Phamacokinetics 1

Question 1

Define drug absorption

Answer 1

the process of transfer of a drug from the site of administration into the systemic circulation

Question 2

What is the most common route of drug administration?

Answer 2

oral

Question 3

How would you give diazepam for a fitting child - status epilepticus?

Answer 3

per rectum

Question 4

how would you give a dye for an X-ray to look at the coronary arteries?

Answer 4

intra-arterial

Question 5

How would you give an anti-emetic for a vomiting pt?

Answer 5

IV

Question 6

How is insulin administered?

Answer 6

subcutaneous

Question 7

Which route of administration is the exception to the rule that a drug must cross at least one membrane to get into the circulation

Answer 7

IV

Question 8

What are the ways in which a drug can pass across a membrane?

Answer 8

passive diffusion through the lipid bilayer
diffusion through pores or ion channels
active transport - carrier mediated
facilitated diffusion - carrier mediated
pinocytosis

Question 9

What factors determine the rate of passive diffusion?

Answer 9

conc gradient
thickness of membrane
SA and permeability of membrane

Question 10

Which direction does diffusion through pores or ion channels occur - against or down the conc gradient?

Answer 10

down the conc gradient

Question 11

What type of substance travels by diffusion through ion channels or pores?

Answer 11

very small water soluble molecules

Question 12

Give an example of a drug that can diffuse through pores/ion channels and what was it used for?

Answer 12

lithium - for manic depression (bipolar)

Question 13

What two processes come under carrier mediated transport?

Answer 13

active transport

facilitated diffusion

Question 14

What does P-gp (multi-drug resistance MDR1) do?

Answer 14

it removes drugs from the cytoplasm to the extracellular side

Question 15

Name one drug that interacts with P-gp and what this results in

Answer 15

Verapamil - increases the concentration of anti cancer drugs in the cytoplasm

Question 16

What is pinocytosis?

Answer 16

A form of endocytosis usually involved in taking up surrounding fluids (and the substances this contains) into the cell

Question 17

Why is drug ionisation needed?

Answer 17

ionic forces form part of the ligand receptor interaction

Question 18

What does the extent of ionisation of a drug depend on?

Answer 18

strength of the ionisable group and the pH of the solution

Question 19

What is the pKa of a drug?

Answer 19

the pH at which half of the substance is ionised and half is unionised

Question 20

Where are weak acids best absorbed and why?

Answer 20

in the stomach, as weak acids are least ionised in acidic conditions

Question 21

What is an acid?

Answer 21

A proton donor

Question 22

Where are weak bases best absorbed?

Answer 22

in the intestine

Question 23

How do we treat aspirin overdose?

Answer 23

administer IV bicarbonate to alkalinise urine, so faster elimination of aspirin

Question 24

What are the advantages of oral administration?

Answer 24

easy
convenient
large SA of s. intestine
large blood supply of s.intestine so rapid adsorbtion

Question 25

What factors affect oral absorption?

Answer 25

drug structure drug formulation gastric emptying 1st pass metabolism

Question 26

How does drug structure influence oral adsorption?

Answer 26

lipid solubility - needs to be lipid soluble to be absorbed from the gut polarisation - highly polarised drugs only partially absorbed and the rest goes into the faeces instability at low pH or when there is digestive enzymes

Question 27

How does drug formulation affect oral absorption?

Answer 27

modified release tablets dissolve slowly or have an enteric coating

Question 28

what factors affect the rate of gastric emptying?

Answer 28

food trauma gastric surgery

Question 29

What are the barriers that an oral drug has to go through to reach the systemic circulation?

Answer 29

intestinal lumen intestinal wall liver

Question 30

What factors in the lumen hinder drug absorption?

Answer 30

digestive enzymes | colonic bacteria

Question 31

What factors of the intestinal wall affect drug absorprion?

Answer 31

Monoamine oxidases are affected by foods efflux transporters eg P-gp on enterocytes short gut syndrome produced by extensive bowel surgery

Question 32

Give an example of a drug that is taken up by pinocytosis?

Answer 32

Amphotericin (antifungal)

Question 33

Which methods of drug administration avoid first pass?

Answer 33

``` per rectum IV sublingual intramuscular inhalation transdermal ```

Question 34

Give an example of a drug which is given transcutaneously

Answer 34

Fentanyl

Question 35

What are the disadvantages to transcutaneous?

Answer 35

limited rate and extent of absorption

Question 36

what are the advantages of transcutaneous?

Answer 36

slow and continued absorption, good for drugs that need a long lasting effect

Question 37

What are the advantages of intradermal and subcut?

Answer 37

avoids the stratum corneum small volume can be given local effect can deliberately limit rate of absorption of drugs

Question 38

What factor is intradermal and subcut absorption limited by?

Answer 38

blood flow

Question 39

For what are depot injections used?

Answer 39

mental health

Question 40

What are the advantages of the intranasal route?

Answer 40

low levels of proteases and drug metabolising enzymes good SA can be used for local or systemic effects

Question 41

What are the a advantages of inhalational methods?

Answer 41

large SA | large blood flow

Question 42

What are the limitations of inhalational methods

Answer 42

risk of toxicity to alveoli | difficult to deliver non-volatile drugs

Question 43

What is the definition of distribution?

Answer 43

The process by which the drug is transferred reversibly from the general circulation to the tissues as the blood concentration increases and then returns from the tissues to the blood when the blood concentration falls

Question 44

What two types of protein can drugs bind to?

Answer 44

plasma proteins | tissue proteins

Question 45

Which protein is involved in the commonest type of protein binding?

Answer 45

albumin

Question 46

Protein binding is always reversible? T or F

Answer 46

F - it can be irreversible eg some cytotoxic chemo drugs

Question 47

Which types of drugs, lipid soluble or water soluble pass easier through the BBB?

Answer 47

lipid soluble drugs

Question 48

Which drugs use the solute carreris that supply the brain with nutrients?

Answer 48

L-Dopa for parkinsons

Question 49

How are drugs removed from the brain?

Answer 49

diffusion into the plasma active transport into the choroid plexus elimination in CSF

Question 50

Which type of drugs, lipid or water soluble, cross the placenta easily?

Answer 50

lipid soluble drugs

Question 51

What two processes are involved in elimination?

Answer 51

metabolism | excretion

Question 52

What is metabolism of a drug?

Answer 52

the transformation of the drug molecule into a different molecule

Question 53

What are the three states of excretion?

Answer 53

solid liquid gas

Question 54

What are phase 1 reactions?

Answer 54

transformation of a drug into a more polar metabolite done by unmasking or adding a functional group oxidations are the commonest reaction carried out mainly by CYP450 enzymes

Question 55

Where are cyp450 enzymes present

Answer 55

in the smooth endoplasmic reticulum of the liver

Question 56

What are phase 2 reactions?

Answer 56

conjugation - formation of a covalent bond between the drug/phase 1 metabolite an dan endogenous substrate eg glucoronic acid. the resulting products are less active and readily excreted by the kidneys

Question 57

What type of compounds are excreted in fluid form?

Answer 57

low molecular weight | polar

Question 58

What type of compounds are excreted in solid form?

Answer 58

high MWT compounds

Question 59

What type of compounds are excreted as gases?

Answer 59

volatile

Question 60

what are the fluid forms of excretion?

Answer 60

urine , bile , sweat , tears , breast milk

Question 61

What are the solid forms of excretion?

Answer 61

faeces and hair

Question 62

What is the eqn for total excretion?

Answer 62

total excretion = glomerular filtration + tubular secretion - reabsorption