PHARMACOLOGY 2

Question 1

what are xenobiotics?

Answer 1

foreign compounds with no nutritional value

Question 2

what is the overall repoonse of patients due to?

Answer 2

Pharmacodynamic effects

Pharmacokinetic effects

Question 3

what does absorption, distribution and metabolism depend on?

Answer 3

Route of administration of drug

Physico-chemical properties of drug

Question 4

how can things diffuse through the cell membrane?

Answer 4

through the lipid bilayer, aqueous channels or special transport proteins eg. carrier/channel proteins

Question 5

what are chemical properties of drugs?

Answer 5

Drug Structure
Molecular Weight
Lipophilicity
Ionisation

Question 6

what are physiological variables affecting drugs absorption?

Answer 6

pH of site
Surface area of memb
Mesenteric blood flow
Gastric emptying
Presence of food 
Efflux transporters

Question 7

what is bioavailability?

Answer 7

% of the administered dose reaching the systemic circulation as unchanged drug (not as metabolites)

Question 8

what is bioavailability governed by?

Answer 8

Absorption

First pass metabolism

Question 9

where do most drugs need to be absorbed into?

Answer 9

the bloodstream, usually from the GI tract

Question 10

where do enteral/oral go to?

Answer 10

to/through epithelium of G.I. tract (any location, from oral to rectal mucosa, could be many formulations

Question 11

what does drugs given parenterally mean?

Answer 11

aside from intestine

Question 12

where do drugs given parenterally cross and avoid?

Answer 12

may cross epithelium (e.g. skin, lung)

may avoid epithelium (e.g. subcutaneous, intramuscular, intrathecal, intraperitoneal injection)

Question 13

what other ways are drugs administered?

Answer 13

directly into bloodstream

some drugs act locally at site of application, topical administration eg skin, eyes, vagina, nasal mucosa, airways

Question 14

what do drugs given directly into the bloodstream allow?

Answer 14

absorption avoided by intravascular administration, e.g. intravenous, intra-arterial.
used for infusion, large volumes

Question 15

what does ADME stand for?

Answer 15

absorption
distribution
metabolism
excretion

Question 16

what is pharmacokinetics?

Answer 16

study of these processes to understand size and duration of response

Question 17

what does distribution depend on?

Answer 17

on molecular size, ability to cross memb and extent of binding to plasma proteins.

Question 18

what does plasma protein binding involve?

Answer 18

Loose electrostatic bonding, especially to albumin (for acidic drugs) and acid glycoprotein (for basic drugs)

Question 19

what is equilibrium established between?

Answer 19

between bound & free form

Question 20

what does equilibrium allow?

Answer 20

reduces free drug conc available in plasma to reach site of action

Question 21

how does elimination occur?

Answer 21

Renal excretion

Liver metabolism Chemical transformation

Question 22

what are the 2 compounds not metabolised, and cleared almost exclusively by glomerular filtration?

Answer 22

Small water-soluble molecules

Some complex carbohydrates

Question 23

what drugs are extensively metabolised?

Answer 23

Lipophilic drugs

Question 24

what would happen to lipophilic drugs if metabolism didn’t occur?

Answer 24

lipophilic drugs would be recycled endlessly through glomerular or enterohepatic re-absorption

Question 25

what reactions are phase I metabolism?

Answer 25

Functionalisation reactions

Question 26

what reactions are phase II metabolism?

Answer 26

Conjugation reactions

Question 27

what reactions are phase III metabolism?

Answer 27

Formation of xenobiotic- macromolecule adducts

Question 28

what is phase I metabolism?

Answer 28

Addition or unmasking of a functional polar group

Question 29

give examples of phase I metabolism

Answer 29

``` Oxidation Reduction Hydrolysis Hydration Isomerisation Miscellaneous ```

Question 30

what occurs to go from phase I to II metabolism?

Answer 30

Addition of a polar group Catalysed by transferases Cofactor donor

Question 31

what are properties of drug-metabolising enzymes?

Answer 31

``` Low substrate specificity May have low reaction specificity Lower catalytic rates but may be present in high conc Substrates are usually lipophilic Enzymes are inducible ```

Question 32

where does drug metabolism mainly occurs?

Answer 32

in 2 sub-cellular compartments in liver Smooth Endoplasmic reticulum cytosol

Question 33

what is the Smooth Endoplasmic reticulum?

Answer 33

Continuous network of filamentous, memb bound channels

Question 34

what happens when the drug reaches the Smooth Endoplasmic reticulum?

Answer 34

Cell disruption breaks the endoplasmic reticulum into small fragments which have metabolising enzymes associated - Microsomes

Question 35

give examples of Microsomal enzymes

Answer 35

Cytochrome P450 Flavin monooxygenase (FMO) Glucuronosyl transferase Epoxide hydrolase

Question 36

give examples of Cytosolic enzymes

Answer 36

``` Aldehyde oxidase Aldehyde dehydrogenase Alcohol dehydrogenase Glutathione transferase Sulphotransferase ```

Question 37

give examples of Mitochondrial enzymes

Answer 37

Aldehyde dehydrogenase | Monoamine oxidase

Question 38

what are oxidation reactions catalysed by?

Answer 38

Cytochrome P450

Question 39

give examples of factors that affect metabolism

Answer 39

``` Competition between substrates Inhibition of enzymes by drugs Induction of enzyme systems Age, nutritional status, liver disease Genetic polymorphism ```

Question 40

how does induction of enzyme systems affect drug metabolism?

Answer 40

Inhibits function of repressor gene therefore operator gene active more mRNA more enzyme protein. rate of metabolism of barbiturates & other drugs increases and drugs become less effective

Question 41

how does genetic polymorphism affect drug metabolism?

Answer 41

individuals or population groups may have less/more of particular enzymes & show slower/faster rates of metabolism

Question 42

what is the role of the liver in drug metabolism?

Answer 42

Major site of drug metabolism & drug metabolising enzymes

Question 43

what is first pass metabolism?

Answer 43

delivery of drug direct to liver after oral administration

Question 44

what compromises metabolism/excretion of drugs?

Answer 44

Liver disease, liver function failure, reduction of synthesis of plasma proteins

Question 45

give examples of inter-individual factors

Answer 45

species sex genetic factors

Question 46

give examples of intra-individual factors

Answer 46

``` age pregnancy stress disease nutrition enzyme induction enzyme inhibition ```

Question 47

what does drug effect in individual patient depend on?

Answer 47

``` Dose, potency, efficacy Mechanism of action Route of administration, extent of absorption Patient compliance Age, body weight, sex Rate of inactivation/excretion (liver, kidney function) Genetic factors Other drugs Placebo effect Disease Tolerance to drug ```