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8/11/2019 BDS PK Class 3
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General
Pharmacology
Elimination
Dr.U.P.RathnakarMD.DIH.PGDHM
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Microsomal Enzyme induction
Drug A Metabolism[24hrs]Enzyme
Drug B
[Inducer]
Enzyme+Enzyme+Enzyme+Enzyme Metabolism[6hrs]
Effect
=No drug effect
OCP Metabolism[24hrs]Enzyme
Drug B
[Rifampicin]
Enzyme+Enzyme+Enzyme+Enzyme Metabolism[6hrs]
Prevents pregnancy
=Pregnancy!
+
+
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Microsomal Enzyme inhibition
Drug A
[Toxic]
Metabolism[24hrs]Enzyme
Drug B[Inhibitor]
Metabolism[72hrs]
Effect
=Drug accumulates
Warfarin Metabolism[24hrs]Enzyme
Drug B
[Erythrymycin]
Enzyme Metabolism[72hrs]
Anticogulant
=Bleeding
+
+
Enzyme
Drug A
[Toxicity]
Warfarin
[Toxicity]
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Non-microsomal enzymes
Genetic polymorphism
INH Long duration of action=Lower doseNon-microsomal Enzyme
Slow acetylators
[40% of polpulation]
INH Short duration of action=Higher doseNon-microsomal Enzyme
Fast acetylators[40% of polpulation]
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Factors affecting Biotransformation1. Age-Extremes of age enzymes may be
deficient
Eg.Chloramphenicol in prematurebabies causes Gray baby syndrome.
2. Malnutrition:- metabolism due to enz.
proteins.3. Liver disease:- metabolism-- so..dose
of drug
4. Genetic: Genetically determined variation inmetabolism
Slow and fast acetylators-INH SCH
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Prodrug
Inactive drug
Converted to active form by metabolism Improved B.A.-L-Dopa and Dopamine
Prolongs duration of action- Fluphenazine
Improves taste- Clindamycin palmitate Reduces ADE-Bacampicillin
Methenamine release Formaldehyde inacidic urine
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Drug ExcretionRemoval of drug and its metabolites
from body Kidney
Lungs
Bile Feces
Sweat
Saliva
Tears
Milk
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Excretion-Kidney
Renal
excretion
Glomerular
Filtration
Tubular
secretion
Tubular
reabsorption
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Glomerular Filtration
Mol.size Depends on Renal blood
flow Plasma protein binding
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Tubular secretion-Active
Carrier mediated
Not affected by PPB Penicillin, Probenecid, Quinine
May use same carrier-Non-specific
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Tubular Reabsorption-Passive
Depends on pH and ionization
Strongly acidic and alkaline-Unionized-
Excreted Weakly acidic-Ionized in alkaline
medium-not absorbed. Eg. Alkaline urineand aspirin toxicity
Weakly basic-Ionized in acidic urine
Eg. Acidification of urine NH4cl or Vit-
C-in Amphetamine poisoning
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Factors affecting renal excretion
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Excretion-Other routes Lungs: Alcohol, G.A,
Faeces: Drugs not absorbed and secretedwith bile
Bile:Excreted in BileReabsorbed from
small intestine-This cycle is E.H.circulationEg.E.Mycin
Skin: As and Hg
Saliva: KI, phenytoin. Li Milk:Milk acidicAlkaline drugs ionized
and accumulate. Eg. TetracyclineADE in
infant
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First order
Zero order
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PLASMA HALF LIFE- t1/2
It is the time required for the plasmaconc. of the drug to be reduced to half ofits original value.
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100
50
150
75
175
87.5
187.5
93.5
193.5
96.5
196.5
98
198
99
199
100
Takes 4-5 halflives to reach steady state concn.
Steady state[Plataeu principle]
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Clinical Importance of Half Life
t helps to determine theduration of action of the
drug.
To determine the frequencyof drug administration.
To determine the time takento achieve the steady state.
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Elimination First order
100 mg administered[100%]
1 t1/2 50mg 50%
2 t1/2 25mg 75% 3t1/2 12.5 mg 87.5%
4t1/2 6.25.mg 93.75%
Take 4-5 halflives for completeelimination of a drug
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Therapeutic drug monitoring-TDM Monitoring drug therapy by measuring plasma
conc.of drugs. Indications
1. Drugs with low margin of safety-Digoxin,Lithium
2. To check Pt. compliance.3. If individual variations are large.- TCA.
4. Potentially toxic drugs used in presence of
renal failure-AMINOGYCOSIDES5. When Pt. does not respond without reason
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How to prolong duration of action of a
drug?
Prolong absorption from site of administration
Oral- SR tablets, CR. ?Eg
Parenteral: Less soluble form, oily prep,
adrenaline
TTS ?Eg
Increase PPB ?Eg
Slow down Metabolism ?Eg
Reduce Renal Excretion ?Eg