Immunology Block: Pharmacology 1 - Jitt Session On Basic Principles

Front 1

what's a drug? POISON? TOXIN?

Back 1

a chemical agent that affects biological systems in potentially useful way.

poison is opposite. drugs become poisons in high amounts.

toxins are poisons of biological origin.

Front 2

`what are the major divisions of pharmacology?

Back 2

pharmakodynamics - what drugs do to the body. drug concentrations, effects over time


pharmacokinetics - what the body does to drugs. absorption, distribution, metabolism, excretion

Front 3

how are drugs absorbed?

Back 3

1. oral (enteral) = intestines

2. parenteral (other than intestine, like IM or subcutaneous)

3. IV.

note that the kidney is the most important method of excretion.

Front 4

what's bioavailiability?

Back 4

the fraction administered which is actually absorbed and circulates.

Front 5

what's a receptor?

Back 5

binds a drug with high affinity and it transduces a signal into a biological effect.

note that albumen and alpha-one-acid-glycoprotein bind drugs like crazy but don't transduce an effect, so they're not receptors.

Front 6

what kinds of receptors are there?

Back 6

enzymes (drugs block enzymes = effect)

ion channels (drugs that block/activate chanels = effect)

extracellular (b1/alpha1)

intracellular (estrogen and other steroids working on the nucleus)

Front 7

drug-receptor interactions - what are the major ones?

Back 7

the most common kind of relationship is ELECTROSTATIC (hydrogen bonds, vanderwalls)

Hydrophobics (important for fat soluble)

Covalent bonding (least common)

Stereospecific (most drugs are stereoisomers whose receptors are specific for that form).

Front 8

aside of working through receptors, how else can drugs work?

Back 8

on other molecules via acid/base (antacids), surfactant changers (amphotericin B), and denaturing proteins (astringents)

Front 9

dose-response curve - what does it look like and what causes it to flatten out?

Back 9

all the receptors being bound causes it to flatten out.

if plotted normally, it's hyperbolic.

if semi-log (drug dose is log), it's sigmoidal. we use this because it's easier to plot the EC50 - the concentration where half the drug's effect is found.

Front 10

what are the two basic mechanisms through which drugs work?

Back 10

agonist - bind to receptor and activate.

antagonist - bind to drug and prevent agonists from working.

note that they depend of EFFICACY and AFFINITY.
Affinity is the probability a drug will bind the receptor. Efficacy is the function it'll have once that happens and is A PROPERTY OF THE DRUG.

Front 11

what's potency?

Back 11

a better descriptor for AFFINITY - drugs with similar effect are compared this way.

note that the drug with the lowest EC50 is the one with HIGHEST POTENCY (half of effect brought about by lowest concentration of drug).

Front 12

what's efficacy?

Back 12

if you see a graph with the EC50's all the same, potency (affinity) is the same.

If you see a graph with different maximal activations, these have DIFFEREN EFFICACIES.

if you don't get 100% response, can be a 'partial agonist'

if really, really low activity, can be considered an "antagonist" 'cause it's blocking the other agonists from coming in and working.

Front 13

what are common methods of action?

Back 13

direct activation of ion channel, activation of G-protein that goes and activates ion channel, G-protein to 2nd messenger, and activation of intraellular enzyme.

Front 14

talk about direct ion channel activation:

Back 14

the receptor is associated with the channel, binding causes it to open. examples are Ach working at neuromuscular junctions, gaba receptors that are excitatory, etc.

Front 15

talk about g-protein second messenger cascades:

Back 15

Gs - turns on adenyl cyclase to turn up cAMP to make lots of pKA.

Also, G-protein activation of PLC, which turns into IP3 and DAG. IP3 will release intracellular Ca++, and DAG will turn up PKC.

NOTE - Gi is NOT 2nd messenger- it's about G-protein opening of ion channels. In the case of the heart's change based on Ach (slowing), it opens K channels to hyperpolarize the cell.

Front 16

what about those linked to enzymes? what's a really common one?

Back 16

this is about tyrosine kinase, so immediately think about insulin and growth factors. EGF, TGF-beta.

Front 17

Talk about competative vs. non-competative antagonists:

Back 17

competative antagonists bind receptors REVERSABLY - so there's constant competition between agonists and antagaonists for the receptor.

this means that with extra agonist, you can overcome the inhibition.

also, this means that the EFFICACY isn't affected. 100% maximal effect is still possible, but with a higher Ec50 (greater concentration needed, so potentcy dropped).

most drugs are competative.

there are also NON-competative - they bind PERMANENTLY and diminish the maximal effect of the agonist. these are relatively rare. called reduction of maximal effect.

Front 18

What's a reverse agonist?

Back 18

when binds, has the OPPOSITE effect of an agonist...not just blocking the effect.

happens when you inhibit something with basal activity.

Front 19

what are other kinds of antagonism?

Back 19

physiological - giving drugs with opposite effects (ach and norepi).

chemical - chelating (one chemical physically binds another).

pharmicokinetic - cause the metabolsim/clearance of another drug to go up.

Front 20

can drugs work on more than one receptor? example?

Back 20

yes - think about norepi. alpha activity causes vasocinstriction, beta activity causes bronchodilation.

happens because the receptors are coupled to different second messengers.

Front 21

are most drugs specific or selective?

Back 21

most drugs are selective. highly specific = only one receptor. most drugs have multiple.

when they're selective, they have one effect at low concentration, then start activating other stuff at high concentrations.

Front 22

what's the theraputic window?

Back 22

the concentration over which it has its intended effect, before having dramatically different new effects ('cause it's selective, not specific).

Front 23

what's ED 50?

Back 23

you can define a drug as either working or not...on or off.

Ed50% is the concentration at which half the population has the desired effect.

Front 24

what's theraputic index?

Back 24

TD50 is the concentration at which half the population has a toxic effect. LD50 is the concentration at which half the population is killed.

TI = TD50/ED50. Want this to BE VERY HIGH - if the TD50 is high and the ED50 is low, there's a BIG DIFFERENCE Between the poisonous and non-poisonous dose.

if it's low (like 2), doubling your dosage is toxic - and this is bad.

Front 25

what's certain safety factor?

Back 25

Ld50/ED99

want thisto be REALLY HIGH, much greater than 1.

Front 26

what's potentiation?

Back 26

AKA synergism - two drugs, if combined, can simply add their effects together. this is additive or summation.

if they combine and exceed their sum, this is POTENTIATION/SYNERGISM. this requires that they act at DIFFERENT RECEPTORS or have different mechanisms. Norepi and cocaine are like this.

Front 27

what's desensitization?

Back 27

can be caused by changing or loss of receptors. loose effect over time.