organic nitrates and combination can lead to severe hypotension

42
Q

What do diuretics do?

A

Lower plasma K+ and predispose to digoxin toxicity

43
Q

What does Sildenafil do?

A

Its mechanism of action potentiates organic nitrates and combination can lead to severe hypotension

44
Q

What is Warfarin used for?

A

Used to thin the blood after clots

Balance needed or bleeding/thrombosis

45
Q

Which three polymorphisms influence Warfarin efficacy?

A

CYP2C9

VKORC

46
Q

What is the CYP2C9 polymorphism?

A

Enzyme in liver
Encodes an enzyme that metabolises warfarin allele 2 and 3
- Both slow and fast metabolisers
Metabolise it slower therefore drug concentration is higher so the warfarin dose needs to be lowered

47
Q

What is the VKORC polymorphism?

A

Protein target
Encodes the drug target of warfarin the vit K epoxide reductase enzyme
Those with G –> A in the promoter are more sensitive to warfarin
- GG is wildtype –> AA needs a lower dose

48
Q

Normal CYP2C9 polymorphism and wildtype VKORC?

A

5-7mg

49
Q

If slow metaboliser?

A

3-4 - 0.5-2mg

50
Q

If GG–>AA mutation?

A

More sensitive

0.5-2mg

Personalised Medicine - Cardiovascular (11 decks)

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