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Interaction module: Environment and genes > Week 1 > Flashcards

Week 1 Flashcards

1
Q

bioavailability meaning

A

proportion of an administered drug which reaches the systematic circulation unchanged and is thus available for distribution to the site of action

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2
Q

intravenous injection achieves what 100% bioavailability

A

all the drugs reaches the systemic circulation unchanged

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3
Q

exposure to first pass metabolism

A

can stop 100% bioavailability

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4
Q

state the different types of mucosal routes

A

submingual, buccal
nasal, eye
vaginal and rectal

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5
Q

subcutaneous injection

A

consistent absorption from small volumes

passive diffusion into bloodstream

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6
Q

4 steps of multistep model of tumourgenesis

A

initiation
promotion stage
progression
metastasis

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7
Q

list 10 hallmarks of cancer

A 
Escaping growth suppression
Activating invasion and metastasis
Sustained proliferative signalling 
Avoiding destruction by the immune system
Inflammations that can promote tumours
Genome instability and mutations
Inducing angiogenesis 
Unlimited replication 
Deregulation of cellular energy and
Resisting cell death
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8
Q

what does cancer involve

A

cancer involves activation of oncogenes
drive proliferation
also involved inactivation of tumour suppressor genes
which means the cancer cell can then escape the cell cycle arrest
and apoptosis.

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9
Q

Hypomethylation of repetitive regions causes

A

genome instability (e.g deletion, insertion)

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10
Q

what is the link between epigenetic tags and genetic changes

A

cytosine in CpG sites can be methylated which will form 5-methylcytosine. Now 5-methylcytosine is actually pretty unstable and sometimes in the genome it can undergo a spontaneous deamination. Now the structure you see after deamination is the thymine base. So methylation has given rise to a spontaneous mutation by converting a cytosine to thymine. So what this shows is that epigenetic and genetic changes sometimes do go hand in hand.

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11
Q

if Normal cells progress to hyperplasia to neoplasia and invasive cells then what happens

A

the overall global level of methylation decreases

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12
Q

But if gene specific hypermethylation at CpG islands located within the promoter will increase

A

region of genes increase

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13
Q

the epigenetic progenitor model of tumorigenesis what is it

A

the first trigger is an epigenetic abnormality but the trigger only primes the cells so they now have the potential to become cancer cells

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14
Q

Totipotent stem cells can do what

A

can give rise to any of the 220 cell types found in an embryo as well as extra-embryonic cells (placenta).

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15
Q

Pluripotent stem cells

A

can give rise to all cell types of the body (but not the placenta).

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16
Q

cancer stem cells are

A

drug resistant

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17
Q

what happens during cancer initiation

A

mutated epigenetic regulators lead to wave of epigenetic abnormalities
which trigger oncogenic cellular reprogramming (e.g. dedifferentiation)
promote the acquisition of uncontrolled self-renewal and formation of CSC

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18
Q

3 stages of epigentic management

A

Early Diagonisis
Prognosis
Prediction
Follow-up

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19
Q

are epigentic modifciations reversable

A

yes

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20
Q

DNA methyltransferase inhibitors (DNMTi)

A

prevention of aberrant DNA hypermethylation

lead to activation of these genes

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21
Q

Histone deacetyltransferase inhibitors (HDACi)

A

proven to reverse the transcriptional repression of multiple genes involved in the processes outlined such as cell cycle progression, differentiation, and apoptosis.

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22
Q

agonists

A

bind to rececptor and stimulate it

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23
Q

partial agonist

A

is an agonist that cannot elicit the same levek of biological response as a full agonist

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24
Q

example of agonist

A

salbutomol

for asthma

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25
Q

anatogonist example

A

Atenolol

used to reduce heart rate

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26
Q

partial agonist example

A

buprenorphine

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27
Q

compeitive antagonist is what

A

they compete for the same binding site as the agonist

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28
Q

non competitive agonist definition

A

the receptor binding site “fit” for the agonist, reducing agonist activity

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29
Q

examples of competitive inhibitor and what its used for

A

Atenolol

Hypertension and cardiac arrhythmia

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30
Q

Examples of therapeutic non-competitive antagonist and what its used for

A

Ketamine

used for an anaesthetic

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31
Q

Transporters function

A

they mediate the movement of specific endogenous signalling molecules and nutrients in and out of cells

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32
Q

what happens at the Metbolisim PK phase

A

where drugs can affect the activity of the liver

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33
Q

what can the induction of cytochrome P450 isoenzymes by one drug do

A

increases the rate of metabolisim
resulting in lower plasma concentrations
toxicity can occur

34
Q

Example of Pharmcokinetic Drug interactions

A

Carbamazepine (an antiepileptic drug) is a potent inducer of CYP3A4

Erythromycin (an antibiotic drug) is potent inhibitor of CYP3A4

Midazolam (a sedative drug) is a substrate of CYP3A4.

35
Q

name some drugs that are affected by P450 enzyme induction

A

Ciclosporin (immunosuppressant), also Citalopram (antidepressant)
Oral contraceptive pill (synthetic oestrogen & progestin)
Warfarin (anticoagulant)
Phenytoin (treatment for epilepsy)
Acetylcholinesterase inhibitors (e.g. Donepezil, a treatment for dementia)
Theophylline (treatment for severe asthma, Tacrolimus (immunosuppressant)
Statins (for cholesterol level control), steroids (broad immunomodulation)

36
Q

How does Opiod Analgesic drugs like codeine work

A

They work by metabolism to morphine by CPY2D6
8% of the population lack the enzyme so they cant metabolise codeine
1% have extra copies of the enzymes so they are rapid metabolisers

37
Q

Some facts about Adverse drug reactions

A

4 in 5 older people (≥ 65 years) take at least one medication
36% of older people take ≥4 medicines simultaneously - Polypharmacy
Older adults are 3 times more likely to suffer ADRs
ADRs account for 5-12% of hospital admissions for older adults
Up to 50% of older patients do not take their prescribed medicines as recommended

38
Q

Definition of Adverse Drug reactions

A

the undesirable effect of a drug beyond it’s anticipated therapeutic effects, occurring during clinical use

39
Q

Explain what it means to be “above therapeutic range”

A

it means a toxic reaction

and is treated by reducing dose

40
Q

Explain what “within therapeutic range” means

A

Its a collateral reaction

it might be unavoidable

41
Q

Explain what it means to be “below therapeutic range”

A

its a hypersuceptibility

avoid using foreknowledge of patient susceptibility

42
Q

what happens during the first dose reaction

A

its a time course related ADR

hypotension

43
Q

What occurs during a time course related ADR

A

Patients become tolerant to these reactions

Patient can continue with treatment, ADR should wear off

44
Q

What happens during late reactions

A

Risk of ADR increases with continued or repeated exposure

Implies need for long-term monitoring +/- prevention

45
Q

what occurs during a late reaction

A

Avoid use of drug in patients who are susceptible

46
Q

Patient Susceptibility ADR includes

A 
Genetic suceptibility 
Advancing age 
Sex
Specific Physiological staates such as pregnancy 
diseases 
Exogenous factors
47
Q

Normal changes due to ageing

cardiovascular give examples

A

Cardiac enlargement
left ventricular failure
Systolic hypertension

48
Q

Normal changes due to ageing

respiratory give examples

A

FEV1 and increased residual volume
susceptibility to respiratory infection
susceptibility to aspiration

49
Q

Normal changes due to ageing

endocrine give examples

A

Insulin sensitivity

Thyroid Hormone production

50
Q

Normal changes due to ageing

gastrointestinal give examples

A

Gastric acid production

Constipation

51
Q

Normal changes due to ageing

Skin/Hair give examples

A

Dry skin
wrinkles
Slower healing (ulcers/sores)
Greying hair

52
Q

Examples Drug sensitivity in older adults

A 
Receptor responses – e.g.  ß-adrenoceptor sensitivity
Altered coagulation factor synthesis
CNS becomes more sensitive to psychotropics / hypnotics
Baroreceptor response less sensitive
Renal clearance reduced
Thirst response blunted
Thermoregulation blunted
Altered immune response
Slower gastric emptying
Reduced plasma albumin
Increased ratio of adipose to lean tissue
Altered liver metabolism
53
Q

Polypharmacy ( taking more than 4 medications) facts

A

Over 65s make up about 14% of population, but consume 40% of the drug budget
4/5 of over 65s are on regular medication
1/3 of over 75s are on three or more drugs
Care home patients take an average of eight medications

54
Q

examples of polypharmacy

A

Anaemia
Depression
Glaucoma
Osteoarthritis

Osteoporosis
Rhinitis
Stroke
Venous eczema

55
Q

Pharmacokinetics can be approached with 4 main phases

A

Absorption,Distribution, Metabolism, Excretion

56
Q

The lipid solubility of a drug is important

A

drug molecules pass through the blood more readily

permeate tissues more efficiently before finding their mechanistic targets

57
Q

What is First Pass Metabolism and how does it affect orally ingested drugs?

A

The Extent of drug metabolism occurring before the drug enters the systemic circulation

58
Q

Which component of blood in particular can significantly affect the rate of drug distribution?

A

Albumin
its an abundant protein in the blood plasma
responsible for drug binding

58
Q

Which component of blood in particular can significantly affect the rate of drug distribution?

A

Albumin
its an abundant protein in the blood plasma
responsible for protein binding

59
Q

Most important site for drug metabolisim

A

Liver

60
Q

What types of enzymatic reactions normally occur in Phase II drug metabolism?

A

They normally drive the conjugation of polar
hydrophilic chemical groups
acetylation

61
Q

What is a key physiological functional outcome of the Phase II drug metabolic reactions?

A

Increased drug solubility in water to enhance elimination meaning they are retained better in the bloodstream more effectively and more eliminated.

62
Q

What does First Order Kinetics mean? What key pharmacokinetic parameter can be derived from a drug’s pattern of elimination?

A

a concentration- dependant process such that higher the concentration of drug in the body, the faster the drugs elimination.

63
Q

Why is it important to review medication use regularly in patients over 65?

A

Chronic kidney disease and decline in renal function is common in over-65s this is because

64
Q

THREE other common and important different types of molecule that can be targeted by drugs and try to give a drug example like in the case of morphine above.

A

ion channel
molecular transporters
Enzymes

65
Q

What is precision medicine

A

it is an approach for disease treatment and prevention that takes into account individual variability
in genes environment and lifestyle for each person

66
Q

what are the advantages of precision medicine

A

Improved ability to predict which treatments will work best for specific patients.
Better understanding of the underlying mechanisms by which various diseases occur.
Improved approaches to preventing, diagnosing, and treating a wide range of diseases.

67
Q

what are the challenges of precision medicine

A

where manufacturers can earn more selling these products to a large population, precision medicines do not provide such opportunity.

68
Q

Why is economic evaluation a useful tool

A

Weighs up both the cost and health outcomes from alternative technologies

69
Q

what are the 3 stages of economic evaluation design

A

comparator
health outcomes
costs

70
Q

challenges with economic evaluation

A

Lack of data with alternatives
Uncertainty
Costing methodology
Constraints and capacity within the NHS
More appraisals and the need for bespoke guidance
Dramatic pace of technological innovation
Equity/ethical concerns

71
Q

differences in outcomes

A

Treatment effect
Bias
Chance

72
Q

what is the best way to a create control

A

Randomisation

73
Q

what are the advantages of Randomised clinical trial

A

Eliminate selection bias
Balance prognostic factors
validity of statistical test

74
Q

what is an uncontrolled clinical trial

A

comparing effects and value of intervention against a control in human subjects

75
Q

what is the definition of a randomised trial

A

it is a controlled trail where the therapies are allocated by a chance mechanism

76
Q

The zelen method what are its disadvantages

A

They have not given consent but are still in the study

if they get ethics they don’t need to be informed.

77
Q

what is the rationale behind cancer treatment

A

Destroy/kill ALL cancer cells
A possible outcome is achieving complete cure

Destroy/Kill MOST cancer cells
A possible outcome is prolonging survival time

Destroy/Kill SOME cancer cells
Outcomes such as eliminating symptoms or preserving quality of life

78
Q

how is treatment efficacy assessed with a tumour response

A

Complete Response: Disappearance of all signs of disease

Partial Response: A reduction of tumour volume by at least 30%

Stable Disease :No significant change

Disease Progression: An increase of tumour volume by at least 20% or new metastases

79
Q

how is treatment efficacy assessed with a ‘survival’ time

A

Overall survival: survival time from the start of treatment
Disease-free survival: survival time prior to tumour relapse after radical treatment
Progression-free survival: survival time prior to tumour progression

80
Q

how do we know that a treatment works

A

the measures of efficacy

any need treatment needs to be compared to a standard treatment

81
Q

what is a half life

A

The time it takes for the plasma drug concentration to halve irrespective of the starting dose”

Interaction module: Environment and genes (7 decks)

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