Week 10 - Pharmacology Flashcards
what is a drug?
any individual chemical that has an effect on the body, good or bad.
what is a medicine?
mixtures of chemicals, including a drug or drugs, packaged up for patient consumption to treat a pathology or symptom
what is a prescription?
a “written order, which includes detailed instructions of what medicine should be given to whom, in what formulation and dose, by what route, when, how frequently and for how long”
what is the difference between pharmacodynamics and pharmacokinetics?
pharmacodynamics is what the drug does to the body (both begin with D) and pharmacokinetics is what the body does to the drug
what is an agonist?
An agonist is a ligand that binds to a receptor and produces a conformational change, signalling for the initiation of some kind of biological response
what is an antagonist?
An antagonist is a ligand that binds to a receptor without producing a conformational change and initiating an intracellular signal.
what is a partial agonist?
A partial agonist is a ligand that activates a signalling pathway to an extent less than the maximum potential of the receptors available
what is an inverse agonist?
a ligand that produces the opposite effect to the full agonist when it binds to a receptor
what is a competitive antagonist?
A competitive antagonist occupies a receptor that would otherwise be occupied by an endogenous molecule and prevents that endogenous ligand from binding.
will not reduce Emax, just the dose needed to reach it
what is a non-competitive antagonist?
interferes with the receptor response in other ways. It binds to a site called an allosteric site, which just means a site other than the agonist binding site, and generally brings about some conformational change that prevents the receptor from working. will reduce the Emax
what is an irreversible antagonist?
a particular form of non-competitive antagonist characterised by antagonism that persists, even after the antagonist has been removed. The antagonism can only disappear when new proteins or enzymes are synthesized. Aspirin, for example, is an irreversible antagonist.
what is receptor affinity?
a measurement of how strong the attachment between the drug and receptor is, and how long it will take to dissociate
what is efficacy?
the extent to which a drug can produce a response when it is bound to all available receptors.
what is ED50?
The ED50 is the dose that produces a response that is half of the Emax.
what is potency?
the amount of drug required for a given response. This is related to how well the drug binds to a receptor, so tends to correlate with affinity, but is also related to the amount of response that the drug will produce, so is also related to efficacy.
Higher potency drugs will require lower concentrations of doses, so the potency is what determines the recommended drug dosage. this is important in drugs with adverse effects, as we tend to want to give the most potent drug
how much do prescriptions cost the NHS?
Prescriptions cost NHS around £15 billion/year or 10% of all healthcare costs
what can drugs do?
• Treating life threatening diseases • Treating risk factors • “lifestyle drugs” o Feel better/improving the perceived quality of life/ sense of well-being • Hedonistic enjoyment
why are medicines a problem?
- 7% of hospital admissions
- 15% of hospital patients have drug-related complication
- Prescribed drugs are now a leading cause of mortality
what are most receptors?
glycoproteins
drug-receptor complex formation is reversible with the biological response being proportional to the fraction of receptors bound
types of receptors for drugs
Channel-linked receptors
G-protein -coupled receptos
kinase-linked receptors
DNA-linked receptors
other kinds of ‘receptor’ – more targets rather than true receptors
• enzyme targets
• voltage-sensitive ion channels
• transporter proteins
what is therapeutic efficacy?
the concept of efficacy is not restricted to comparing the effects of drugs that act at the same receptor
the term therapeutic efficacy is used to describe the comparison of drugs that produce the same therapeutic effects on the biological system but do so via different pharmacological mechanisms
what is the therapeutic index?
the ratio between the ED50 of therapeutic affect and adverse effects
mostly the dose to do half the possible harm will be 100X greater than that to do half the possible good
how does interpersonal variation arise?
Arises because of various factors (e.g. differences in receptor number and structure, receptor-coupling mechanisms and physiological changes resulting from differences in genetics, age, health etc)
what is desensitisation?
Biological response to a drug diminishes when it is given continuously or repeatedly
Tachyphylaxis – desensitization that occurs very rapidly
Tolerance- more gradual loss of response to a drug – over days or weeks
causes of desensitisation
downregulation of receptor numbers
changes in receptor function or structure
exhaustion of mediators such as depletion of signalling molecules
physiological adaptation
increased drug metabolism - repeated exposure to a drug increases the liver’s capacity to metabolise it
what are the four stages of pharmacokinetics?
- Absorption
- Distribution
- Metabolism
- Excretion
what are the methods of absorbtion?
• Enteral
o Oral (PO)
o Buccal (under the tongue)
o Sublingual (SL)
o Rectal (PR)
• Parenteral
o Intravenous (IV)
o Intramuscular (IM)
o Subcutaneous (SC)
o Inhaled (INH)
• Topical application (directly onto site)what must an oral medication be to be successful?
- Be swallowed
- Survive gastric acid
- Avoid unacceptable food binding
- Be absorbed across the gastro-intestinal mucosa
- Survive hepatic first-pass metabolism and the enterohepatic circulation
benefits of oral
- Convenient
- Simple
- Can be easily self-administered
benefits of intravenous
- No concerns about absorption
- Rapidly achieved high drug concentrations
- No “first pass” effect
benefits of intramuscular
- Simple to administer
- Unpredictable rate of absorption
- Painful
benefits of subcutaneous
- Can be administered parenterally
- Absorbed well from subcutaneous fat
- Can be injected by patients
which methods of administration have the first pass effect?
oral and gastric
how are nitrates given?
under the tongue as they do not survive the gastric route
what does the speed drug distribution depend on?
the level of protein binding in plasma (mostly to albumin, which causes slower distribution) and water/lipid solubility
high water solubility and protein binding will mean the drug stays in the blood for longer.
more lipid soluble will distribute faster
size of the molecule is also a factor
what are the four phases of pharmacokinetics?
absorbtion, distribution, metabolism, excretion,
what is the volume of fluid of the different body compartments?
plasma - 4L
interstitial fluid - 12L
intracellular fluid - 32L
how to work out the volume of distribution?
C0 = D/Vd
C0 is the initial plasma concentration
D is the amount of drug administered
Vd is the amount of drug that has distributed
what is the livers effect on drugs?
reduces biological activity, increases water-solubility (for excretion)
Phase I metabolism – oxidation in microsomal mixed function oxidase system (usually inactive after)
Clinically, phase I is really important because this is the site of a lot of drug interactions as some drugs can induce/inhibit metabolism of other drugs.
Phase II metabolism – conjugation by either acetylation or glucuronidation
Drug can be excreted straight away, undergo both phases, just phase I, just phase II
how can drugs affect metabolism?
• Induce metabolism
o Produce more metabolising enzymes
Anti-epileptic drugs such as phenytoin
Chronic alcohol
• Inhibit metabolism
o Produce less metabolising enzymes
Erythromycin
important when administering drugs which require stable plasma concentrations such as warfarin
describe first-pass metabolism
- After oral does
- Must pass the gut wall and liver
- Can be metabolised before reaching the systemic circulation
- Pro-drugs can be activated this way
what are the ways a drug can be excreted?
- Kidney main organ of excretion (renal) (low weight water soluble drugs)
- Biliary excretion (common for drugs that undergo conjugation with glucuronide and drugs with a larger molecular weight)
- Faeces
- Breast milk
- Sweat
what happens to highly lipid soluble drugs?
cannot be excreted as they are reabsorbed in the kidney
what is entero hepatic circulation?
After liver metabolism, drugs or drug metabolites enter the bile and are carried into the intestinal lumen. There some drugs will be excreted in faeces (faecal excretion). Drugs that are sufficiently lipid soluble may be reabsorbed and re-enter the portal vein. This recycling between the liver, bile, gut and portal vein is known as entero-hepatic circulation.
It prolongs the residence time of drugs in the body, and therefore their effects.
The recycling of glucuronide conjugates requires the presence of bacterial flora. These bacteria have enzymes capable of hydrolysing conjugates, reverting the conjugate to a phase I metabolite that can be reabsorbed. Broad-spectrum antibiotics and other drugs that can inactivate or kill the bacterial flora can therefore reduce reabsorption and drug availability.
what is drug clearance?
Drug clearance can be defined as the volume of plasma which is completely cleared of drug per unit of time; it is usually defined as volume divide by time (ml/min or L/hr). It is predominantly caused by liver metabolism and renal excretion. Clearance is related to half-life in a way that drug with a high rate of clearance have a short half-life.
what is bioavailability?
Bioavailability is the fraction of the administered dose of unchanged drug that reaches systemic circulation. For drugs that are given intravenously their bioavailability is 100%, as all of an intravenous dose will enter the systemic circulation. However, this is not the case for drugs given via other routes (such as oral route). Therefore the definition of oral bioavailability is the AUCoral/AUCintravenous for the plasma concentration-time graph, expressed as a percentage.
