drug interaction - 1 file download
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Types of drug interaction:
1. Pharmaceutical “Chemical Interaction” in vitro:
• EPI , erythromycin gluceptate or cephalothin sodium
decomposed in alkaline PH so don’t mix with I.V. solution of
aminophylline
• Phenytoin Na+
will ppt in acidic solution so don’t mix with
dextrose solution
2. Pharmacokinetics = Biopharmaceutical:
• ADME
1) Absorption
2) Distribution
3) Metabolism
4) Excretion
1st
Absorption:
• In CHE the F.O.C is
absorption of an orally
Digoxin F.O.C blood supply to GIT
drug from GIT .
• EPI make vasoconstriction so absorption of local
anesthetics.
• Purine & Purine antimetabolite compete on the same carrier so
absorption of each other .
Drug Interaction
Types of drug interaction:
Pharmaceutical “Chemical Interaction” in vitro:
erythromycin gluceptate or cephalothin sodium
decomposed in alkaline PH so don’t mix with I.V. solution of
will ppt in acidic solution so don’t mix with
Pharmacokinetics = Biopharmaceutical:
, so blood supply to GIT is , so the
absorption of an orally administrated drugs is , so give
Digoxin F.O.C blood supply to GIT ∴∴∴∴ absorption of
EPI make vasoconstriction so absorption of local
Purine & Purine antimetabolite compete on the same carrier so
absorption of each other .
Pharmaceutical “Chemical Interaction” in vitro:
erythromycin gluceptate or cephalothin sodium
decomposed in alkaline PH so don’t mix with I.V. solution of
will ppt in acidic solution so don’t mix with
, so blood supply to GIT is , so the
, so give
absorption of
EPI make vasoconstriction so absorption of local
Purine & Purine antimetabolite compete on the same carrier so
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2nd
Distribution:
• Drug bounds + free “give action”
• VPA displace Phenytoin from plasma proteins binding site so
free Phenytoin conc.∆ ∴∴∴∴ Phenytoin toxicity
• Aspirin displace VPA VPA toxicity
• Quinidine displace Digoxin from plasma proteins binding site so
cause Digoxin free conc.∆ ∴∴∴∴ Digoxin toxicity
3rd
Metabolism:
• Inducers :
I. CNS : Phenytoin , CBZ , Phenobarbital
II. Chemical : Tobacco , Chronic alcohol
III. Herb: Grape fruit , Bitter orange , Garlic , St john wart
IV. Antimicrobial: Isoniazid
• Inhibitors:
I. GIT: Omeprazole , Cimetidine
II. Antimicrobial: Ciprofloxacin , Levofloxacin , azole family “ketoconazole”
Ritonavir , Saquinavir , Erythromycin , Metronidazole
III. Others: Verapamil , Haloperidol , Methadone , Gemfibrozil
Ex.Smocking: Theophylline Metabolism cause Theophylline Failure
Ex.Cimetidine: atorvastatin Metabolism ∴∴∴∴ atorvastatin toxicity
4th
Excretion “Through Kidney”:
• Filtration:
Theophylline blood supply to kidney so ∴∴∴∴ Glomerular filtration ∴∴∴∴
no time for reabsorption so Theophylline excretion of other drugs
• Active Secretion:
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Probenecid & Penicillin use the same carrier for secretion from the kidney
∴∴∴∴Probenecid Penicillin excretion so prolong its t½ ∴∴∴∴ long acting Penicillin
• Reabsorption:
NaHCO3 is a urine alkalinizer cause amphetamine reabsorpAon & cause
aspirin excretion.
Others example for interactions through absorption:
1- Charcoal
Cholestyramine + Drug absorption
Kaolin ∴∴∴∴ absorption
Bentonite
Acarbose
2- Tetracycline Divalent (Ca+2
)
Quinolone Trivalent (Al+3
)
By Laxative or Prokientic ( Ach)
∴∴∴∴ Absorption amount of controlled release tab
Decrease
3- GIT Motility
By narcotics or anticholinergic
∴∴∴∴ absorption rate
+ Chelation
Absorption ∴∴∴∴
Cation
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4- Antacid, PPI ,H2RA ( acidity ) + Ketoconazole
Ketoconazole absorption
5- GIT Flora digoxin absorption in presence of normal flora
Oral contraceptive requires flora to be absorbed
3. Pharmacodynamic interaction:
• Synergism 1+1=3:
Ex. Sulfamethoxazole + trimethoprim.
• Antagonism 1+1=zero:
Ex. EPi + β.blocker
Ex. Warfarin + Vit.K
Ex. Narcotic + Naloxone
• PotenAaAon 0+1=2 :
Ex. Carbidopa + L.dopa
Ex. Clavulanic acid + Amoxicillin
Require acidity for absorption
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Food & Drug Interaction
• Wheat grass, Coenzyme Q10, Spinach, Broccoli.
Provide source of Vit.K ∴∴∴∴ a dietary antagonize Warfarin effect.
• Ginger, Garlic, Feverfew Warfarin Effect.
Food May absorption of:-
• Morphine
• Dicumarol oral anticoagulation
• Phenytoin
• Griseofulvin
Food May absorption of:-
• NSAIDs
• Aspirin
• Acetaminophen
• Antibiotic
Food has no effect on the absorption of:-
• Theophylline
• Metronidazole
Note:
Theophylline
“Bronchodilator”
Fatly Food
Immediate release
(Food has no effect)
Controlled release
(Food absorption)
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Note:
Chronic alc. Inducer
Acute Alc. Inhibitor
4. Pharmacogentics:
Poor
Metabolizar
“PM”
2 defecAve
allele
Doesn’t
affected by
inhibitor
Intermediate
Metabolizer
1 Wild
1 DefecAve
Normal
Metabolizer
2 Wild
alleles
Extensive
Metabolizer
“Em”
1 Wild
1 Amplified
Doesn’t
affected by
inducer
Ultra Rabid
2 amplified
alleles
Doesn’t
affected by
inducer
Note:
Normal allele = wild
gene responsible for metabolism
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PM
Drug X Drug X
EM
PM
The same
AUC
Drug X + Inhibitor
EM
Double
AUC
Drug X + Inhibitor
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Significance of Interaction
1) Trimethoprim & Sulfamethoxazole increase the efficacy of each
other (synergism)
2) Clavulanic acid decrease breakdown of amoxicillin
3) Hydrochlorothiazide & Triamterene neutralize the K+ level
(antagonism)
4) Fatty food Phenytoin absorption (pharmacokinetic)
5) Probenicid Prolong penicillin t½ (pharmacokinetic)