4. drug interactions

7/21/2019 4. Drug Interactions

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Drug

InteractionsDr. Jatin Dhanani



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



"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



AdverseDrug Interactions



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



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



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



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



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#



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



*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



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



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



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



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



Pharmacodynamic druginteractions

#t receptor level #t tissue or systemic level

(ynergism

Additive (upraadditive

Antagonism



#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



Drug interaction

xtended to

Drug – food interactions

Drug – herbal interactions

Drug – laboratory test interactions

Drug – disease interactions



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



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



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



Thank You

4. drug interactions

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