S2 - Pharmacokinetics and Pharmacodynamics Flashcards

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1
Q

Define Pharmacokinetics

A

study of movement of a drug into and out of the body

what the body does to the drug

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2
Q

Define Pharmacodynamics

A

study of drug effect and mechanisms of action

what the drug does to the body

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3
Q

Define Pharmacogenetics

A

the effect of genetic variability on the pharmacokinetics or dynamics of a drug on an individual

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4
Q

what is the therapeutic window

A

the range of plasma concentrations over which drug exerts its therapeutic effects without causing significant adverse reactions

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5
Q

what does ADME stand for

A

Absorption
Distribution
Metabolism
Elimination

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6
Q

Define bioavailability

A

the relative amount fo a drug that reaches systemic circulation once the drug molecules have gone through their first hepatic circulation
Bioavailability ( for oral) = amount of drug reaching systemic circulation(AUC oral) / total amount of drug administered (AUC IV) AUC= Area under the curve
thus, all drugs administered IV have 100% bioavailability , if there is less, the drug has undergone absorption/first pass metabolism

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7
Q

what is bioavailability affected by ?

A

Absorption (drug formulation, age, food ; lipids soluble > water soluble, vomiting ) and first pass metabolism ( metabolism that occurs before the drug enters systemic circulation e.g. in gut lumen/wall or liver)

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8
Q

what is distribution ?

A

ability to dissolve in the body and occurs in arteries, capillaries, interstitial fluid, cell membranes and then target tissues. affected by lipophilicity ( freely moves across memb) and by hydrophilicity (movement depends on SA and pKA)

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9
Q

once in circulation, are drugs bound ?

A

many are bound to proteins E.g albumin and globulins .
Only free drugs have a pharmacological effect - bind to cellular receptors, pass tissue membrane and gain access to cellular enzymes

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10
Q

what is protein binding affected by

A

hypoalbuminaemia
pregnancy (decreased binding as GFR and protein excretion increases)
Renal failure
Displacement by other drugs

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11
Q

how does changes in protein binding affect drug distribution ?

A

affect if there is high binding, low VD and a narrow therapeutic ratio

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12
Q

Define Volume of Distribution Vd

A

measure of how widely a drug is distributed in body tissues
summaries the movement out of plasma -> interstitial –> intracellular components
Small Vd- less penetration of intracellular components
Large Vd - more penetration
Vd(L) = dose(mg)/[drug(mg/L)] at time=0 or peak plasma concentration

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13
Q

what is the relationship of Vd and half life

A

half life is proportional to Vd, longer half-life greater distribution. Tissue distribution can be affected by blood flow, lipid solubility and disease states

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14
Q

describe metabolism in terms of pharmacokinetics

A

occurs in liver via phase 1 and phase 2 enzymes which increases ionic charge and eventually form water soluble products which are easily eliminated. Can involve metabolism of a pharmacologically inactive or active compound to other active compounds (pro-drugs e.g codeine –> morphine)

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15
Q

describe phase 1 enzymes

A

carried out by CP450 which involves redox reactions. CP450 mainly present in liver and metabolise toxins such as carcinogens and pesticides
CP450 induction shall reduce plasma levels of a drug. CP450 inhibition shall increase it

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16
Q

describe phase 2 enzymes

A

by hepatic enzymes which catalyse sulphation and methylation.

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17
Q

what is metabolism affected by

A

metabolism is different in many individuals ; lower in kids and elderly, women are slow ethanol metabolisers, size of human

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18
Q

describe elimination in terms of pharmacokinetics

A

main route is through kidney and is determined by glomerular filtration, passive tubular reabsorption, Active tubular secretion

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19
Q

define clearance

A

rate of elimination of drug from the body (usually=GFR)

half life is inversely proportional to clearance so a reduction shall increase T1/T2

20
Q

what is first order kinetics ?

A

Linear ; rate of elimination is proprotional to drug conc,a constant fraction of drug is eliminated in unit time
half life can be defined

21
Q

what is zero order kinetics ?

A

non-linear rate of elimination is a constant

most drugs initially exhibit first order then zero order kinetics at high doses

22
Q

why is drug monitoring essential ?

A

zero order drugs are more likely to result in toxicity as small dose changes can produce large increments in plasma conc.

23
Q

what is a steady state and why is it important

A

situation where the overall intake of a drug is in dynamic equilibrium with its elimination. During repeated drug administration a new steady state is achieved in 3-5 half lives irrespective of dose or frequency of administration
for e,g digoxin has a large Vd and half-life is 40 hours, 5 half lives to steady state will be >1 week so need loading doses achieve a rapid therapeutic effect

24
Q

what is loading dose and why are they useful

A

an initial higher does of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose.
useful when you want a drug with a long half life to have an immediate effect rather an effect in a week or so. these drugs require a low maintenance dose to maintain the steady state
loading dose = Vd X [Drug} target

25
Q

describe elimination half lives

A

slope of the curve = elimination rate constant (K)
k= ratio of clearance (Cl) to VD
t1/2= Vd/Cl or t1/2 is proportional to VD or inversely proportional to Cl
In chronic kidney disease
Clearance (kidney) is proportional to renal function (GFR)
t1/2 is proportional to 1/clearance (GFR)

26
Q

what are agonists

A

binds to receptor and changes its conformation to activate it and generate a response . Has affinity, intrinsic efficacy and efficacy. activate endogenous proteins

27
Q

what are antagonists ?

A

binds to receptor and inhibits the binding of endogenous agonists. Has affinity but no intrinsic efficacy and no efficacy . antagonise, block or inhibit endogenous proteins

28
Q

where do drugs work

A

cell surface receptors, transport inhibitors and enzyme inhibitors

29
Q

describe some mechanisms of drug action

A

disruption of structural proteins, being enzymes and reacting chemically

30
Q

define affinity

A

tendency of a drug to bind to a specific receptor(Kd- a lower value indicates a higher affinity)

31
Q

define intrinsic efficacy

A

ability of a drug to bind to a receptor and activate it

32
Q

Define efficacy

A

ability of a ligand to generate a response as a result of the receptor or receptors being occupied

33
Q

Define potency

A

Does required to produce the desired biological response

34
Q

define Emax

A

max response we can measure

35
Q

Define EC50

A

conc of drug which causes 50% max response

36
Q

Define Bmax

A

max binding capacity

37
Q

Define KD

A

conc of drug which gives 50% occupancy of available receptors.
Full agonists give 100% response while partial agonists give 50% response but allow a controlled response and work in low levels of ligand

38
Q

what are competitive antagonists and non- competitive antagonists ?

A

competitive compete w the agonists but non comp bind to the allosteric site which reduces the effects of an agonist

39
Q

Whats IC-50

A

conc of antagonist giving 50% inhibition

40
Q

what is drug selectivity

A

the more the selective a drug for its target, the less chance it will interact

41
Q

define some drug -drug interactions

A

interactions can either enhance/reduce therapeutic outcome through actions on receptors. Drug interactions can occur via different receptors or different tissues

42
Q

what is enzyme induction ?

A

increasing the amount of enzyme present for a specific action

43
Q

what are examples of Cp450 inducers or CP450 inhibitors

A

inducers : Phenytoin, Carbamazepine

Inhibitors : omeprazole, disulfiram

44
Q

what are some drug - disease interactions

A

Renal disease - low GFR so reduced clearance of some renally excreted drugs - digoxin
hepatic disease - reduced clearance of hepatic metabolised drugs, Reduced CYP 450 activity, much longer half lives . Examples - opiates in cirrhosis
cardiac disease - falling cardiac output leads to excessive response to hypotensive agents and reduced organ perfusion

45
Q

describe a drug - food interaction

A

grapefruit juice inhibits many CP450 isoenzymes reducing clearance of many drugs - Simvastation
Amiodarone (Long QT), terfenadine (Long QT)

46
Q

what is an ADR ands its causes

A

an unwanted or harmful reaction which occurs after administration of a drug
Risks : reckless prescribing, extreme ages
Drug response varies based on weight, size, ages, genetics, health, placebo effect and method of administration E.g dose or frequency