Diagnostics and therapeutics
08/10/2019
Pharmacology – how drugs behave in the body
Clinical pharmacology or therapeutics – Applying pharmacology to specific treatments
All drugs are poisons – in most cases, drugs work at a lower dosage for therapeutic effects,
but overdosing is possible and can cause toxic effects. Some drugs can be effective for one
organ/system but can be effective for another.
Doses are guesses- in some patients the drug may not work, whereas in others it may work
e.g. acne medications can only work for specific skin types, olanzapine 2mg for anxiety
patients and 20mg for psychotic patients.
Side effects – physiological effects on the body other than the intended beneficial effect.
Prostaglandins – pro-inflammatory factors. Paracetamol can stop synthesis of these to stop
the pain, but can lead to side effects such as stomach damage (prostaglandins protect
stomach)
Chemical names > non-proprietary name e.g. Acrivastine > proprietary/trade name e.g.
Benadryl
Dose – amount administered at a single point in time
Dosage – amount administered per unit of patient body mass (more specialised, long-term)
Dosage forms
solid - (tablet, capsule), tablet coatings to protect drug from body and vice versa.
Protective - (enteric protection. extended-release, gel caps) e.g. aspirin is able to
damage the lining of the stomach, so has a coating to allow it to safely enter the
intestines to be absorbed. Gel caps.
Liquid (injectable, topical, liquid medicine.
Always refer to specialised drug leaflet
Active ingredients in the drug is the drug itself
11/10/2019
Amount of drug entering body must equal the rate at which the body removes the drug
(balancing in-flow without-flow)
Dosage depends on patient’s physiological state at the time (all doses are guesses)
Maximum effective concentration – top concentration of normal therapeutic range
Minimum effective concentration – lowest concentration of the normal therapeutic range
Pharmacodynamics – study of how drugs interact with the body and produce their effects.
The drug acts along the lock and key model – the drug (key) only fits with its specific protein
receptor (lock), this is the recognition phase. Upon binding, the transduction phase is where
the receptor sends some messages in response e.g. it opens an ion channel, allowing ions to
enter, or signalling to release a certain increase or decrease of something.
The induced fit model is a better explanation for the drug and receptor interaction.
, Affinity – how WELL the drug fits, how suitable it is (high affinity means low concentration
and vice versa). A drug that has the right shape and charge to fit the receptor and stimulate
the cellular response has a strong affinity.
Avidity – How good the interaction is. So, the avidity needs to be considered when guessing
the dosage of the drug.
Agonist (molecule that binds to receptor and triggers the desired effect), Antagonist (gives
some effect but it’s minimum, its very much like a blocker, but instead is a competitor for
the binding site in the substrate instead of just blocking it completely), Reversal agents
(completely reverses the effects, displaces the agonist), and blockers (blocks action my
occupying specific part of receptor).
Competitive and non-competitive agonists , ones that either compete for the active binding
site or not
Partial antagonist / partial agonist
Non-receptor mediated
Km – concentration in which you achieve 50% of the maximum speed.
Sigmoidal curve (S-shaped cure) – not as efficient as a straight line
Potency – concentration of drug required to produce an effect of given intensity
Efficacy – maximum response achievable from drug
EC50 – Half maximal response concentration (50% of efficacy), Effective Concentration at
50%.
Therapeutic index (TI) and margin of safety – compares amount of therapeutic agent that
causes therapeutic effect and amount that causes toxicity. The ratio of the dose that causes
adverse effects at an incidence/severity.
Toxic dose (TD) – the toxic dose for up to 50% of population
Effective dose (ED) – the effective dose for 50% of population
Narrow therapeutic index (margin of safety) – narrow therapeutic range is when the
maximum and minimal effective dose are close together.
15/10/2019
Pharmacokinetics (PK) –
The bucket analogy – water being poured into the bucket is being leaked out at different
rates depending on the hole AND how much water is being poured in ; this describes the
rate in which the body will excrete the drug from the body
Initial larger dose “loads” the bucket (body)
Smaller “maintenance” dose matches the bodies rate of elimination to maintain body levels.
Total daily dose – combined amount of drug (mass) x the number of doses administered in a
given day.
Trough concentration (lowest drug concentration) and peak concentration (highest drug
concentration).
(A) – Administration of drug; parenteral (through intestines), and non-parenteral (outside
intestines). (intravenous, intraarterial, intramuscular etc.)
A – Absorption (commonly in small intestine, microvilli on surface area to help with
absorption). The larger the surface area and also more blood flow to the area, the better the
absorption.
, D – Distribution ; how the drug moves throughout the body. Some proteins in the blood (i.e.
albumin) will bind to the drug. Tissue perfusion and tissue quality can also effect
distribution, as well as how much fat they can move through in the tissues. There’s around
60% of water within the body which can distribute the drug, but there must be enough of
the drug in the body.
M – Metabolism; the liver will try to change the “poisonous” drug into something more
excretable, maybe improving the hydrophilic properties of the drug and helping to better the
effects. Rectal administration is helpful when to avoid digestion by the liver.
E – Elimination
Per os – through a body opening e.g. mouth, ear canal.
Per rectum – rectal administration (for people who can’t swallow tablets)
Topical – applied to surface of skin (epidermal administration)
Aerosol administration – into lungs via air or gas solution
Passive diffusion – random movement of drug molecules down concentration gradient
Facilitated diffusion – passive transport mechanism across cell membrane, doesn’t require
cell energy to move the molecules but instead uses a carrier molecule
Active transport – cell uses energy to move molecules across cell membrane (or to reset
carrier molecule)
Lipophilic – dissolves in fat but not in water
Drugs are commonly weak bases, but the pH of the stomach is 1-2 and the intestines are
around 7.4, so ionization by water will need to be considered.
Bioavailability – amount of drug available upon absorption
The rebound effect – refers to lipophilic drugs that can accumulate in fat tissues. Mainly in
drugs that have to enter the brain (i.e. anti-psychotics); these drugs will stay in the tissues
for a while there’s still some in the bloodstream, but the distribution is random, maybe
causing undesired effects, quitting “cold turkey” is not okay or missing a dose because you
“feel better” doesn’t work and can cause rebound effect symptoms.
18/10/2019
Enteropathic circulation – via the intestines or liver
Biotransformation (drug metabolism) – process where drugs are chemically altered by liver
enzymes. The altered drug molecule is a metabolite.
Fastest way of eliminating toxins (once vomiting or faecal excretion aren’t possible) is via the
urine. The liver will make the toxin as water-soluble as possible.
^ to make it more water soluble, you attach something to it that is also water soluble i.e.
glucose, OH groups – the drug/toxin must be at moderate size (most drugs are) in order for
the attached group to have the desired effect
Most drugs don’t have any reactive groups
Phase one (preparation?) – The liver transforms an existing non-reactive group into a
reactive group through reduction and oxidation.
Phase two (conjugation) – bio transforming your metabolites into something more water-
soluble.
Age / gender / drug interactions are all able to effect biotransformations.
Clearance – your body gets rid of a certain enzyme or molecule depending on the ratio of
excretion, absorption, measure of fluid in the body, and other factors. Clearance is the GFR
of creatine, if the GFR is low there is a problem with the kidneys.
