Hit & Run Drugs/ Suicidal Inhibitors by Jerin (PharmD)

1. HIT&RUN
DRUGS
SUICIDALINHIBITORS
By-Jerin Samuel (16Q1416)
01

2. CONTENTS
Why Hit and Run?
Hit & Run/Suicide Inhibitors
Types of Inhibitors
Suicide Enzyme Inhibition
Clinical Significance
03
04
07
08
12
02

3. WHYHITANDRUN?
The effect of the Accident
continues, even after the
person who caused the
accident leaves. Affected
person still continues to
suffer.
03

4. HITANDRUN/SUICIDEINHIBITORS
Arethedrugswhoseeffectlastsmuchlongerthanthedrugitself.
Because,adrugwitharelativelyshortt½stillabletoproduceeffect
longafterithasbeeneliminated-itsintracellularactionandpartial
bindingtothereceptorlongaftermostoftheextracellulardrughas
beeneliminated
04

5. HITANDRUN/SUICIDEINHIBITORS
Theyareremovedorexcretedfromthebody
Buteffectofthedrugsstillcontinues
Examples:M=MAO Inhibitors
O=Omeprazole(PPI)
G=Guanethidine
R=Reserpine
A=Aspirin
AfterFewhoursofadministrationofdrugs
05

6. PROTONPUMPINHIBITORS(PPI)
06
MOSTEFFECTIVEFORGASTRICACIDSUPPRESSION
PLASMAT1/2LIFE:0.5-2HRS
DURATIONOFACTION:24HRS
IRREVERSIBLEINHIBITIONOF(H+/K+ATPASE)PROTONPUMP
SYNTHESISOFNEW (H+/K+ATPASE)REQUIRES18-20HRS
(ACIDSECRETIONRESUMESONLYAFTERTHEFORMATIONOFTHENEWENZYME)
EXAMPLE:-

7. SUICIDEENZYME
INHIBITION
SubstrateAnaloguebinds
totheactivesite&
producesanabnormalproduct
Abnormalproductbinds
totheenzymeandmakes
ininactive
IRREVERSIBLE INHIBITOR
08
MECHANISM BASED INACTIVATION

8. ENZYME
SUBSTRATE
E-SCOMPLEX
PRODUCT
ENZYME
WITHOUTANINHIBITOR
09

9. ENZYME
SUBSTRATE
ANALOGUE
E-ICOMPLEX
ABNORMAL
PRODUCT
ENZYME
WITHASUICIDEINHIBITOR
10

10. ABNORMAL
PRODUCT
ENZYME
WITHASUICIDEINHIBITOR
INACTIVE
ENZYME
INACTIVATION OF ENZYME
11

11. ASPIRIN
ENZYME : CYCLO-OXEGENASE
USE : ANANLGESIC
ANTIPYRETIC
ANTI-INFLAMMATORY
DISULFIRAM PENICILLIN 5- FLUROURACIL
CLINICALSIGNIFICANCE-SUICIDEINHIBITORS
ENZYME : ACETALDEHYDE
DEHYDROGENASE
USE : ALCOHOLISM
DEADDICTION
ENZYME : - BACTERIAL
TRANSPEPTIDASE
USE : ANTIBIOTIC
ENZYME : - THYMIDYLATE
SYNTHASE
USE : ANTICANCER
12

12. 13

13. 14

14. CONCLUSION
The pharmacokinetics and dynamics of "hit and run" drugs outline many clinical implications.
a. The duration of action of the drug may be longer than the actual stay of the drug in the body
due to this "hit and run" effect as in the case of Reserpine and Omeprazole.
b. The pharmacodynamic actions of "hit and run" drugs may be due to some irreversible or
permanent changes in the enzymes or cellular functions as with aspirin, MAOIs, and cortisone.
c. The "hit and run" effect may be responsible for some ADR or may even be the reason for a
lesser risk of a particular ADR. E.g. DDVAP and atypical antipsychotics.
d. The "hit and run" effect may be seen with the parent compound but may not be seen with the
metabolite e.g. selegiline.
e. "Hit and run" effect of some drugs (cocaine) may cause euphorogenic effects.
f. The "hit and run" effect may be responsible for the “post-antibiotic effect” as with
aminoglycosides.
15
Int J Med Health,Hit and Run Drugs: Revisited, Sci.Sudhindra Prathap A October 2012,Vol-1;Issue-4

15. THANKYOU