Introduction to Healthcare Science Flashcards
(229 cards)
1
Q
What is the difference between a drug and a medicine?
A
- A drug is a substance that alters normal physiological function
- A medicine is the means by which drugs are delivered to the sire of action in the body
2
Q
Difference between pharmacology and therapeutics?
A
- Pharmacology is the study of drugs and their affects
- Therapeutics is the treatment of diseases
3
Q
What is pharmacodynamics?
A
How the drug acts
4
Q
What is pharmacokinetics?
A
How the body acts on the drug
5
Q
What are the main routes of administration?
A
- Enteral (oral)
- Nasogastric
- Sublingual
- Controlled release
- Rectal
- Parenteral (IV)
- Skin
- Eye
- Lungs
- Nose
6
Q
What is the therapeutic index?
A
- Ratio between lethal dose and therapeutic dose
- The higher the index, the safer the drug (How close is the safe dose to the toxic dose)
7
Q
What are the main stages to consider in pharmacokinetics?
A
Absorption
Distribution
Metabolism
Excretion
8
Q
How is the duration of action of a drug measured?
A
Half life
9
Q
What is a drugs half life?
A
Time taken for the concentration of the drug in the blood to decrease by half
10
Q
How can we influence a drugs duration of action?
A
Modified release, controlled release, slow release
11
Q
Advantages of controlled release drugs?
A
- Less dosage frequency and more patient adherence
- Reduce incidence of adverse effects
12
Q
Disadvantages of controlled release drugs?
A
- Expensive
- Lack of standardisation
13
Q
What is a drugs bioavailability?
A
The percentage or fraction of the administered dose which reaches the systemic circulation of the patient
14
Q
What are the factors affecting bioavailability?
A
- Dose form
- Chemical form
- First pass metabolism effect
15
Q
How is drug distribution measured?
A
Two compartment model (blood and tissues)
Volume of distribution is a theoretical concept that measures the extent to which a drug moves into the tissues
- Large volume of distribution most in the tissue
- Small volume most in blood
16
Q
How is drug elicitation measured?
A
Described by clearance
- Clearance is the volume of plasma completely cleared of drug per unit time
17
Q
Where does drug elimination occur?
A
Major site is the liver but also happens in the GI tract, kidneys and lungs
18
Q
Where does drug excretion occur?
A
- Major site is the kidney but also GI tract, saliva, sear, breast milk
- If GI tract, sometimes reabsorbed
19
Q
How long does it take to reach a steady state of drug concentration in blood?
A
Usually around 5 half lives and the same to go back down
20
Q
Why are modified release drugs better?
A
Modified release would hopefully show less harsh peaks so less likely to go into the toxic dose or dipping into the sub-therapeutic level
21
Q
What needs to be considered when choosing the right route of administration?
A
- System or local
- Speed of action
- Duration of action
- Bioavailability
- Accuracy of dose
- Adverse effects: some routes will have more than others
- Patient status: do they need to be able to swallow, does it need injection
22
Q
What is drug clearance?
A
- Clearance is the volume of plasma completely cleated of drug per unit time
- Cp – concentration of drug in plasma
23
Q
What is drug metabolism?
A
- Changes one chemical compound into another
- Usually makes molecules more water soluble to enable excretion by the kidney or biliary system
- Usually changes drugs into less active agents
24
Q
What are the two phases of liver metabolism?
A
Phase 1
- Catalysed by cytochrome p450 enzymes by oxidation, hydrolysis reduction etc – enhancing the solubility
- Often still chemically active
Phase 2
- Conjugation by adding a glutathione, methyl or acetyl group
- More water soluble and easier to excrete
- Less active or inactive
25
Do drugs always undergo both stages od liver metabolism?
Drugs may undergo only one of these phases or both- not a particular order
- E.g. Aspirin: Phase 1 – hydrolysis to salicylic acid and Phase 2- conjugation with glycine or glucuronic acid
Pro drugs such as Enalapril
- Hydrolysis of its ethyl ester (phase 1_
- Metabolite is active drug but poorly absorbed when giving orally
26
Give an example of a drug with a toxic metabolite?
Paracetamol
27
How is paracetamol metabolised?
```
Phase 1 to toxic metabolite
- The OH on the benzine ring is metabolites (loses H) to form NAPQI which directly attacks cells causing liver injury
Phase 2 to non-toxic metabolites
- Conjugation with glutathione
- Stops build-up of toxic metabolites
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28
What happens when take too much paracetamol?
If take too much, there is not enough glutathione to prevent toxicity for phase 2
29
What is the treatment for parceatamol overdose?
Treatment gives acetylcysteine within 8 hours (donor for glutathione)
30
What is first pass metabolism?
If a drug is extensively metabolised in the liver, we say it undergoes first pass metabolism so very little drug is actually absorbed into the blood – affects the bioavailability
31
Gice an example of a drug that has first pass metabolism?
E.g. propranolol needs high dosage orally because of first pass metabolism. If given on IV then first pass metabolism doesn’t occur and can have a much lower dosage
32
What kinds of administration acids first pass metabolism?
IV
Sublingual
Buccal
33
What is the effect of hepatic impatient on drug metabolism?
- Needs to be severe to affect it
- Can lead to accumulation and toxicity
- To drug being less effective
34
What other effects are caused by reduced liver metabolism?
- Reduced clotting
- Fluid overload
- Hepatic encephalopathy
- Reduced protein binding
35
What tests are used to assess hepatic function?
```
Bilirubin
- By product of red blood cells, conjugation in liver, raised levels lead to jaundice, first sign or problem
- Alkaline phosphatase
- Aminotransferases
- Albumin whole blood tests
- Prothrombin time
Urine
- Bilirubin- indicative of hepatic obstruction
```
36
Are all drugs metabolised prior to excretion?
No
| E.g. Aminoglycosides antibiotics – want it to get to the kidneys before being metabolised
37
What are the main stages of excretion in kidneys?
Glomerular filtration
- Small drugs pass easily from blood through glomeruli
- Large drugs will not be filtered
Tubular secretion
- Active process against chemical gradient
- 2 carrier transport system- basic drugs and acidic drugs
Tubular reabsorption
- Passive
- Transported back into blood along with water to maintain fluid volume
38
What is renal clearance?
It is the amount of drug removed by kidney over specific time
39
How does renal clearance affect dosage?
- Extent of clearance will determine dose needed
- Highly renally cleared drugs with narrow therapeutic index eg digoxin and gentamicin will need careful dosing in renal impairment
40
How is renal function assessed?
- Uses creatinine blood levels
- Break down product which is removed at a fairly constant rate
- Measuring levels of creatinine in blood and should be fairly level and if rise than the kidneys aren’t working properly
41
What can affect renal assessment by creatine levels?
- It is formed by muscle breakdown so strenuous, high meat ingestion or low muscle mass could impact the levels
- If have low levels of muscle mass and the levels look normal- suggests problem as should be higher than normal
42
What is E-GFR?
- Another way to measure renal function
- Uses serum creatinine, age, sex and race
- Based on Modification of Diet in Renal Disease (MDRD) formula
- e-GFR and creatinine clearance only estimate of renal function monitor levels in critical drugs
43
Why should renal function be assessed for dosage?
Adjust the dosage based on the level of renal impairment as it will affect excretion
44
What drugs can cause renal and hepatic impairment?
- E.g. ACE inhibitors affect renal and anti-epileptic drugs affect hepatic
- NSAIDs renal impairment and increased bleeding Risk in severe hepatic impairment with reduced clotting factors
- Paracetamol in overdose causes direct hepatic damage
45
What are drug interactions?
When two or more drugs interact in such a way that the effectiveness or toxicity of a drug is affected
46
What is the effect of drug interactions?
They can be harmful by increasing drug toxicity or reducing drug efficacy. They can also be beneficial by increasing blood levels or additive therapeutics
47
What percentage of patients experience drug interactions?
```
Potential interactions
- Hospital 2.2 – 30% of patients
- Community 9.2- 70.3% of patients
Actual interactions
- Much lower
- 0.5-1% of patients
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48
Who are at higher risk of drug interactions?
- Elderly people: take more medication, renal function deteriorates, other diseases
- People taking more drugs
- Impaired renal or hepatic function
- Certain genetic characteristics
- Concomitant disease
49
When are drug interactions usually occur?
Drug is being started or stopped as the body can adapt to changes
50
What else affects drug interactions?
Affected by the drugs half-life, mechanism of interaction, ‘as required’ drugs (e.g. pain killers)- if they’re not taken continually than the body doesn’t adapt
51
What are the main types of pharmacodynamic interactions?
Additive interactions
Antagonistic
Disturbances in electrolyte balance
52
What are additive interactions?
- Pharmacological effect (if they act on the same site/function, will likely work together)
- Same toxicity- both cause liver toxicity than can add together and increase damage
53
What are antagonistic interactions?
Opposite action of the drugs – cancel each other
54
How do disturbances in electrolyte balance cause drug interactions?
E.g. Digoxin has a narrow therapeutic window and can become more sensitive to it if there is a change in electrolyte balance by something like a diuretic
55
What are pharmacokinetic drug interactions?
Drugs may not be related in their actions but can affect the way the drug is handled by the body rather than its mechanism
56
What two ways can drug interaction affect absorption?
Rate is affected by the time to reach site of absorption
- This is rarely of clinical importance as total amount absorbed is usually unchanged
Extent of absorption
- Formation of complexes- drugs form a complex in GI tract which is insoluble and can’t be absorbed
- Changes in pH of the stomach e.g. antacid- this could affect the ionisation of the drug (charge more difficult to pass through, reducing level of absorption)
57
What are the main types of drug interactions which effect distribution?
Displacement interactions
- Some drugs are bound to plasma proteins
- Only free component is pharmacologically active or metabolised/excreted
- One drug can displace another
58
What is meant by the effect od drug interactions being transient?
- Body can adapt to situations
- If the level of free drug increases (active amount of drug) but it will be metabolised and extracted to will return to normal
- Body will return to normal in a few days
59
When are drug interactions more likely to be a problem?
if a drug is as required e.g. warfarin and aspirin. If regular, aspirin displaces the warfarin but body metabolites warfarin. If as required than the equilibrium is not re established
60
Why is phase 1 metabolism a common area of drug interaction?
P540 enzymes are sensitive to induction and inhibition and many drugs are metabolised by these enzymes
61
How do enzyme inducing drugs affect metabolism?
Enzyme inducing drugs: barbiturates, tobacco, carbamazepine etc. Reduced effect of another drug taken as it will stimulate the body to produce more P540 enzymes and break down other drugs - reduced effect of other drugs
62
How do enzyme inhibiting drugs affect metabolism?
Enzyme inhibition such as allopurinol, erythromycin. These drugs are blocking the metabolism of other drugs and the effect will be seen more quickly – increased effect of other drugs
63
What are the three processes where drug interactions can occur in excretion?
Glomerular filtration
- Partially controlled by prostaglandins – of drug affects this such as NSAIDs then will affect rate
Tubular reabsorption
- Only non-ionised form of drug can diffuse
- Depends upon drug pKa and urinary pH
Tubular secretion
- Competition for the excretory mechanism
- One drug will therefore be retained in the body- impact the levels of the drug and cause a build up
64
How should a patient be monitored for pharmacodynamic interactions?
- Same pharmacological effect: Monitor the therapy, more adverse effects
- Same toxic effects- monitor the adverse effects
- Antagonistic effects- monitor effects of therapy
- Disturbances in electrolytes- monitor electrolytes, monitor adverse effects
65
How should a patient be monitored for pharmacokinetic interactions?
```
Increased blood levels
- Look for signs of toxicity
- Adverse effects more likely
Decreased blood levels
- Look for signs of decreased effectiveness
- Is the condition controlled?
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66
How does the BNF classify the severity of interactions?
- Severe: the result may be life threatening or have a permanent affect
- Moderate: The result could cause considerable distress or partially incapacitate a patient. They are unlikely to have life threatening or result in long term effects
- Mild: The result is unlikely to cause concern or incapacitate the majority of patients
- Unknown: Used for those interactions that are predicted, but there is insufficient evidence to hazard a guess at the outcome
67
How does the BNF classify levels of evidence?
- Study: For interactions where the information is based on formal study including those for other drugs with the same mechanism e.g. known inducers, inhibitors
- Anecdotal: Interactions based on either a dingle case report or a limited number of case reports
- Theoretical: Interactions that are predicted based on sound theoretical considerations. The information may have been derived from in vitro studies or based on the way other members in the same class act
68
How do drugs interact when they have a similar pharmacology?
When two drugs have a similar pharmacology are more likely to impact each other. Sometimes this is good and work together but sometimes too much of an effect
69
How do drugs interact when they have a similar toxicity?
Patients are more likely to experience toxic effects if they take two drugs with similar adverse effects
70
How do drugs interact when they have antagonistic effects?
Medicines with opposite actions will cancel each other out
71
How do drugs interact when there are disturbances in electrolyte balance?
Patients can experience adverse effects if there is an imbalance in their electrolytes. Other medications like diuretics can cause this imbalance. This can change the effect or toxicity of the drugs e.g. digoxin which has a very narrow therapeutic window, changing electrolyte makes it reach toxic levels
72
How do drug interactions occur by distribution displacement?
- Plasma proteins have specific binding sites that a drug can attach to but rugs have to free to be active. Some of the drug will be released to replace the free drug when it is cleared from the body
- Drug interactions occur when both drugs are competing for the same binding site
- The drug with the greater attraction for the protein will displace the drug with lesser attraction.
- The impact of this is to increase the proportion of free drug in the blood stream which increases the therapeutic effect of the drug. - the effects are short lived as the body restores the equilibrium.
- Many interactions are now known to be more complex
73
How do drug interactions occur by enzyme induction?
- One drug induces more enzymes which metabolise another drug
- This leads to increased metabolism which decreases the amount of the other drug in the body and sub therapeutic levels
- Synthesis of enzymes takes time so the impact of this type of interaction will take two to three weeks to be seen.
74
How do drug interactions occur by affecting glomerular filtration?
- The blood flow to the kidney determines the rate of glomerular filtration. The blood flow to the kidney is controlled by prostaglandins. Drugs which interfere with prostaglandin synthesis will have an impact on blood flow to the kidney and hence to GFR
75
How do drug interactions occur by affecting tubular reabsorption?
- Small molecules pass into the glomerular filtrate and can diffuse back into the blood and be retained by the body.
- The rate of diffusion back into the blood is dependent upon the ionisation status of the drug.
- The non-ionised form of drug will be more likely to diffuse back into the blood.
76
What affects the ionising status of a drug?
The ionisation status depends upon drug pKa and the pH of the glomerular filtrate. If the pH of the glomerular filtrate means the drug is largely in the ionised state then it will be less likely to diffuse back into the blood and will be lost in the urine
77
How do drug interactions occur by affecting tubular secretion?
- The body is able to eliminate some molecules from the blood by actively excreting them into the glomerular filtrate.
- This can lead to an interaction when two drugs are actively secreted by the same mechanism
- There is competition and one of the drugs is preferentially secreted into the glomerular filtrate. The 'winner' is lost in the urine whilst the 'loser' is retained in the blood
78
What is a CT scan?
```
Computerised Tomography (CT)
- form of X ray imaging
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79
When were x rays invented?
1895
80
How does a CT image form?
- Measure the X-ray attenuation (hoe much energy lost from the source) through the object. Denser materials lose more energy (like bones)
- Acquire attenuation along projections over 360 degrees for each slice
- Reconstruct attenuation of each volume element by filtered back projection
- The values for each voxel attenuation values are calculated relative to water- named Hounsfield units e.g. bone 400 units, air -1000
81
What are hounsfield units?
CT scan
- The values for each voxel attenuation values are calculated relative to water- named Hounsfield units e.g. bone 400 units, air -1000
82
How are CT scans used in cardiac?
- Take entire image of heart in less than a heartbeat
- Assessment of calcification in the coronary arteries and give a score based on the density
- Bright white bits are very dense and show calcification
- Score called igaston score based on the density
- Can assess occlusion of the coronary artery and blood flow
83
What is a CT angiograph?
Visualising the blood flow
- used iodine based contrast
- Time injection of the contrast and CT scan can see where the blood flows and identify stenosis of arteries or any major blood vessels
84
How are CT scans used in orthopaedics?
- Complicated joints in the body e.g. hips and vertebrae
- High spatial resolution and allows 3D reconstruction
- Can see prolapse of vertebral discs
- Helps guide reconstructive surgery planning
85
How are CT scans used in oncology?
- Visualisation can be difficult in areas of the body so CT scans are very useful. E.g. prostate – where does it become the rectum – balance between not treating all the cancer and toxicity for the rectum
- Also look at response for treatment – help facilitate personalisation of treatment. Lung cancer patient imaging during treatment
86
How does 4D CT work?
- Collect data into ‘bins; corresponding to the same point in the respiratory cycle
- Reconstruct multiple images representing the different breathing phases (typically 10 bins used so 10 CT scans)
- Uses a belt or a spirometer to measure the breathing rate
- Requires multiple rotations at each slice to gather enough projection data in all bins. Therefore, increased time and dose
87
What is a PET scan?
Positron Emission Tomography (PET)
88
What do PET scans measure?
- Functional imaging technique
| - Doesn’t see anatomical information but metabolic activity
89
How do PET scans work?
- Uses a tracer (biological behaviour with a known behaviour in the body) labelled with a radioactive substance such as F-FDG (fludeoxyglucose- analogue of glucose). Replace oxygen with fluorine-19
- It is therefore taken up by areas with metabolic activity but because its not a true glucose molecule it will not be metabolised and will be stuck within the cell – emits a positron and can see areas of activity
90
What areas show on a PET scan?
- Brain always hot.
- Activity also collects in the bladder and in brown flat
- Tumours
91
How can PET scans be disturbed?
- Patients physical activity will be seen on scan– where the muscle has been used so patients have to keep still
92
Why does the radioactive label of the tracer give a signal in a PET scan?
When stuck in the metabolically active tissue, - it decays with positron emission – F18 is radioactive and will decay with (positively charged electron).
- This will then move in the body till it meets an electron and annihilate which will give off the energy as gamma rays in opposite directions.
- This will travel straight out of the patient to hit the detectors and will know that the event occurred between the two opposite points.
- This occurs lots of time and can build an image of the location of the tracer in the body
93
How have PET scans been approved upon>
- More detectors, the greater the resolution that can be imaged – number od detectors have doubled every 2 years
94
What is the advantage of a PET-CT scan?
- PET-CT machines combine PET scan with anatomical information of a CT scan
- Images inherently fused and identify the anatomical locations of the activity
95
What are the main applications of PET scans?
Brain image
- Alzheimer’s disease (lower brain activity than normal)
- Various neuro-receptors (schizophrenia, mood disorders)
Cardiology
- Diagnostic imaging of heart disease, stress testing (image at rest and after exercise or injection with stimulant)
Pharmacokinetics
- Used in drug development to look at uptake and elimination of drug
Oncology
- 90% of all scans
96
What is the benefit of using PET scans to investigate tumours?
- Measures the primary disease but also metastatic disease
- Improve intra -clinician variability – give the same answer. More difficult with just anatomical CT information
- Helps differentiate tumour from associated atelectasis
- Helps distinguish where normal tissue ends and tumour begins
97
What limits the type of tracers which can be used in PET scans?
The half life of the radioactive isotope
- F18 110 miniates – used now
- C11 20 minutes
- O15 2 minutes – would have to treat patients as the labelling is being done
98
Why are different tracers used in oncology?
- Different tracers to look for different things within the patient. Can use multiple different tracers in the same patient to look at these things. Can be done before and after treatment to look at progress of the tumour.
- Cell proliferation
- Blood flow
- Hypoxia
- Neuroendocrine tumours
- CNS
- Prostate membrane activity
99
What are the disadvantages of PET scans?
Scan dose
- Radioactive into patient – secondary cancers
Low spatial resolution -4mm
Scans can be long 10-30 mins
– patient needs to stay otherwise blurring and PET/CT misalignment
100
What is sound?
Mechanical vibrations moving through a medium
101
What is the speed of sound?
The speed of sound is dependent on the density of the medium
- Air= 340m/s
- Tissue= 1540m/s
102
What type of wave is sound?
It is a longitudinal wave – motion and direction of travel are parallel
103
Why does sound travel faster through denser mediums?
Sound travels faster through denser mediums because energy transfer occurs quicker between particles closer together
104
What is ultrasound?
Audible frequency is 20Hz- 20kHz and ultrasound is >20kHz
105
What is sound frequency?
Frequency is the number of oscillations per second in Hz
106
What frequency is medical ultrasound?
Medical ultrasound is 2-15MHz and require systems that oscillate at very high frequencies
107
How is an ultrasound carried out?
- Different probes and transducers for different clinical applications e.g. wider curved probes are used in pregnancy while narrower can be inserted into the airways to look at the lungs
- Oscillating electrical current is applied to piezoelectric crystals at probe face
- This generates mechanical vibrations at the probe face (2-15 MHz). Probe is placed on the patient skin surface and vibrating sound waves travel through the patient
108
How is an ultrasound image formed?
- Place probe on patient’s skin and add coupling gel which improves transfer between probe and patient
- Generates vibrations into the patient which encounters different structures and bones and are either transferred through the medium or reflected back
- Vibrations that are reflected back hit the transducer face which creates a vibration in the crystal which is converted into an electrical signal
109
How is the depth of a structure determined in an ultrasound?
By the time it takes for reflected vibration to return to the probe
110
What does the strength of an ultrasound signal show?
Strength of the signal varies depending on the density of the structure
111
How artefacts introduced into ultrasound?
Vibrations can also reflect or transmit at different angles or scatter and can result in artefacts in our image
112
What is the dollar effect?
- When the source is moving, the waves travel in the direction of the source and bunch together but when move away they get spread out
- Can therefore measure the frequency shift between these areas – closer together waves is a higher frequency
- The frequency change determines the velocity and direction of travel of the sour
113
What is the doplar effect used for in ultrasound?
- Can determine the speed of the blood flow through arteries
- Used to examine stenosis of a blood vessel
- Can see when goes through stenosis the velocity increases and then when moves out of the stenosis there is turbulent currents
114
What is colour flow doplar?
- Visualise direction and speed of travel
- Looking for areas of turbulence – again stenosis and aneurysms
- Or for scanning an umbilical cord- blood flow in two directions
115
What are the advantages of ultrasound?
- Inexpensive compared to other scanners
- Non invasive
- No ionising radiation
- Easily transportable around a hospital
116
What is an MRI?
Magnetic Resonance Imaging (MRI)
117
What is the basic principle of MRI?
- Dependent upon hydrogen atoms within the body
- Large proportion of the body is water which has lots of hydrogen
- Hydrogen nucleus consists of single proton which has a nuclear spin
- Spinning charge produced magnetic field- magnetic dipole formed
118
How does an MRI work?
- Spinning charge of proton produced magnetic field- magnetic dipole formed
- The protons are pointing in random directions in the body but when placed in MRI scanner (magnetic field), it aligns with the magnetic field (B0).
- If excite magnetisation with radio waves which push into the transverse plane. This net magnetisation is spinning in transverse plane.
- When turn off the radiation, the magnetisation wants to relax to equilibrium position by transverse relaxation (T2) and longitudinal recovery (T1).
- This net magnetisation is spinning around and decreases to 0. This generates a current in the coil on the patient which detects these oscillations. This can be detected overtime
119
What are the two ways that the magnetisation returns to equilibrium in an MRI?
The magnetisation wants to relax to equilibrium position by transverse relaxation (T2) and longitudinal recovery (T1)
- Different tissues have different T1 and T2 times and will be seen at different brightness.
120
What is an MRI angiography?
- Can inject contrast agent to make a video and look at at any damage to vessels
- Don’t have to acquire X rays
121
What is contrast enhanced MRI?
- Image legions such as tumours
- Injected gadolinium contrast agent and because vessels are leaky in tumours, it releases into the interstitial fluid so can highlight the tumour more easily
- Inform whether a tumour is responding to treatment
122
What is a functional MRI?
- Blood oxygen level dependant MRI
- Ask patient to move and part of the brain controlling will require more oxygen
- Different signals from oxyhaemoglobin and deoxyhaemoglobin
123
What is a cardiac MRI?
- Visualise the structure and the function of the heart
- Can produce video
- Assess the valves
- Measure injection fraction
- Can use contrast agents to look at myocardial infusions
124
What can cause MRI artefacts?
- Aliasing – the field view is not large enough for the structure
- Patient motion- blurring of the image
- Zipper artefacts- if there is any RF interference
125
Why is MRI used in radiotherapy planning?
- Define structures easier than in a CT scan
126
What are the main parts to an MRI scanner?
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Casing and shielding
- Reduces the magnetic field that comes out of the scanner- keep within the scanner for the patient
Magnet
- Superconducting coil which is bathed in liquid helium to keep to a low temperature (-269 degrees C)
Shim coil
- Homogeneous magnetic field
- Prevent distortions
Gradient coils
- Allow to determine where the signal is coming
Vacuum layer
- Thermal insulation
Body coil
- Sends radio waves into the patient
- Detect the transverse current
Additional receiving coil
- Closer to the patient
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127
What are the hazards of MRI?
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Projectile affect
- Ferromagnetic materials attracted to magnet
Implantable medical device safety
- Pacemakers, cochlear implants
Biggest danger is complacency
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128
What are the main characteristics of a CT scan?
Ionising radiation
High spatial resolution
Density information for radiotherapy planning
129
What are the main characteristics of a PET scan?
Ionising radiation
Functional information
Poor spatial resolution: needs fusion with CT
130
What are the main characteristics of an ultrasound scan?
Non-ioinising radiation
Poor beam transmission through air or bone
Can quantify movement over time
131
What are the main characteristics of a MRI scan?
Non-ioinising radiation
Very good soft tissue
Functional and anatomical information
132
What are somatic variants?
- Variants absent in the gametes and occur during foetal development or any time after birth in any cell of the body except the germline
- Variant not passed on to offspring
133
What are germline variants?
- Variant present in the gamete, variation present in every cell and the germline and can be passed into the offspring
- Sometimes give an increased chance of developing a disease. 5-10% cancers associated with germline change
134
When is a disease considered rare?
less than 5 in 10,000 people
135
How many people in total are affected by rare diseases?
affect 1 in 17 people
136
What % of rare diseases are genetic?
80
137
What is Long QT syndrome?
- Sudden death due to ventricular arrhythmias
- Beta blockers and pacemakers as treatments
- Identifying the genetic change as causing this allows triggers such as cold and noise to be avoided and appropriate treatments given
138
Why is pharamcogenetics important?
- Adverse drug reactions are an issue with many drugs with 70% thought to be unavoidable
- Genetics could be used to optimise drug responses and minimise side-effects
- Can indicate how a drug will be metabolised or how effectively it will hit a target
139
Give an example of the use of pharacogenomics to improve treatment?
Azathioprine is an immunosuppressant drug used in the treatment of autoimmune conditions. It is converted to an active form by enzyme called TPMT and prevents conversion toxic by product which affects bone marrow. Variants in TPMT can result in low or absent enzyme activity. If investigate genome, can inform the dose of azathioprine to prevent these toxic affects
140
How is genetics used to investigate infectious disease?
Pathogens have their own genomes and by examining can establish diagnoses and drug susceptibility
141
Give an example of the use of genetics in infectious disease
TB
- Some drug resistant
- Genetics can reveal the stain allowing diagnosis and whether the strain is drug resistant. This previously took month now a week- reducing the time they are infectious stopping the spread and increasing their treatment
- WGS can be used to link individual cases – shared sources of infection and identify people before they have symptoms reducing how long they are infectious for
- Also used to manage epidemics
142
How many bases make up the human genome?
3 billion base pairs
143
What are the main functions of proteins?
Proteins are essential or life: structural, transporter, enzymes
144
What is an allele?
Allele is used to describe different versions of the same gene
145
What % of the genome is coding?
2
146
What is the function of the non-coding genome?
- Non-coding are vital for regulation
| - Also have structural roles such as telomeres- repetitive sequences at the end of chromosomes to prevent degradation
147
What is the average number of changes between humans genomes?
3 million
148
What are the main keys in a pedigree?
- Circles females and squares males, diamonds unknown
- P pregnancy
- Triangle is miscarriage
- Triangle with line is termination
- Shaded is affected
- Brackets is an adoption
- Line is marriage and slashes is separated
- Two lines is consanguity – blood relatives
- Identical twins is two lines and a horizontal line and fraternal just diagonal lines
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What are the benefits of pedigrees?
- Refine diagnosis: Variability and similarities in families
- Patterns of inheritance: Distinguish between conditions with similar presentations
- Likelihood of affected relatives
- identify family members who need it
- Need to be referred to another specialist
- Correct family misconceptions
- Build trust with patients
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What are the main ethical issues in genomics?
- Consent and confidentiality issues
- Discussing with family members: Should offer family members testing who have the chance of being affected
- Sharing information for research: Asked if they want to participate and Need clear conversations about how will be used stored and anoynomised
- Disclosing test results
- Genomic testing in children
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Do predictive test results have to be disclosed?
Currently, UK regulation says predictive testing does not to be disclosed unless for Huntington’s disease life insurance policies with over £500,000
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Should children have genomic testing?
Current guidance is only when beneficial to test the child- not late onsent diseases
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What are common patient misconceptions about inheritance?
Common misconceptions include that if no one in the family has it then it cannot be inherited and feeling like they follow after one parent so will have inherited that condition too
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Outline meiosis
- Formation of gametes
- Germ cell
- Meiosis I: Replication coccurs and homologous recombination for crossing over event- unique combination of alleles. 1-4 crossover events per homologous pair per meiosis
- Meiosis II: No replication occurs but instead spindles are pulled to the opposite side of the cells and sister chromatids separated to form haploid cells- our daughter cells
- Production of the sperm occurs at puberty but eggs before birth up to meiosis I and then continues to meiosis II at puberty
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How do errors occur in DNA recombination?
- If chromosomes misalign could lead to duplications or deletions
- Misaligns with non-homologous chromosome could lead to a translocation – balanced or unbalanced
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What is the difference between a robertosonian translocation and a reciprocal?
- Reciprocal translocation are swaps between two different chromosomes and robertsonian are when breaks occur ar or near the centromere on an acrocentric chromosome, resulting in the long arm of the one chromosome fusing with another
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How do errors occur in meiosis?
Error in meiosis will result in a the gamete having the variant meaning the resulting individual will have the alteration in every cell in their body including germ cells so could be passed on to future generations
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How do errors occur in mitosis?
- Occur at any stage in life
- Result in mosaicism if passed onto daughter cells
- If occurs during embryonic development than the alteration will likely be present in large numbers and can have a wide range of presentations depending on which part of the body the affected cells give rise to
- After birth- localised area- e.g. cancer
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How do errors occur during chromosome segregation?
- Fail to segregate properly during division and result in aneuploidy
- E.g. in meiosis – down syndrome – trisomy 21
- If occurs in mitosis it can result in mosaicism
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How many protein encoding genes are there in the human genome?
20,000
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How re there more proteins than genes?
- Way more proteins than there are genes- could be 100 proteins to one gene.
- Alternate splicing is a way this can happen as well as post translational modifications
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Give an example of the importance of identifying the specific variant within a gene for treatment?
CFTR can be caused by problems with protein folding or interfere with its function. If its mis-folding it can be treated with a drug called a corrector which helps the folding – important to know what the variant does as they are treated differently
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What are the characteristics of an autosomal dominant condition?
- 50% chance of affected child
- Seen in every generation
- Passed by both parents and affects males and females equally
- If both parents have the condition then there is 25% chance that the child will have two copies of the variant and could present with a more severe phenotype e.g. familial hypercholesterolaemia
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What are the characteristics of an autosomal recessive condition?
- 25% of affected child
- Both parents carriers
- Affects males and females
- Often related parents
- Siblings in the same generation
- Both parents are carriers
- 50% chance of offspring being a carrier
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What are the characteristics of an X-linked recessive condition?
- Rarely affects females
- Mother will pass to their son 50% of the time and have 50% chance of a female carrier
- Males cannot pass to their son but will pass to their daughter so will be a carrier
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What are the characteristics of an X-linked dominant condition?
- Both males and females
- More significant disease than affected females
- Rare
- Affected males can’t pass to their son
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What are the characteristics of a mitochondrial condition?
- Maternal inheritance
- All offspring will inherit
- Affects both males and females
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What is multi factorial inheritance?
When a condition is in caused by the combination of genes (each increasing the chance of disease) and the environment
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Define epidemiology
The study of the occurrence and distribution of health-related states or events in specified populations of this knowledge to control the health problems
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Define incidence
The number of instances of illness commencing, or of persons falling ill, during a given period in a specified population; more generally, the number of new health-related events in a defined population in a given time.
It is expressed as a percentage of a population or as a rate per 1000.
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Define prevalence
o Prevalence is the ratio of the number of cases of a disease present in a statistical population at a specified time or in a given time period and the number of individuals in the population at that specific time
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How do you calculate prevalence
Prevalence = incidence x duration
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What is absolute risk?
Absolute Risk= Number of events/Total population at risk
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What is relative risk?
Risk in group 1/Risk in group 2
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What is attributable risk?
Attributable risk is the risk from a non-exposed group from the risk of an exposed group
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What are odds?
- Odds is the number of events divided by the number of non-events
- Mathematically odds is the probability of the event/ (1-probability of the event), whilst risk is just the probability of the event
- Can be used in epidieomology to compare risk between two groups, e.g. could compare the odds of exposure of one group/ odds of exposure in the other group
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What are the stages of an outbreak investigation?
- Determine the existence of an outbreak
- Implement immediate control measures
- Define a case
- Find the cases
- Epidemiological investigation
- Microbiological investigation
- Environmental investigation
- Make conclusions
- Implement more specific control measures
- Communicate
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Why does data need to be standardised?
In epidemiology, we want to compare disease measures in different populations but if they have different ages than any differences seen may just be due to age- confounding factor. Therefore, need to standardise the populations
- This is most commonly done for age and sex but can be applied to other confounding factors such as ethnicity and socio-economics
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What is direct standardised?
Age specific rates in the population are applied to the proportion of people in each age band in a specified reference population. This method produces a directly age-standardised rate (DASR)
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What is indirect standardised?
The observed mortality pattern in a population is compared with what would have been expected if the age-specific rates had been the same as in a specified reference population. This produces a standardised ratio (SMR)
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How does using standard populations standardise results?
A national population structure is often used as the reference population, such as that of England and Wales, but standard populations have also been constructed for international comparisons
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What are ecological studies?
- Most observational studies measure data at an individual level. In an ecological study, the unit of observation is at population or community level.
- The disease and exposure are measured in a number of populations and their relationship is examined
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When are ecological studies looked at?
Useful to look at geographical locations or when the outcome can be measured better at a community level
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What is a disadvantage of ecological studies?
Vulnerable to confounding factors such as age and aggregation bias: the trend seen at the community level might be opposite to what is seen at the individual level
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What are time trends and when are they used?
- Many diseases show fluctuations in incidence with time and analysis will show if the fluctuations correlate with any other changes
- Useful to assess impact of vaccination programmes
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What are cross-sectional studies?
- Often descriptive studies that show an association between exposure and outcome e.g. prevalence of diabetes in adults over the age of 40 years
- Analytical studies measure the outcome and exposure: measure the prevalence of obesity in the same population as the prevalence of diabetes
- Consist of a single examination of a population without any follow up- data collected at one time point
- Measure attitudes, behaviours, health conditions and risk factors
- Need to define the sampling frame which is the target population
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What are case control studies?
- In case control the outcome has already occurred- data on risk is retrospective
- Recruit people with the disease of interest and use a group of people from the same population who do not have the disease. They are then compared for the prevalence of the risk factor of interest
- Odds and odds ratios used
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What are the issues with case control studies?
- Cases may be drawn from a variety of places
- Controls need to be taken from the same population as the cases
- Recall bias and observer bias: the person with the disease is more likely to remember the timeframe than someone who didn’t have it
- Reverse causality
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What are the advantages of case control studies?
- Useful for rare outcomes
- Can examine multiple exposures
- Useful for outcomes with long latent periods
- Quick and inexpensive
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What are cohort studies?
- Outcome has not occurred at the time of the investigation
- People with and without exposure are followed up over time to examine the proportion that develop the outcome
- Compare risk of exposed and unexposed groups
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What are the advantages of cohort studies?
- Useful for rare exposures
- Can examine multiple outcomes
- Ascertainment of exposure bias may be maintained
- Temporal relationship can usually be made clear
- Direct management of incidence in exposed and unexposed groups
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What are the disadvantages of cohort studies?
- Inefficient for rare outcomes
- Can be expensive and time consuming
- Validity is affected by follow-up
- Retrospective studies need adequate records
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What control measures are put in when there is an ourtbreak?
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Early treatment
Infection control
Safe drinking water
Sanitation
Hygiene
Health promotion
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How do you search the literature for epidieomological evidence?
To search the literature, produce a research question using PICO: Population of interest, intervention, comparison and outcome
E.g. Among a community during an outbreak, does the administration of oral cholera vaccine verses no vaccine decrease the incidence of cholera and the associated morbidity and mortality
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What databases are used to search in epidemiology
- The John Rylands library subject page for medicine
| - Databases include: Medline, Embase and Scopus
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What is the highest form of epidemiological evidenced?
Metanalysis is the highest form of evidence
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What is deprivation?
- Refers to unmet needs caused by a lack of resources if all kinds not just financial. The index of multiple deprivation attempts to measure a broader concept of multiple deprivation made up of several distinct dimensions, or domains of deprivation.
- These include income deprivation, employment deprivation, health deprivation and disability, education skills and training deprivation, barriers to housing and services, living environment deprivation and crime.
- These are combined into to an overall index which is used to rank every small area in England
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What can cause an association in studies?
- Chance (5% random chance when statistical significance)
- Bias (problem with how the study was run)
- Confounding factors
- Truth
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What are the Bradford hill criteria for causation?
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Strength of association
Consistency
Specificity of the association
Temporal sequence of association
Biological gradient
Biological plausibility
Coherence
Experiment
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What is confounding?
Confounding is when the observed association is due, totally or in part to the effects of differences between the study groups (other than the risk factor interest) that alters their risk of developing the outcome of interest.
For a variable to be a confounder, the variable must be independently associated with the outcome, must be associated with the exposure under study and should not lie on the causal pathway between exposure and disease
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What are the main models that explains socio-economic inequalities in health?
Behavioural model
Materialist model
Psycho-social model
Life-course model
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What is the behavioural model that explains socio-economic inequalities in health?
There are differences in health damaging or health promoting behaviours between socio-economic groups such as diet, drugs, alcohol and tobacco consumption, physical activity, and uptake of immunisation, contraception and antenatal services. Differences in health behaviour explain only about one-third of the differences in mortality (evidence from long running cohort studies such as the Whitehall study).
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What is the materialist model that explains socio-economic inequalities in health?
Poverty exposes people to health hazards. Disadvantaged people are more likely to live in areas where they are exposed to harm such as air-pollution and damp housing. Higher rates of childhood respiratory disease are associated with damp housing. The Black Report concluded that materialist explanations are the most significant. The full impact of living standards, however, can only be understood over the course of the life term. Both in the UK and internationally, inequalities in health tend to follow a steady gradient rather than there being a threshold.
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What is the Psycho-social model that explains socio-economic inequalities in health?
Social inequality results in psychological effects with physiological impacts. Psycho-social risk factors include social support, control and autonomy at work, the balance between home and work, and the balance between efforts and rewards. There is both individual level evidence (such as the Whitehall study) and country level evidence.
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What is the life-course model that explains socio-economic inequalities in health?
Health reflects the patterns of social, psycho-social and biological advantages and disadvantages experiences by an individual over time. The chances of good or poor health are influenced by what happens in-utero, in early childhood and over the lifetime. Disadvantages may accumulate through life both as a child and as an adult. Those with poor home conditions as a child are more likely to experience occupational disadvantage.
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What is screening?
Screening is a process of identifying apparently healthy people who may be at increased risk of a disease or condition. They can then be offered information, further tests and appropriate treatment to reduce their risk and or any complications arising from the disease or condition
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What can screening do?
Screening can save lives or improve quality of life through early detection of a condition and reduce the chance of developing a serious condition
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What are the negatives of screening?
- In any screening programme there are false positive and false negative results
- They do not give a diagnosis and should be followed up with diagnostic tests
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What screening programmes are offered in pregnancy?
- Infectious disease (HIV, Hepatis B and Syphilis)- 8-12 weeks
- Combined test: Down syndrome, Edwards syndrome and Patau’s syndrome – 10-14 weeks
- Sickle cell anaemia – test parents as carriers – 10 weeks
- Physical abnormalities (11 physical conditions)- 18-21 weeks
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What screening programmes are offered in newborns?
- Physical examination (eyes, heart and hips)- 3 days after birth
- Hearing test- birth
- Blood spot test (9 rare conditions such as cystic fibrosis)- 5 days after birth
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What screening programmes are offered in adults?
- Diabetic eye screening
- Cervical cancer screening
- Breast cancer screening
- Bowel cancer screening
- Abdominal aortic aneurysm screening (AAA)
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What is the UK national screening committee (NSC)?
- Chaired by deputy chief medical officer for England
- Uses research evidence, pilot programmes, economic evaluation
- Ensures more good than harm at a reasonable cost
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What should be considered when considering a screening programme?
- Misdiagnosis and over diagnosis
- Is there an effective treatment for disease?
- Is early treatment beneficial?
- Anxiety caused to patient
- Cost
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What are the four main criteria for screening programmes set by NSC?
The condition
The test
The treatment
The screening programme
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What is required for the condition to offer a screening programme?
- Is it an important health problem?
- Is there detectable disease markers?
- Cost
- Psychological impact for those effected and carriers
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What is required for the test to offer a screening programme?
- Simple, safe and validated test
- distribution of test values understood and cut of value defines
- Further diagnostic investigation
- Criteria for subset of mutations and why others aren’t included
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What is required for the treatment to offer a screening programme?
- Effective treatment with evidence for benefit of early treatment
- Which people should be offered treatment?
- Clinical management should be optimised first
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What is required for the screening programme to offer a screening programme?
- Evidence from randomised controlled trials that the programme is effective in reducing mortality or morbidity
- Ethically accepted by health professionals and the public
- Benefit should outweigh physical and psychological harm
- Cost of programme balanced in relation to expenditure of medical care as a whole
- All other options have been considered
- Adequate staffing
- Evidence based information explaining consequences of testing to allow patients to make an informed choice
- Eligibility criteria scientifically justified to public
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Who has a TB vaccine?
- Only considered required if parents or grandparents are from a country with high incidence of TB or born in area with more than 40/100000 cases of TB
- It is not very effective against respiratory forms of TB found in adults and is therefore rarely given to people over 16
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Why is TB unequally distributed?
New migrants, ethnic minorities and those with social risk factors are disproportionately affected
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What are the symptoms of TB?
- A persistent cough that lasts more than 3 weeks and usually brings up phlegm, which may be bloody
- Weight loss
- Night sweats
- High temperature
- Tiredness and fatigue
- Loss of appetite
- Swellings in the neck
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How effective is the BCG vaccine?
A metanalysis showed that it is 70-80% effective against severe forms of TB such as TB meningitis that occurs in children
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What are the side effects o the BCG vaccine?
- It leaves a BCG scar, sometimes can have a more severe skin reaction but should heal in weeks
- Serious side effects such as an allergic reaction are very rare
- Can lead to headache, fever and enlargement of a lymph node
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What kind of vaccine is the BCG?
Intradermal vaccine – cannot be given by a practice nurse
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What vaccines do newborn babies have?
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Eight weeks
- Diphtheria, tetanus, polio etc
- PCV
- MenB
- Rotavirus
12 weeks
- Diphtheria, tetanus, polio etc
- Rotavirus
16 weeks
- Diphtheria, tetanus, polio etc
- PCV
- MenB
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What is the role of the Joint Committee on Vaccination and Immunisation?
- Advice UK health departments on immunisations for the prevention of infections following evidence on the burden of the disease, on vaccine safety and efficiency on the impact and cost effectiveness of immunisation strategies
- Considers and identifies factors for the successful and effective implementation of immunisation strategies
- Identify knowledge gaps relating to immunisations or immunisation programmes
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Define health
The extent to which an individual or group is able to satisfy basic human needs, change or cope with the environment and realise aspirations
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Why is public health important?
- Reducing premature death
- Minimising the effects of disease, disability and injury
- Promoting a healthier population
- Sustainable healthcare system
- Focus is prevention
- Population health needs
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What are the three main points to control an outbreak?
- Source
- Pathway
- Receptor
