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Introduction To Pharmacology
September 1999

Last updated 04/10/00 12:26 PM



Give a drug to effect change for desired outcome( NS, HR, bioelectric process), and effect a pathophysiological process( medical pharm is a reason to treat, diagnose, prevent a fundamental purpose

A drug is a substance that interacts with a biological process, and interact with a receptor molecule, on the cell membrane or in the cell. Drugs are formulated for action and for delivery. Its concidered a ligand which is a substance that interacts with a biological process by fitting into a receptor molecule.

Nutritional substances are drugs which do not undergo rigorous testing

How to get drug to target site – solubility(water or lipid) & where receptor is

Solubility – concider route – if the target isnt in the GI then drug needs to cross gut membrane, so the process involves absorption of drug into the compartment of the body its designed for.

Process of absorption

PHARMACOKINETICS - solubility, absorption, distribution, elimination( metabolism & excretion), active ingredient & formulation such that it augments



Ligands – size- small size increases specificity and distribution

Shape- inc specificity, isomers (levo & dextro) used in racemic mixtures but the inc in the selectivity is in one shape or the other RT where it fits – this inc specificity.

Heparin is a big molecule 50K Daltons, and therefore it does not distribute into the intracellular space. Think of heparin vs lovenox.(low molecular weight)

electrical properties( extent of ionization) interactions with, receptor types, facilitate absorption and distribution. There are agonists & antagonists. Competitive antagonists, non competitive antagonist, mass action . Ligands can directly interact with ion on the nicotinic receptors

Receptor – specific affect or cascade of effects. There are spare, desensitizing, upregulating, downregulating

Know the classification of drugs, and side effects related to the calsses

Graphs – linear, logarithmic, efficacy, potency, response, EC50, Emax, therapeutic goals related to EC50,

Toxicity, potency, rt shift

Integrate text to give us a foundation @ how drugs work, get in. Learn @ concepts and relate them to clinico pharmaco therapeutics

This course is rote memorization. Katzung is good – its in the library

FIGURE 2 – 8 ligands bind to receptor and receptor now interacts with another molecule such as an enzyme( JAK,STAT) Ligand binds to a receptor ΰ cascade pf eventsΰ cellular response IE ach binds to channelΰ channel opens ΰ Na goes into cell ΰ action potential vs NO or steroid enter the cell and then interact via cascade effect ΰ turn on genes and cause its effect (this one is longer lasting and also takes longer to act)

FIGURE 2.6 – ligands interact with receptor to activate or inhibit.

Ligands agonist form- binds to receptor and activates a process ΰ direct effect such as opening a Na channel & indirect effect – like G protein activatedΰ adenylate cyclase ΰ stimulates c AMP from ATP ΰ acts as a 2nd messanger (amplification)

Antagonist – blocker – binds to a receptor and blocks or prevents event receptor acitivation





Radio or histo chamicals label ligands and trace where they go.

We need to learn how to look at graphs FIG 1



MI patient – beta block and nervous patient overcomes beta blockade via endogenous chatech release

Non competative

Max response altered with dec # receptors to hook with drug, but EC50 is the same

Efficacy prop to # receptors blocked, but EC50 not affected secondary tp diminished mass action response, spare receptors??????????? Dose dependent . If knock out 20% of the receptors then knock out 20% or the response, this relationship is proportional.



Graded dose response curve looks at biological cells as opposed to a group of study participants.

Agonists stimulate binded receptors – Full agonist

Partial agonist – stimulates receptors but not as well as FA, see inc HR but not as well as with max response. FIG 6



Agonist if FA or PA depending on its affinity and whether phosphoralation is saturated

Cascade and amplification determine whether agonist is FA or PA see pg 10 – CPMRS

Fig 7


O conc – partial agonist competes with FA but doesn’t elicit full response, but dampens the effect of the FA, check HR in presence of inc conc. Mass action plays a role

Antagonist (blocker), CA – usually reversable, NCA – usually 1 block, RA – reversable, IA – irreversable

CA - competes with some binding site as agonist – weak bonds and mass action

NA – weak bonds, come onn and off. Doesn’t compete with some sites as agonists – usu irreversable

blocker, covalent bonding means high affinity

Alpha, AR phenoxybenzamide – high affinity, not reversable, receptors need to be downgraded –

regulated. So NC IB ΰ downgrading so new receptors need to be made.

Inderal is a CA and there is no change in EMAX FIG



Fig 9 B = blocker

Look and compare the NCB – it takes away the # of receptors in process and no change in affinity occurs so the EC50 is the same

Dose response curve is good at comparing the different concentrations of drugs.

Therapeutic Index - TI

Quantal response – it is or it isnt FIG 2 – 19 in handout

TI. Potency for individual, check for partial conc graded dose response curve vs. Quantel dose effect, QDE. Potency is graded on DR Curve. QDR curve ~ population and looks at different drugs comparatively.

GDR – potency individual drug, selectivity, drug x vs cough supression – look at response close to receptors. Max effect – yes

QDE – potency – pop drug – drug,

selectivity – sense of marker relationship to dose.

Max effect no because one may or may not have a headache at a specific conc

Titration occurs and start woth lower dose 1st – this gives some sense of what variability of how

Respondants react

Reasons why drugs ?????????

NC agonist EC50 the same, max response is ½

Can swithc to see what does what antagonist to agonist and visa, check EC50, efficacy, potency, and what changes, what parameters are affected..

PHARMACOKINETICS – goal is to get drug to receptors. Most drugs are designed toward specific receptors but exceptions do exist – mannitol osmotic diuretic, but it changes osmolarity by pulling water out of bloodΰ urine excr – there is an end effect.

Most drugs have affinity for a specific receptor so as to ellicit a specific response – ie B2 inc HR and bronchodilates

Absorption is affected by molecule size( usu < 1 KD) , type of transport across the cell membrane(SD, AT, CMT) PCN is via AT thru renal tubules, solubility – lipo, hydro

HENDERSON H eq – (HA = weak acid)

HA < H+ + A- this is for a weak acid where HA gives up a proton, (becomes charged)


BH+ < H+ + B (the B gives up the H charged part of the molecule, now its not charged)


An acid in > acidic environment is uncharged

A base in > basic environment is uncharged

Get drug across cell membrane, make it uncharged

A charged molecule attracts water because its polar, so give drug which works in blood a charge

Water goes to an acid with a charge A-

Water goes to a base BH+ with a charge

Ionization constants – most drugs are weak bases

Most weak acids have low pKa but not tylenol

HA, if pH is lower than pKa , then there is > uncharged molecules, more drug is unionized

If HA is in a > acidic environment, then the pKa is low and > molecules are uncharged, the acid is



The further away the pH is from the Pka there is a higher # of charged molecules present.

PH < pKa ΰ charged

PH > pKa ΰ uncharged & bases end up uncharged

FIG 11






Distribution is influenced by blood flow – brain, heart, liver is determined by the

bld flow,

by cap perm (placental or BBB vs kidney or spleen fenestrations/junctions in cap walls)

by plasma protein binding, major ones ( albumin, globulin, lipoprotein, RBCs)

drug reaches target place if free from PP- inc PP binding keeps drug in circulatory system.

PP bound drug has inc ½ life and a changed rate of clearance, there are enzymes in the lung and

blood. Drugs bound to PP are not filtered by the kidney. HA have inc affinity to PP, ASA coumadin

Weak bases have low affinity - ethanol.

Pts with dec albumin need to change dose – ie burns and dec albumin CL = clearance

Metabolism = biotransformation – changes soluability of parent compound from lipid to aq soluability,so it will be excreted from the kidney. Lipid soluble doesn’t get filtered out of kidney so phase 1 and phase 2 reactions are necessary.

Metabolic activity varies precursor-prodrug – maintain parent and metabolite ie benzidiazepines, also think of activity.

1st pass after Po through liver. Most biotransformation occurs in the cell’s microsomes – smooth ER lisosomes, mitochondria & change lipids to aq in the microsomes.

FIG 12


Oxidation is via an independent family of enzymes called cytochromeP450 – CP450, which exists in all cells mostly in liver, and they are responsible for Ph 1 biotransformation.and also for upregulation & downregulation.

These induce ph 1 -- CYP3A & CYP2B- liver, 60% relevent drugs , genes to them exist

Drug metabolism – lipid to keep lipid soluable.

Toxicity – usually less with metabolism though exceptions do exist ie: tylenol undergoes ph 1 ΰ toxic

Metabolite ΰ ph 2(glutathione conjugation) ΰ detoxified

If there is too much toxins , there may not be enough enzyme or GSH to get rid of the toxins, & since liver is so involved and has so much CP450 – th eliver can become toxic ie tylenol OD.

Gluco upregulates CYP3A and dec enzymes activity for ph 1 biotransformation for metabolites


Side effects – every thing causes side effects. o2 oxidizes protein; and water intox can cause death reaking havoc with lytes etc, so everything is toxic – toxicity is dose dependent ie water – a lot is required to be lethal, and botulism – a very small amount is lethal. LD is lethal dose. Understand the distance between the ED & LD. Drugs with a wide TI are safest. Know TI

Toxicity – lethal, carcinogenic, tetragenic, mutogenic, so its not so much death but the other variables.

Next time – follow drawing –HA through organs

Drug A not metabolizedby liver, is freely filtered by kidneys, is a weak acid, pKa of 6.5, if urine ph is 5 what happens to drug. Does it stay in tubulus, get reabsorbed, or get excreted.




Think about precursor of ASA GI why it gets ols where it does, is it metabilized, how is it destroyed and excreted.

Thes renal excretion other poreres.


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