Pharma

Question 1

First pass metabolism

Answer 1

Any metabolism before the blood i.e. gut lumen (acid), gut wall (P glycoprotein efflux), liver

Question 2

Bioavailability =

Answer 2

the fraction of a drug reaching a particular body compartment

Question 3

Vd=

Answer 3

How much volume we’d need to keep the total body conc equal to the plasma conc. Vd is low for drugs that stay in the blood and high for drugs that go to muscle/fat/etc

Vd = dose of drug given/ plasma conc

Question 4

Factors affecting distribution

Answer 4

Volume of distribution 
Protein binding (if bound then it can't have an effect)

Question 5

Give examples of drugs with volumes of distributions from low to high

Answer 5

Ibuprofen, warfarin (lowest Vd i.e. stay in blood)
Alcohol, insulin, dextrose
Paracetamol, caffeine
Cocaine, diazepam
Haloperidol, TCAs

Question 6

Describe drug route from mouth to liver

Answer 6

Mouth, gut lumen, gut wall, portal vein, liver

Question 7

Potency =

Answer 7

amount needed to produce a given effect (depends on efficacy and affinity)

Question 8

Vd relates to our body fluid volumes- explain

Answer 8

Our plasma is 5%, about equal to heparin’s Vd so it stays in blood
ECV is 20%, about equal to gentamicin which stays outside cells and can’t enter very well
Total water is 55%, about equal to drugs that cross cells easily such as ethanol
Drugs with a Vd greater than our body volume go everywhere and are hard to remove by harm-dialysis e.g. TCAs, haloperidol

Question 9

Vd is proportional to…

Answer 9

half life (higher Vd, longer half life)

Question 10

Outline our fluid compartment numbers

Answer 10

42L total, 2/3 ICF 1/3 ECF

Question 11

Why do drugs get conjugated

Answer 11

So they become water soluble to be eliminated

Question 12

What is phase I and II metabolism

Answer 12

Both in liver
Phase I is oxidation, reduction, dealkylation and hydrolysis reactions. CYP450s carry out redox reactions (e.g. 2D6, absent in 7% white, hyperactive in 30% East African, metabolises codeine and inhibited by haloperidol)
Phase II is conjugation

Question 13

What are first order and zero order kinetics

Answer 13

First order- elimination is proportional to amount of drug. Called linear

Zero order- elimination is at the same rate and does not vary with drug concentration. More likely to cause toxicity.

Some drugs have both e.g. paracetamol is linear and then non-linear when saturated

Question 14

How many half lives to reach CpSS (concentration plasma steady state) and how many half lives to eliminate

Answer 14

4-5 half lives

Question 15

What’s the point of loading doses

Answer 15

Allow us to get to CpSS without waiting for 4-5 half lives if the half lives are long
Loading dose = Vd / target CpSS

Question 16

What is k?

Answer 16

Elimination constant
K = Clearance / Vd
T1/2 = Vd / Clearance

Question 17

EC50 and Emax

Answer 17

EC50 is concentration at 50% effect

Emax is max effect

Question 18

What is Km

Answer 18

Concentration at half the Vmax (max velocity)

Question 19

Is the Vmax and Km different to the enzyme with:
a competitive inhibitor
a non-competitive inhibitor

Answer 19

Comp: same Vmax, different Km

Non-comp: different Vmax (lower), same Km

Question 20

Define affinity

Answer 20

How well it binds to receptor

Question 21

Efficacy

Answer 21

How much drug achieves its effect

Question 22

Potency

Answer 22

How much of a drug is needed to produce desired response

Question 23

Therapeutic index

Answer 23

EC50 of adverse effect / EC50 of desired effect
TD50 : ED50 (toxic to effective dose)
Used to quantify the therapeutic window (minimum toxic concentration - minimum effective concentration)

Question 24

What is P-glycoprotein

Answer 24

Efflux transporter, found in GI (moves back into gut lumen), kidneys (moves into urine), liver (moves into bile)
Grapefruit juice inhibits
St Johns wort induces

Question 25

What could affect metabolism

Answer 25

Genetics of CYP450s e.g. 2D6 (7% white absent 30% East African hyperactive for codeine) Portal blood flow Inducers (St Johns wort) or inhibitors (ethanol) of CYP450s

Question 26

Give a pharmacokinetic drug interaction example

Answer 26

I.e. affecting ADME. Alginates (gaviscon) reduce absorption of other drugs Or aspirin displaces warfarin from albumin --> excessive bleeding

Question 27

Give a pharmacodynamic drug interaction example

Answer 27

Agonism/antagonism at same receptor e.g. salbutamol is a beta agonist and stall is a beta blocker

Question 28

Describe disease-drug interactions

Answer 28

Renal disease: e.g. CKD impaired clearance so longer half life of renally excreted drugs e.g. digoxin Hepatic disease: impaired clearance of hepatic cleared drugs e.g. opiates in cirrhosis can lead to coma CVS disease: impaired hepatic and renal perfusion so impaired clearance

Question 29

What's a normal QT interval and what can happen if its prolonged

Answer 29

350-450ms. If prolonged can cause torsades de pointes, a form of VT that can become VF. Sotalol, cocaine, TCAs can prolong QT

Question 30

Give examples of off target and on target ADRs

Answer 30

Beta blockers on-target ADR of bradycardia, off target bronchospasm

Question 31

Antagonists have affinity but no efficacy. Agonists have...

Answer 31

affinity and efficacy

Question 32

Grapefruit juice...

Answer 32

is a CYP450 inhibitor

Question 33

Obesity ____ Vd so need ___ dose

Answer 33

Increases Vd, need higher dose

Question 34

Kd

Answer 34

affinity between site and ligand

Question 35

Why is LDL bad for vessels

Answer 35

Enters arterial wall, becomes oxidised, oxidised LDL enters macrophages to become foam cells, activates T cells, mitogenic for SM cells, inhibits macrophages, increases platelet aggregation, toxic to endothelial cells.

Question 36

How do statins work? name one

Answer 36

Simvastatin. Inhibit cholesterol synthesis in hepatocytes via inhibiting HMG-CoA reductase

Question 37

When should you prescribe statins and name ADRs

Answer 37

When 20% 10yr risk of CVD or familial hypercholesterolemia. | ADRs myopathy, arthralgia

Question 38

What are fibric acid derivatives/ fibrates

Answer 38

PPAR agonists, treatment for hypertriglyceridemia by increasing LPL production to decrease TGs. As an adjunct to diet ADRs cholelithiasis and abnormal LFTs (contraindicated in hepatic or renal or gallbladder disease)

Question 39

What does nicotinic acid do

Answer 39

Increase HDL-C Decrease VLDL and coronary events ADRs peptic ulcer activation, hepatotoxic, pruritus Contraindicated in peptic ulcer disease, acute liver disease

Question 40

What does ezetimibe do

Answer 40

Inhibits GI LDL absorption and increases hepatic LDL Rs, circulating enterohepatically ADRs abdo pain, diarrhoea Adjunct to diet and statins in hypercholesterolemia