MT1

Question 1

Define Drugs

Answer 1

Therapeutic agent;

Any substance, other than food, used in the prevention, diagnosis, alleviation, treatment or cure of a disease

Question 2

Pharmacodynamics is…

Answer 2

what drugs do to the body;

The study of the relationship of drug concentration to drug effects

Question 3

Pharmacokinetics is…

Answer 3

The quantitative study and characterization of the time course of drug concentrations in the body;
Describes the time course of drug concentrations in the body;

Question 4

Potency

Answer 4

Related to the amount of agonist needed to produce an effect of a given magnitude;
Usually expressed as ED50 where low ED50 = high potency

Question 5

ED50

Answer 5

dose to achieve 50% of the maximum effect achievable with that agonist

Question 6

Efficacy

Answer 6

related to the maximum effect that can be achieved with a particular agonist;
Usually expressed as Emax where high Emax = high efficacy

Question 7

Emax

Answer 7

The maximum effect that can be achieved with that drug

Question 8

Maximum efficacy is defined as

Answer 8

the maximum effect achieved with the endogenous receptor agonist

Question 9

Inverse agonists

Answer 9

stabilize inactive state of a receptor or destabilize the active state.
Their effect is to reduce constitutuve receptor activation

Question 10

Chemical antagonism

Answer 10

direct interaction of two substances in solution such that the effect of one or both is lost.

Question 11

Physiological antagonism

Answer 11

Indirect interaction of two substances with opposing physiological actions

Question 12

Pharmacological antagonism

Answer 12

blockage of interaction of one substance with receptor by another substance

Question 13

Competitive Antagonists (3)

Answer 13

Bind reversibly to the receptor;
Inhibition can be overcome by increasing [agonist];
Primarily affect agonist potency;

Question 14

Non-Competitive Antagonists (3)

Answer 14

Bind irreversibly (eg. covalently) to the receptor or reversibly/irreversibly to an allosteric site;
Inhibition cannot be overcome by increasing [agonist];
Primarily affect efficacy;

Question 15

What kind of antagonist reduces the number of receptors available for activation by agonists?

Answer 15

Non-competitive antagonists

Question 16

Superagonists

Answer 16

Rare;

>100% Emax;

Question 17

Drug desensitization

Answer 17

The effect of a drug often diminishes when given continuously or repeatedly

Question 18

Receptor mediated desensitization

Answer 18

Loss of receptor function;

Reduction in receptor number;

Question 19

Non-receptor mediated drug desensitization

Answer 19

REducation of receptor-coupled signalling components;
Reducation of drug concentration;
Physiological adaption

Question 20

ADME

Answer 20

Absorption
Distribution
Metabolism
Excretion

Question 21

Routes of administration

Answer 21

SYSTEMIC: enteral, parenteral

LOCAL: topical

Question 22

Enter drug administration

Answer 22

Desired effect is systemic (non-local), substance is given via digestive tract;

Ex. Oral route

Question 23

Oral route of drug admin

Answer 23

Enteral route;
Most common and convenient route;
Subject to FIRST PASS EFFECT (metabolism by intestine/liver enzymes);
So not suitable for drugs that are rapidly metabolized, acid labile, known to cause GIT irritation;

Question 24

First pass effect

Answer 24

Metabolism of drug that reduces amount of drug that ultimately reaches the systemic circulation (bioavailability)

Question 25

Parenteral drug admin

Answer 25

desired effect is systemic (non-local), drug is given by route other than digestive tract;

Question 26

Transmucousal druf admin

Answer 26

A parenteral form of drug admin;
Includes:
Buccal - under tongue
Insufflation - snort
Inhalation

Question 27

Injection drug admin

Answer 27

A parenteral form of drug admin;
Usually intravenous, intramuscular, or subcutaneous;
Intravenous is rapid to bloodstream because it is direct and give 100% bioavailability;
By-pass first pass effect;
Suitable for acid labile drugs;
But may require professional admin, high costs, sterile preparation;

Question 28

Oral drug absorption

Answer 28

the process by which a drug moves from the site of admin to the site of measurement (usually blood)

Question 29

Drug Distribution

Answer 29

The process by which drug REVERSIBLY leaves the blood and is distributed throughout the tissues of the body

Question 30

Drug distribution depends on (4)

Answer 30

1 - blood flow (lung, kidney, liver > brain, skeletal muscle > adipose, bone)
2 - Ability of drug to transverse cell membranes
3 - degree of binding to blood proteins
4 - unique proterties of drug/tissue

Question 31

Why is volume of distribution ‘apparent’?

Answer 31

It assumes equal partitioning throughout body (eg pl concentration is equal to that of all other volumes)

Question 32

Factors contributing to a high volume of distribution

Answer 32

Physiological properties of drug:

• high lipophilicity, low polarity, low ionization and low MW
• Increased ability to traverse pl membranes

Physiological properties of tissues:

• iodine containing drugs transported to thyroid
• adipose can accumulate large amounts of lipid-soluble drugs

Question 33

factors contributing to a low volume of distribution

Answer 33

• low lipophilicity, high polarily, high ionization, high MW

- ability to bind to blood proteins (eg blood serum albumin)

Question 34

Binding of drug to blood proteins (albumin)

Answer 34

Contributes to a low volume of distribution.
Albumin-bound drugs are generally therapeutically inactive;
Binding is reversible - can be displaced by another drug, Displacement can lead to a dangerous increase in blood concentration of drug
Concerning for highly bound drugs with narrow therapeutic window

Question 35

Major determinant of action of drugs in the body

Answer 35

Elimination - metabolism and excretion.

Question 36

Elimination of lipophilic drugs

Answer 36

Most drugs are lipophilic and only partially ionized at physiological pH

• poorly excreted by kidney and liver
• Metabolism increases their polarity, ionization and water solubility

Question 37

Why are lipophilic drugs poorly excreted by kidney and liver

Answer 37

• bind to plasma proteins, inhibiting glomerular filtration
• reabsorption at renal tubules and biliary epithelium
• partitioning into lipid-rich tissues (adipose)

Question 38

Bioavailability - define

Answer 38

the amount of administered drug that reached the systemic circulation in unchanged form

Question 39

Cytochrome P450

Answer 39

CYP Gene Superfamily

• 57 individual genes
• Multiple physiological roles
• Families 1, 2, 3, are most relevant to drug metabolism
• Major contributors to Phase 1 metabolism
• Extremely broad substrate range (multiple isoforms, low specificity for substrates)
• Expression levels vary among individuals - so diff pharmacokinetics
• Enzymatic activity can be inhibited by drugs and diet components (decreases rate of metabolism of co-administered drugs / most common cause of adverse drug interactions)
• Expression levels can be induced by drugs and diet components resulting in increased rate of metabolism of co-administered drugs

Question 40

CYP 3A4

Answer 40

• most relevant enzyme to human drug metabolism
• most abundant CYP in intestine and liver (first-pass effect)
• very broad substrate specificity
• metabolizes 50-70% of drugs

Question 41

Interindividual differences in drug metabolism

Answer 41

1 - diet + env (incl. co-administered drugs, smoking, job)
2 - Age (generally drug, metabolism is reduced in elderly and children are different)
3 - Disease (generally reduces metabolism)
4 - Genetic Factors (polymorphisms for drug metabolizing enzymes)