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7/21/2019 4. Drug Interactions
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Drug
InteractionsDr. Jatin Dhanani
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modification of response to one drug by another
when they are administered simultaneously
or in quick succession
Quantitative Qualitative
Outcomes of drug interactions
1)Loss of therapeutic effect
2)Increase/decrease in pharmacological activity
3)Toxicity)!eneficial effects
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"rug interaction
results in
Beneficial effects Adverse effects
Combinations
Co – trimoa!ole "evodopa # carbidopa $enicillin # probenecid
%hia!ide diuretics # triameterine Amoicillin # clavulinic acid
%reatment of $oisoning
&thyl alcohol in methyl alcohol poisoning Desferioamine in iron poisoning $rotamine sulfate in heparin poisoning
'ther chelating agents in mineral poisoning $hysostigmine in atropine poisoning
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AdverseDrug Interactions
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Factors increases chances
(elf medication %reatment with semi qualified paramedical staff or
quacks
)ndue* indiscriminate prescribing
Drug with steep D+C or low therapeutic inde ,nown en!yme inducer or inhibitor
-ollows !ero or saturation kinetics
Drug which use for prolonged period of time with precise
maintenance of plasma conc. (everely ill patients who receive many drugs at a time
&lderly – having multiple pathology / so receiving many
drugs at a time
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Pharmacological basis for
drug interactions
%hiopental sod. # succinyl choline – precipitate/inactivation
0ydrocortisone # heparin or penicillin – inactivation
of heparin or penicillin
(od. salt of $henytoine barbiturates sulfonamides.0eparin penicillin – never added in Detrose sol. –
precipitated
In vitro In vivo
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In vivo drug interactions
#ltered $IT #%sorption
Altered p0 Altered bacterial flora
formation of drug chelates or complees
Drug induced mucosal damage
altered 12% motility
&harmaco'inetic &harmacodynamic
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Altered p0
Ex1., antiacids Increase the pH Decrease the tablet
dissolution
of Ketoconazole (acidic)
Ex2., H2 antagonists↑H
!herefore, these drugs "ust be searated b# at least 2h
in the ti"e of ad"inistration of both
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Altered intestinal bacterial flora
E$., In 1%& %f atients recei'e digoxin..%& or "ore of thead"inistered dose is "etabolized b# the intestinal flora
*ntibiotics +ill a large nu"ber of the nor"alflora of the intestine
Increase digoxin conc.and increase its toxicit#
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Ex 1 !etrac#cline interacts -ith iron rearations
or
il+ (/a20 ) nabsorbable co"lex
Ex 2 *ntacid (alu"iniu" or "agnesiu") h#droxide
Decrease absortion of
cirofloxacin b# 3&
due to chelation
Compleation or chelation
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*ntineolastic agents e.g., c#clohosha"ide'incristine
rocarbazine
Inhibit absortion
of se'eral drugseg., digoxin
etoclora"ide (antie"etic)
Increase absortion of c#closorine due
to the increase of sto"ach e"ting ti"e
Increase the toxicit#
of c#closorine
Drug3induced mucosal damage
Altered motility
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Dislace"ent fro" las"a rotein binding
Depends on the affinity of the drug to plasma protein
&henytoin (*+), Tol%utamide (-+), and .arfarin (+)
highly %ound to plasma protein
"rugs that displace these agents are #spirin
ulfonamides
phenyl%uta0one
Altered distribution
Dislace"ent fro" tissue binding
"igoxin highly tissue %inding
uinidine displace the digoxin and increase its toxicity
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Altered metabolism
n0yme inhi%ition
Adverse
consequences 2ncrease bleeding
tendency with dicumerol
when given with
cimetidine (evere respi depression
with morphine when
given with 4A'2s
Enzyme induction
Therapeuticallybenecial reactions
2ncrease accessibility of"3D'$A in brain when
given with carbidopa
Disulfiram as deaddiction
+eversal of skeletalmuscle paralysis due to
d3tubocurarine by
neostigmine
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n0yme induction
consequences Contraceptive failure
5refampicin and phenytoin
inhibit action of 'C pills6
7arfarin require higherdose if given along with
en! inducer barbiturates
Barbiturates induce its
own metabolism if givenfor longer time 5tolerance
development6
$aracetamol toicity in
chronic alcoholic patient
Therapeutic
utilization of enzinduction %o treat neonatal
8aundice9
phenobarbitone inducefetal hepatic glucuronyl
transferase which
metaboli!e bilirubin
4.5 enz#"e induction in'ol'es rotein s#nthesis .!herefore,
it needs ti"e u to 6 -ee+s to reach a "axi"al effect
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Altered excretion
Altered 1lomerular filtration 4ethylanthines – increase renal blood flow
Altered reabsorption Alkali!ation of urine by sod. bicarbonate – increase
ecretion of acidic drugs like aspirin barbiturates Acidification of urine by ascorbic acid or ammonium
chloride – increase ecretion of basic drugs like
amphetamine / morphine
Altered tubular secretion $robenecid blocks active tubular secretion of
penicillin cephalosporin !idovudine and so prolongs
the action
:uinidine decrease tubular secretion of digoin
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Pharmacodynamic druginteractions
#t receptor level #t tissue or systemic level
(ynergism
Additive (upraadditive
Antagonism
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#t systemic/ tissue level Loss of antihypertensive effect of AC&
inhibitors / A+Bs by ;(A2Ds such asindomethacin ibuprofen piroicam 5possibly due
to inhi%ition of vasodilator &$ formation by
kidneys leading to ;a retention6
evere hypotension with 1%; when given withsildenafil
!radycardia with CCB 5sp. verapamil6 and <3
blockers
4ypo'alemia with loop diuretics # thia!ide Lithium toxicity with diuretics 5"i absorption
increase at $C%6
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Drug interaction
xtended to
Drug – food interactions
Drug – herbal interactions
Drug – laboratory test interactions
Drug – disease interactions
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Drug food interactions
$resence of food 5sp. fatty food6 = absorption
of most drugs
4ilk decreases absorption of iron and
tetracycline 1rapefruit 8uice 3 > absorption of cyclosporine
but inhibit metabolism of phenytoin
tetracycline and amioderone Cheese reaction
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Drug herb interacitons
#loe5vera – late have laative properties andalso = blood sugar level – laatives and anti3
diabetic drug require caution
$arlic,$inger 6 $in'go %ilo%a – increase
bleeding tendency with antiplatelet andanticoagulant drugs
$arlic – decrease gastrokinetic effect of
metoclopramide domperidone and cisapride
t7 8ohn9s .ort – leads to photo toicity if use
with tetracycline sulfonamide or $$2 / increase
C;( depression of C;( depressant drugs
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Drug laboratory testinteractions :ephalosporin – false #ve urine sugar test
"iuretics – interfere with electrolyte 5;a#,#6
result
strogen in contraceptive pills – increase
thyroin value b*c of = in thyroglobulin level
#lcohol 3 > ?3glutamyl transferase level
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