PHARMACOTHERAPEUTICSDr Baltazar

Branch of medical sciences w/c is most concerned w/ rational

development of drugs effective and safe use of drugs (RDU or
RUD)
Proper evaluation of drugs & other chemical entities in human for
the diagnosis, prevention and disease syndromes
Single blind triads
!Physician & associates "ut not the patient #now the su"s "eing
used
Double blind triads
!$either the individual administering the component nor the patient
#nows the identity of the su"stance %ll the materials are coded
including the test su"stance and the place"o and, if possi"le an
already #nows active su"stance therapeutically similar to the one
"eing tested
(&tandard reference at positive control)
Develo!ent o" #e$ Drug
%nimal study!'uman study
'uman dose!(nitial sample human dose would "e a fraction of a
minimal effective dose in the animal study
)* +in effective dose,-.mg
(f rat!test animal!human dose is 1/2000 of 10
Dog test animal!human dose is 1/10 of 10
Mon%e&s' orangutan!human dose is of ME dose
Dose is gradually increase until a response appears or until ma*
tolerated dose is esta"lished dose w/c doesn/t elicit undesira"le
effect $o individual should "e e*posed to more than a single dose
in short period of time preventing effect
01hen drugs cause effects w/c are undesired, they #nown as
Adverse R(ns )Side e""e*ts
Pla*ebo is defined as the psychologic/physiologic effect of a
therapeutic drug or procedure w/c is not rel to its specific
pharmacologic act
Ma(+ tolerated dose!dose w/c are not elicit undesira"le effects %
particular valua"le techni2ue to ensure relia"ility of results is the
Cross Over+
#e$ Drug Develo!ent and Aroval Pro*ess
#e$ C,e!i*al Entit&
&ources3
Drug synthesis
+olecular modification
(solation from plants

Pre *lini*al Studies
4hemistry
Physical properties
Biological pharmacology
5o*icology
Pre formulation

Investigational
#e$ Drug
Ali*ation -I#D.
&u"mission
6D% Review
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4linical 5rials
Phase (
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C/I#ICA/ TRIA/S I# THE DE0E/OPME#T O1 A #E2 DRU3
I# HUMA#
456&rs5 P,ase I +easurement of pharmacologic action, potency,
side effects (pharmacodynamics) pharmaco#inetics usually in
normal, healthy volunteers done "y clinical pharmacologist in
research setting
754&rs5 P,ase II aims to demonstrate conclusively efficacy in rel
to safety
7)arly selection of few patients with disease syndrome
Determination of a drug efficacy and dosage ranges special
5o*icity studies of indicated
48ate3 large num"er of clinical pts longer period of therapy
754&rs5 P,ase III large scale comparative trials in p*, designed
to esta"lished efficacy, compare the new drug w/ other availa"le
t*, esta"lished optimal dosage, determine incidence of %DR
"efore drug is licensed for mar#eting set up "lind or dou"le "lind
study w/ randomi9ed selection of p* & controls Dosage form and
routes of admin clearly defined
756 P,ase I0 further esta"lished usefulness and safety %pproval
of $D% "y 6D% for mar#eting surveillance of the safety and
efficacy of the drug "y the manufacturer who reports periodically
for the 6D% Drug may"e w/ drawn if une*pected undue to*icity
"ecomes evident
Drug may "e released only for limited use in selected patient
under surveillance "y physician participating
3E#ETIC E11ECTS 2)C MODI18 DRU3
BIOTRA#S1ORMATIO#

)$:;+%5(4
R)%45(<$
)=%+P8) &<6
DRU>&
)66)45&
->?PD deficiency %cetylsalicylic acid
%cetophenetidin
$itrofurans
P!%minosalicylic acid
Prima2uine and others
@!%mino2uinolines
Auinidine
&ulfonamides
%cute hemolytic
anemia
B>lucuronyl
transferase deficiency
%cetophenetidin
4hloral hydrate
4odeine
4hloramphenicol
(ndomethacin
+orphine
$icotinic acid
Pro"enecid
)*aggerated
drug to*icity
Cy!%minolevulinic acid
synthetase
Bar"iturates
4hloro2uine
)strogens
>riseofulvin
&ulfonamides
%cute
intermittent
porphyria
DPseudocholinesterase
deficiency
&uccinylcholine Prolonged apnea
E%cetylase deficiency (sonia9id Peripheral
neuropathy
?+ethemoglo"in
reductase deficiency
4hloro2uine
Diaminodiphenylsulfone
(DD&)
Prima2uine
+ethemoglo"in
#e$ Drug Ali*ation
-#DA.
&u"mission
6D% review
Pre approval Product
inspection
6D% %ction
Post !ar%eting
Phase (F 4linical studies
4linical
pharmacology/5o*icology
%dditional (ndication/%DR
Reporting
Product defect reporting
Product line )*tension
Pre*lini*al Studies
4ontinued
8ong!term animal to*icity
Produced formulation
+anufacturing
4ont vols
Pac#age G la"el margins