BDS PK Class 3

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

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BDS PK Class 3