Basic Pharmacology Flashcards
1
Q
Drug Definition
A
- Chemical substance of a known structure, which when administered, produces a measurable biological effect
- Can be therapeutic, toxic, cosmetic or illegal
- BNF - British national formulary (lists all the current liscenced drugs available in the UK)
- MOA - mechanism of action
- ADRs - adverse drug reactions
2
Q
Drug Interaction
A
- Drugs have an effect by interacting on a specific target (usually a protein) - either increasing/decreasing function or activity:
Receptors
- drugs can bind to membrane receptors & either activate/block intracellular processes
- agonist - activate cell receptors
- antagonist - block activation
Ion Channels
- traffic of ions in/out of a cell effect membrane potential & electrical activity
- e.g local anaesthetic drugs block action potentials in nerve axons
Enzymes
- drugs can bind to the enzyme’s active site & prevent substrate conversion
- or can allosterically change the enzyme’s structure (conformational change to block or enhance catalytic activity)
Genes/DNA
- genes active within a cell determine function/activity
- drugs containing genes/DNA/rNA are useful in preventing aberrant activity e.g uncontrolled replication in cancers
Other drugs
- drugs may directly/indirectly target other drugs a patient is taking
- drug-drug interactions
- may effect prescribing regime - one drug may cancel out the function of another drug being used
3
Q
Pharmacodynamics
A
- The measurement of how effectively a drug works
- What the drug is doing to the body at a particular dose
- Being able to quantifiably measure the effect of a drug (e.g blood pressure) allows you to plot the trajectory of how the patient is responding to a course of treatment
- Can only have a meaningful measurement if there is a baseline to compare against
- Can never make assumptions - must have a physical measurement
- Critical component - estabilishing the right dose for the desired affect & patient saftey
- Typically drugs have a spectrum of doses that are effective - ends of the spectrum are uneffective/toxic
- Drug trials can determine the ‘goldilocks zone’ - a range of doses that have the right effect but are not toxic
4
Q
Clinical Trials
A
- Produce a series of robust & reproducable evidence to prove that a drug is safe and of benefit to a patient
- Placebo - a person’s hopes & beliefs about a treatment combined with their suggestibility can have a significant biochemical effect
Blinded trial - recipient does not know if he is recieving the actual drug or a placebo - removes bias
Double-blind trial - both the recipient & administrator do not know if it is the actual drug or a placebo - more complete understanding of drugs effectiveness & bias removal
Randomised control trial - a number of similar people are divided into two groups - experimental or control/comparison. One recieves the actual treatment & other recieves a placebo - reduces bias, see how effective the intervention was & allows outcomes to be measured at specific times
5
Q
Journey of a Drug
A
- Can be described by considering each of the seperate components of pharmokinetics
- To track the drug once it has been administered, we need a superficial undertanding of stages, once it has been consumed
Components of Pharmokinetics:
- absorption
- distribution
- metabolism
- excretion
6
Q
Drug Absorption
A
Absorption
- oral drugs need to be absorbed across the physical barriers between stomach & circulation
- must pass physical barriers e.g enzymes & chemical barriers that may degrade it
- absorbtion can be via diffusion (lipid-soluable), active transport or aqueous pores (polar drugs)
- bioavailability: the percentage of pharacologically active drug that makes it into the circulation (is available) following oral administration
- intravenous adminsteration may give the drug a higher bioavailability but is harder to achieve logistically
7
Q
Drug Distribution
A
Distribution:
- the drug distributes itself into various tissues/organs
- distribution effect is due to body function e.g cardiac output & reigional blood flow to tissue, determines how much of a drug is delivered to a specific tissue
- chemical structure of the drug & physiological structure of the tissue (similarity of both) determines distribution
- lipid soluable drug will diffuse into a adipose tissue easily
- lipid solubility is influenced by local pH, will determine how much of the drug will actually get to it’s target
- a weakly alkaline drug in alkaline solution will not dissociate (& become highly ionised) so will remain relatively hydrophobic and therefore diffuse - vis versa
8
Q
Drug Metabolism
A
Metabolism:
- drug metabolism refers to the enzyme-mediate processes that occur largely in the liver that deactivate a drug & make it water soluable (ready for excretion)
- body percieves the presence of a drug as a potential biohazard so will actively break it down using liver enzymes
- drug-metabolising enzymes are inducable - only act in the presence of a drug, efficiency
- phase I enzymes chemically modify drugs into an intermediate metabolite in preparation for phase II
- phase II fully deactivates the drug, renders it inert & makes it water-soulable ready for excretion
9
Q
Drug Excretion
A
Excretion:
- physically removing the drug metabolite from the body
- most significant route is via renal extrection - water-soluable drug is filtered out of the blood, into urine by the kidneys then lost as urine
- ‘hepatobillary excretion’ - the drug metabolite is trafficked direct from the liver through the common bile duct, into the aqueous environment of the lumen of the gut & lost as faeces
- any disease affecting the kidneys/liver can have a huge impact on drugs excreted via these routes
- often routine to check kidney function in elderly patients before administering certain drugs as routine doses may build up to toxic levels
10
Q
Adverse Drug Reactions
A
- Any unwanted/unexpected effects of drugs
- If a patient’s pharmokinetic processes are derranged then there may be an unexpected fluctuation in what the drug dose achieves
- Therapeutic index of a drug - ratio of the highest dose before a side effect occurs: the lowest dose of drug that gives a therapeutic effect
- As the drug is administered, repeated dosing is needed to keep a therapeutic concentration maintained in the plasma
- If the kidneys aren’t functioning correctly, each ‘top-up dose’ may push the concentration too high & it will enter the toxic range
- Drugs with a wide therapeutic index are preferred as there is more of a buffer for pharmokinetic disturbances
- Pharmokinetics have an effect of pharmodynamics
- Role of prescriber - knowlegde of both components for saftey & to minimise the risk of patients experiencing ADRs
11
Q
Contraindications
A
- Certain patient demographics (e.g pregnancy) should not recieve certain drugs even if on paper, the choice of the drug might seem appropriate
- BNF lists contraindications for all UK liscenced drugs
- Pregnancy is an instance where certain drugs may need to be avoided - due to previous evidence or the uncertainty of effects
12
Q
Trial Components - Controlled
A
- Control arm - some patients are given a placebo
- Subjects are not told if they are controls (typically)
- Provide a vital ‘baseline reference’ to compare other volunteers against
- Allows researchers to see if the drug/active treatment is actually causing an effect
13
Q
Trial Components - Blinding
A
- Occurs to avoid biassing the experimental results
- Single-blinding - subject of the drug doesn’t know what type of drug they are getting/if they are a control
- Double-blinding - doctor giving the drug also doesn’t know what type of drug or if placebo is given, only trial co-ordinator knows
14
Q
Trial Components - Randomisation
A
- Making sure as diverse a group of subjects recieves the treatment as possible
- Not to bias any data by concluding results from a single demographic
- Less bias, more robust conclusions are
15
Q
Trial Components - ‘Crossed Over’
A
- Somepoint in the trial, every patient recieves every treatment available (including placebo)
- Avoids bias & makes conclusions more robust - every patient may respond differently
- Not always possible - subject may withdraw early, trial treatment may cure their condition & exclude them from trial)
