12 Pharmacology Introduction Flashcards
Pharmacology definition
the study of effect of drugs on the function of living systems (with respect to therapeutic drugs)
What’s involved in pharmacology (4)
Discovery and development of new medicinal products to treat disease
Improve drug effectiveness and reduce unwanted side effects
Understanding individual variation in drug response
Undertsanding why some drugs cause tolerance of addiction
Physiology/Pathophysiology - multicellular organism chemical communication
Multicellular organisms have a system of chemical communication they use to coordinate their cells and organs
Physiology/Pathophysiology - endogenous chemical evolution
Endogenous chemical molecules have evolves to fine-tune the control of cells and physiological functions (eg. Neurotransmitters and hormones)
Drug definition
substance when introduced to the body produces a biological effect for an intended purpose
Poison definition
Intended to have harmful effect on the body
Drug and poison link
All drugs are poisons - the dose determines that a thing isn’t poison - at therapeutic levels drugs are safe and effective
Where do drugs come from (3)
- Natural products - plants / microbes / animals
- Changing structure of an existing molecule
- Serendipity (“by accident“)
Where do drugs come from - natural products
Poppy - morphine (painkiller / addictive) —> heroin (addictive illegal drug)
Salicylic acid (painkiller - very bitter non-compliance) —> aspirin (painkiller)
Both of these were converted from the 1st substances to the 2nd but Dr Felix Hoffman (semi-synthetic 1898-1899)
Where do drugs come from - serendipity
Sildenafal - developed as an anti-angina drug (now known as viagra - billion dollar blockbuster for Pfizer)
Molecule to man
Select disease (indication) —> identify target (protein, DNA etc.) —> synthesis selective ligand —> assess function
When do drugs not work
Molecules in an organism vastly outnumber drug molecules —> random drug distribution throughout the body - no pharmacological effect
A drug wont work unless it is bound’
Pharmacokinetics pathway
Drug administration
Absorption
Distribution (intra/extravascular space / protein binding / tissue stores
Metabolism
Excretion
Pharmacodynamics pathway
Transfer to the site of action from pharmacokinetics distribution
Drug concentration at the site of action (interaction with regulatory proteins)
Molecular targeting
Drug mechanisms of action (MOA)
Response to drug (efficacy and toxicity)
CLINICAL OUTCOMES
Pharmacodynamics
“the effect of drug on the body”
Pharmacodynamics investigates the mechanisms of drug action - including molecular, cellular and physiological effects of a drug relationship between drug concentration and effect.
Confirms drug safety and efficacy / minimises adverse effect / optimum doagase
Drug targets include cellular coupons at…
Receptors / ion channels / transporters / enzymes
Extracellular / cell membrane / intracellular
Ways a drug interacts with a target to produce a biological effect, whats this determined by?
Intermolecular forces, steric match and the type of bond formed
Small molecule drug binding site (description)
defined pocket/cavity in the structure of the drug target
Where may drug-target interaction occur
at the active or orthostatic site (endogenous interactions occur)
allosteric site elsewhere on the drug target
Why do some drugs bind to their targets reversibly and some irreversibly
Depend on bond types formed
Affinity
Binding strength of a drug to a target
Drug efficacy
Ability of a drug to elicit a response once bound to drug target
Agonists
endogenous or exogenous molecules that have affinity for and efficacy at a receptor to elicit a biological response
Antagonists
molecules that have affinity for a receptor to limit the effect of agonists but lack intrinsic efficacy
Drug selectivity - whats it determined by
Determined by affinity and efficacy for one target vs another
Each drug target recognises only a small number of molecules of which have some structural similarity (eg. Histamine receptors)
What are different receptors for the same endogenous agonists called?
Subtypes
some drugs exhibit selective activity towards different subtypes
Potency
Among of drug expressed as a concentration or dose needed to produce a defined effect
Mechanisms of drug actions, what does this refer to
process by which a drug produces a biological effect
On what levels can mechanisms of drug actions be observed
Can be observed at multiple levels - molecular, cellular, physiological events that produce the observed outcomes
Mechanisms of drug action - what does this include
may involve blocking, limiting, activating or enhancing a physiological process
… have specilised by physiological function
Targeted cells / tissues
