DIGESTER GPAT DISCUSSION CENTER : MAKES STUDY EASY

BIOPHARMACEUTICS

DIGESTER -253
MECHANISM OF ABSORPTION

1. Transcellular / intracellular – Most common pathway for drug transport

• Non saturable
Follow first order kinetic
Passive Expressed by: Fick's law of diffusion
diffusion dQ DAK o / w
 (C  C )GIT
dt h
Pore Also known as connective transport, bulk flow, and
Passive transport filtration.
transport Suitable for low molecular weight.
Ion-pair Based the charge of membrane.
transport Unionised ˃ anions ˃ cations
Carrier Structure specific carrier (lock-key arrangement)
mediated Saturated transport
diffusion Mixed order kinetics
Ion transport Responsible for transportiong ions in or
Active Primary out.
transport active ABC ATP binding cassette
transport Transport small foreign molecules
Symport (Co- Involve movement of both the molecule in
transport) the same direction.
Secondary Example: Na+ glucose symporter
active Antiport Involve moment of molecule in the
(Counter- opposite direction. Example: Expulsion of
transport) H+ ions using the Na+ gradient in the
kidney
2. Para cellular/ intercellular
Permeation Basically through an openings.
through tight Example: Insulin and cardiac glycoside taken by this mechanism.
junction of
epithelial cells
Persorption Permeation of drug through temporary opening cell into lumen.
3. Vesicular transport - Energy dependent process
Pinocytosis Uptake of fluids. Example: Sabin polio vaccine, Botulism toxin
Phagocytosis Absorption uptake of solids
Example: Vitamin A, D, E, K, insulin

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DIGESTER -254
POLYMORPHISM

a) Substance exists in more than one crystalline form.

b) Polymorphs are different from each other from – Solubility, Melting
point, Density, Hardness, Compression.
c) Order of solubility – Amorphous ˃ Metastable ˃ Stable
d) Method to determine polymorphism
i. x-ray diffraction
ii. NMR technique
iii. Optical crystallography
Polymorphs
iv. Hot stage microscopy
v. Melting point determination
Two types of polymorphs
Enantiotropic polymorph Monotropic polymorph
One which can be reversibly changed One which is unstable at all
into another form by altering the temperatures and pressures.
temperature or pressure.Example: Example: Glyceryl stearates.
sulphur

DIGESTER -255
INFLUENCE OF DRUG ON PKA ON DRUG ABSORPTION

For better For complete Comment

absorption excretion
Unionized > Ionized >
ionized unionized
For acidic pKa > pH pH > pKa Acidic drugs are more unionized
drug in acidic medium & more ionized
in basic medium
For basic pH > pKa pKa > pH Basic drugs are unionized in
drug basic medium & more ionized in
acidic medium
pH = pKa pH = pKa 50% is ionized and
50% is unioized

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DIGESTER -256

FACTOR AFFECTING ABSORPTION

Diluents • Tetracycline + diluents such as dicalcium phosphate (DOP)-poorly/

not absorbed
• Hydrophilic aqueous binder show better dissolution profile with
poorly wettable drugs (phenacetin)
• PEG-6000 (binder) + phenobarbitone-poorly soluble complex
• Non-aqueous binder such as ethyl cellulose –related drug
dissolution
Disintegrants • overcome the cohesive strength of tablet & break them upon
contact with water
• Adsorbing disintegrates (bentonite & veegum) - should be avoided
with low dose drugs (digoxin, steroid & alkaloids).
• Microcrystalline cellulose-at high compression force-retard drug
dissolution.
Lubricants • Reduce inter particle friction & sticking or picking
• Commonly used lubricants are hydrophobic
Coatings • Order of dissolution
• Enteric coat>sugar coating>non-enteric film coating
• Shellac-it change dissolution profile at aging (on prolonged
storage), prevented by adding little PVP in coating formulation
Suspending •  the viscosity of the medium
agent • CMC + Amphetamine un-absorbable complex
Surfactant They may increase absorption or may be decrease absorption
Mechanism to increase Mechanism to decrease absorption of
absorption of drug by drug by surfactant
surfactant
Increase wetting by Formulation of drug micelle complex
increasing effective surface (un-absorbable) above CMC
area
Better membrane contact & Large surfactant –show laxative action
enhance membrane
permeability
Bile salt (anionic) & lysolecithin (nonionic) promote absorption of
hydrophobic drugs (steroid, oil soluble vitamin & Griseofulvin)
Complexing Complexing agents alter the stability, solubility, molecular size,
agents partition coefficient & diffusion coefficient of a drug.
Mechanism by which drug Complex
absorption
Enhance dissolution Ergotamine tartrate + caffeine
Enhance lipophilicity PABA + caffeine
Enhance membrane Heparin + EDTA (heparin normally not
permeability absorbed from GIT)
Complexation may decrease absorption when tetracycline + calcium
(milk, antacid), iron (haematinics), magnesium &
aluminium(antacid)
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DIGESTER -257
IMPORTANT TERMINOLOGY IN DRUG DISTRIBUTION

Perfusion rate The volume of blood that flows per unit per unit volume of
tissue.
Highly perfused tissue Lungs, Kidney, Liver, Heart, Brain, Adrenals
Moderately perfused Muscle and Skin
Poorly perfused Fat and Bone
Distribution rate Perfusion rate
constant Ke =
K tb
ktb = Tissue and blood partition coefficient
Volume of Amount of drug in body (X)
distribution Vd =
Plasma drug concentration (c)

DIGESTER -258
MARKERS USED FOR DETERMINATION OF REAL VOLUME OF DISTRIBUTION

COMPARTMENT MARKERS
Plasma Evans blue, idocyanine green, I-131 albumin
Erythrocytes Cr-51
Extracelluar fluids Raffinose, Insulin, Mannitol, Radio isotopes of Na, cl, Br,
SO4
Total body water Heavy water, Antipyrine, Tritiated water (HTO)

DIGESTER -259
PHYSIOLOGICAL BARRIER FOR DISTRIBUTION OF DRUG

Capillary endothelial • Molecular weight less than 600 dalton diffuse through this
barrier membrane.
• Drug size < 50 dalton’s – Bulk flow
• Lipophilic drugs with 50-600 dalton’s – Passive diffusion
• Polar ionized drugs of size > 50 dalton’s – Active transport
Blood brain barrier • Highly specilized pericytes and astrocytes.
• Allows highly lipid soluble unionized drugs.
• Approach for improve penetration of drug through BBB
Used penetration enhancer – Dimethyl sulphoxide
Osmotic disruption by using – Mannitol
Using drug carrier – Dipyridine redox
Blood cerebrospinal • CSF formed from choroid plexus.
fluid barrier • Highly lipid soluble drugs cross through barrier
• Sulphamethaxazole and trimethoprim

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DIGESTER GPAT DISCUSSION CENTER : MAKES STUDY EASY

Blood placental • Drugs having molecular weight < 1000 dalton’s

barrier • Highly lipid solubility. Example – Ethanol, Sulphonamide,
NSAIDS
• Cross by endocytosis – immunoglobulin
• Cross by carrier mediated transport – Essential nutrients for
fetal growth
Blood testis barrier • Barrier located at sertoli sertoli cell junction.

DIGESTER -260
BINDING OF DRUGS TO BLOOD COMPONENTS
Albumin ˃ α-Acidglycoprotein ˃ Lipoprotein ˃ Globulin
S. NO PROTEIN DRUGS BIND
1 Human serum albumin
Site-1 Warferin and Phenyl butazone, Naproxen,
azapyrone binding site Indomethacin, Sulfonamides,
Phenytoin, Bilirubin
Site-2 Diazepam binding site Benzodiazepine, Ibuprofen, Probencid
Site-3 Digitoxin Few drugs, Digitoxin
Site-4 Tamoxifen binding site Tamoxifen
2 α1 Acidglycoprotein Imipramine, Amitryptline,
Nortryptylline,Propranolol
3 Lipoprotein Chlorpromazine, Diclofenec,
Cycloserine A
4 α1 globulin Steroid like carticosterone & thyroxin
5 α2 globulin Vitamin ADEK and cupric ion
6 β1 globulin Bind with ferous ion
7 β2 globulin Bind with carotinoids
8 γ globulin Bind with antigen
9 Hemoglobin Phenylbutazone, Pentobarbital,
Phenothiazine
10 Carbonic anhydrase Acetazolamide & Chlorthalidone
11 Cell membrane Imipramine & chlorpromazine

DIGESTER -261
EXTRA VASCULAR TISSUE DRUG BINDING

EXAMPLE OF EXTRA VASCULAR TISSUE DRUG BINDING ARE

Liver Epoxides of halgoenated hydrocarbon, paracetamol, and antihistamines
Skin Chloroquine, phenothiazines interact with melanin
Eyes Chloro quine, phenothiazines interact with melanin of eyes and lead to
retinopathy
Hair Arsenicals, chlorquine, phenothiazine
Bones Tetracycline bind to bones and teeth leads to odontogensis resulting in
brown yellow colouration of teeth
Fats Thiopentla and pesticide DDT
Nucleic acids chloroquine, quinacrine bind to DNA
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DIGESTER -262
METABOLISM

Drug metabolizing organs: Liver > Lung > Kidney > Placenta > Adrenal > Skin
Drug metabolizing enzymes
catalyse oxidative, reductive hydrolytic and
Microsomal enzymes (present
glucuronidation reactions (majority of drugs
in endoplasmic reticulum)
catalysed by this process)
Catalyze oxidative reactions, reductive, hydrolytic
Non microsumal enzymes reactions, conjugation reactions other than
(Present in cytoplasm) glucuronidation. Eg: - oxidases, peroxidases,
dehydrogenases esterase's.

DIGESTER -263
METABOLITES WITH THEIR RELATIVE ACTIVITY

DRUGS METABOLITES
Phannacologic inactivation
Active Inactive
• Amphetamine Phenylacetone
• Phenobarbital Hydroxy phenobarbital
• Phenytoin p-hydroxy phenytoin
• Salicylic acid Salicylic acid
No change in pharmacological activity
Active Inactive
• Amitriptyline Nortriptyline
• Imipramine Desipramine
• Codeine Morphine
•Phenvlbutazone Oxyphenbutazone
• Diazepam Temazepam
Digoxin
• Digitoxin
Toxicological activation
Active Reactive intermediator
• Isoniazide Tissue acylating intermediate
• Paracetamol Imidoquinone of N- hydroxylated metabolite
Pharmacologic activation
Prodrug Active
• Aspirin Salicylic acid
• Phenacetin Paracetamol
• Enalpril Enalaprilat
Change in pharmacological activity
• Ipronizide Isoniazid
• Diazepam Oxazepam

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DIGESTER -264
BIOTRANSFORMATION REACTION

Phase – I reaction
Oxidative • Most abundant & most common metabolic reaction
reaction • For oxidation reaction require molecular oxygen (O2), reducing
agent NADPH (mixed function oxidases) & Cyt.P450
• Mixed function oxidases – located in ER of hepatic cells, it is
composed of electron transport chain consisting of components
1. A heme protein-k/a Cytochrome P450(terminal oxidase)
2. Flavoprotein k/a Cytochrome P450 reductase (electron
carrier)
3. Phosphatidylcholine -heat stable
 Mg ion also required for maximal activity of mixed function
oxidases
Reductive  Reductive reactions generate metabolites with polar
reaction functional group which undergo further conjugation or
biotransformation.
 These are reversible reactions leading to conversion of
inactive metabolite to active drug removal and hence results
in prolongation of action
Hydrolytic In this the functional groups like esters, ethers, amides, hydrazides
reaction are hydrolyzed and results in loss in large fragments of molecules
Phase – II reaction
 Phase-II reaction involve transfer of glucuronic acid, sulfate, glycine to drugs or
metabolite of phase-I reaction to form polar, rapidly excretable
pharmacologically inert conjugates.
 Real drug detoxification pathways
 The moieties transferred are simple, endogenous molecules with large
molecular size.
 Strongly polar or ionic in nature and make the substrate water soluble.
 Conjugation reactions are capacity limited.
 Capacities of important conjugation
 Glucuronidation >Amino Acid Conjugation > Sulfation >Glutathione
Conjugation
Conjugation • Most common & most important phase-II reaction
with Glucuronic • Conjugating moiety-D-glucuronic acid (derived from D-glucose)
acid
Conjugation • Sulfation is conjugated by non-microsomal enzymes
with Sulphate • It is a saturable process
moiety
Conjugation • Conjugation with -amino acids like glycine, glutamine and less
with extent to aspartic acid, taurine, serine are observed
-amino acid • Extensively occurs in liver mitochondria
• Reaction can be used in estimation of liver function

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Conjugation • Glutathione is nucliophilic (due to- SH group) tripeptide

with Glutathione • Conjugation with glutathione protects the tissue from reactive
and mercapturic moieties such as OH, NH2 and SH which lead to tissue necrosis,
acid carcinogenesis, mutagenesis, teratogenesis
Acetylation Acetylation is an important metabolic pathway for drugs
containing primary amino groups.
Methylation • Methylation is different from other phase II reactions in
following.
 The metabolites are non-polar, water soluble
 The metabolite have similar or greater activity than parent drug.
 Responsible for biosynthesis and inactivation of endogenous
amines.

DIGESTER -265
PHYSICOCHEMICAL PROPERTIES OF DRUG

 Physicochemical properties of drugs such as molecular size, shape, Pka,

acidity/basicity, lipophilicity, steric and electronic characteristic of drug
influences metabolism.
 Chemical factors:- chemical factors effects metabolism involves factors
inducing and inhibiting metabolism
Chemical factor
1. Induction of drug metabolizing enzymes (enzyme inducers)
 Properties of enzyme inducers
 They are lipophilic compounds & have long elimination half life
 Mechanism of enzyme inducer
 Increase liver size & liver blood flow
 Increase stability of enzyme
 Increase synthesis of cyt. P450 & decrease its degradation
 Increase microsomal protein content & proliferation of smooth ER
 Results of enzyme induction
 Decrease in pharmacological activity
 Increase activity if metabolites are active
 Alter physiological status due to increase metabolism of endogenous
compounds
 Auto induction / self-induction :- some drugs stimulates their own
metabolism for ex. –carbamazepine, meprobamate, cyclophosphamide &
rifampicin
2. Inhibition of drug metabolizing enzymes (enzymes inhibitors)-more
imp clinically as compare to enzyme induction

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2.1 Direct inhibition occur by 3 mechanism (direct inhibition is rapid

process)
Competitive inhibition:-
 Structurally similar compounds compete for same site on an enzyme
 It is reversible
 Ex. Methacholine inhibit Ach metabolism by competing AyreS0073
esterase
Noncompetitive inhibition:-
 Structurally unrelated compounds interact with enzyme & prevent the
metabolism
 Ex. lead, mercury, arsenic & organ phosphorus compounds non
competitively bind
 Ex. INH inhibit the metabolism of phenytoin
Product inhibition (auto inhibition):-
 Metabolic products compete with the substrate of the same enzyme
 Xanthine oxidase inhibitor ex. Allopurinol & MAO inhibitor - phenelzine
2.2. Indirect inhibition
Repression :- decrease in enzyme content It is due to
 Fall in enzyme synthesis by ethionine, puromycine, actinomycine D
 Rise in enzyme degradation by carbon tetra chloride, carbon disulfide,
disulfiram.
2.3. Environmental chemicals
 Environmental chemicals such as DDT, polycyclic aromatic by hydrocarbon
have enzyme induction effect.
 Organ phosphorus compound insecticide and heavy metals such as
mercury, tin, nickel, cobalt & arsenic inhibits metabolism.

DIGESTER -266
RELATIONSHIP RENAL CLEARANCE VALUES AND MECHANISM OF ACTION

RENAL RENAL CLEARANCE MECHANISM OF

EXAMPLE
CLEARANCE RATIO RENAL CLEARANCE
Drug filtered and Glucose
0 0
reabsorbed completely
Drug filtered and Lipophilic drugs
<130 Above 0, Below 1
reabsorbed partially
130 1 Drug filtered only Creatinine, Inuline
Drugs filtered as well as Polar, Ionic drug
>130 >1
secreted actively
Clearance equal to Iodopyracet, para
650 5
renal plasma flow rate amino hippurate

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DIGESTER -267
EXCRETION PATHWAYS, TRANSPORT MECHAISMS AND DRUGS EXCRETED

EXCRETORY
MECHANISM DRUGS EXCRETED
ROUTE
Urine Glomerular filtration, Free, hydrophilic, unchanged
active secretion, active/ metabolites/conjugates of MW < 500
passive reabsorption
Bile Active secretion Hydrophilic, unchanged
drugs/metabolites/conjugates of MW > 500
Lung Passive diffusion Gaseous and volatile, blood and tissue
insoluble drugs
Saliva Passive diffusion, active Free, unionised, lipophilic drug some polar
transport drugs

Milk Passive diffusion Free, unionised, lipophilic drugs (generally

basic)
Sweat Passive diffusion Free, unionised, lipophilic drugs
Intestine Passive diffusion Water-soluble, ionised drugs

DIGESTER -268
INFLUENCE OF BLOOD FLOW RATE AND PROTEIN BINDING

CHANGES IN TOTAL CLEARANCE DUE TO

Drugs with ↑ Blood low ↓ Blood low ↑ Binding ↓ Binding
High ER (Above 0.7) ↑ ↓ No change No change
Low ER (Below 0.3) No change No change ↓ ↑

DIGESTER -269
HEPATIC AND RENAL EXTRACTION RATIO OF SOME DRUGS AND METABOLITES

EXTRACTION RATIO
HIGH INTERMEDIATE LOW
Propranolol Lidocaine Aspirin Diazepam
Hepatic Nitroglycerine Morphine Codeine Phenobarbital
extraction Isoprenaline Quinidine Phenytoin
Nortriptyline Theophylline
Procainamide
Some penicillin's Hippunc Some penicillin's Digoxin Furosemide
Renal
acid Several sulphates Procainamide Cimetidine Atenolol
extraction
Several glucuronide Cimetidine Tetracycline

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DIGESTER -270
COMPARTMENT MODEL

One compartment open model

Intravenous KE = First order elimination rate
bolus dX constant
= -K E X
administration dt X = Amount of drug in the body at
any time
Intravenous KE = First order elimination rate
 C - C  -K E t
infusion log  ss  = constant
 C  2.303
CSS = Steady state concentration
Extravascular dX/dt = Rate of change in the
admistration dX dX ev dX E amount of drug in the body
= -
dt dt dt dXev/dt = Rate of input
dXE/dt = Rate of output
Two compartment open model
Intravenous bolus Cc = Distribution exponent +
Cc = A e -αt + B e _βt
administration Elimination exponent
Intravenous Css = Steady state concentration
infusion X o,L = C ss VC Vc = Volume of central compartment
XoL = Loading dose
Extravascular C = Absorption exponent +
C = N e-Kat + L e-αt + M e-βt
administration Distribution exponent + Elimination
exponent

DIGESTER -271
BIOAVIBILITY STUDY
1. Pharmacokinetic method: - Indirect method
1.1. Plasma level • Most reliable method
time study • Single dose study method require collection of sample for 2-3 half
life after drug administration
• If drug follow one-compartment 3 sample points in I.V.
• If drug follow two-compartment 5-6 sample points in I.V.
1. Peak plasma It is the maximum plasma drug concentration obtained after
conc.(Cmax) extravascular administration. It is expressed as gm.ml or ng.ml
2. Peak time (tmax) The time required reaching maximum plasma drug concentration. It
indicates time of maximum rate of absorption. Unit is minutes or hours
3. Area under the It is a measure of extent of absorption or fraction of dose that reaches
curve (AUC) the systemic circulation.
1.2. Urinary • Principle -The Urinary excretion of unchanged drug is directly
excretion study proportional to the plasma conc. of drug
• Determination of bioavailability using urinary data should be
conducted only if at least 20% of drug excreted unchanged in urine
• Collection of sample up to 7 biological half life
• Determining the drug which is excreted unchanged in the urine
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2. Pharmacodynamics method:- Direct method

2.1. Acute • It is used when Bioavailability measurement by pharmacokinetic
pharmacological methods is difficult, inaccurate & non reproducible
response • Acute pharmacological response – such as ECG, EEG & pupil diameter
measured by
• Pharmacological effect time curve
• Dose response graph
2.2. Therapeutic Theoretically most definite method
response (clinical Demerits:-
response) – based • Quantitation of observed response is too improper
on observation of • Bioequelance study are usually conducted by using Cross over design
clinical responses

DIGESTER -272

BCS CLASSIFICATION

RATE LIMITING
CLASS SOLUBILITY PERMEABILITY STEP IN EXAMPLES
ABSORPTION
Class - I High High Gastric emptying Metoprolol,
propranolol
Class - II Low High Dissolution Nifedipine,
Naproxne
Class -III High Low Permeability Cimetidine,
Metformin
Class - IV Low Low Case by case Taxol

DIGESTER -273
BCS CLASSIFICATION FOR EXTENDED RELEASE DOSAGE FORM

CLASS SOLUBILITY PERMEABILITY IVIVC

Ia High & site High & site IVIVC level A expected
dependent dependent
Ib High & site Depend on site & IVIVC level C expected
dependent narrow absorption
window
IIa Low & site High & site IVIVC level A expected
dependent dependent
IIb Low & site Depend on site & Little or no IVIVC
dependent narrow absorption
window
Va : Acidic Variable Variable Little or no IVIVC
Va : Basic Variable Variable IVIVC level A expected

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DIGESTER -274

BIOPHARMACEUTICS DRUG DIPOSITION CLASSIFICATION SYSTEM (BDDCS)

ELIMINATION
CLASS SOLUBILITY METABOLISM EXAMPLE
PATTERN
Predominantly Diltiazem
Class - I High Extensive
eliminated by liver
Class - Predominantly Itraconazole
Low Extensive
II eliminated by liver
Poor metabolism, Doxycylines
Class - eliminated unchanged
High poor
III by renal and biliary
route
Poor metabolism, Ofloxacin
Class - eliminated unchanged
Low poor
IV by renal and biliary
route

DIGESTER -275

LIST OF THE IMPORTANT PHARMACOKINETIC ADME INTERACTION

Object drugs
Tetracycline
fluoroquinolones like
ciprofloxacin,
penicillamine
Cephalexin,
sulphamethoxazole,
trimethoprim, warfarin
and thyroxine
Sulphonamides, aspirin
Ferrous sulphate
Ketoconazole,
tetracycline, atenolol
Aspirin, diazepam,
levodopa, lithium
carbonate, paracetamol,
mexiletine
ABSORPTION INTERACTIONS
Precipitant drugs Influence on object drug
1. Complexation and Adsorption
Antacids, food and Formation of poorly soluble and
mineral supplements unabsorbable complex with such
containing Al, Mg, Fe, heavy metal ions
Zn, Bi and Ca ions
Cholestyramine Reduced absorption due to
adsorption and binding
2. Alteration of GI pH
Antacids Enhanced dissolution and
absorption rate
Sodium bicarbonate, Decreased dissolution and enhence
calcium carbonate absorption
Antacids Decreased dissolution and
bioavailability
3. Alteration of Gut Motility
Metoclopramide Rapid gastric emptying; increased
rate of absorption

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Levopoda, lithium Anticholinergics Delayed gastric emptying ; decreased

carbonate, mexiletine (atropine) rate of absorption
Object Drugs Precipitant Drugs Influence on Object Drugs
4. Inhibition of GI Microflora
Digoxin Antibiotics Increased bioavailability due to
(erythromycin, destruction of bacterial flora that
tetracycline) inactivates digoxin in lower intestine
Oral contraceptives Antibiotics Decreased reabsorption of drugs
(ampicillin) secreted as conjugates via bile in the
intestine
5. Malabsorption Syndrome
Vitamin A, B12 Neomycin (and Inhibition of absorption due to
Digoxin colchicines) malabsorption /steatorrhoea caused
by neomycin

DISTRIBUTION INTERACTIONS (COMPETITIVE)

DISPLACED DRUGS DISPLACERS EFFECT

Anticoagulants Phenylbutazone, Increased clotting time;
(warfarin) chloral hydrate, Increased risk of haemorrhage
salicylates
sulphonamides
Tolbutamide Sulphonamides Increased hypoglycaemic
effect
Methotrexate Sulphonamides , Increased methotrexate
Salicylic acid toxicity
Phenytoin Valproic acid Phenytoin toxicity

METABOLISM INTERACTIONS

DISPLACED DRUGS DISPLACERS EFFECT

1.Enzyme Induction
Corticosteroids, oral Barbiturates Decreased plasma levels;
contraceptives, decreased efficacy of
coumarins, phenytoin, object drugs
tolbutamide, tricyclic
antidepressants
Corticosteroids, oral Phenytoin do
contraceptives,
theophylline, cyclosporin
Object Drugs Precipitant drugs Influence on Object drugs
Oral contraceptives, oral Rifampicin Do
hypoglycaemics,
coumarins

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DIGESTER GPAT DISCUSSION CENTER : MAKES STUDY EASY

2. Enzyme Inhibition
MAO inhibitors Enhanced absorption of
(phenelzine, pargyline, unmetabolised tyramine;
- etc. increased pressor
activity; potentially fatal
risk of hypertensive crisis
Grapefruit juice Enhanced absorption of
- drugs; increased risk of
toxicity
Phenytoin Decreased absorption of
folic acid due to
- inhibition of an enzyme
responsible for its
absorption
Chlorpromazine, Increased plasma half-
haloperidol life of tricyclics; increased
- risk of sudden death from
cardiac disease in such
patients
Metronidazole, Increased anticoagulant
Phenylbutazole, activity; risk of
- chloramphenicol haemorrhage
Hypoglycaemia may be
precipitated
Xanthine oxidase Increased toxicity of
-
inhibitors (allopurinol) antineoplastics
Cimetidine Increased blood levels of
-
object drugs

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