pharmacology 2 - intro 2

Question 0

if a drug is administered i/v then what is the absorption?

Answer 0

no absorption as already in blood!!!

Question 1

what is absorption of a drug? what does it depend on? (3)

Answer 1

the passage of a drug from the site of administration to the bloodstream.

• solubility (non-ionised = more soluble)
• physiological properties eg. what is the blood supply like to the tissue (fat vs muscle)
• site of administration!

Question 2

name some routes of administration?

Answer 2

I/V, oral, I/P, S/C, I/M, rectal, transdermal, epidural, inhalation, i/o(osseous)

Question 3

what is the bioavailability of the drug?

Answer 3

quantifiying drug absorption. extent to which an administered drug dose enters systemic circulation.

Question 4

what does parenteral administration mean? 3 ways?

Answer 4

injecting - the route by which the drug GI tract is bypassed.
i/v - most rapid, give slowly, some irritants (cancer) by drugs given this way.
i/m - delayed action, depends on muscle, good for farmers.
s/c - lots of space.

Question 5

parenteral vs oral:?

Answer 5

oral is good for home usage/owners.
parenteral is more rapid, reliable
oral not good if they are inappetent or vomiting
see drug instructions!!

Question 6

explain oral administration? depends on? some drugs may become ionised in stomach -how? what can be done about this?

Answer 6

stomach and intestine environments are different (ph)
some drugs may be ionised in the stomach 9weak bases) and therefore, not absorbed properly. (erythromycin) for this reason it would need an enteric coating to allow it to pass through the stomach and be absorbed in the intestine where the ph is higher.

• speed of gastric emptying
• presence of food - read instructions.

Question 7

what is the first pass effect?

Answer 7

this means removal of a % of the drug as it passes through the liver. via the portal circulation from the stomach. this means it may not reach the systemic circulation. eg. lidocaine.

Question 8

may also give drugs sublingually or rectally? how are they absorbed?

Answer 8

through the mucosa

Question 9

what can you do with drug formulation to delay release at first? eg. bolus . what happens if you add adrenalin to a drug?

Answer 9

intentionally delay release of the drug from the site of admin. can have sustained release/controlled release eg. over time.
if you add adrenalin - causes local vasoconstriction and reduces the absorption rate of the agent from the site.

Question 10

what is AUC? regards to a graph. 3 things?

Answer 10

area under the curve. it indicates total exposure to the drug. used to difine bioavailabilty( how much of drug is available to systemic circulation - extent to which it enters/is available to the systemic circulation intact!)
used to calculate clearance too!!!

Question 11

equation of bioavailability from the curve?? what does F stand for?

Answer 11

f = AUC(ORAL) / AUC(IV)

AUC(IV) - 100% as all goes to the systemic!!!
F = bioavailability!!!

Question 12

what are the factors affecting distribution? (3)

Answer 12

movement across membranes
blood flow to the origional tissue
lipid solubility (depends on ionisation)

Question 13

explain plasma protein binding? eg? bound drug acts as a? how does it affect half life?

Answer 13

eg. albumin. some drugs bind higly to plasma proteins. binding is reversible!, bound drug cannot move across membranes and cannot be eliminated. it acts as a resevoir!!! half life can indicate this. more protein bound = longer half life.

Question 14

bound drugs are central and not filtered! (PPB) this can be affected in 3 ways? how does it affect toxicity?

Answer 14

1. hypoalbuminaemia - increased free drug amount in blood. may get toxicity!
2. uraemia - increased free drug as more urea/creatinine to bind to albumin and displace the drug.
3. combinations of PPB drugs can displace each other - increase tosicity!

Question 15

what is the degree of PPB of NSAIDS?

Answer 15

easily toxic as 99% bound. 1% free drug. so double thelevel of free drug by just a 1% increase in free drug. - easily toxic!!!

Question 16

explain volume of distribution? Vd? how do you work it out? from a graph? LITRES/KG.

Answer 16

the amount of tissue to which the drug distributes is directly proportional to the concentration of drug in the plasma. if have a larger volume with same amount of drug - HIGHER Vd.

vd = dose/Co (concentration at time o)

known dose given so that F - 100% (bioavailibility.) less steep line = Co. (see pg. 7) peak conc after equilibrium reached and before elimination begins!.

Question 17

what does the Vd of a drug tell you? TBW = ? if VD is 0.3 what does it mean? if it is 2l/kg? if it is 0.6l/kg?

Answer 17

TBW = 0.6L/KG. ECF = 0.1-0.3l/kg.

• if Vd id=s in the order of 0.1-0.3 then durg water soluble and probably in the ECF
• if Vd is 0.6 then probably in both
• if Vd is high then probably accumulating in a certain site after distributing.

Question 18

2 routes for elimination of a drug?

Answer 18

1. biotransofrmation

2. excretion

Question 19

explain biotransformation? what will enhance this route of eilimination?

Answer 19

metabolism of a drug - changes from/to the active form. lipid solubility will enhance this route! (non-ionised)

Question 20

excretion of a drug? what will enhance this?

Answer 20

removal from the body (open model) water solubility enhances this! - renal excretion? biliary?

Question 21

biotransformation? a route of elimination of a drug. metabolism. occurs in? 2 phases of reaction?

Answer 21

usually in liver but also, kidney, gut, lung.
phase 1 reactions: hydrolysis, oxidation, reduction (lose an electron in oxidation)
phase II - glucuronidation. (add side group)

Question 22

explain phase I OXIDATION REACTIONS in biotransformation? eg of enzyme?

Answer 22

mainly hepatic microsomal enzymes which are oxidases. P45O!!! NADPH + p450 +H+ - reduced P450 + NADP+ (enzyme reduced)
reduced P450 +O2 - actives O2 complex (combine with O2)
active O2 complex + drug - oxidised drug +P450 +H2O. (oxidises drug and enzyme released.)

Question 23

some drugs alter the phase I reaction by inducing or inhibiting the enxymes (P450 - MICROSOMAL) ? eg?

Answer 23

• inducers - phenobarbital, diazepam, phenylbutazone (bute). enhance their own metabolism and others.
• inhibitors - cimetidine, reduce their own rate of metabolism and that of others.

Question 24

generally metabolites are inactive. what else could they be?

Answer 24

they could also be active. prodrugs - transformed to active form ounce metabolised. may be toxic. (paracetamol in cats)

Question 25

phase II reactions are normally? which species cant do this?

Answer 25

glucuronidation. cats cant do this - paracetamol toxic!!

Question 26

elimination of drugs? by what?

Answer 26

excretion - kidney. water solubility important. glomarular filtration depends on blood flow. /size of molecule.
active transport.