PHARMACOLOGY

*Study of drugs sub special or scope.

*Study of interaction of chem. with living system
*Study of manner in which functions of living system is affected by
drugs
1.PHARMACODYNAMICS
-Action and effects of drugs
-Action of drugs on the body
-Drug site of action, therapeutic as well as side effects, which
comes hand in hand with the therapeutic effects.
2.PHARMACOKINETICS
-How the body handles the drugs
-Actions of body on drugs
-Fate of the drug from the time the drug is taen to e!cretion. "his
includes time of admin. , routes with available dosage, form,
absorption, drug distribution, drug metabolism, redistribution and
drug e!cretion.
3.PHARMACOGNOSY
-Science of drug sources and origin of drugs and physical and
chemical properties. #plants, animal, mineral and synthetic$
4.PHARMACOTHERAPEUTICS OR CLIN. PHARMACOLOGY
(Prescripi!"#
-Drug application in the management of various dse. , %!
#prescription$ of drugs is included here. Drugs are prescribed to
relieve, alleviate symptoms, cure, and prevent dse.
-&iven to replace or supplement drug use %D' are governed by(
S-afety
A-ffordability
)-eed
*-ffectiveness

$.POSOLOGY
-Dosages of drugs( how much+ "herapeutic dose #minimum,
average, ma!imum$
%.TO&ICOLOGY
-Adverse effects of drugs and how to manage its effects
-,ethal or to!ic effect and dose of drugs and antidotes
'.PHARMACOGENETICS
-"his includes adverse drug reaction related to genetic
predisposition #families-racial$
(.TERATOGENIC PHARMACOLOGY
-Deals with drugs problems, adverse effects and malformations on
developing embryo.
-.ncludes teratogenic drugs and adverse drug reaction or the
product of conception #fetus$
).PHARMACY
-Drug dispensing
AD*ERSE DRUG REACTION
-)ot dose related allergy #Ag and Ab$
-Dose related to!ic effects #to!ic dose$/Allergenic reaction
-Side effects #min., ave., ma!.$
-"eratogenic effect
-&enetic defect #en0yme deficiency$
-Allergenic reaction
PHARMACOKINETICS
-1iologic response is related to(
Drug concentration

At site of action

%elated to the dose

Fraction that reaches the site is dependent(

2.route of administration
3.dosage form
PHYSIOLOGIC +ACTORS IN+LUENCING DRUG
CONCENTRATION
4HA%5A678.)*".6S(
2A,SORPTION- drug ability to enter blood stream
3.DISTRI,UTION-drug movement to various sites
9.,IOTRANS+ORMATION- alteration #metabolism of chemical
structure of drugs$
:.E&CRETION-ability of living system to remove a drug and its
biotransformed products #metabolites from internal environment$
D7S*-----drug conc.-------response #binding site$
DOSE RESPONSE RELATIONSHIP
1iotransformation --------------- *!cretion
; ; -------------- 7ther site
Dose----- 1lood--------- Active site-------------- response
. Absorption . Distribution . .
. . . .
. . . .
. 4harmacoinetics------- . 4harmacodynamics .
. . . e-
. . conc. response----------------- n.s
. relationship
.<<<<<< Dose %esp. relationship<<<<<<<<<<<<<<<<
#4osology$

-G!./s i" P0.r1.c!2i"eics
2.5inimi0e in effective conc. of drug.
3.5a!imi0e therapeutic conc.
9.Avoid to!ic conc.
"herapeutic dose
5inimum dose 6eiling effect
5a!imum dose
Average dose
A,SORPTION
-"he process by w-c a drug enters the bld. Stream w-o being
chemically altered.
+ACTORS THAT IN+LUENCE THE RATE O+ A,SORPTION
2."ype of transport.
3.4hysicochemical properties of drugs #lipid solubility, ioni0ation$.
9.4rotein binding.
:.%outes of administration #most parenteral is intravenous$.
=.Dosage form.
>.6irculation of site of absorption.
?.Drug conc. #inc. conc. faster$. @asoconstriction-delay absorption.
@asodilation-fast absorption
Drug absorption is measured in hrs. A minutes.
TYPES O+ TRANSPORT
A. PASSI*E
a.$ Filtration - compds. cross mem. by
hydrodynamics flow.
b.$ Simple
%ate of drug transfer is directly proportional to their conc. gradient
across the membrane speed of passage is determined by ,.4.D
S7,'1.,."B.
#,ipid to H37 partition coefficient$
*"he higher the lipid to H37 partition coefficient, the greater the
rate of transfer across membrane.
*)on-ioni0ed drugs has greater rate of transfer than ioni0ed
drug.
)on-ioni0ed form depends on dissociation constant #p8a$ of the
drug A on pH of the medium shown by
HENDERSON3HASSEL,ACH E4UATION
p8a C pH D log conc. of non-ioni0ed acid
conc. of ioni0ed acid
Eea acid or acidic drug
p8a C pH D log conc. of ioni0ed base
conc. of non-ioni0ed base
1asic drug
Drug w-c are wea acid A base are highly absorb
Strong acid A base are less absorb
"heories(
)on-ioni0ed
,ipid soluble drug Absorbed
)on-polar drug
.oni0ed drug
)on-lipid soluble-H37 sol. )ot absorbed
ACIDIC DRUG #ph 9$ is absorbed best in the acidic medium
#stomach$ non-ioni0ed. *!. salicylates A barbiturates.
,ASIC DRUG #pH F$ is absorbed best in basic medium
#s.intestine$ non-ioni0ed. *!. plant alaloids
1.+ILTRATION- #no energy is reGuired$ H37 flows thru
membranes pores carrying with it any solute molecules whose
dimension are less than those of the pores. Ehen H.4. or 7.4.
e!ists across membranes. Solutes molecular w-c are greater than
2HH-3HH donIt pass thru
- .s the predominant process by w-c drugs cross most capillary
endothelial membranes.
*g. .)* J considered as basic drug #Alaloidal$
,.SPECIALI5ED TRANSPORT #involved membrane$ assoc.
6H7) carrier for drugs.
a. Active transport
b. Facilitated transport
c. 4inocytosis J speciali0ed transport of large molecule A protein
#greater than 2,HHH daltons$
1.ACTI*E TRANSPORT
a. Solute crosses the membrane against conc. gradient.
b. "ransport mechanism becomes saturated of high solute conc.
showing a transport ma!
c. 4rocess is selective for certain ionic or structural configuration.
d. .f 3 compounds are transported A will compitively inhibit the
transport of others.
e. "ransport process can be inhibited non-compitively by
substance w-c interfere w- cell metabolism.
2. +ACILITATED DI++USION
Sol. is not transferred against a conc. gradient. )o energy
reGuired.
3.PINOCYTOSIS J invaginated A engulf. Speciali0ed transport of
large molecule and 6H7) #greater than 2,HHH daltons$
"his comple! process the cells invaginate a small portion of the
cellular membrane and engulf a droplet of e!tracellular fluid
containing the compound.
Sie 60erei" c.rrier 1e7i.e7 7r89 r."sp!r is i1p!r.":
2.%enal tubule 9.1ld. brain barrier
3.1iliary tract :.&."
)on-polar drug - absorbed
*4olar drug J not absorbed
*Kuarternary ammonium compd.
-)ot absorb not transverse on in bld. brain barrier.
"ertiary
-Absorb A transverse bld. brain barrier.
,ipid sol. Jhighly absorbed
H37 sol. Jnot absorbed
PROTEIN ,INDING
-4lasma albumin binds maybe acidic drug.
1asic drug maybe bound by 1.globulin and acid glycoprotein.
4lasma
6H7) binding drug

?=L Free drug --------------- 41D #stage depot$
=L
#'nbound$
Drug

-Absorption
---1iotransformation
----- Distribution
---- ---- *limination #*!cretion$ F%**
DRUG ;PHARMACOKINETICS
A. 1!re P,D -FHL
-3HL free
-Has longer onset, longer duration
-" M longer, less freGuent, less prod. Administration
1./ess P,D - 3HL
- FHL free
- has shorter onset, longer duration
-%apidly e!creted, absorbed, biotransformed, " M shorter
T < -time wherein M drug in the plasma is reduced to M. #biologic
half life$
Highly 41D-has longer " M, 23hrs or more than 23hrs.*
,ess 41D-shorter " M, :hrs or 9hrs.*
METHODS +OR DELAYING DRUG A,SORPTION
2.'se of @asoconstrictors
Adrenalin w- local anesthetic delaying absorption, it will reduce
systematic to!icity A prolong the anesthetic effect of the drug.
3.'se an insoluble slow release form #poorly$ sol. salt ester or
comple! #4rocaine 4enicillin$.
9.*sterification of Steroid hormone
#"estosterone 4ropionate$-Steroid
#Flophena0ine Decanoate$-Anti-psychotic
:.Substance implantation of solid pellet #*stradiol$-rate of
absorption is proportional to the surface area of the implant.
=.4hysical characteristics of a preparation may also be changed by
combination #.nsulin Ninc suspension$.
.nsulin- fine amorphous susp. rapidly absorbed.
Ninc- susp. of large crystals w-c are slowly absorbed.
COLD COMPRESSION
-4romote vasoconstriction, slow absorption.
HOT COMPRESS OR MASSAGES
-4romote vasodilation, fast absorption.
*ASCULARITY
-5ore bld. supply in area faster bld. absorption, less bld. supply
slower absorption.
DRUG DISTRI,UTION
I. ,!7= >/8i7 c!1p.r1e"s
a. *!tracellular #plasma$ :=L of body weight
b. .nterstitial #2>L$
c. ,ymph #2-3L$
d. .ntracellular #9H-:HL$
e. "ranscellular #3.=L$
.nduces 6SF, intraocular, peritoneal, pleural, synovial A digestive
secretion enters the transcellular compartment to the e!tracellular
compartment a drug most cross a cellular barrier.
II.,/7. ,r.i" ,.rrier
-1rain is in accessible to many systematically acting drugs.
Disruption of this barrier can occur in the( A. 4resence of
inflammation #4enicillin$
1.4eptides #1radyinin, *nephalin, .nc. bld.brain barrier
permeability inc. pinocytosis$
6.*!treme Stress Jrenders the barrier permeable to drugs
#4yridostigmine$ a cholinesterase inhibitor.
D."ertiary Ammonium 6ompounds
-"ransverses the 111
*.,ipid Jsol. drugs transverses thru barriers.
F.,ipid Jinsol. Drugs are mainly confined to plasma A interstitial
fluid.

THERAPEUTIC INDE&
-%atio of the dose that produces
-"o!icity to the dose w-c produces clinically desired effective
response
"herapeutic .nde!Cto!ic dose
a ,D-,ethal dose
*D-*ffective dose -therap.
C"his is a measure of drugs safety since a large value indicates
that there are margin between doses that effective and doses that
are to!ic.
A.



1.
Fast absorption Slow absorption
*.ncrease bioavailability
*)on-ioni0ed increase lipid
solution
*"ertiary amines on 11&
*Drug in vial
*Acidic #stomach$
*Sublingual
*Eea acid and base
*,ipid in solution
*Steroid hormone
*Ninc and insulin
*7ral route
*4rocaine and penicillin
*.oni0ed water solution
*4rotein bound
*Acid and base
*1asic #stomach$
*@asoconstriction of area
I3ORAL ,IOA*AILA,ILITY
-"he fraction of administered drug that gains access to the
systemic circulation in a chemical unchanged formed for e!ample,
if 9HHmg of a drug is taen orally and 2=Hmg of this drug is
absorbed unchanged then the
.ncrease bioavailability Decrease bioavailabilty
Sublingual 6apsule
.@ @asoconstrictor
Ampulles 7ral route
@ials )on-lipid
)on-ioni0ed rectal 4oorly sol-ester
4arenteral route .oni0ed-polar
Subcutaneous-basic #s.i$ Steroid
II3+ACTORS THAT IN+LUENCE ,IOA*AILA,ILTY
2.first pass hepatic metabolism #liver$ from biotransformation
#presystemic$ drugs undergoing metabolism has low or decrease
bioavailabilty.
3.drug absorption
-Decrease absorption-low availability
-Fast absorption-high bioavailability
-Slow absorption-low bioavailability
III3PLACENTAL ,ARRIER-lipid soluble drugs
7H-centrally acting tetracyclic anti-depressant
-"eratogenic drugs penetrate the placenta
*!ample(
THERAPETIC INDE&
Drug A----=HHmg lethal dose C 9.9mg
2=H mg therapeutic dose
Drug 1----=HHmg C 2Hmg
=Hmg effective dose
-Safety higher margin
-increased ".., the safer the drug is
-Decreases ".., the more to!ic the drug is
*F%** D%'&
- Active, absorbed further, distributed
-5etabolism and eliminated-e!crete
*4%7"*.) 1.)D.)& D%'&
-Storage #temporary$
-.nert drug
*7)S*" 7F *FF*6"
-"ime taen drug to time effect
-Free drug short onset of effect
*D'%A".7)
-From time you get the effect to alter the time of effect gone
-Free drug short duration
-4rotein bound longer duration
*1A%%.*%
-)ot accessible to drug
-7nly readily absorbed drugs
-*!ample( tertiary amines, non-polar
*"7,*%A)6*- increase effect of drug used for a period of time
-*!ample( if there is a drug that has the same as the inducer #of
the same pathways$ then it diminished the effect of the drug.
-THE DRUG ACTION IS TERMINATED ,Y:
2. 5etabolism
3. 1iliary e!cretion
9. %enal e!cretion
,IOTRANS+ORMATION-is a process wherein a drug undergoes a
chemical change due to its interaction with an endogenous
en0yme system #or due to a non-en0ymatic reaction$
%esulting in an increase of polarity of the drug.
*5ain purpose is to mae the drug more readily e!cretable.
Ehy should a drug undergoes
,IOTRANS+ORMATION?
*"o convert a drug to more e!cretable metabolite.
*"o convert a pharmacologically active drug to an active drug to an
active metabolite #prolong$ or long acting drug.
*"o convert an inactive to an active metabolite.
*"o convert a drug into a more to!ic metabolite.
ORGAN RESPONSI,LE +OR ,IOTRANS+ORMATION
2. ,iver-maOor DD5S eg. 6ytochrome 4:=H
3. 8idney
9. ,ung
:. &." #intestine$
CLASSI+ICATION O+ THE CHEMICAL REACTION OR EN5YME
,IOTRANS+ORMATION
PHASE I REACTIONS-convert the parent. Drug to a more polar
drug metabolite by(
a. 7!idation-addition of o!ygen.
b. %eduction-removal of o!ygen.
PHASE II3CON@UGATION OR SYNTHETIC REACTION
.nvolves coupling the drug or its polar metabolite w- an
endogenous substrate
Such as glucoronate, sulfate, acetate or an amino acid.
PHASE I3REACTION
A.# O&IDATION
-.s carried out by a group of monoo!ygenases #o!idative en0yme
found in the hepatic endoplasmic reticulum. "his non o!ygenase
are usually a large family of isoen0yme called cytochrome 4:=H
which activates molecular o!ygen using reducing eGuivalents such
as ).67".)A5.D* AD*).)* D.)'6,*7".D* 47: #)AD4H$
Catalytic cycle for cytochromic P450 dependent monooxygenase
rxn.
%educed step 2
D4D Flo-4ro Drug-Fe9D %7H
#fluro-4rotein$ 6ytochrome D
4:=H H37
Step =
pH Fle-4ro step 3
7!idi0ed Drug Fe3D
73FeD73 3H
5icrosomal #*n0ymatic$ Drug 1iotransformation %eaction
PHASE I
A.O&IDATI*E REACTION
2.Aliphatic Hydro!ylation-4entobarbital, 4henylbuta0one
3.Aromatic Hydro!ylation- 4henytoin
9.*po!idation- 1en0opyrene, Aflato!in
:.)-Hydro!ylation-Dia0epam, 4ra0epam 5ethadone
=.7-Dealylation-codeine
>.=-Dealylation-5ethylthiopurine
?.)-Hydro!ylation- 3 AcetylAminofluorene
F.Sulfo!idation- 6hloroproma0ine
P.Desulfonation- 4arathion
2H.Dehalogenation- Halothene
,.# REDUCTION3REDO& RECYCLING3ELECTRON A66*4"7%
-Kuinone containing drugs wherein this Guinone containing drugs
is converted to an unstable semiGuinone w-c undergoes auto
o!idation A molecular o!ygen, forming F%** %AD.6A, #Super
o!ide w-c are to!ic$
%*D'6".7)
%edo! recycling
7
)AD4H ; .. - 73 Supero!ide

F,A-4%7 2 -; -; 3
..
)AD4 7
; .. -
- .. ; 73 molecular 73
Semi Kuinone
A.REDUCTION R&N.
2.)itroreduction J6hloramphenicol 6lona0epam
3.A0oreduction J 4rontosil
9.%eductive dehalogenation J 6arbon tetrachloride
:.%edo! recycling J Do!orubicin, 5itomycin
,.HYDROLYSIS Jaddition of H3H A cataly0e
2.*ster hydro!ylysis JAcetylcholine, Succinyl choline, Aspirin,
4rocaine
3.Amide J4rocainamide, ,idocaine, .ndomethacin
9.4eptide J4ro insulin #a parent drug .)A6".@*$
**ster A Amide Jproduces carbo!ylic acid metabolism.
PHASE II CON@UGATION
"he formation of glucoronides is cataly0ed by hepatic
glucoronyl transferases located in the endoplasmic reticulum,
these en0ymes 'S* '%.D.)* D.4H7S4HA"* &,'67%7)A"*
as the donor of &,'67%7)A"*.
PHASE II3CON@UGATION REACTION
%eaction type *n0yme *!ample
2.glucuronidation
#1D6$-most
common
'D4-
glucoronyl
transferase
1ilirubin
Dia0epam #an active drug
becomes an active
metabolite$
6hloramphenicol
3.sulfation *AA Sulfotransfera
ses
*sterases, androsterone,
acetaminophen
9.acetylation .S Acyl co-a
transferases
.sonia0id, sulfonamide
:.methylation )" 5ethyl
transferases
)orepinephrine, thiouracil
=.glutathion
conOugation 1*
&HS
transferases
1romoben0ene, ethacrynic
acid

INDUCTION O+ THE DRUG META,OLI5ING MICROSOMAL
SYSTEM (I"78ce !r I"0iAie7#
How does it occur+
*"here is prior e!posure to the drug #pre induction$
*"he inducers binds to the specific-receptor molecule in the
cytoplasm of the hepatocyte forming an inducers receptor
comple!.
*"he receptor-inducer comple! is then translocated into the
nucleus A interacts w- the D)A resulting transcription of the
specific genes.
*"he m%)A transcribed from D)A subseGuently translated leading
to synthesis A incorporation of new cytochrome 4:=H into the
membrane of the smooth endoplasmic reticulum.
TACHYPHYLA&IS TOLERANCE- fast toleranceQ develop by
months even by year.
SIGNI+ICANCE O+ DMMS INDUCTION
2..nactivation or diminishing effect of the drug #development of
tolerance$.
3."here is an increase metabolism of other drug taen
simultaneously by the inducer.
9."here is an increase metabolism of drugs having the same
biotransformation pathway of the inducer.
*7f drugs that enhance drug metabolism in humans.
INDUCER-dec. the metabolism of drugs given simultaneously.
INDUCER DRUGS BHOSE META,OLISM IS ENHANCED
2.6hlorcycli0ine Steroid hormones
3.*thchlorrynol Earfarin
9.&lutethimide Antipyrine, glutethimide, warfarin
:.&riseofulvin Earfarin
=.4henobarbital 1arbiturates #for steroids$
A other barbiturates 6hloramphenicol
6hlorproma0ine
6ortisol, 6oumarin
Desmethylimipramine
Digito!in
Do!orubicin, estradiol
4henyl 1uta0one
4henytoin #anti epileptic$
Kuinine, warfarin
"estosterone
>.4henybuta0one Amino pyrine, cortisol, digito!in
?.4henytoin 6ortisol, de!amethasone
Digito!in, theophylline
F.%ifampicin 6oumarin,
#Anti-"1$ digito!in, methadone, metoprolol,
7ral contraceptive,
4rednisone, propanolol, Guinidine
*Drugs that inhibit metabolism of other drugs in human
INHI,ITOR DRUG BHOSE META,OLISM IS INDUCED
#4rolong effect$
2.Alloparinol Antipyrine, dicumarol, pronemecid, tolbutamide
6hloramphenicol
.sonia0id
3.6imetidine 6hlordia0epo!ide, dia0epam, warfarin
9.Dicumarol phenytoin
:.Disulfiram Antipyrine, ethanol, phenytoin, warfarin
=.8etocona0ole 6yclosporine
>.4henylbuta0one 4henytoin, tolbutamide
?.7ral contraceptive Antipyrine
*R%*".7) 7F D%'&
D%'& -------------A1S7%4".7)

D.S"%.1'".7) 5*"A17,.S5

1.7"%A)SF7%5A".7)
*R6%*".7)

8idney-main organ ,iver-main organ
5inor roots of e!cretion 5inor organ
2.&."-1iliary-fecal e!cretion 2.8idney
3.5ammary-mil e!cretion 3.&."
9.,')&S 9.,ungs
:.Salivary-saliva
=.Sweat glands-sweat
>.,acrimal-tears, hair, nails, sin
M.C!r pr!cess i"D!/De i" 0e re"./ 0."7/i"9 !> 7r89
2.&lomerular filtration. #4rolong drug effect$
3."ubular reabsorption. #4rolong drug effect$
9."ubular secretion. #Eill not prolong drug$
Filtration of a drug at the glomerulus depends on the molecular
si0e of the drugs.
"ubular secretion
-'sually occurs in the pro!imal tubules A generally involves
organic acid such as penicillin, aspirin A diuretics.
"ubular reabsorption of drugs-occur in pro!imal A distal part of the
nephron. #Eherein drug goes bac to the circulation$
+.c!rs 0. 6i// pr!1!e T8A8/.r re.As!rpi!"
2..7).NA".7) as non-ioni0ed
3.pH of D%'&-if the drug is same pH of the glomerulusQ it is
reabsorb.
9.,.4.D S7,'1.,."B
-AGueous drug doesnIt reabsorb
Ki"eics !> 1e.A!/is1 #inetics is the study of rates of reaction$
2.First order inetics
-"he rate of drug metabolism is directly proportional to the
concentration of free drug.
"his means that a constant percent of drug is metaboli0e per unit
time. "he drug concentration does not saturate the en0yme or
carrier system.
3.Nero order inetics
-A constant #saturated$ unit of drug is metaboli0e per unit of time.
"he en0yme responsible for metabolism is saturated by a high free
drug concentration and the rate of metabolism remains constant
over time. " his occurs with drug given over large doses or drugs
such as aspirin ethanol, A phenytoin.
C/e.r."ce
-.s the apparent volume of a biologic fluid from w-c a drug is
remove by elimination processes per unit of time.
*.g. ,.@*%, %*)A,
Re"./ C/e.r."ce
-"he volume of plasma that needs to be cleared per unit time, the
rate of drug removal that taes place in the idneys.
*ffect of '%.)* pH and %*)A, 6,*A%A)6* for drugs that
undergo tubular reabsorption.
,.ses-cleared rapidly by maing urine more acidic.
2.A54H*"A5.)*
3.6H,7%7K'.)*
9.,*@7%4HA)7,
:..5.4%A5.)*
=.5*6A5B,A5.)*
>.K'.).)*
Aci7-cleared rapidly by maing urine alaline.
2.A6*"AN7,A5.D*
3.)."%7F'%A)"7.)
9.4H*)71A%1."A,
:.4%71*)*6.D
=.SA,.6B,A"*
>.S',FA"H.7N7,*
HA,F ,.F* #D2-3$ is the time it taes for the plasma cone or the
amount of drug in the body to be reduced by =HL.
@olume of distribution-relates the amount of drug in the body to the
concentration of drug in the blood or plasma.
6learance-measures of the bodyIs ability to eliminate a drug.
HA,F ,.F* of a drug is inversely related to its clearance A directly
proportional to its vol. of distribution.
CLINICAL SITUATION RESULTING IN INCREASING DRUG
HAL+ LI+E
2.Diminished %*)A, 4,AS5A flow for e!. in cardiogenic shoc,
heart failure or hemorrhage.
3.Eith addition of a second drug, which displaces the 2
st
drug from
A,1'5.), hence increases the volume of distribution of the drug.
9.Eith decrease e!cretion-renal diseases.
:.Eith decrease metabolism, for eg. Ehen another drug inhibits its
biotransformation.
S"*ADB S"A"* #"o maintain the drug in the body$
-A steady state plasma concentration of drug occurs when the rate
of drug elimination is eGual to the rate of drug administration.
.nhibitors-.nc. t 2-3
-.n general, drug absorption, distIn. elimination #biotransformation
A e!cretion$ process follows 2
st
order inetics
-After .@ administration, the absorption of drug follows 0ero-order
inetics.
-Do not allow a drug to be taen #ne!t dose$ beyond "2-3 because
it will tamper its therapeutic effect.
PHARMACODYNAMICS E DRUG RECEPTOR
Definition of terms
2.RECEPTOR-a macromolecular component of a cell that interacts
w-a drug leading to a chain of biochemical events resulting to an
observable effects of drug action. "hey are most protein in nature.
3.A++INITY-is the ability of a drug to bind to a receptorQ or it is the
ability of a drug to have full occupancy of the receptor sites.
9.E++ICACY OR INTRINSIC ACTI*ITY-is the ability of the drug to
activate the receptor site leading to a chain of biochemical events
#resulting to an observable effects of drug action$
:.AGONIST-is drug that has affinity and efficacy.
=.ANTAGONIST-is a drug that has affinity but has no efficacy.
"hey inhibit the action of the agonist.
>.PARTIAL AGONISTFANTAGONIST (p8re .".9!"is$-a drug
that has affinity A produces little efficacy.
TBO +UNCTIONS O+ RECEPTOR
1.LIGAND ,INDING
-%eceptor binds to endogenous regulatory ligand such as
hormones, neurotransmitter and auntocoids to produce
physiological normal fn!.
2.MESSAGE PROPAGATION
-A receptor regulate the activity of a certain en0yme #receptor-
effector system$ w-c is the effector that synthesi0es the second
messenger w-c in turn propagate the signal or message.
*g. %eceptor-effector sys. -Synthesis of 9 endogenous 9I=
5onophosphate #cyclic A54$
Adenylyl cyclose*n0ymes

%eceptor-effector system
+EATURES O+ RECEPTOR
2.4rotein( lipoprotein, glycoprotein
3.5ol.wt. :=-3HH ilodaltons
9.Drug binding( reversible, specificity to binding is not absolute
-,eading to drug binding to several receptor types
:.%eceptors are saturable because of definite number of receptor.
=.Specific binding of receptor results in signal transduction via
second messenger to intracellular site.
>.5ay reGuire more than one drug molecule to bind to receptor to
generate signal.
?.5agnitude of signal depends on the number of receptors
accepted.
F.%eceptor must have properties of recognition and transduction.
P.1y acting on receptor, drug can enhance, diminish or bloc
generation or transmission of signal.
2H.Drugs are receptor modulators and do not confer new
properties on cell or tissue.
22.%eceptor can be upregulated or down regulated.
+OUR MOLECULAR MECHANISM ,Y BHICH RECEPTOR
TRANSDUCE SIGNALS
2.Direct receptor control of ion-channel. #,igand-gated$ or #voltage-
gated$
3.%eceptor-controlled generation of second messenger #&-
protein-camp or &-protein-4hosphoinositide system$
9.%eceptor-initiated phosphorylation involving "yrosineinase.
:.%eceptor-initiated steroid hormone activity.
ION CHANNEL RECEPTOR
"he mechanism of action of several hormones and
neurotransmitters is due directly to enhanced movement of ions
across the plasma membrane. "he hormone or the
neurotransmitter receptor #ligand bound receptor$ is itself an ion
channel.
.7) 6HA))*,
%*6*4"7%
.7) S*,*6".@."B *FF*6"
2.)icotinic-Acetyl
6holine receptor
)aD 8D Depolari0e
3.&A1A 6l Hyperpolari0e
9.&lycine 6l Hyperpolari0e
:.&lutamate
a$ )-methyl-
Daspartate
)a, 6l, 8
b$ KuisGualate )a, 6l Depolari0e
c$ 8ainate )a, 8 Depolari0e
NICOTINIC ACETYLCHOLINE RECEPTOR
-.s found on the smooth membrane cell #seletal$ end plate in the
neurotransmitter Ounction of all autonomic ganglia and on the 6)S.
"he rate of the acetylcholine receptor is to convert the binding of
the neurotransmitter acetylcholine into an electrical signal in the
signal in the cells of the organ containing the receptor. .t opens a
pore for )aD or 8D ions to pass through the cell membrane leading
to depolari0ation of cell membrane potential.