Inducers, inhibitors and the rest of it

Question 1

CYP 450 Inducers

Answer 1

BullShit CRAP GPS induce rage

Barbituates
St Johns wort
Carbamazepine and oxcarbazepine
Rifampicin
Alcohol (Chronic)
Phenytoin
Griseofulvin
Phenobarbital
Sulfonylureas

Question 2

CYP 450 inhibitors

Answer 2

SICKFACES.COM

Sodium valproate
Isoniazid + Imipramine 
Cimetidine
Ketoconazole
Fluconazole
Alcohol (Acute) + Allopurinol 
Chloramphenicol
Erythromycin (All macrolide with the exception of azithro)
Sulfonamides
.Grapefruit juice
Ciprofloxacin
Omeprazole
Metronidazole

Question 3

P-GP substrates

Answer 3

Don’t touch A rabid dogs

Digoxin, Tacrolimus, apixaban, Rivaroxaban, Dabigatran

Question 4

P-GP inducers

Answer 4

Senior Sargeant Policeman PORCS induces fear
Smoking
St Johns wort
Phenytoin
Phenobarbital
Oxcarbazepine
Rifampicin
Carbemazepine

Question 5

P-GP-Inhibitors

Answer 5

G-PACMAN stops the chomp
Grapefruit
Protease inhibitors
Azoles
Cyclosporin and cimetidine
Macrolide Abx
Amiodarone
Non-DHP CCBs (Diltiazem and verapamil)

Question 6

Drugs ok with MOAIs

Answer 6

MAOIs interact with heaps. 
E-MAIL 
Ibandronic acid
Metoprolol
Alprazolam
Latanoprost
Eostrogen (OCP)

Question 7

Increase digoxin levels

Answer 7

Queen Vicotria Collects Monthly Instalments Payments
Quinidine
Verapamil
Cyclosporin
Macrolides
Itraconazole
Propafenone
Spiranolactone

Question 8

Amiodarone + Digoxin + Warfarin

Answer 8

Amiodarone increases warfarin concentration and Increases digoxin concentration too.

Question 9

SSRI and SNRI affect to be wary of

Answer 9

Increases bleeding risk

Question 10

Sodium valproate and lamotrigine combination

Answer 10

Valproate inhibits lamotrigine metabolism. Also increases risk of rash.

Question 11

Four different ways to calculate clearance

Answer 11

Cl = elimination rate constant x Vd 
Cl = (dose x bioavailability)/AUC
Cl = Maintenance dose/steady state
Cl = 0.7 x (Vd/half life)

Question 12

What is the livers relationship to clearance

Answer 12

Water soluble drugs can simply be excreted in the urine. However, highly lipid soluble drugs (i.e. non-polar) need to be metabolised into more water soluble substances to be excreted.
This typically occurs in the liver.
The fraction of drug removed from the circulation as it passes through the liver is represented by the HER. i.e. if this were = 1, the hepatic blood flow is equivalent to clearance.

Hepatic clearance therefore = HBF x HER

Question 13

Drugs that observe zero order kinetics

Answer 13

Alcohol, aspirin, Phenytoin, Theophyline - Like a TAAP

Question 14

Zero order vs first order kinetics

Answer 14

First order kinetics describes drugs that elimination is dependant on the concentration within the system. I.e. if there is lots of drug in the system, more can be cleared for a given time compared with lower concentrations. Graph appears like a quarter pipe- i.e. a logarithmic scale.
In zero order - clearance is constant regardless of the dose.
A change in dose leads to a disproportionate change in concentration.

Question 15

Competitive antagonist

Answer 15

Still able to reach maximum effect but will either take longer, or require a higher concentration. I.e. a drug that tries to bind to the same site as the agonist.

Question 16

Non-competitive antagonist

Answer 16

Will never be able to be reach maximum effect due to an inhibitor binding to a seperate site and causing a change to the functioning receptor.

Question 17

Potency

Answer 17

is the amount of drug required to produce an effect of given intensity. A highly potent drug evokes a larger response at lower concentrations.
This is typically measured by the EC50. I.e the concentration of drug required to reach 50% of the efficacy.

Question 18

Efficacy

Answer 18

The maximum effect that can be achieved with a drug regardless of concentration

Question 19

Therapeutic index

Answer 19

The dose at which half of the adverse effects occur i.e. LD50 (lethal dose 50%)/ED50 (efficacious dose 50%)

Question 20

Volume of distribution definition

Answer 20

Vd = Total amount in body/ Blood plasma concentration
It is however a constant - it is a reflection of the amount of compartments a drug can access. I..e plasma only medications will have a Vd <15.
This being said - protein binding may give a falsely elevated Vd due to the degree of drug that is inacitvated due to being protein bound

Question 21

What is notable about the pharmacodynamics of propanolol?

Answer 21

It is highly protein bound - more than 90%

Question 22

What is the major determinant of a loading dose

Answer 22

Volume of distribution is the key determinant - think of it as ‘filling up’ the compartments.

Question 23

Definition of bioavailability

Answer 23

The proportion of drug that makes it to the systemic circulation. It is dependant on two factors:
- Absorption from the GIT and also degree of first pass metabolism
AUC Oral/AUC IV for same dose

Question 24

Partition co-efficient

Answer 24

Concentration in the lipid phase/concentration in the aqueous phase
I.e. if a high partition co-efficient there is a higher degree of lipid solubility
The higher the partition coefficient, the more membrane soluble is the substance

Question 25

Medication examples that shouldn’t be taken with food and why

Answer 25

Doxycylicne : Ca2+ binding which prevents absorption

Cholestyramine can bind to warfarin and thyroxine

Question 26

• CYP3A4 Metabolisers and inhibitors

Answer 26

o Metabolisers:
 Cyclosporine, warfarin, quinidine, terfenedine, carbamazepine, lovastatin, methylprednisolone
o Inhibitors: (the prescription of these drugs enhance the levels of drugs above)
 Erythromycin, ‘azole’ anti-fungal agents, verapamil, diltiazem

Question 27

• CYP2D6 Metabolisers and inhibitors

Answer 27

o Metabolises pro-drug codeine to morphine
 Small % of people are poor metabolisers of CYP2D6 – has little analgesic effect
o Inhibited by:
 Quinidine, neuroleptics, fluoxetine

Question 28

Warfarin notable increase in INR

Answer 28

-	Notable drugs that decrease INR:
o	Carbemazepine, phenytoin (can be inhibitor and inducer but >decrease)
o	Rifampicin
o	Cholestyramine
o	St John’s Wort

RECIN

Question 29

Function of P-Glycoprotein

Answer 29

The normal function of P-glycoprotein is that it sits on either intestinal lumen and effluxes substrates – so inhibits the concentration of drugs (churns them out)

Question 30

Why do we randomise in trials

Answer 30

To reduce confounders

Question 31

Why do we blind in trials

Answer 31

To reduce observer bias

Question 32

• Preclinical studies:

Answer 32

o	Identification of a promising compound 

o	Laboratory testing 

o	Animal testing - esp rodent models 

o	Safety evaluation 
o	Preliminary pharmacokinetics

Question 33

• Phase I Clinical Trials:

Answer 33

o Focus on safety and side effects – Is the drug safe, what are the side effects, how does the drug work in the body

Question 34

• Phase II Clinical Trials:

Answer 34

Focus of efficacy and dosing/frequency of dosing.

Question 35

Phase 3

Answer 35

Specific target population. Is the drug effective in the target group.

Question 36

• CYP2C19

Answer 36

o Clopidogrel, PPIs
o Genetic testing is available but not recommended for routine testing for “clopidogrel resistance”
o Loss of function is associated with increased stent thrombosis in PCI