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)