Case 1- clinical reasoning and Pharmokinetics

Question 1

Clinical reasoning

Answer 1

The process by which you gather information from patient presentation, process the information, come to an understanding of the patients problem, plan and implement interventions with the patient, evaluate outcomes, and finally reflect and learn from the process.

Question 2

System 1- clinical thinking

Answer 2

Impulsive and voluntary, its our first impression and influences system 2

Question 3

System 2- clinical reasoning

Answer 3

Slower and more conscious. We generate hypothesis about the patient and then try to prove/ disprove them in parallel to history and examination

Question 4

Deductive clinical reasoning

Answer 4

Proposing a general rule and then seeking to disprove or prove it, so you get a specific conclusion. Problem: rule could be necessary but not sufficient.

Question 5

Hypothetical deductive reasoning

Answer 5

We use clinical reasoning skills to propose a hypothesis then either prove or disprove it through examination, we come up with the most likely diagnosis.

Question 6

Dual case deductive reasoning

Answer 6

Use system 1 with pattern recognition and thinking of your initial hypothesis, use system 2 to refine our conclusions.

Question 7

Worse case scenario deductive reasoning

Answer 7

Useful when there’s lots of information, you can then try to rule this out. The worse cases scenario will differ between different people depending on risk factors.

Question 8

Mistakes in clinical reasoning

Answer 8

• Anchoring which is relying too much on the little information we are given.
• There’s also search satisficing, when we find a convenient answer that fit’s we stop searching.
• Confirmational bias, we think of a hypothesis and only search for information that supports it and doesn’t refute it.
• Heuristics, using rules of thumb and mental shortcuts
• Cognitive miser function, reverting to system 1 in order to save energy i.e. if you are busy.

Question 9

Volume of distribution (VD) equation

Answer 9

Vd= D/Co

D is drug dose and Co is initial concentration

Question 10

Using a graph to work out Vd

Answer 10

To calculate Co and VD from the dose, you would draw a line graph with time on the X axis and plasma concentration on the Y axis. We can then record the known plasma concentration of the dose after certain time periods on the graph. We then extrapolate backwards to t=0 in order to get the Co. You can then use the equation Vd= D/Co to work out the Vd.

Question 11

Half life calculation

Answer 11

To calculate half-life you measure the time taken for any plasma concentration to half, it doesn’t matter which plasma concentration you choose the half life will be consistent. Can also be calculated by using t1/2 = 0.693/Kel

Question 12

Clearance equations

Answer 12

Cl= Kel x Vd
Cl = (0.693/ T1/2) x Vd

Question 13

Clearance

Answer 13

The volume of plasma that has been cleared of the drug per unit time (clearance of plasma). Every hour the body removes the amount of drug that is found in “X” L of drug.

Question 14

Volume of distribution

Answer 14

This is the volume of a fluid that a drug would need to be dissolved into, to account for the dose needed to produce a certain plasma concentration. A drug given with a dosage of 100mg has a measured plasma concentration of 10 mg/l. This means that the volume distribution would be 10L

Question 15

What would make a half life smaller

Answer 15

If the clearance of the drug is higher, the half life will be smaller as its more quickly removed from the system

Question 16

How blood flow affects drug absorbtion

Answer 16

Drugs will be more quickly distributed to areas of the body that receive large amounts of blood flow (e.g. heart, kidneys) than to areas that receive little blood flow (e.g. skin, adipose).

Question 17

How receptor effect drug response

Answer 17

If the drug has little affinity for the receptors it will be given at a higher dose which may cause adverse side effects. If two drugs are competing for the same binding site, they will displace each other leading to potential toxicity

Question 18

Other factors that effect drug absorption

Answer 18

1. Physiologically, a drug’s absorption is enhanced if there is a large surface area available for absorption (e.g. villi/microvilli of intestinal tract) and if there is a large blood supply for the drug to move down its concentration gradient.
2. The presence of food/other medications in the stomach may impact drug absorption – sometimes enhancing absorption and other times forming insoluble complexes that are not absorbed (it depends on the specific drug).
3. Some drugs are inactivated before they can be absorbed by enzymes, acidity, bacteria, etc.

Question 19

Fast metabolisers of drugs

Answer 19

Possess a wild type enzyme which has normal activity. There will be a lower plasma concentration of the parent drug and higher concentrations of the metabolite. Generally they have a normal therapeutic response.

Question 20

Slow/ poor metabolisers

Answer 20

Posses either a defective enzyme which has reduced activity or do not express the enzyme at all. Higher plasma concentration of the parent drug, lower concentration of the metabolite. Leads to a bigger response, may need a reduction in drug dose.

Question 21

Zero order kinetics

Answer 21

If following administration, the metabolising enzymes become saturated, then the rate at which drug plasma concentration reduces will be linear as the enzymes are working at max capacity. The rate at which drug levels decline is independent of plasma concentration. Drugs which are zero order are more likely to produce toxic plasma concentrations and cause adverse effects. Straight line going down a diagonal

Question 22

First order kinetics

Answer 22

The greater the dose, the more metabolising enzymes there are and the greater the rate the drug is removed. The curve is steeper with higher drug plasma, plasma drug levels decline at a rate proportional to plasma concentration.

Question 23

Loading dose (D)

Answer 23

The initial dose of a drug

Question 24

Dosing rate

Answer 24

The rate at which the dose of the drug must be administered to maintain the desired plasma concentration of the drug

Question 25

What does Vd depend on

Answer 25

Drug permeability across membrane, binding with compartments (accumulation within tissues) and pH partition. If the Vd of the drug is near the body’s water content it means that it is highly water soluble. If the VD is very high it is likely that the drug is accumulating in cells and there is less in the plasma.

Question 26

Steady-state

Answer 26

The equilibrium point where the amount of drug administered exactly replaces the amount of drug secreted, its achieved between 4 and 5 drug half life’s

Question 27

Steady state equation

Answer 27

Steady state concentration (Css)= (Bioavailability x Dose) / (Interval dosing x Clearance)

Question 28

Loading dose to achieve a steady state

Answer 28

When its desirable to rapidly achieve the therapeutic range of a drug, so they can quickly cause their effect. There is an increased risk of overshooting the therapeutic range with risks of adverse effects

Question 29

Loading dose equation (steady state)

Answer 29

Loading dose = Vd x desired Css (steady state plasma concentration)

Question 30

Maintenance dose

Answer 30

Is used once the steady state drug concentration is achieved, subsequent doses only need to replace the amount of the drug lost to metabolism and excretion

Question 31

Maintenance dose equation (steady state)

Answer 31

Maintenance dose= clearance x desired Css

Question 32

The rationale for loading doses of drugs

Answer 32

If the drug is administered via IV or continuous infusion then the steady state is achieved and the plasma concentration of the drug is within the desired therapeutic range. If a drug is administered at high doses with large intervals, there will be periods of overshooting and undershooting which can cause adverse side effects. You should therefore do a sufficient dose at close time intervals. The steady state is not immediately achieved after the first dose.

Question 33

How genetic variation affects response to drugs

Answer 33

Fast metabolisers and slow metabolisers. Also when there is polymorphic variation in the expression and activity of drug metabolising enzymes, there will be variation in their ability to metabolise drugs

Question 34

How being elderly affects drug metabolism

Answer 34

• Elderly people may have compromised cardiovascular function and therefore reduced blood flow to the GI tract. This would reduce the ability of drugs to be picked up by the blood steam following absorption
• In elderly patients lean body mass tends to be less so standard dosing per Kg will produce a higher plasma concentration.
• Body fat increases in elderly patients meaning there are more fat reservoirs for lipid soluble drugs.
• Liver function tends to be reduced in elderly patients, therefore metabolic phase 1 oxidation reactions are slowed, this means there is reduced drug metabolism.

Question 35

How pregnancy affects drug absorption

Answer 35

• In pregnancy total body water (TBW) increases, this shifts the equilibrium away from plasma protein bound drugs, towards more drugs being unbound in the plasma. As there are more free drugs in the plasma, more of the drug can now be removed be excretion.

Question 36

How organ damage affects drug absorption

Answer 36

• Bowel surgery, migraines and cardiac failure are all associated with problems of decreased absorption
• Cirrhosis of the liver effects liver blood flow, meaning drugs have a longer half life as drugs are metabolised at a lower rate and remain in the body for longer.

Question 37

How neonates affect drug absorption

Answer 37

• Neonates have a high TBW (total body water) of around 80%, drugs will have a high volume of distribution meaning a higher dose will be required to achieve desired plasma concentrations.

Question 38

How is social class classified

Answer 38

A group of people with similar status sharing comparable levels of power and wealth. Can be classified with the socio-economic classification which consider economics, cultural and social factors. You get split into 7 groups

Question 39

Health inequalities

Answer 39

Systematic differences in health between different groups within a society, such as social class/ socio-economic status/ deprivation or ethnicity. The lower a persons social position the worse their health is likely to be. This affects everyone in society not just the poorest. I.e. doctors will have better health then teachers who will have better health then waiters

Question 40

How location effects mortality

Answer 40

People in south west have a lower mortality then those in the North East, particularly bad when comparing people in lower classes. People in more deprived areas have higher infant mortality, childhood obesity and mental illness

Question 41

Why does disease variation exist between different ethnicities

Answer 41

Social factors and where they are placed within society. I.e. structural racism and because they are more likely to have low paying jobs.

Question 42

What causes health inequalities

Answer 42

Social determinants, health behaviours and psychosocial factors

Question 43

Social determinants of health inequalities

Answer 43

The conditions in which people are born and grow up in. Can be housing, health and care services, water and sanitation, unemployment, working environment, education, agriculture and food production.

Question 44

Inverse care law

Answer 44

People who need the most care often require the least

Question 45

Health inequalities- health behaviours

Answer 45

Alcohol consumption, smoking, drug use, diet or exercise. Can be due to adverse psychological characteristics or because they are more culturally acceptable

Question 46

Health inequalities- psychosocial factors

Answer 46

How social inequalities make people feel. People may feel more dominant. Has a biological effect i.e. being lower class may raise cortisol level and lead to chronic stress. High stress jobs (among those who are worse paid) can lead to obesity.

Question 47

Epidemiology

Answer 47

The study of the distribution and patterns of health and disease

Question 48

Mortality

Answer 48

The number of deaths in a given area or time for a particular cause

Question 49

Incidence

Answer 49

The frequency or rate of a particular disease

Question 50

Prevalence rate

Answer 50

The number of people in a population who have a disease at a certain time

Question 51

Demographic information- population census

Answer 51

Collecting data from all the people in a certain population, either the entire country or part of it. It occurs at regular intervals and is organised by the government. The census is then published, people legally have to cooperate and provide the information.

Question 52

Demographic information- registration

Answer 52

Birth certificates, death certificates and marriage certificates. Required by law to complete them

Question 53

Demographic information- sample survey

Answer 53

Collected from a sample of individuals instead of the whole population, care should be given to ensure its representative

Question 54

Evidence based practise

Answer 54

The idea of explicitly using evidence when making decisions about the care of a patient

Question 55

The 5 steps of evidence based medicine

Answer 55

• Ask a clinical question
• Acquire the best evidence
• Appraise the evidence- examining research to assess its trustworthiness, value and relevance
• Apply the evidence
• Assess your performance

Question 56

Importance of evidence based medicine

Answer 56

Has made medicine safer and more effective then medication based on superstition and folk law.

Question 57

Where to find evidence based practise

Answer 57

Knowledge can quickly go out of date so you have to critically assess knowledge. Peer reviewed papers are more reliable as well as sources that are cited a lot. Recognised organisations are very reliable as they are reviewed by peers and updated regularly. Textbooks can go out of date

Question 58

Evidence based triad

Answer 58

Combines evidence, patient values and clinical expertise

Question 59

Case control study

Answer 59

Both exposure and outcome (disease) have occurred before the start of the study. The study goes backwards from effect to cause. It uses a control or comparison group to support or refute an inference.

Question 60

Cohort study

Answer 60

Two or more groups of people are selected on the basis of differences in their exposure to a particular agent, i.e. a vaccine or surgical procedure. The groups are then followed up to see how many in each group develop a particular outcome. The follow up period is measured in years or decades. Can be used to study incidence, causation and prognosis.

Question 61

Cross-sectional study

Answer 61

Involves looking at data from a population at a specific point in time. Can be current or retrospective. Observational or descriptive in nature, you cannot use them to determine the cause of something. They are often inexpensive and fast. It is often used as a platform for further research.

Question 62

Randomised control trial

Answer 62

Aim to compare doses or treatment in two or more groups. Participants are randomly assigned to their group and matched for factors (age and sex) for comparable results. Questions asked are better if they are interventions, i.e. is this drug better than a placebo?

Question 63

Systematic review

Answer 63

Overviews of primary research that is focused on a question which aims to identify, appraise, select and synthesise all high quality research relevant to that question. The Cochrane collaboration is an independent group of specialists in healthcare who create high quality systematic research.

Question 64

Meta-analysis

Answer 64

Provides a systematic review of a quantitively (statistical) estimate of overall benefit. Aims to be balanced and impartial.

Question 65

Level 1= hierarchy of evidence

Answer 65

Meta analysis
Systematic reviews of randomised control trials
Randomised control trials

Question 66

Level 2= hierarchy of evidence

Answer 66

Systematic reviews of case control and cohort study
Case control studies
Cohort studies

Question 67

Level 3= hierarchy of evidence

Answer 67

Evidence from non-analytic studies i.e. case reports

Question 68

Level 4= hierarchy of evidence

Answer 68

Expert opinion

Question 69

Development of guidelines by NICE and SIGN

Answer 69

Based on the best available evidence which has been heavily scrutinised. They are routinely updated as more evidence becomes available. The evidence is scrutinised by a wide range of people from practitioners to family members. The guidelines are then reviewed again before they are published.

Question 70

Challenges of applying evidence based knowledge

Answer 70

Evidence can be unclear and contradictory, for example different studies may go against each other. Side effects may not be immediately obvious. It may be something else which is causing the change and not the thing which is being investigated. Long process. Patients may not give all the information in a history; in a trial you are dependent on the reliability of the volunteers. How do you determine if a trial is statistically significant? Hard to do trials on a niche illness or disability. Doctors trying to avoid liability. Evidence may not be in line with the patients own beliefs. Sponsorship behind certain research papers causing conflict of interest. Some papers have to be paid for so less people can access it. Media bias, for example, the MRI scandal.

Question 71

Information uncertainty

Answer 71

Uncertainty related to lack of knowledge, talk to a more senior colleague or do your research

Question 72

Uncertainty on how we interact

Answer 72

May not feel like we have a good relationship with the patient

Question 73

Intrinsic uncertainty

Answer 73

Uncertainty related to the world we live in and the lack of control we have other it. For example, how a disease will progress and why someone is so affected by pain.

Question 74

Clinical uncertainty

Answer 74

We need to know how to manage our own and our patient’s uncertainty. Important to talk through it,.