Introduction to Healthcare Science Flashcards
What is the difference between a drug and a medicine?
- 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
Difference between pharmacology and therapeutics?
- Pharmacology is the study of drugs and their affects
- Therapeutics is the treatment of diseases
What is pharmacodynamics?
How the drug acts
What is pharmacokinetics?
How the body acts on the drug
What are the main routes of administration?
- Enteral (oral)
- Nasogastric
- Sublingual
- Controlled release
- Rectal
- Parenteral (IV)
- Skin
- Eye
- Lungs
- Nose
What is the therapeutic index?
- 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)
What are the main stages to consider in pharmacokinetics?
Absorption
Distribution
Metabolism
Excretion
How is the duration of action of a drug measured?
Half life
What is a drugs half life?
Time taken for the concentration of the drug in the blood to decrease by half
How can we influence a drugs duration of action?
Modified release, controlled release, slow release
Advantages of controlled release drugs?
- Less dosage frequency and more patient adherence
- Reduce incidence of adverse effects
Disadvantages of controlled release drugs?
- Expensive
- Lack of standardisation
What is a drugs bioavailability?
The percentage or fraction of the administered dose which reaches the systemic circulation of the patient
What are the factors affecting bioavailability?
- Dose form
- Chemical form
- First pass metabolism effect
How is drug distribution measured?
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
How is drug elicitation measured?
Described by clearance
- Clearance is the volume of plasma completely cleared of drug per unit time
Where does drug elimination occur?
Major site is the liver but also happens in the GI tract, kidneys and lungs
Where does drug excretion occur?
- Major site is the kidney but also GI tract, saliva, sear, breast milk
- If GI tract, sometimes reabsorbed
How long does it take to reach a steady state of drug concentration in blood?
Usually around 5 half lives and the same to go back down
Why are modified release drugs better?
Modified release would hopefully show less harsh peaks so less likely to go into the toxic dose or dipping into the sub-therapeutic level
What needs to be considered when choosing the right route of administration?
- 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
What is drug clearance?
- Clearance is the volume of plasma completely cleated of drug per unit time
- Cp – concentration of drug in plasma
What is drug metabolism?
- 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
What are the two phases of liver metabolism?
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
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
Give an example of a drug with a toxic metabolite?
Paracetamol
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
What happens when take too much paracetamol?
If take too much, there is not enough glutathione to prevent toxicity for phase 2
What is the treatment for parceatamol overdose?
Treatment gives acetylcysteine within 8 hours (donor for glutathione)
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
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
What kinds of administration acids first pass metabolism?
IV
Sublingual
Buccal
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
What other effects are caused by reduced liver metabolism?
- Reduced clotting
- Fluid overload
- Hepatic encephalopathy
- Reduced protein binding
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
Are all drugs metabolised prior to excretion?
No
E.g. Aminoglycosides antibiotics – want it to get to the kidneys before being metabolised
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
What is renal clearance?
It is the amount of drug removed by kidney over specific time
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
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
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
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
Why should renal function be assessed for dosage?
Adjust the dosage based on the level of renal impairment as it will affect excretion
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
What are drug interactions?
When two or more drugs interact in such a way that the effectiveness or toxicity of a drug is affected
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
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
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
When are drug interactions usually occur?
Drug is being started or stopped as the body can adapt to changes
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
What are the main types of pharmacodynamic interactions?
Additive interactions
Antagonistic
Disturbances in electrolyte balance
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
What are antagonistic interactions?
Opposite action of the drugs – cancel each other
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
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
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)
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
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
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
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
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
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
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
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
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?
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
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
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
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
How do drugs interact when they have antagonistic effects?
Medicines with opposite actions will cancel each other out
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
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
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.
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
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.
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
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
What is a CT scan?
Computerised Tomography (CT) - form of X ray imaging
When were x rays invented?
1895
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
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
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
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
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
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
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
What is a PET scan?
Positron Emission Tomography (PET)
What do PET scans measure?
- Functional imaging technique
- Doesn’t see anatomical information but metabolic activity
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
What areas show on a PET scan?
- Brain always hot.
- Activity also collects in the bladder and in brown flat
- Tumours
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
