Lecture 42 - Pharmacogenetics Flashcards
What are genomics?
relating to the genome i.e. total DNA/RNA
what is pharmacokinetics?
What the body does to the drug
What is Pharmacodynamics?
What the drug does to the body
What is stratified medicine?
Selecting therapies for groups of patients with shared biological characteristics
What is personalised medicine?
Therapies tailored to the individual
what is Germline?
Hereditary
What is meant by somatic?
Acquired, in non-germline cells, not hereditary
Give 5 general types of genetic variations that affect drug action:
1) gene amplification
2) single nucleotide polymorphisms
3) deletions and insertions
4) translocations
5) promoter polymorphisms
What is the most common, life-limiting, recessively inherited disease in the UK.
Cystic Fibrosis
What is the prevalence of cystic fibrosis in the uk?
Prevalence of 1/2500 newborns in the UK
What is the calculated carrier frequency of Cystic fibrosis?
1/25
What causes 75% of UK cases of Cystic fibrosis?
F508del in CFTR gene causes 75% of UK cases
What is Ivacaftor?
A CFTR potentiator
What age is Ivacaftor available from?
Available to patients from 6 years of age
What test must you have to use Ivacaftor?
Must have had a sweat chloride test
What are single nucleotide polymorphisms?
A common type of genetic variation
May change protein structure/activity e.g. missense changes
How do genetic variations affect drug action?
they change proteins used in absorption, activation, targets, catabolism and excretion of drugs
What are the two broad effects of genetic variations on drug affect?
1) drug inactivation leading to a poor/ no response
2) over-active drug resulting in excess toxicities and adverse reactions
How does autosomal recessive affect taking drugs ?
most severe side effects seen in those homozygous for the variant, heterozygote less/unaffected
How does autosomal dominant affect taking drugs ?
single copy of the variant is enough to cause the problem
What is X - linked recessive?
males carriers of the variant at risk
What is mitochondrial inheritance?
From mothers only
What is the drug metabolic pathway?
Absorption
Activation
Altered target
Catabolism (breakdown)
Excretion
What are the consequences to getting the drug diagnosis wrong?
Inactive drug – poor / no response
Over-active drug – excess toxicities (adverse reaction)
Financial costs to Health Services
