Pharmacology

Question 1

minimum effective concentration- what?

Answer 1

To achieve an effect a drug must have a minimum effective concentration in the plasma

Question 2

what is the calculation of therapeutic window?

Answer 2

TR= MTC (maximum tolerated concentration)/ MEC (minimum effective concentration)

Question 3

is a small or large therapeutic window safer in a drug?

Answer 3

A large therapeutic window is safer in a drug

-this means theres a large gap between the minimum effective concentration (MEC) and maximum tolerated concentration (MTC)
-the smaller the gap the more likely the body will not be able to tolerate a drug

Question 4

examples of drugs with a large therapeutic window?

Answer 4

-Penicillins
-Benzodiazepines

larger therapeutic window= safer

Question 5

examples of drugs with a small therapeutic window?

Answer 5

-Digoxin
-Warfarin

smaller therapeutic window= more unsafe

Question 6

what is the quantal dose response relationship?

Answer 6

Quantal dose response relationship:
-plots the fraction of the population that responds to a given dose of drug against the drug dose
-the response measured is quantal (present or not present) instead of graded like change in bp

note: i think it basically is finding out what dose of drug has an effect on the average population???

Question 7

explain what could be found in drugs that produce responses in 50% of the population?

Answer 7

-Median effective dose (ED50)
-Median toxic dose (TD50)
-Median lethal dose (TD50)

Question 8

what are pharmacodynamics?

Answer 8

drug A modifies the effect of drug B without altering concentration in tissue fluid

dynamics= drug= duo/ dynamic between the duo

Question 9

what are pharmacokinetics?

Answer 9

Drug concentration over time

Not easy to predict + Involves absorption, distribution, metabolism + excretion

kineTIC= clock ticks= drug conc over time

Question 10

what can affect absorption? (phamacokinetics)

Answer 10

-drugs that increase/ decrease the rate of stomach emptying
-specific drugs that cause problems with normal bacteria for gut absorption

Question 11

examples of drugs that increase/ decrease stomach emptying- affecting absorption in pharmacokinetics

Answer 11

Metoclopramide- increases stomach emptying, this can increase absorption (drugs are absorbed in enterocytes in intestine so faster if they leave stomach)

Atropine- decreases stomach emptying and so decreases absorption

Question 12

what antibiotic reduces absorption + efficacy of COC?

Answer 12

rifampicin
-due to destroying the gut bacteria

Question 13

what is volume distribution?

Answer 13

the theoretical volume occupied by a drug compared to plasma concentration

VD= amount of drug/ plasma concentration

Question 14

what type of drugs cause a low volume distribution?

Answer 14

Drugs that are highly pound to plasma protein (do not get distributed into fat tissue)
-Large, charged drugs

Question 15

what type of drugs cause a large volume distribution?

Answer 15

Drugs that are highly distributed into fat tissue compartments (small+ lipophillic)

Question 16

what occurs to volume distribution in prgnancy?

Answer 16

Volume distribution increases:
-increase in GFR causes more proteins to be excreted
-less proteins for drugs to bind to
-increase in fat stores
-leads to higher distribution of drugs into fat tissue compartments (higher volume distribution)

Question 17

what is half life?

Answer 17

time required to reduce the amount of drug in the body to 1/2

Question 18

what is zero order elimination vs first order elimination?

Answer 18

zero order elimination:
-rate of elimination is constant
-depends on time not concentration of drug ingested

first order elimination: (more common)
-the rate of elimination is directly proportional to drug concentration
-can take 4 to 5 half lives to reach steady state

Question 19

how does the bioavailability vary for IV or PO formulations?

Answer 19

IV= 100% bioavailability
PO= <100% bioavaialbility

bioavailability= fraction of drug avaialble to systemic circulation in an unchanged form

Question 20

what is the first pass effect?

Answer 20

-refers to the pre systemic metabolism or elimination of a drug reducing bioavailability

pill> intestinal epithelium (enterocyte) > liver (hepatocyte) then either metabolism in hepatocyte or bile excretion (either way its bioavailability will be reduced due to going through bowel and liver)

Question 21

what may change distribution of a drug?

Answer 21

drugs bound to plasma protein may be displaced by a second drug increasing their free concentration (would be able to move into fatty compartments increasing volume distibution)

Question 22

what are the phases of drug metabolism?

Answer 22

Phase I- P450 oxidation, reduction and hydrolysis

Phase II- conjugation (sulfation, methylation, acetylation, glucuronidation)

Question 23

what part of pharmacokinetics particularly affects elderly?

Answer 23

Metabolism (especially phase II)

Question 24

what can effect phase I of metabolism?

Answer 24

P450 hepatic inducers and inhibitors

Question 25

role of P450?

Answer 25

P450 is an enzyme that breaks down drugs in the body- allowing them to be metabolised

Question 26

effect of P450 inducers?

Answer 26

P450 inducers break down more drug (enhance metabolism) and decrease efficacy of drugs

Question 27

example of a drug that is commonly affected by P450 enzyme inducers/ inhibitors?

Answer 27

Warfarin

Question 28

examples of P450 inducers?

Answer 28

CRAP GPS induces my rage= inducers= metabolise + clear drug faster= decrease efficacy of drug (e.g. WARFARIN) Carbamazepine Rifampicin Alcohol Phenytoin Griseofulvin Phenylbarbital Sulfynureas (gliclazide)

Question 29

examples of P450 inhibitors?

Answer 29

These drugs INHIBIT P450 and so stop the metabolism of the drug, increasing toxicity in the body= potentiates effects -Sodium Valproate -Omeprazole -Fluoxetine (SSRIs) -Erythromycin (macroliders) -Ketoconazole -Isoniazid (TB medication) -Sulfonimides -Chloramphenicol -Amiodarone -Quinidine -Grape fruit juice

Question 30

what effect would clarithromycin have if combined with warfarin?

Answer 30

Clarythromycin is a P450 inhibitor -this would mean Warfarin wouldnt be metabolised as fast so would be potentiated more bleeding!!

Question 31

what is elmination/ clearance?

Answer 31

volume of the body cleared of a drug over a unit of time clearance= rate of elimination/ plasma concentration clearance= volume distribution x elimination constant

Question 32

what determines time of steady state being achieved?

Answer 32

half life

Question 33

what determines the magnitude of steady state?

Answer 33

clearance and dose

Question 34

what could cause excessive dosage and/or decreased clearance?

Answer 34

-normal variation -genetic enzyme deficiency -renal failure -liver failure -old age -very young age -P450 enzyme inhibition

Question 35

what would cause too low of a dosage or increased clearance?

Answer 35

-poor absorption -high first pass metabolism (passing through gut to be absorbed and then passing through liver to be metabolised) -genetic hypermetabolism -enzyme P450 induction -non compliance

Question 36

what is Vmax and Km

Answer 36

Vmax= reaction rate when enzyme is fully saturated Km= half of Vmax

Question 37

what occurs to Vmax and Km in competitive enzyme inhibition?

Answer 37

Vmax the same Km is higher

Question 38

what occurs to Vmax and Km in non competitive inhibition?

Answer 38

Vmax decreases Km remains the same

Question 39

what part of pharmacokinetics is altered in severe liver disease?

Answer 39

impaired drug metabolism if liver disease is severe resulted from: decreased liver blood flow + decreased enzyme metabolism capacity

Question 40

what is an example of a highly protein bound drug with a low TR?

Answer 40

phenytoin

Question 41

what is there a reduced production of the liver in liver disease (not p450 related) and how does this affect drugs

Answer 41

Reduced synthesis of plasma proteins (hypoproteinaemia) -causes increased toxicity of highly protein bound drugs with a low TR (e.g. phenytoin) -as there will be less proteins and so higher amount of phenytoin volume distribution Reduced synthesis of clotting factors -enhanced sensitivity to anticoagulants (warfarin)

Question 42

what drugs can worsen ascites in liver disease?

Answer 42

NSAIDs

Question 43

what can worse hepatic encephalopathy?

Answer 43

all sedatives

Question 44

where are drugs excreted?

Answer 44

mainly the kidneys

Question 45

what does renal excretion of drugs do to half life?

Answer 45

renally excreted drugs have a longer half life -so may need a loading dose for rapid effect

Question 46

why does dosage of renally excreted drugs have to change with increase in age?

Answer 46

renal function declines with age if a drug is eliminated prodominantly by kidneys it will accumulate and the maintenance dose must be reduced

Question 47

how is dosing adjusted?

Answer 47

Total daily maintenance dose can be reduced by: -Reducing the size of individual dose (at unaltered interval) OR -Increasing the interval between doses (at unaltered individual dose)

Question 48

what makes elderly more vulnerable to adverse effects of drugs?

Answer 48

due to: -impaired renal elimination -increase sensitivity of target organs to drugs (e.g. brain, kidney) -polypharmicy

Question 49

drugs to watch out for in elderly?

Answer 49

-digoxin -antihypertensives -CNS depressant drugs -Warfarin -NSAIDs

Question 50

what effect does digoxin have on elderly?

Answer 50

-increased risk of toxicity because of diuretic induced hypokalaemia and renal impairement

Question 51

what effect do antihypertensives have on elderly?

Answer 51

increase risk of falls due to baroreceptor functions

Question 52

what effect do CNS depressants have on elderly

Answer 52

increased sensitivity of the brain due to inhibitory effects and reduced elimination

Question 53

what effects do NSAIDs have on elderly?

Answer 53

increased risk of adverse effects of renal function and gastro toxicity