Introduction to Pharmacology Flashcards
Learning Outcomes
- define terms including drug, pharmacology, toxicology, therapeutics
- distinguish between a drug’s chemical, generic and brand names and appreciate the usefulness of common endings in recognising a drug’s class
- list the various sources from which drugs are derived
- describe, with appropriate examples, the interaction of drugs with binding sites on a variety of protein and non-protein targets
What is a drug?
Any chemical which affects physiological function in a specific way
•medicinal compound for treatment of disease/symptoms?–paracetamol, penicillin?
•substance of recreation/abuse?–heroin and cocaine?
•toxin or poison?
•everyday substance–caffeine, nicotine, alcohol?
What is pharmacology?
The study of the way in which the function of living things is altered by chemical agents
What is toxicology?
The study of toxic or harmful effects of chemicals, their mechanisms and conditions of occurrence
What are therapeutics?
The branch of medicine concerned with the use of drugs to treat a disease or its symptoms
What are the different names drugs can have?
- Chemical–too unwieldy for routine use e.g N2-[(1S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline
- Generic (non-proprietary)–officially approved, abbreviated chemical name –common endings often provide clues to chemical class, pharmacological action–used in international scientific publications and on prescriptions Example: ending ‘..PRIL’ = Angiotensin converting enzyme inhibitors Block synthesis of vasoconstrictor peptide Angiotensin II (captopril, enalapril, ramipril, lisinopril etc)
- Commercial (brand) –often more catchy, but random, contain little useful information about class, mechanism
From what sources can drugs be derived?
- individual chemicals purified from cells and tissues –traditionally plants –examples: atropine from Atropa belladona, morphine from Papaver somniferum
–less often amphibians, reptiles, occasionally mammals e.g. porcine insulin
–bacteria, streptokinase enzyme produced by haemolytic bacteria, effective, cheap drug used to dissolve blood clots
•chemical synthesis by pharmaceutical industry–synthetic derivatives (at first simple chemical modification of natural chemicals extracted from tissues)
–drug discovery, development programmes–computer modelling of targets/fit-rational drug design–initially small simple molecules, increasingly complex today
- large scale production of recombinant human proteins–protein-based therapies e.g. human insulin for diabetes
- antibodies to human proteins e.g. tocytokine mediators for treating inflammatory disease
What pathway do drugs take to work in the body?
- drug is administered into human body–tablet, inhalation, injection, cream, eye drop etc
2, may act locally or else need to enter bloodstream to travel to intended site of action–oral drugs need to be absorbed from gut and pass via liver into bloodstream»>
- finds and interacts with a specific molecular target (which may be located on/inside particular cells) in order to produce an effect
What bonds are involved in binding drugs to their molecular targets?
•binding of most drugs to proteins is sufficiently unstable that it can be reversed
•ionic bonds probably most important–complimentary chemical nature of drug and target
•weak hydrogen bonds and van der Waals forces also contribute
•covalent bonds generally not involved–tend to be so strong that almost irreversible
binding pockets are highly specific, small changes in chemical structure of drug or target can have major implications for drug-target interactions
Classification of drugs based on their action on molecular targets requires knowledge of
•Nature of molecular site
•Nature of drug’s interaction with that site
Drugs acting on targets located inside cells need to be small/lipid-soluble or use a carrier mechanism to cross cell membrane
What is the molecular basis for drug selectivity?
- ‘ideal’ drugs only interact with specific molecular target in a particular tissue to cause desired therapeutic effect in that tissue–activation/inhibition of the same specific target if present in other tissues could cause unwanted effects–route of administration is important
- in practice drugs are ‘selective’ rather than ‘specific’ and unwanted effects are common–enough of the drug might also interact (less strongly-weaker bonds-poorer fit) with alternative molecular targets to cause undesired effects especially when the drug is present at higher concentrations
What are some molecular targets for drug action?
•proteins –ion channels –membrane transporter (carrier) proteins –enzymes (intracellular, extracellular) –non-cellular proteins –receptors
- nucleic acids
- miscellaneous targets
What are the 3 ways ion channels can interact with drugs as channels?
•Blockers
•Allosteric modulators
–inhibitor
–facilitator
What is the role of blocking ion channels?
Blockers physically block pore of open channels
Example:drug:lidocaine(local anaesthetic)
target: voltage-operated sodium channel(especially small diameter sensory nerve fibres/pain pathways)
What are allosteric modulators?
Allosteric Modulators -passage through channel pore regulated by gate opening/closing due to chemical or electrical signals, mechanical force
-allosteric modulators cause shape change in channel protein on binding elsewhere on the protein
-This affects properties of gate and influences time for which channel is open (and ions can move)
Inhibitor:less ions can enter, ↓ response
Facilitator:more ions can enter, ↑ response
Example of an inhibitor modulator?
–drug: amlodipine
–target: voltage-operated (electrically-gated) Ca2+channel
–↓entry of calcium ions required for vascular smooth muscle contraction, so ↑ blood vessel dilatation, ↓ blood pressure–also relax coronary vascular smooth muscle,↑ coronary blood flow (↑ oxygen supply to heart muscle)
E.G- hypertension, angina prophylaxis
