intro to pharmacology Flashcards
what is pharmacy?
the handling of drugs
- preparing, presenting and dispensing
what is pharmacology/toxicology?
science of drugs
- drug design and synth
- research into effects and mechanisms of drugs
- absorption, metabolism and excretion of drugs
what is therapeutics?
the medical use of drugs (treatment of diseases and their symptoms)
how do drugs work?
most drugs at on normal cells (affect normal cell function)
- chemicals which bind to molecules in cells (usually proteins) and in doing so mimic (agonists) or block (antagonists) the action of endogenous molecules or processes
what are chemotherapeutic drugs?
agents that act against infectious micro organisms or cancer cells by exploiting biochemical differences between host and target cell
what are chemotherapeutic drugs used for?
treat infections and cancers - work less well on cancer as the cells are similar to normal cells
- drugs can be chemically identical or similar to an endogenous (growing from within) molecule of chemically distinct from any known endogenous molecule
where are binding sites for drugs found?
on enzymes, carrier molecules, ion channels and receptors
what are receptors
proteins, generally in the cell membrane, designed to recognise a messenger of great specificity at a specific recognition site (lock and key)
what happens when a drug binds to a receptor?
once binding site is occupied the receptor undergoes a conformational change and the signalling cascade is initiated, changing the function of the cell
what is the affinity of a drug KD for its receptor?
the conc of drug required to occupy 50% of the receptors at eqm
what is affinity?
how tightly the drug will bind to the receptor’s specific recognition sites
what effect does high affinity have on KD?
low KD - little drug needed to half-occupy receptors
what is efficacy?
ability to activate the receptor so a response is produced (likelihood of the conformational change which leads to signalling cascade)
what are agonists?
drugs that activate receptors
what are antagonists?
drugs that bind to receptors but do not activate them
what is the dose - response curve and what is its shape?
a plot of proportion of receptors occupied [P] against drug concentration [D]
rectangular hyperbole
what is the shape of log[dose]-response curve
symmetrical sigmoid
why may a drug have high potency?
high affinity to receptor, high efficacy or low metabolic breakdown in the body
what are the properties of an agonist?
high affinity and efficacy
what are the properties of an antagonist?
high affinity but low efficacy
what do reversible competitive antagonists do?
produces a shift right of the agonist dose-response curve as it competes for the binding sites with the agonist
- size of right shift is dependent on the conc of antagonist
- if enough agonist is made then it will overcome the antagonist
what do irreversible competitive antagonists do?
produce a suppression of the maximum response
- degree of suppression is dependent on conc of the antagonist
- block by antagonist is not surmountable by increasing agonist conv
- this type of binding cannot be overcome by function of time, antagonist conc, drug metabolism and insertion of new receptors into the membrane
drug potency- what is the most effective drug?
one that works at minimal concs
chemotherapeutic agents - amoxicillin mechanism
inhibits synthesis of peptidoglycan - which forms the bacterial cell wall
chemotherapeutic agents - erythromycin mechanism
inhibits protein synthesis by action on 50s ribosomal subunit
chemotherapeutic agents - tetracycline mechanism
taken up selectively into precaryotic cells inhibits protein synth by competing with tRNA for binding to ribosome
chemotherapeutic agents - metronidazole mechanism
cause DNA strand breakage ; taken into cells and reduced to active form; reduction foes not occur in mammalian cells
what drug names do drugs have (3 types)
proprietary
common
chemical
what is Pharmacodynamics
describes what the drug does to an organism
-sum of all of the actions of a drug, incl side effects
what is pharmacokinetics?
describes what the organism does to a drug
-(absorption, distribution, metabolism and excretion)
what does pharmacokinetics determine?
how quickly it acts in a patient
- whether the target area is local or systemic
- how long the effects last
what is drug absorption governed by? And why?
lipid solubility
- as unless drug is injected intravenously it must pass several lipid bilayers
what are local anaesthetics?
weak bases
where are drugs given orally absorbed?
small intestine
- enter the portal circulation and then the liver where they may be extensively metabolised
what is bioavailability?
the proportion of drug reaching the circulation
absorption and distribution - when drug enters circulation where does it go?
rapidly distributed around the body but then must penetrate the tissues to work
absorption and distribution - what are drugs bound to? what is the effect of this?
plasma proteins
-slows entrance into tissues
drug elimination - how are drugs eliminated from the body?
metabolism and excretion
drug elimination - what is the metabolism of drugs?
the conversion of drugs from one molecule to another which may be active or inactive
drug elimination - what are the phase 1 reactions
Catabolic reactions which break down the drug into products which may be more toxic or active than the current drug
drug elimination - what are the phase 2 reactions
Synthetic reactions involving conjugation of chemical groups to produce drugs that may be water soluble.
drug elimination - where does detoxification of drugs usually take place?
liver
drug elimination - where else than liver can metabolism take place
plasma, gut and the lungs
drug elimination - where are most enzymes catalysing phase 1 reactions
liver cells in smooth ER (microsomal enzymes)
drug elimination - what can these microsomal enzymes be induced by?
some other drugs
effect ; speeding the metabolism of other drugs
drug elimination - where is drug excretion?
mainly via kidneys
drug elimination - how do drugs enter the kidneys?
drug elimination - lipophilic drugs
can easily diffuse out of nephrons and back into the blood so aren’t removed well
drug elimination - what is the half life of a drug
time taken for the substance to halve from its original amount
drug elimination - what is the effect of age on elimination
decreases with age so elderly take smaller doses
Drug Interactions - pharmacodynamic interactions
drugs which have similar or opposite actions or side effects
drug interactions - pharmacokinetic
A drug which alters the absorption, metabolism, distribution and excretion of another drug
drug interactions - what can occur when there is induction of hepatic enzymes by drugs
- can decrease the effectiveness of other drugs which are metabolised by the enzymes
- can increase the effect of other drugs which are metabolised by these enzymes
e. g. erythromycin and midazolam
Clinical Phases of Drug Testing - what occurs in phase I
- Small Scale
- Use healthy volunteers
- Test for pharmacokinetics, side effects and potency
Clinical Phases of Drug Testing - what occurs in phase II
- Medium Scale
- Use patient volunteers
- Test for efficacy of drug and to find the optimum dosage
Clinical Phases of Drug Testing - what occurs in phase III
- Large scale
- Again using patient volunteers
- Test for efficacy, optimise the dosage, incidence of side effects
- Double blind trial is usually done to compare new drug with current drugs or a placebo
Clinical Phases of Drug Testing - what occurs in phase IV - post licencing
• Drug is monitored for efficacy and safety
