Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Year 3- CVD > CVD Drug development: an overview > Flashcards

CVD Drug development: an overview Flashcards

1
Q

What is evidence based medicine?

A

‘integration of best research evidence w clinical expertise + patient values

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What does evidence based medicine require?

A

Requires latest scientific evidence to be applied to clinical practice

Involves assessment of research in terms of category + level of evidence

Category + level is used to define strength of recommendation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How is EBM classified?

A

1a (best)
Systematic reviews of randomised clinical trials

1b
Individual randomised clinical trials

2a
Systemic reviews of cohort studies

2b
Individual cohort studies + low-quality RCTs

3a
Systematic reviews of case=controlled studies

3b
Individual case-controlled studies

4
Case series, poor quality cohort + case-control studies

5
Expert opinion based on clinical experience

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the classes of drugs currently used to treat CVD?

A

Nitrates
Beta-blockers
Ca2+ channel blockers
Diuretics
ACE inhibitors
Angiotensin receptor blockers
Anti-arrhythmics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Example and effect of Nitrates:

A

Example:

Gylceryl trinitrate

Effect:
Stimulate NO release causing vasodilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Example and effect of Beta-blockers:

A

Examples:
Carvedilol, bisoprolol, nebivolol, atenolol

Effects
Block B-adrenoreceptors, reducing effect of adrenalin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Example and effect of Ca2+ channel blockers:

A

ex:
Verapamil, diltiazam, amlodipine
eff:
Relaxes arterial SMCs, increases vasodilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Example and effect of Diuretics:

A

Furosemide, bumetanide,
bendroflumethiazide

effects:
Act on kidney to increase salt + water loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Example and effect of ACE inhibitors:

A

Captopril, ramipril, lisinopril

effects:
Inhibits ACE, salt, water loss + vasodilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Example and effect of Angiotensin receptor blockers :

A

Valsartan, losartan, candesartan

Angiotensin receptor antagonists, increase vasodilation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Example and effect of Anti-arrythmics:

A

Amiodarone, digoxin, verapamil

Reduce electrical activity of the heart

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Example and effect of Thrombolytics :

A

Alteplase, reteplase, tenecteplase
streptokinase

Activate plasmin system, fibrin
breakdown
Anti-platelet drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Example and effect of anti-platelet drugs :

A

Aspirin, clopidogrel

Inhibit platelet aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Example and effect of anti-coagulants :

A

Wafarin, heparin, FIIa and FXa inhibitors

Inhibit clotting cascade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Example and effect of statins:

A

Simvastatin, pravastatin, atorvastatin,
lovastatin

Decrease cholesterol production,
increase LDL receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Example and effect of fibrates :

A

Bezafibrate, ciprofibrate

Shift from LDL to HDL profile

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the 3 stages of a project?

A

Drug discovery- candidate molecules chosen on basis of pharmacological properties

Preclinical development- non-human studies, toxicity testing, pharmacokinetic analysis + formulation

Clinical development- volunteers + patients, efficacy testing, side-effects + potential dangers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Steps in DRUG DISCOVERY:

A

Target identification/selection

Lead finding + optimisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Target identification/selection

A

Drug targets are functional proteins- e.g., receptors, enzymes, transport proteins e.g., ARBs
Limitations not biological by emerging adverse effects during clinical testing, cost + complexity of drug discovery + development (regulation)

20
Q

Lead finding + optimisation

A

Cloning of target protein
Assay to measure functional activity
Automated systems to allow for speed + economy
High-throughput screening of large compound libraries
Natural products, fungal, plants, bacteria e.g., antibiotics + sirolimus
Lead optimisation, complex chemistry to increase potency, selectivity + stability

21
Q

PRECLINICAL DEVELOPMENT

A

Pharmacological testing for hazardous acute effects

Preliminary toxicology testing

Pharmacokinetic testing for absorption, metabolism, distribution + elimination

Chemical + pharmaceutical development to assess feasibility of large-scale synthesis + purification as well as stability

22
Q

CLINICAL DEVELOPMENT

A

Phase 1, 2, 3 + 4

Clinical trial in its simplest form is ‘application of experimental variable (treatment to person or group of persons + observation during or following treatment to measure its effect’

Outcome measure may be death, occurrent or recurrence of morbid condition, or difference indicative of change e.g., BP measurement

23
Q

What are the types of clinical trials?

A

Uncontrolled trial- everyone gets the treatment (rarely done nowadays)

Controlled group- a treated group is compared w a control group
- Standard therapy is given to control group
- Placebo is given to control group
2 or more active treatments may be compared

Randomised controlled trial- individuals or communities are allocated randomly to each study group e.g., treatment/placebo

24
Q

List some clinical trial design issues:

A

Ethical issues- protection of human subjects

Implications of eligibility criteria- sampling

Degree of masking

Randomisation

Intention to treat analysis

Selection of interventional + comparison groups

Selection of end points

Interpretation of results

Trial duration

Selection of traditional vs equivalence testing

25
Q

Analysis+evaluation of clinical trials

A

Key experimental design issues
Bias
Internal + external validity
Analysis + presentation of clinical trials results
Interpretation

26
Q

Key design issues for human clinical trials?

A

Target population
-What groups are being investigated?
-Can sufficient number of individuals be recruited?
-Ethical approval?

How are endpoints to be defined/what data is to be collected?

Specify study protocol
-Will treatments be assigned at random?
-Sample size calculations?
-How will treatments be given?
-Will subjects be followed over time?

Analysis of data
-What statistics will be used to summarise the results?
-What statistical tests will be used for hypothesis testing?

Interpretation + biological/clinical significance of the results obtained

Sources of bias (systematic error) in clinical studie

27
Q

What are the different types of bias?

A

Selection bias
Performance bias
Attrition bias
Detection bias
Reporting bias

28
Q

Selection bias

A

Systematic differences between baseline characteristics of the groups that are compared

29
Q

Performance bias

A

Systematic differences between groups in the care that is provided, or in exposure to factors other than the interventions of interest

30
Q

Attrition bias

A

Systematic differences between groups in withdrawals from a study

31
Q

Detection bias

A

Systematic differences between groups in how outcomes are determined or measured

32
Q

Reporting bias

A

Systematic differences between reported + unreported findings

33
Q

What validates an investigation?

A

Internal Validity:
study is internally valid if the study conclusions represent the truth for the individuals studied bc the results were not likely due to the effects of chance, bias or confounding

External Validity: (generalizability) = study is externally valid if the study conclusions represent the truth for the population to which the results will be applied bc both the study populations + the reader’s populations are similar enough in important characteristics

34
Q

Analysis and presentation of clinical trial results

A

Clinical trials contain 4 main types of figures = flow diagrams, Kaplan-Meier plots, forest plots + repeated measures plots

35
Q

Interpretation- what factors can affect interpretation of clinical trials from conception to dissemination of the results

A

Investigator/author- inadequate power, multiple testing errors, biases, conflicts of interest, combined endpoints, noninferiority trials

Reviewer- inadequate expertise, bias, poor quality review

Editor- publication bias, impact + priority

Practitioner- bias, advertising

Media/public- institutional hype, media hype, limited expertise, competing interests

Other investigators- over-intepreted meta/mega-analysis

36
Q

How can imaging of CVD help diagnosis/ drug development?

A

Heart- cardiac function, perfusion + contractility
Assess non-invasively by US, SPECT, PET + MRI
Arterial walls- narrowing or arterial walls + Ca2+ deposition
Molecular level- cellular + molecular level detection of pathways of relevance to disease

37
Q

Why consider imaging for CVS drug development?

A

Image, track + quantify molecular biomarkers not amenable to biopsy e.g., heart + vasculature
Effectiveness of new treatments can be determined w smaller patient populations + shorter trials

38
Q

Surrogate endpoints

A

= “a surrogate endpoint of a clinical trial is a laboratory measurement or physical sign used to substitute for a clinically-
meaningful endpoint that measures directly how a patient
feels, functions or survives. Changes induced by a therapy on
a surrogate endpoint are expected to reflect changes in a
clinically-meaningful endpoint”

39
Q

What evidence is needed for imaging to be a surrogate for clinical endpoints

A

Measure changes in plaque volume/burden
Measure changes in plaque composition
Be reproducible + repeatable
Correlate w clinical outcome

40
Q

Examples of drugs used

A

Proteins
Antibodies
Oligonucleotides

insulin/tPA

41
Q

TARGETING CHOLESTEROL HOMEOSTASIS: PCSK9 inhibitors

A
  • PCSK9 targets LDL
    receptors for
    degradation
  • Decreases the ability
    to uptake cholesterol in
    the liver and remove
    from the circulation
  • PCSK9 mAbs prevent
    LDLR degradation,
    promote recycling and
    cholesterol uptake
  • PCSK9 timeline for drug
    development
  • Incredibly short discovery phase
    and development of PCSK9
    inhibitors
42
Q

Phase 1 of clinical trial:

A

A small number of people, who may be healthy volunteers, are given the medicine.
The drug is being trialled in human volunteers for the first time.
Researchers test for side effects and calculate what the right dose might be to use in treatment.
Researchers start with small doses and only increase the dose if the volunteers do not experience any side effects, or if they only experience minor side effects.

(NOT RANDOMISED)

43
Q

Phase 2 of CT:

A

The new medicine is tested on a larger group of people who are ill. This is to get a better idea of its effects in the short term.

44
Q

Phase 3 of CT

A

Carried out on medicines that have passed phases 1 and 2.
The medicine is tested in larger groups of people who are ill, and compared against an existing treatment or a placebo to see if it’s better in practice and if it has important side effects.
Trials often last a year or more and involve several thousand patients.

45
Q

Phase 4 of CT:

A

The safety, side effects and effectiveness of the medicine continue to be studied while it’s being used in practice.
Not required for every medicine.
Only carried out on medicines that have passed all the previous stages and have been given marketing licences – a licence means the medicine is available on prescription.

Year 3- CVD (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions