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BASIC PROCESSES OFDRUG THERAPY

R. G. ALVERO, MD., MSc, PSECP2012 - 2013

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PROCESS INVOLVED INDRUG THERAPY

1. Pharmaceutical Process

2. Pharmacokinetic Process

3. Pharmacodynamic Process

4. Therapeutic Process

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PHARMACEUTICAL PROCESS

Is the drug getting from theformulation into the patient?

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PHARMACEUTICAL PROCESS

Is the drug getting to its site of

action?

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PHARMACODYNAMIC PROCESS

Is the drug producing required

pharmacological effect?

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THERAPEUTIC PROCESS

Is the drug pharmacological effect beingtranslated into a therapeutic effect?

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PHARMACEUTICAL PROCESS

What can determine whether a drug isabsorbed from the gut or not?

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PHARMACOKINETIC PROCESS

relationship between the dose &the concentration of unbound drug

based on the abstractmathematical modelling of the finecourse of drug concentrations intheoretical compartments

Physiologically based approach?

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PHARMACOKINETIC PROCESS

Fundamental Parameters:

Clearance

Volume of Distribution

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PHARMACOKINETIC PROCESS

If the total body clearance, VD & thefraction excreted unchanged areknown, the rest can be predicted

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PHARMACOKINETIC PROCESS

Predicted

Renal Clearance (L/hr)*fraction excreted unchanged = renal Cl

total Cl

Renal Cl = fraction excreted unchange x total CL

= 0.1 x 80= 80

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PHARMACOKINETIC PROCESS

Predicted

Hepatic Clearance (L/hr)* fraction excreted unchanged = (1 fe) (1 - 0.1)

= 0.9

* fraction metabolized = hepatic Cltotal Cl

Hepatic Cl = 0.9 (80)

= 72 L/hr

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PHARMACOKINETIC PROCESS

Predicted

Hepatic Extraction Ratio

* Hepatic Extraction Ratio = hepatic Clhepatic BF

= 72/90

= 0.8

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PHARMACOKINETIC PROCESS

Predicted

Max Oral Bioavailability

* fn = (1-E4)

= 1 0.8= 0.2

* F = (fg) (fn)= 1 x 0.2= 20%

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PHARMACOKINETIC PROCESSES

PredictedRenal Clearance (L/hr) 8Hepatic Clearance (L/hr) 72Hepatic Extraction Ratio 0.8Max Oral Bioavailability 20Affected by Liver Enzymes

when given PO YesAffected by Liver BF

when given IV Yes Dose in Liver Disease Yes

Dose in Renal Disease NoHalf Life 4Dosing Schedule 6Time to Reach SS 20

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PHARMACOKINETIC PROCESS

Ask the following question to predictclinical situations likely to require care:

1. It is mainly metabolized? Or mainly

excreted?2. If metabolized, does it have high or low

hepatic Cl?

3. What is the t

4. Are there complicating factors such asactive metabolites?

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PHARMACODYNAMIC PROCESS

How do drugs produce effects?

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PHARMACODYNAMIC PROCESS

Types of Pharmacological Actions of Drugs

1. Direct effect on a receptor

2. Indirect alteration of the effect of anendogenous agonist

3. Inhibition of transport process

4. Enzyme inhibition

5. Enzyme activation6. Misc.

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THERAPEUTIC PROCESS

Translation of pharmacological

effect therapeutic effect

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If a patient appears not to be responding totreatment with a particular drug analyze the processes if drug

therapy

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Thank you for your

attention!!!