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Flashcards in Pharma Deck (40)
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First pass metabolism

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


Bioavailability =

the fraction of a drug reaching a particular body compartment



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


Factors affecting distribution

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


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

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


Describe drug route from mouth to liver

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


Potency =

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


Vd relates to our body fluid volumes- explain

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


Vd is proportional to...

half life (higher Vd, longer half life)


Outline our fluid compartment numbers

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


Why do drugs get conjugated

So they become water soluble to be eliminated


What is phase I and II metabolism

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


What are first order and zero order kinetics

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


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

4-5 half lives


What's the point of loading doses

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


What is k?

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


EC50 and Emax

EC50 is concentration at 50% effect
Emax is max effect


What is Km

Concentration at half the Vmax (max velocity)


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

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


Define affinity

How well it binds to receptor



How much drug achieves its effect



How much of a drug is needed to produce desired response


Therapeutic index

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)


What is P-glycoprotein

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


What could affect metabolism

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


Give a pharmacokinetic drug interaction example

I.e. affecting ADME.
Alginates (gaviscon) reduce absorption of other drugs

Or aspirin displaces warfarin from albumin --> excessive bleeding


Give a pharmacodynamic drug interaction example

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


Describe disease-drug interactions

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


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

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


Give examples of off target and on target ADRs

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