Pharmacology Lecture 1

Front 1

Pharmacology

Back 1

Study of drugs, interactions with living systems,
understanding physical,
chemical properties,
effects in the body,
use of drugs, understanding how drugs are absorbed, distributed, metabolized and excreted.

Front 2

Clinical Pharmacology

Back 2

Study of drugs in humans, in patients and healthy people.

Mostly therapeutics, to prevent and treat.

Front 3

Therapuetics (Pharmacotherapeutics)

Back 3

use of drugs to diagnose, prevent or treat disease, medical use

Front 4

Chemical name

Back 4

chemical description; complex, not commonly used

Front 5

Generic name

Back 5

Non-proprietary name, given by United States Adopted Name Council.

Each drug only has one generic name, most commonly used (ex: ibuprofen)

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Trade name

Back 6

Proprietary name, created by drug companies, name approved by the FDA (must be).

Fillers and other ingredients added to them. (ex: ibuprofen- advil, motrin). May affect how people react to them

Front 7

Effectiveness

Back 7

elicits the intended response



Major Properties of an Ideal Drug

Front 8

Safety

Back 8

Does not produce harmful effects. Impossible to avoid, may be minor. Always a risk.

Major Properties of an Ideal Drug

Front 9

Selectivity

Back 9

Produces only the response for which it is given.


Major Properties of an Ideal Drug

Front 10

Therapeutic Objective

Back 10

Provide maximum benefit with minimal harm. Benefits outweigh risks.

Front 11

Administration

Back 11

-drug dosage (strength),

-route of administration

-timing of administration

(Factors Determining the Intensity of Drug Responses)

Front 12

Pharmacokinetics

Back 12

how the body affects the drug

- processes:
absorption, distribution, metabolism & excretion

(Factors Determining the Intensity of Drug Responses)

Front 13

Pharmacodynamics

Back 13

how the drug affects the body

processes involve drug-receptor binding followed by the events that lead to the response.

(Factors Determining the Intensity of Drug Responses)

Front 14

Individual Variation

Back 14

- physiological factors- weight, age,gender

-pathophysiology- any chronic illness, esp. liver diseases; kidneys (b/c of excretion

- genetic factors- can alter metabolism

(Factors Determining the Intensity of Drug Responses)

Front 15

Direct penetration

Back 15

crosses membrane by penetrating through it.

-Lipid soluble only.

-Most common method

Front 16

Transport systems

Back 16

-carry the drug across membrane.

-Selective, carry only specific drugs

-Most common: P-glycoprotein - transports drugs out of cells (liver, brain, kidney)

Front 17

Passage through channels & pores

Back 17

-very small to pass through

-Rare b/c most need transport or direct penetration

Front 18

Absorption

Back 18

-mov’t of the drug from its site of administration into blood.

Front 19

Distribution

Back 19

-drug mov’t from blood to interstitial space of tissue into the cells.

Front 20

Metabolism

Back 20

- enzymatic processes that alter the drug (biotransformation)

-Occurs in the liver – the hepatic microsomal enzyme system. P450 system

Front 21

Excretion

Back 21

- movement of drug and metabolites out of the body

The removal of drugs from the body, primarily through kidneys.

When kidneys not functioning, drug levels are increased. Dosages have to be lowered.

Front 22

Bioavailability

Back 22

- extent to which a drug is absorbed and transported to the target tissue.

-Defines extent to which drug is absorbed and transported to tissue

Front 23

Factors affecting drug absorption

Back 23

- rate of dissolution
- surface area
- blood flow
- lipid solubility
- pH partitioning
- site of absorption

Front 24

rate of dissolution

Back 24

- how easily drug dissolves. Dissolves easy = quicker absorption

Front 25

surface area

Back 25

-the larger the surface area the quicker the drug will be absorbed.

Ex: PO meds (usually absorbed in small intestine

Front 26

blood flow

Back 26

- absorbed quicker from sites with high blood flow

Front 27

lipid solubility

Back 27

-drugs with high lipid solubility are absorbed quicker b/c can penetrate quicker

Front 28

pH partitioning

Back 28

difference in pH of plasma/blood & pH at site of admin, greater the difference the more easily absorbed b/c tries to balance difference

Front 29

site of absorption

Back 29

-absorption vary depending on the site of admin, route

Front 30

Routes of Administration

Back 30

-intramuscular

-intravenous

-subcutaneous

-oral/PO

Front 31

Influences on absorption

Back 31

1.food or delayed gastric emptying

2.drug interactions- some meds taken together impair absorption

3.coating

4.solubility of the drug, pH

Front 32

intravenous

Back 32

administered directly into blood stream no membrane to cross

advantages: rapid onset, tight control over drug levels, can use large amount of fluid to make less harmful to veins or toxic to body. Some meds harmful to take PO

disadvantages: dangerous – too fast, can’t take it back, inc risk of infection, cost.

Front 33

intramuscular

Back 33

injection into muscle, easily absorbed
-alternative route for IV meds- some meds don’t dissolve

-depot preps- give large amount of med into muscle and absorbed slowly over time

advantages: used for meds that don't dissolve well, depot prep

disadvantages: painful, damage to local tissue, nerve damage.

Front 34

subcutaneous

Back 34

injection into subcutaneous tissue.

Smaller needle. Technique different for different thickness of skin.

Same advantages and disadvantages as IM.

Morpine can be given IM or subcutaneous

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oral/PO

Back 35

absorbed in the stomach or the intestine

advantages: convenient, easier to use, less expensive.

disadvantages:
-inactivation or destruction of drug,
-GI irritation,
-absorption variable from pt to pt.

-not all meds can be given PO (ex- insulin gets deactivated in stomach)

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tablets

Back 36

-mixture of drug plus binders & fillers.

-Different manufacturers have different binders & fillers

Front 37

enteric-coated preparations

Back 37

-coated so will dissolve in intestines but not stomach.

-the coating protects drug or protect the stomach.

PROBLEM- absorption is variable; those with delayed gastric emptying;
sometimes are not absorbed at all

Front 38

sustained release preparations

Back 38

-capsules filled with coated spheres that contain the drug.

- Coatings dissolve at variable rates ensures release of drugs all day, take once

PROBLEM- expense

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other formulations

Back 39

- applied to the skin, eyes, nose, ears, vaginally, rectally, inhalation, bronchodilators

Front 40

blood flow to the tissues

Back 40

Drugs delivered by blood stream & rate of delivery determined by blood flow to tissue.

More blood flow, more distribution

Front 41

ability of drug to exit vascular system

Back 41

exit at the capillary beds, easily pass between capillary cells EXCEPT at:

-blood/brain barrier

-placenta

-protein binding

Front 42

blood brain barrier

Back 42

protects the brain from toxic substances

- tight junctions between the capillary cells so through the cells – lipid soluble, med with transport system

BUT can be hard to treat CNS infection (can put reservoir right into brain)

Front 43

placenta

Back 43

protective barrier. Lipid soluble can pass thru barrier.

DANGER: can cause detrimental affects to fetus

Front 44

protein binding

Back 44

most common albumin, which can’t pass through capillary walls & stays in bloodstream.

If known that drug binds to protein, not given PO, given IV instead

Front 45

ability of drug to enter cells

Back 45

lipid solubility and the presence of a transport system.

Some drugs do not cross cell membrane – bind with receptors on cells and can enter

Front 46

Effects of Drug Metabolism

Back 46

- accelerated renal drug excretion

-drug inactivation

-increase therapeutic action

-activation of drugs

-increase or decrease toxicity

Front 47

accelerated renal drug excretion

Back 47

unable to excrete lipid soluble drugs
metabolism converts lipid soluble drugs into compounds easier to excrete.

Front 48

drug inactivation

Back 48

convert active compounds to inactive forms/component

example- anesthesia

Front 49

increase therapeutic action

Back 49

increase effectiveness of some drugs by converting into more active form.

Example- codeine

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activation of drugs

Back 50

inactive compound (prodrug) into an active form

Front 51

increase or decrease toxicity

Back 51

Decrease in toxicity occur when drug converted into inactive form.
Increase occur when drugs transformed into toxic substances.

Front 52

Factors that influence Metabolism

Back 52

- age

- induction of drug metabolizing enzymes

- first-pass effect

- poor nutrition

- drug competition

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age

Back 53

- infants sensitive to drugs until liver matures (age one)

Front 54

induction of drug metabolizing
enzymes

Back 54

-increase drug metabolism:

+drugs cause liver to produce drug-metabolizing enzymes through induction.

Induction increase metabolism of drugs -> inc doses needed to maintain therapeutic levels.

Front 55

first-pass effect

Back 55

rapid hepatic inactivation of a drug.

To prevent use other routes than PO, because drug can be metabolized by liver immediately and become ineffective

Front 56

poor nutrtition

Back 56

Cofactors needed for metabolism

Front 57

drug competition

Back 57

compete w/ each other for metabolism if use same metabolic pathway

->dec rate of metabolism, drugs can accumulate and become toxic

Front 58

Steps in Drug Excretion

Back 58

- GLOMERULAR FILTRATION

- PASSIVE TUBULAR REABSORPTION

- ACTIVE TUBULAR SECRETION

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GLOMERULAR FILTRATION

Back 59

All drugs except those bound to albumin are filtered through the glomerular membrane.

Front 60

PASSIVE TUBULAR REABSORPTION

Back 60

lipid-soluble drugs reabsorbed into blood –not excreted.

Front 61

ACTIVE TUBULAR SECRETION

Back 61

Active transport systems pump drugs from blood into the urine for excretion.

example P-glycoprotein, pumps for organic acids/bases

Front 62

Factors that Affect
Renal Drug Excretion

Back 62

- PH DEPENDENT IONIZATION

-COMPETITION FOR ACTIVE TUBULAR TRANSPORT

- AGE

Front 63

PH DEPENDENT IONIZATION

Back 63

can speed up excretion of drugs by changing pH of the urine we can speed up excretion; causes ionization of drugs

Front 64

COMPETITION FOR ACTIVE
TUBULAR TRANSPORT

Back 64

competition can delay excretion and prolong the effects of the drug

Front 65

AGE

Back 65

infants’ kidneys not fully developed.

Elderly- decline in renal function, renal excretion declines

Front 66

Plasma Drug Levels

Back 66

monitored to regulate drug responses. Adjust up or down

- therapeutic range

-MEC

-toxic concentration

Front 67

THERAPEUTIC RANGE

Back 67

between minimum effect concentration & toxic concentration

This is where we see desired drug affect.

Some drugs have small therapeutic range and have to monitor

Front 68

MEC

Back 68

minimum concentration that is effective – anything below it is not effective

Front 69

Toxic concentration

Back 69

- toxicity occurs

Front 70

Half-Life

Back 70

time required for amount of drug in body to decrease by 50%.

Drugs with short half-lives = excreted quickly. Means dosing interval would be short

Drugs with long half-lives = excreted more slowly. Means take less often or smaller doses

Front 71

Drug Dosing – Time course

Back 71

- single dosing

- multiple dosing

Front 72

Single Dosing

Back 72

plasma levels of drug in plasma go up as drug is absorbed.

Go up to therapeutic level and then goes down. Depends on metabolism and absorption

Drug therapeutic at MEC then it will be therapeutic.

Plasma levels decrease when metabolized and excreted.

Front 73

Multiple Dosing

Back 73

accumulation of drug in the body; stays within therapeutic range

Front 74

plateau

Back 74

drug level constant – 4 half lives

Front 75

peak and trough

Back 75

- highest concentration, must stay below toxic level)

and

- lowest point, check before give meds).