Introduction to Pharmacology Flashcards
What is the meaning of pharmacokinetics?
This is what the body does to the drug (breaking it down, metabolising, absorbing).
What is the meaning of pharmacodynamics?
This is what the drug does to the body (binding, drug- receptor interaction, the biological action on the body).
What is the meaning of drug?
A chemical substance of known structure, when administered to living organism, produces a biological effect (interact to change biological processes).
What is the meaning of medicine?
usually (not necessarily) contains one or more drugs which is administered with intention of creating therapeutic effect.
What is the meaning of therapeutics?
Use of drugs to diagnose, prevent and treat illness.
What is the meaning of formulations?
How the drug is packaged (different chemical substances including active drug combined to produce medicine- excipients).
What is the meaning of excipients?
Substances formulated alongside the drug (make it acceptable to body and make it to the site). For example, coating/ waxes so can protect from stomach acid.
What are the 3 names that drugs have?
-chemical name (chemical structure)
-generic name (class of drug molecule belongs to)
-proprietary name (manufacturers name for drug)
What is a ligand?
A molecule that binds to a receptor (ACh)
What is a receptor?
The molecular target for a drug (ACh receptor)
What is a agonist?
A molecule that activates a receptor (excite molecule membrane-local depolarisation).
What is an antagonist?
Blocks or reduces agonist mediated responses.
What are the 2 types of ligands?
Exogenous and endogenous.
What is exogenous ligand?
Comes from outside the body (morphine)
What is an endogenous ligand?
Comes from within the body (ACh).
What substances could a ligand be?
Drug, NT or hormone.
What kind of receptors do ligands act on?
Different receptors (muscarinic and nicotinic)- different effects with same ligand depending where in the body and which receptor.
What is the meaning of target in reference to drugs?
A molecule that is accessed by drug to produce a therapeutic effect.
For example, aspirin is distributed all around the body but mostly never reach the target (some molecules bind with the target protein by ‘accident’).
What are features of an ideal drug?
-desirable pharmacological action
-acceptable side effects
-reach target at right conc. and at right time (conc too low, not sufficient enough to treat)
-remain at site of action for sufficient amount of time
-be rapidly and removed from body when no longer needed.
What is the meaning of affinity?
How well the ligand binds to the receptor (strength go agonist- receptor interaction).
How do drugs produce effects?
Usually interact in structurally specific (lock and key). Steric interaction (based on spatial 3D relationship).
What are 2 properties that affect drug- receptor binding?
Physio chemical properties- electrostatic charges.
Steric properties- physical shape.
What is the link between genetics and responses to drugs?
Drug targets are proteins, proteins encoded in genome, possible genetic variation in receptors (different structures in different people) and therefore could lead to different responses to the same drug.
What has a major impact on the action the drug will have?
Cellular or tissue target (same drug is having different effects in different tissues).
What are the 4 common protein targets?
-Receptors
-Ion channels
-Carrier molecules
-Enzymes
What are the features of receptors?
-biologically relevant molecular site with which a drug binds to produce a response.
-once ligand binds, slightly changes shape allowing ions to pass into the cell
-ACh activated endogenous
-nicotine activates exogenous
What are an example of receptors?
G- proteins linked to trans- membrane receptors.
Process of G proteins being released.
Ligand binds, activates intracellular second message cascade (cellular excitability all over cell), modulation of other ion channels (alter way some genes activated).
Down- regulation of G-proteins linked with receptors.
What are features of ion channels?
-Movement of ions across membranes
-complex membrane protein (physical pore)
-selectivity filter (which ions come in and out)
What are features of carrier proteins?
-facilitators for transport (across membranes)
-active transport, facilitated diffusion
-inhibitor/ false substrates are common drug types
What are features of enzymes?
-enzyme inhibitor- normal reaction is blocked by drug
-eg aspirin (pain, inflammation and clotting)- blocks thromboxane and prostaglandins (sensitise free nerve endings).
What is the process with enzymes for an abnormal metabolite being produced?
The false substrate takes the place of the endogenous substrate, deters the function of enzyme by taking place of the original and producing inappropriate product.
What is the process with enzymes for an active drug being produced?
Starts with pro-drug- codine converted in liver to morphine (activated) therefore forming active drug.
What are the 3 families of drugs that interact with enzymes?
-enzyme inhibitors
-false substrates
-prodrugs
What is drug specificity?
Extent to which the drug only produces the desired effect without causing any other physiological changes.
Do drugs have complete specificity?
No, non-specific are very likely, drugs likely to be promiscuous (bind to many other receptors).
More likelihood of non-specific interactions becoming significant with larger doses.
What are the side effects like with non- specific interactions?
Less potent effect (desired effect will hopefully be the strongest).
With regards to Pharmakinetics, what are the 4 processes that determine the onset and duration of drug action in the body?
-Absorption
-Distribution
-Metabolism (some directly metabolised and never find target)
-Excretion (many excreted without interacting with tissues)
what is the meaning of drug- cell interaction?
The drug having the effect on the body.
What is the meaning of absorption?
Process by which the drug reaches the systemic circulation.
What is absorption affected by?
-route of administration (inject, pill, inhale)- MUST BE IN SOLUTION
-permeation (how ligand physically gets through different barriers in the body).
What are the 2 routes of administration?
-enteral (via gut- oral, rectal)
-parenteral (not via gut- injection, topical)
What are the pros and cons to enteral administration?
-low infection risk
-very simple (self- administer)
-harsh environment in stomach
-first pass metabolism
What is the process of first pass metabolism?
-after taking the dose of the drug- gut wall contains enzymes that can break down some of that drug and so immediately excreted
-some is lost through metabolism in the gut
-blood supply from gut doesnt join systemic circuit, so sent straight to liver
-liver is primary organ for drug metabolism (inactivate drug)- so lose quite a lot of the active drug- reduced bioavailability.
What are the pros and cons to topical administration?
-local effects (high conc in local area)
-limited first pass metabolism
-suited to slow continuous administration
-risk of systemic absorption
-low infection risk
-process of lipid permeation (must be lipid soluble)
What kinds of injections are there?
-Intravascular (directly into bloodstream)
-Intramuscular (injected into skeletal muscle)
-Subcutaneous (absorbed from subcutaneous tissue)
-Dermal (dermal vascular layer)
-Depot injection (usually suspended in formulations- slow release over long period of time).
What is the definition of bioavailability?
Proportion of active drug that reaches the systemic circulation and is free to bind to its target (some aren’t metabolised at all and so rely on excretions).
How do routes of administration effect the bioavailability curve?
-Intravenous (not a lot of absorption, no 1st pass metabolism, instant bioavailability)
-Oral (broader and slower peak, takes time to be absorbed and distributed)
-Slow release (long period of time, absorbed in tissues before entering systemic circulation)- very long peak.
What are the 3 factors affecting distribution?
-Protein binding
-Blood flow
-Membrane permeation/ tissue solubility
What is protein binding?
-Dynamic equilibrium for most drugs, binding reversible
-only unbound fraction can cross membranes or bind to receptors (produce pharmacologic effect)
-if plasma proteins (albumin) bind to drug- not likely to get from circulatory system to target.
What is impact of blood flow on distribution?
-primarily through circulatory
-tissue perfusion rate per tissue is important
Where is perfusion the largest?
In the lungs- absorbed readily, therapeutic dose builds up a lot quicker.
What is the impact of membrane permeability on distribution?
-Fick’s law
-lipophilicty- have to balance- want to pass but also soluble in H2O
Which types of molecules diffuse easier across the membrane?
Uncharged, non- ionised molecules.
What are the 2 phases of metabolism?
1= produces toxic metabolites
2= converts toxins into soluble metabolites for excretion
What is the order of the phases?
No order- 2 can happen before 1 or in the absence of 1.
After phase 1, what is the molecule called?
Derivative.
After phase 2, what is the molecule called?
Conjugate (completely soluble and inactivated)
What occurs during phase 1?
Involves oxidation, reduction, hydrolysis reactions.
-changes polarity of substance, increase water solubility, reduce pharmacological activity, may activate prodrugs.
What occurs during phase 2?
Conjugation- adding of endogenous substance (making it water soluble and biologically inactive)
What is the process of excretion?
Nephron processes filtered drug metabolites, only unbound drugs processed, reabsorption of lipophilic drugs (drug metabolites can end up in fingernails).
What is the process of biliary excretion?
Primary excretory route
-hepatocyte uptake=bile=duodenum=excretion in faeces
What can gut bacteria do to the drug?
Can re-activate (convert drug back to its original form) so reabsorbed into intestinal wall, re-circulate in blood and metabolised in liver and re-secreted into bile.
