Basic principles

Question 1

What are the four aspects of pharmacokinetics?

Answer 1

• absorption
• distribution
• metabolism
• excretion

Question 2

What is pharmacodynamics?

Answer 2

the concentration of a drug at its site of action and the resulting pharmacological effects and blood stream/tissue concentrations

Question 3

Describe the concept of ‘volume of distribution’

Answer 3

• extent of distribution of the drug across the body (space that can contain the drug)
• usually correlates with roughly with the area it is ‘distributed’ too
  (e.g. aminoglycosides disperse largely to the ECF, 20% is the approx Vd)
• not usually a ‘range’ as cannot be sepcified in the body per se

Question 4

What are the two main factors that effect Vd

Answer 4

• distribution across the body (e.g. muscle, fat etc)
• the extent of tissue binding

Question 5

What is drug clearance?

Answer 5

The measure of the body to eliminate the drug
Equation = rate of elimination / concentration

Question 6

What does the term bioavailability refer to?

Answer 6

• active pharmaceutical component that enters the systemic circulation (i.e. the bloodstream)
  *oral medications - this would be absorption and first pass metabolism

Question 7

What is the purpose of a loading dose?

Answer 7

This enables reaching an intended concentration instantaneously. The loading dose is obtained from the V(d)
*a maintenance dose is required to keep meeting this concentration

Question 8

What is the PK parameter that determines the maintainence dose rate

Answer 8

Clearance

Question 9

Why is the half life important?

Answer 9

Helps determine the dosing interval and the time needed to reach steady state

Question 10

What is zero order elimination?

Answer 10

This is here concentrations of a drug fall at a constant rate (e.g. ethanol)

Question 11

What is first order elimination?

Answer 11

Elimination depends on a concentration-dependent relationship

Question 12

What is steady state and how is it calculated?

Answer 12

• medication must be supplied at at equal rate towards its elimination at a given concentration
• maintainence dose rate = clearance x steady state concentration

Question 13

True or false - volume of distribution only describes the proportion of unbound drug

Answer 13

False - includes protein bound or unbound drug

Question 14

What is the formula for half life

Answer 14

T(1/2) =0.693 Vd / CL
If high Vd, high half life
If high CL, low half life

Question 15

If there is a drop in albumin, would this affect protein binding of drugs?

Answer 15

Unlikely to as clearance is dependent on free drug clearance

Question 16

What types of drugs traverse lipid membranes - ionised or unionised?

Answer 16

Unionized

Question 17

What is P glycoprotein?

Answer 17

It is the efflux transporter protein that helps in transporting drugs to various organs
In the gut, PGP pumps drugs back into the lumen, decreasing their absorption

Question 18

Describe the concept of systemic clearance

Answer 18

Question 19

Describe how liver metabolism of drugs occurs

Answer 19

1) biotransformation of a parent drug to one or more metabolites
2) excretion of unchanged drug in the bile
3) both

*hard to measure directly, so often calculated by systemic clearance - renal clearance

Question 20

What is the formula for half life?

Answer 20

T(1/2) =0.7 x V / clearance

Question 21

List 3 factors that alter absorption

Answer 21

• lack of gut absorption
• too lipophilic (can’t cross water layer adjacent to cell) or hydrophilic (can’t cross lipid membrane)
• P glycoprotein - this pumps drug put of gut wall cells

Question 22

What is first pass elimination/metabolism

Answer 22

This is when the drug is metabolised by the liver before moving to the systemic circulation

Determined by extraction ratio = liver clearance / hepatic blood flow

Question 23

What is the most important parameter in defining a steady state drug dosage regime?

Answer 23

Clearance

Question 24

What is the equation for dosing rate?

Answer 24

Dosing rate = clearance x target concentration

Question 25

Explain how the ageing process can affect absorption?

Answer 25

Consequence of decreased blood flow to the tissues, GIT and alteration in stomach pH *clinical application of this - some medications may enhance this effect >> use of omeprazole may lower gastric pH subsequently affecting B12 absorption >> inconsistent eating habits (e.g. a high protein meal with phenytoin results in less absorption due to a higher amount of drug becoming protein bound >> reduction of subcut and transdermal meds due to reduced blood flow

Question 26

Explain the difference between first pass and phase I metabolism

Answer 26

- first pass - metabolism of a drug prior to reaching the systemic circulation - phase I - early reactions that break down drugs

Question 27

In the ageing process, how is first pass metabolism affected?

Answer 27

- first pass reduced as part of the ageing process (resulting in a HIGHER peak concentration) - good examples of this are amitriptyline, verapamil, opiods

Question 28

In the ageing process, how is phase I metabolism affected?

Answer 28

- reduced - clinical application - decreased clearance of metabolised medications (e.g. warfarin) *note no affect on peak concentration

Question 29

Is renal clearance affected by the ageing process?

Answer 29

- not confirmed evidence wise - unsure if reduced renal clearance related to pathophysiology vs. ageing

Question 30

Describe the half life and Vd of ampicillin

Answer 30

- short half life (<1.5 hour) and therefore a low volume of distribution *this is enabled by glomerular filtration and renal tubular secretion

Question 31

What is the electrolyte disturbance associated with ampicillin?

Answer 31

sodium

Question 32

What is the role of anticholinergics?

Answer 32

- block/inhibit the neurotransmitter acetylcholine at central and peripheral nerve synapses - downstream effect of blocking the parasympathetic nervous system - two main receptors - antimuscarinic and nicotinic

Question 33

Outline the key adverse effects of anticholinergic medications at toxic levels

Answer 33

Central (CNS blockage) - agitation/confusion/delerium - seizures Peripheral (various) - hyperthermia - flushed/tachycardia - reduced gut motility, urinary retention - blurred vision, NARROW angle glaucoma

Question 34

What are some key contraindications for anticholinergics?

Answer 34

- some conditions make elderly people more susceptible to anticholinergic activity (e.g. dementia) - elderly Px - increased permeability of BBB

Question 35

Explain why in a patient with AD, anti-cholinergic medications would not be useful

Answer 35

- in mild-mod dementia - cholinergic medication may be used *anti-cholinergics could offset this - example - donepazil

Question 36

What is the concept of high anticholinergic load?

Answer 36

This is where there can be a cumulative, sedative effect of taking multiple medications with anticholinergic properties

Question 37

What is the risk associated with switching a patient from a biologic to a biosimilar medication?

Answer 37

- potential initiation of anti-drug antibodies *possibility to make the biologic and biosimilar medication ineffectie

Question 38

List 3 drugs that are common CYP3A4 inducers

Answer 38

- carbemazipine - phenytoin - rifampin - dexamethasone

Question 39

How is hydrocortisone metabolised and what drugs should be avoided to prevent an addisonian crisis?

Answer 39

- via CYP3A4 - any inducers could reduce the plasma concentration of hydrocortisone (e.g, carbemazipine)

Question 40

What will happen to a patient on ketoconazole and hydrocortisone?

Answer 40

increased levels of hydrocortisone as ketoconozole is an inhibitor of CYP3A4

Question 41

List 3 drugs that are inhibitor enzymes

Answer 41