How drugs work?Or

How do they ‘know’ to go from my stomach to my head

and not my foot?

Basic Biopharmaceutics

Objective of Drug Therapy

To deliver the right drug, in the right concentration, to the right site of action and at the right time to produce the desired effect.

(of course in the right patient!)

Clinical Trials 10-15 years from lab to US patients Only 1 in 5000 compounds make it to human

testing Only 1 in 5 tested in humans is approved Testing Phases in Humans

Phase I (ADME) Phase II (w/dz) Phase III (Special study) Phase IV (post-mkt)

Generic Medications Patent on parent agent Hatch-Waxman Act 1984 Pharmaceutical Co

ANDA filed with FDA Bioequivalent Labeling Review

Pharmaceutically equiv. Therapeutically equiv.

Types of Drug Action

React physically

React chemically

Modify metabolic activity & enzyme systems

Change osmolarity of blood

Interfere with normal cell function

Modify ion channels

Modify creation, release or control of neurotransmitters or hormones

Receptors

Cellular material at the site of action

Lock & keyAgonist

Antagonist

The Love Cocktail

Concentration & Effect

Blood concentration – time profileMEC minimum effective concentration

MTC minimum toxic concentration

Onset of action

Therapeutic window

Duration of action

Half-life• The time taken for the drug

Concentration to decline by 50%

….OR

The time taken for 50% of the drug to be eliminatedThe time taken for the drug concentration to fall to half the original value

After 4 half lives, elimination is 94% completeAfter 7 half lives, elimination is 99% complete

After 1 half life, elimination is_____complete

Bioequivalence Terms

Bioavailability

Bioequivalency

Pharmaceutical equivalent

Pharmaceutical alternative

Therapeutic equivalent

Pharmacokinetics Pharmacodynamics

How a drug MovesWhat the body does to a drugADME

AbsorptionDistributionMetabolismExcretion

DiffusionPassive diffusionActive transport

How a drug BehavesWhat the drug does to the body

BeneficialToxic

Absorption Distribution

Gastric emptying

Intestinal movement rate

Blood flow rate

Permeability of tissue membranes

Protein binding

Metabolism Excretion

LiverEnzyme induction

Enzyme inhibition

Gall bladderStores metabolites

Enterohepatic cycling

First-Pass metabolism

KidneysNephron

Glomerular filtration rate

Factors Affecting Drug Response

Age

Gender

Pregnancy

Genetics

Body weight

Psychological factors

Adverse Drug Reactions

CNS effects

Hepatotoxicity

Hypersensitivity or Allergy

GI effects

Nephrotoxicity

Hematological effects

Drug dependence

Teratogenicity

Carcinogenicity

Idiosyncrasy

Drug-Drug Interactions

Absorption Distribution Metabolism Excretion

Binding in GIT

GI empty

Displacemt

and effect

Enzyme induction

GFR

Renal Secretion

Gastric pH

Intestinal

Metabolism

Enzyme inhibition

Urinary Re-absorption

Drug-Diet Interactions

Absorption Distribution Metabolism Excretion

Gastric emptying

Gastric motility

Dosage form

Interacting chemically

FoodHi fat meals

Level of nourishment

AdminTime

Food MixProtein

Carbohydrate

Fat

Calories

ProteinInc.GFR

Dec.reabsorption

Dec.secretion in the kidney

Drug Disease States

Hepatic Circulatory Renal Thyroid

Cirrhosis

Obstructive jaundice

Acute viral hepatitis

Cardiovascular Disorders

Decrease Blood Flow

erratic absorptn

liver metabolm

Effect on drug elimination

Effect on plasma protein binding

Creatinine levels

Hypo- Hyper-

Types of drug actionReceptors

Concentration & effect

Pharmacokinetics & dynamics• Absorption, distribution,metabolism, excretion

• Factors affecting drug responses

Adverse drug reactionsInteractions

CASE STUDY!

Precipitating Event 1st Week SRJC Professional Program

35yr old, average wt to ht male presents to clinic with facial flushing, anxiety, palpitations, mild temporal HA

Hx: S/P Hep C in remission

Personal Hx: unremarkable

Social Hx: smokes ½ ppd, coffee 4-6 cups

Drinks tangerine juice with a splash of lime

VS: BP 146/90 P 99 T normal

MED List: APAP 1000mg qid prn HA, Mylanta prn gastritis, Inderal 20mg BID,

OTC herbal aphrodisiac

Dx: anxiety reaction frequently ppts migraine

POINTS TO PONDERTreatment plan?

Lifestyle modifications?

Pharmacokinetics?

Factors altering drug response?