Drug interaction 2
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Pharmacokinetic drug interaction
A- Absorption
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Pharmacodynamic (PD)
• Affects drug action directly
Pharmacokinetic (PK)
• Affects plasma conc. with time (ADME)
Retrospective VS prospective
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When the precipitant drug affects at least one of the following:
A. Absorption B. Distribution C. Metabolism D. Excretion Of the object drug Change in object drug’s
plasma conc. (Cp)
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A- Absorption
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1. Adsorption 2. Complexation/ chelation 3. GI PH change 4. GI motility change 5. Malabsorption 6. Action on bacteria flora
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Object drug Precipitant drug
Concomitantly administered oral drugs
Kaolin, Charcoal or antacids
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1. Adsorption
2. Complexation/ chelation
3. GI PH change
4. GI motility change
5. Malabsorption
6. Action on bacteria flora
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Chelation
M
L L
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outcome Drug B Drug A
Non-absorbable complex
Warfarine Digitalis Thyroid
cholestyramine
Poorly soluble chelate
Tetracycline Al+3, Ca +2, Mg +2, Fe +2, Bi+2, Zn +2
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1. Adsorption 2. Complexation/ chelation 3. GI PH change 4. GI motility change 5. Malabsorption 6. Action on bacteria flora
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Acid + base = Salt (ionized) A- B+ A- B+
Absorbable form of most drugs is the non-ionized
form
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result ionization Agent
increasing
PH
Drug
absorption
(extent)
increased Antacid, PPI, H2#
Weak acid
absorption
(extent)
decreased Antacid, PPI, H2#
Weak base
absorption
(extent) ????
decreased Antacid, PPI, H2#
Ketononazole (poorly sol. Weak base)
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Aspirin + Omeprazole
Amphetamine + Cimetidine
Ketoconazole + Alomag
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1. Adsorption 2. Complexation/ chelation 3. GI PH change 4. GI motility change 5. Malabsorption 6. Action on bacteria flora
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1) Readily soluble drugs
Ex. Captopril and Astemizole + Anticholinergic Rate of absorption (Atropin, propantheline, TCA, PZ& pethidine)
+ Prokinetics Rate of absorption (Metoclopramide, Domperidone & cisapride)
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2) Poorly soluble drugs
Ex. Digoxin and dicumarol + Anticholinergic extent of (Atropin, propantheline, TCA, PZ& pethidine) absorption + Prokinetics extent of (Metoclopramide, Domperidone, cisapride) absorption
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3) Actively transported drugs
blood
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GI lumen
Receptor
Drug
intestine
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3) Actively transported drugs
Ex. Riboflavin + Anticholinergic extent of (Atropin, propantheline, TCA, PZ pethidine) absorption + Prokinetics extent of (Metoclopramide, Domperidone, cisapride) absorption
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4) Acid labile drugs & drugs
undergoing GI metabolism
Ex. Of acid labile: antibiotics Ex. Of GI metabolizing drugs: L-dopa + Anticholinergic extent & rate of (Atropin, propantheline, TCA, PZ pethidine) absorption + Prokinetics extent & rate of (Metoclopramide, Domperidone, cisapride) absorption
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5) Potent single dose drugs
Ex. Hypnotics & analgesics + Anticholinergic rate & effect of (Atropin, propantheline, TCA, PZ pethidine) absorption + Prokinetics rate & effect of (Metoclopramide, Domperidone, cisapride) absorption
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1. Adsorption 2. Complexation/ chelation 3. GI PH change 4. GI motility change 5. Malabsorption 6. Action on bacteria flora
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outcome Object drug Precipitant drug
Extent of absorption
Concomitant oral drugs
Neomycin, MTX, Amino salicylic acid, Cytotoxic agents,
5-FU
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1. Adsorption 2. Complexation/ chelation 3. GI PH change 4. GI motility change 5. Malabsorption 6. Action on bacteria flora
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Bacteria flora Warfarin synthesizes vit. K Vit. K antagonist coagulation coagulation
bleeding
Antibiotics