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Stage 2 > BP Theme 1 > Flashcards

BP Theme 1 Flashcards

1
Q

why do dentists need to know about principles of drug action

A
  • To be able to use and prescribe drugs rationally
  • Dental patients may already be taking drugs
  • To keep up to date with developments in pharmacology and therapeutics
  • Individual drugs will come and go but the principles will remain the same
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2
Q

what is pharmacology

A

how drugs can affect the human body or the host response to a pathogen

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3
Q

what 2 aspects is pharmacology split into

A

pharmacodynamics and pharmacokinetics

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4
Q

what is pharmacodynamics

A

effects of a drug on the body

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5
Q

what are the two elements of pharmacodynamics

A
  1. Molecular interactions by which drugs exert their effects because there are specific targets.
  2. Influence of drug concentration on the magnitude of response –> therapeutic vs toxic.
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6
Q

pharmacodynamics allows us to determine the appropriate dose range for patients, why is this important

A

tell us how much drug we need to give the patient for it to work on the receptor

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7
Q

pharmacodynamics allows us to Compare the effectiveness and safety of one drug to another, why is this important?

A

one receptor may need less

of 1 drug than another to exert the same effect.

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8
Q

what is pharmacokinetics

A

what the body does to a drug

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9
Q

what are the 4 processes of pharmacokinetics

A

absorption
distribution
metabolism
excretion

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10
Q

what does absorption in pharmacokinetics involve

A

from site of administration into the blood

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11
Q

what does distribution in pharmacokinetics involve

A

drug can reversibly leave the bloodstream and distribute into the interstitial
and intracellular fluids of tissues

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12
Q

what does metabolism in pharmacokinetics involve

A

body inactivates the drug through enzymatic modification

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13
Q

what does excretion in pharmacokinetics involve

A

drug is eliminated from the body in urine, bile or faeces –>body’s response to an
exogenous chemical is to remove it (retainment of drug may have side effects).

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14
Q

what does the Study of pharmacokinetics allow us to:

A

Design and optimise treatment regimens for individuals e.g. deciding on the route
of/frequency/duration of treatment.

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15
Q

why is the drug called antihistimine

A

stops histamine which causes indiscriminate immune response

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16
Q

where in the nose does antihistamine work

A

H1 receptors

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17
Q

is the nose the sole location for antihistimine

A

no, in the stomach as well (peristalsis and gastric acid) - receptors are different

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18
Q

how does the antihistimine tablet get to the nose

A

stomach> intestines> liver >bloodstream

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19
Q

why does another antihistimine tablet need to be need to be taken the next day

A

metabolised and excreted , prolonged retention causes more side effects

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20
Q

what are the sources of drugs

A

naturally occurring
synthetic- insulin
biologics

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21
Q

what is biologics

A

chemically produced biological entities

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22
Q

how do drugs interact

A

shape- lock and key

charge distribution

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23
Q

order of bond strength (weakest first)

A

vdw
hydrogen
ionic
covalent

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24
Q

what else is important in drug interactions

A

hydrophobicity
ionisation (pKa)
conformation of target
stereochemistry

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25
Q

what are the 4 main targets of drug action

A

receptors
carries
enzymes
ion channels

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26
Q

example and drug name for receptor

A

B2 adrenoreceptor for salbutamol to treat asthma

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27
Q

example and drug name for ion channels

A

voltage gate na+ channel for lidocaine for a local anaesthetic

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28
Q

example and drug name for enzymes

A

transpeptidase for aspirin used as an analgesic

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29
Q

example and drug name for carriers

A

proton pump for omerprazole used for anti ulcer

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30
Q

what do antidotes do

A

e.g. acetylcysteine to treat poisoning with paracetamol (overdose)

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31
Q

what do antacids do

A

stop indigestion by neutralising stomach acids

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32
Q

what do laxatives do

A

pulls water into foetal matter e.g lactulose

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33
Q

how are receptors targets for drug action

A

they are the target for endogenous transmitters

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34
Q

how are enzymes targets for drug action

A

they are biological catalysts which facilitate biochemical . reactions

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35
Q

how are ion channels targets for drug action

A

they’re pores which span membranes to allow selective passage of ions

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36
Q

how are carrier molecules targets for drug action

A

they transport ions and small organic molecules across cell membranes

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37
Q

what are the two types of chemicals that can bind to receptors

A

agonists and antagonists

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38
Q

what is an agonist

A

ligand (drug, hormone or neurotransmitter) that combines with receptors to elicit a cellular response

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39
Q

what is an antagonist

A

An antagonist is a drug which blocks the response to an agonist

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40
Q

how do drugs interact with ion channels

A

they block or modulate the opening/closing e.g. increasing frequency ion channels opens up or capacity of ion channel

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41
Q

how do drugs interact with enzymes

A

either inhibit or act as a false substrate

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42
Q

how do drugs interact with carriers

A

either transported in the place of the endogenous substrate or inhibit transport

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43
Q

what is an example of allosteric drug action at ion channels

A

benzodiazeopines acting on GABAa receptors - given to anxious patients

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44
Q

what is the action of benzodiazeopines on GABAa receptors

A

binds allosterically enhance the effect of GABA, GABA binds to ion channel, increased Cl- conductance , hyperpolarisation, decreased excitability so reduced anxiety

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45
Q

what is orthosteric binding site

A

normal binding site

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46
Q

what is allosteric binding site

A

different binding site

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47
Q

what is the normal enzymatic process for inflammation after immune activation, cell injury etc.

A

phospholipids in plasma membrane break down via phospholipase A2, this creates arachidonic acid which is broken down by cylcooxygenas to prostaglandin –> inflammation etc.

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48
Q

how do NSAID e.g. ibuprofen act to reduce inflammatory response

A

they interact with the cyclooxygenase which prevents conversion of arachidonic acid to prostaglandins

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49
Q

what is an example of an agonist

A

histamine acts as an agonist at the H1 receptor in the smooth muscle to increase local blood flow

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50
Q

what is an example of an antagonist

A

terfenadine acts as an antagonist at the H1 receptor in the smooth muscle to decrease local blood flow

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51
Q

how are receptor sub types identified

A
  • on the basis of selectivity agonists and/or antagonists

- cloning techniques

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52
Q

what activates receptor

A

bound agonist, once activates has altered physical and chem properties

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53
Q

what 4 receptor types respond to drugs

A

ligand gated ion channels
g-protein couples receptors
enzyme linked receptors
intracellular receptors

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54
Q

what are the two channel linked (ionotropic) receptors

A

ligand gated & voltage gated

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55
Q

how do ligand gated channel linked receptors work and what is an example

A

require agonist to open channel

e.g. nicotinic acetylcholine receptor, actCh causes skeletal muscle to contract by opening ligand-gated channels

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56
Q

how do voltage gated channel linked receptors work and what is an example

A

require change in electrical charge across membrane e.g na+ channels in nerve cell membranes

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57
Q

how do local anaesthetics work

A

blocking voltage-gated na+ channels and stop pain

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58
Q

how do muscle relaxants work

A

nicotinic Ach receptor antagonists are inhibitors of the nicotinic receptor which causes muscle contraction. so we get relaxation

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59
Q

what are g-protein coupled receptors

A

single polypeptide chain with 7 trans-membrane helices
3 subunits- alpha, beta, gamma
2 mechanisms

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60
Q

what is an example of α/β adrenoceptors

A

epinephrine (will bind to the receptors)

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61
Q

what is an example of β2 adrenoceptors

A

salbutamol (interact with receptors as separate entity)

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62
Q

what are the different variations in α subunits

A

Gs, Gi, Gq and Go

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63
Q

what do the variant α subunits allow for

A

lots if different signalling

dictates second msgr activation or deactivation

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64
Q

what is the action of Gs

A

activates adenylyl cyclase

activates ca2+ channels

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65
Q

what is the action of Gi

A

inhibits adenylyl cyclase

activates K+ channels

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66
Q

what is the action of Gq

A

activates phospholipase C

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67
Q

how does g-protein signal transduction work

A

drug binds to receptor, releases gdp, a subunit dissociates and activates adenylyl cyclase, this catalyses the formation of cAMP, cAMP activates other receptors. (when drug absent receptor reverts to its resting state

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68
Q

what is an example of g-protein signal transduction

A

adrenoreceptors

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69
Q

how are adrenoreceptor subunits activated

A

by adrenaline and noradrenaline

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70
Q

what is salbutamol

A

Beta 2 receptor agonist- bronchodilation- asthmatic patients

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71
Q

what is atenolol

A

Beta 1 receptor antagonist- ot blocks beta 1 receptors in the heart thus inhibiting the accelerated heart rate

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72
Q

what are the receptor sub types of adrenoreceptors and what is their corresponding a-subunit and effect

A

a1 - Gq -activates PLC- vasoconstriction
a2 - Gi- inhibits adenyl cyclase- auto-inhibition of neurotransmitter release
B1 - Gs- stimulates adenylyl cyclase- accelerated heart rate
B2 - Gs- stimulate adenylyl cyclase- bronchodilation

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73
Q

what acts on kinase linked receptors

A

hormones/growth hormones/steroids

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74
Q

why do kinase linked receptors take longer to occur

A

due to protein phosphorylation

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75
Q

what are the different forms on kinase linked receptors

A

receptor tyrosine kinase i.e. insulin
serine/threonine kinase
cytokine
guanylyl cyclase-linked

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76
Q

what happens when the ligand binds in kinase linked receptors

A

dimerization (pull 2 receptor molecules together) which activates autophosphorylation cascade

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77
Q

what is an example of a kinase linked receptor

A

insulin

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78
Q

how does insulin work once it binds

A

it activates receptor tyrosine kinase in B subunit. tyrosine residues of B subunit are auto-phosphorylated. receptor tyrosine kinase phosphorylates other proteins e.g. insulin receptor substrates

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79
Q

what are nuclear receptors

A

family of 48 soluble receptors intracellular based unlike others the drug must enter into the cell

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80
Q

what are examples of nuclear receptors

A

estrogen receptor- estradiol and tamoxifen

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81
Q

what are the 2 major classes of nuclear receptors

A 
class I- endocrine ligands (steroids, hormones)  
class II - ligands are lipids
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82
Q

where are class I nuclear receptors and what do they form

A

cytoplasm, form homodimers

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83
Q

where are class II nuclear receptors and what do they form

A

nucleus, form hetrodimers

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84
Q

what does binding to hormone response elements initiate

A

gene transcription changes (positive/negative)

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85
Q

outline class I nuclear receptor signal transduction

A

lipid soluble drug enters cell, binds to nuclear receptor, drug receptor translocated into the nucleus, drug receptor unwinds chromatin, transcription, new mRNA, new proteins, new effects

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86
Q

how many binding sites does Nachr have

A

hetromers- have 2 sites and homomers have up to 5 sites

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87
Q

what are the drug-receptor interactions of the future for orthosteric sites

A

full and partial agonists
inverse agonists
reversible competitive antagonists
irreversible competitive antagonists

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88
Q

what are the drug-receptor interactions of the future for allosteric sites

A

positive, negative, allosteric antagonists

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89
Q

what are the drug-receptor interactions of the future for effector regions

A

non competitive antagonists

channel activators

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90
Q

what is the response when the agonist, salbutamol, binds to B2-adrenoreceptor complex

A

agonist-receptor complex= salbutamol-B2-adrenoreceptor complex
action=increased cAMP
effect=bronchodilation

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91
Q

specifically which G protein receptor is the B2-adrenoreceptor

A

Gs

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92
Q

what is the dose response curve also known as

A

concentration-effect curve

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93
Q

what is meant by dose

A

how much you give e.g. 5mg tablet

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94
Q

what is meant by concentration

A

how strong it is in the body, concentration in the plasma that has therapeutic effect

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95
Q

what does the sigmoidal shape for the semi-logarithmic plot of the dose response curve show us

A

the threshold range for concentration, the linear response, and the maximal response

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96
Q

what is a graded dose response

A

response of a particular system: isolated tissue, animal or patient

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97
Q

what is a quantal dose response curve

A

measures population based effects

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98
Q

what are the benefits of plotting a dose response curve

A

allows estimation of Emax

allows estimation of EC50

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99
Q

what is meant by Emax

A

maximum effect given by a particular concentration

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100
Q

what is meant by EC50

A

dose required to produce 50% of maximal response

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101
Q

how can efficacy be determined

A

Emax

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102
Q

how can potency be determined

A

EC50

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103
Q

what is meant be affinity

A

the strength which an agonist/drug binds to a receptor - form a stable complex

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104
Q

how is receptor saturation measured

A

maximum number of binding sites (B max)

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105
Q

how can affinity be measured

A

ratio of association and dissociation

k1/k-1

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106
Q

what is is k1

A

the rate of association of the agonist with the receptor

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107
Q

what is k-1

A

the rate of AR complex dissociation

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108
Q

what would the k1 and k-1 be like for a high affinity drug

A

large k1

small k-1

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109
Q

what is KD

A

characterises affinity - physiochemical constant like Avogadros number

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110
Q

what does KD tell us

A

the conc of ligand at which 50% if the available receptors are occupied

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111
Q

does the KD change for a given receptor

A

no its the same for a given receptor and drug combination in any tissue, in any species anywhere in the universe

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112
Q

what is the relationship between Kd and affinity

A

inverse

lower Kd –> greater affinity

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113
Q

what is the eq for affinity

A

k1/k-1

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114
Q

what is the eq for Kd

A

k-1/k1

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115
Q

how would you see which agonist has the highest affinity on the graph

A

the one with the lowest Kd (Kd determined by drawing line for 50% receptors occupied)

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116
Q

what is meant by a potent drug

A

those which elicit a response by binding to a critical number of receptors at a low conc (high affinity) compared with other drugs acting on the same system with lower affinity

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117
Q

what characteristics will a highly potent drug elicit

A

binds well, strong effect, quick effect

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118
Q

what does potency depend on

A

affinity of drug
efficacy of drug
receptor density
efficacy of stimulus-response mechanisms used

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119
Q

what is the relationship between ec50(dose to produce 50% max response) and potency

A

lower the ec50 the higher the potency

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120
Q

do agonist with a higher potency tend to have a higher affinity

A

yes

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121
Q

what happens if there is a linear relationship between receptor occupation and biological effect

A

Kd and EC50 equal e.g. 50% receptor occupation would cause 50% effect

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122
Q

why might a system said to have spare receptors

A

receptors can amplify signal duration and intensity which means only a fraction of total receptors for a specific ligand may need to be occupied to elicit maximal response from the cell

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123
Q

what is efficacy

A

describes the ability of an agonist to activate a receptor i.e. to evoke an ‘action’ at the cellular level.
refers to the maximum effect an agonist can produce regardless of dose

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124
Q

what is the efficacy and AR* like for a full agonist

A

high efficacy

AR* very likely

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125
Q

what is the efficacy and AR* like for a partial agonist

A

low efficacy

AR* less likely

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126
Q

how does a full agonist produce maximum response

A

by pushing eqm completely to the RHS while occupying only a small % of receptors available

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127
Q

why is a partial agonist unable to produce maximal response

A

even when occupying all available receptors it cant because it doesn’t initiate the same signalling response a full agonist does. it falls short of maximal response the system is capable of producing

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128
Q

what does the maximum response in full agonists correspond to

A

the max response that the tissue can give

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129
Q

why are partial agonists beneficial

A
  • if we dont want a max response as it may cause a problem if the full response is too large
  • alleviates some of the side effects
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130
Q

what is an example of a treatment where a partial agonist is given

A

breast cancer treatment- giving a partial agonist will maintain the oestrogenic response but at a lower concentration

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131
Q

what is varenicline used for

A

nicotine receptor partial agonist for smoking cessation

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132
Q

what is tamoxifen used for

A

estrogen receptor partial agonists for use in estrogen dependent breast cancer.

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133
Q

what is aripiprazole used for

A

antipsychotic – partial agonists at selected dopamine receptors

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134
Q

why might a drug that we expect to act as a full agonist elicit the response equivalent to a partial agonist

A

depends on how the receptor reacts in response to the drug binding

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135
Q

what does the two state model predict

A

that a receptor can exist in two forms, AR and AR*

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136
Q

what is meant by constitutive activity

A

receptors can activate in the absence of ligand e.g. R*

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137
Q

what is the ternary complex model

A 
there are 4 active states of the receptor 
AR*
AR*G
R*G
R*
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138
Q

what is meant by RG

A

g protein turns the receptor on

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139
Q

what is meant by AR*G

A

dimerising with a G protein turns the receptor on, not the agonist

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140
Q

apart from receptors activating in the absence of a ligand (constitutive activity), what else does new evidence suggest

A

receptors can change state depending on GPCR function

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141
Q

what is meant by an inverse agonist

A

when you bind something with some level of activity it can turn down the signal of the receptor- not inhibitory and NOT ANTAGONIST!!

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142
Q

why do inverse agonists turn receptor activity down

A

they have a higher affinity for the AR(inactive) state than for the AR* (active state)

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143
Q

which classical competitive antagonists display inverse agonist activity

A

Cimetidine (H2), pirenzepine (M2), atropine (M)

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144
Q

what are examples of inverse agonists

A

β-carbolines on GABAA receptors – anxiogenic rather than anxiolytic

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145
Q

what do allosteric modulators do

A

they will change the affinity of a drug to a receptor

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146
Q

how do benzodiazpines act on GABAa receptors

A

BZ bind allosterically and enhances the effect of GABA

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147
Q

what effect do benzodiazapines have on KA and efficacy

A

increases KA for GABA

increase efficacy of GABA

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148
Q

what are allosteric modulators- Positive (PAM)

A

not active aline but increase affinity and/or efficacy of endogenous agonists

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149
Q

what are examples of PAM

A

diazepam, propofol & isoflurane

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150
Q

what are allosteric modulators -Negative (NAM)

A

not active alone but decrease affinity and/or efficacy of endogenous product

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151
Q

what are examples of NAM

A

mGluR5 dipraglurant

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152
Q

what is desensitisation of receptors

A

effect of drug reduces with continual/repeated administration (tachyphylaxis)

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153
Q

what are the contributing factors to desensitisation of receptors

A
  • Conformational changes in receptor
  • Internalisation of receptors
  • Depletion of mediators
  • Altered drug metabolism
  • Other physiological responses (homeostatic).
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154
Q

why is it difficult to measure how well an antagonist is working

A

because all its doing is stopping agonist

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155
Q

what receptor does the antagonist propanol bind to and what is its effect

A

B-adrenoreceptor

decreases blood pressure

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156
Q

what are the general classes of antagonists

A

chemical
physiological
phramacological

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157
Q

what is a chemical antagonist and an example

A

Binding of two agents to inactive a drug (chelating agents)

Example - protamine binds (sequesters) heparin

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158
Q

what is a physiological antagonist and an example

A

Two agents with opposite effects cancel each other out.

Example – glucocorticoids and insulin

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159
Q

what is meant by an irreversible antagonist

A

binds with such strength receptor function doesn’t come back until the body produces new receptors

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160
Q

what can antagonists be categorised into

A

receptor antagonists (pharmacological) and non receptor antagonists (chemical and physiological)

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161
Q

what can receptor antagonists be split into

A
  • active binding site (reversible & irreversible)

- allosteric binding (reversible & irreversible)

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162
Q

why is allosteric binding non competitive

A

as long as you have the active site you can still have the main endogenous product binding to that receptor and turning it on, so its cannot be competitive

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163
Q

what type of antagonist is one that binds orthosterically and reversibly

A

competitive antagonist

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164
Q

what type of antagonist is one that binds orthosterically and non-reversibly

A

non competitive active site antagonist

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165
Q

what effect do antagonists have on efficacy

A

there will never be an active receptor so there wont be an efficacy for antagonist so AR* does not exist

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166
Q

what is a competitive antagonist

A

binds orthosterically and reversibly- prevents antagonist from binding

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167
Q

what shift on the agonist-response curve does a competitive antagonist cause

A

parallel shift to the right

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168
Q

how can a competitive antagonist be overcome

A

increased agonist concentration

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169
Q

what is a non-competitive (irreversible) antagonist

A

binds orthosterically to form irreversible covalent bonds with the receptor

170
Q

what shift on the agonist-response curve does a non-competitive (irreversible) orthosteric antagonist cause

A

Causes parallel shift to right of the agonist-response curve and reduced maximal asymptote

171
Q

what does a non-competitive allosteric antagonist cause

A

signal transduction rather than receptor effects

downstream responses are blocked e.g. Ca2+ influx

172
Q

what shift on the agonist-response curve does a allosteric non-competitive antagonist cause

A

reduces slope and maximum of dose response curve

173
Q

why in the presence of a competitive antagonist does the curve have the same maximal response and the linear portions are parallel

A

the competitive antagonist binds reversibly with receptor which can be overcome by increased conc of agonist. the only difference is a shift to the right

174
Q

how can the dose ratio be calculated with an agonist and antagonist

A

(agonist+antagonistEC50)/agonist EC50

175
Q

what is the schild plot for competitive antagonist

A

How strong an antagonist is at inhibiting a receptor system

176
Q

what does zero show on the schild plot

A

the conc needed to inhibit agonist by 50%

177
Q

what is the equation for the schild plot

A

r-1=[B]/Kb

r=dose ratio
B=antagonist conc
Kb=antagonist dissociation constant

178
Q

what do pA2 values show

A

describe the activity of a receptor antagonist in simple numbers

179
Q

what is the relationship between pA2 and Kb

A

pA2=-logKb

180
Q

when is the schild plot relevent

A

only if the relationship is linear and the slope of the schild plot=1
must be competitive antagonist

181
Q

why is the dose ratio important for clinicians

A
  • The extent of antagonist inhibition depends upon the concentration of the competing agonist which varies
  • the extent of inhibition depends on the antagonist’s conc (differences in metabolism or clearance influence plasma concs)
182
Q

the dose response curve decreases, it wont hit 100%, for a irreversible antagonist, why is this

A

Putting in extra agonist will not bind to receptor due to antagonist binding

183
Q

what does irreversible antagonism do to EC50

A

increases it

184
Q

what is the duration of effect of irreversible antagonism related to

A

receptor turnover

185
Q

what shift on the agonist-response curve does irreversible antagonism cause and why

A

right

receptor reserves allow for this

186
Q

why might the curve for irreversible antagonism be mistaken for competitive antagonism

A

looks like the same shift to the right however with irreversible there is a corresponding decrease in response

187
Q

why are weak partial agonists also irreversible antagonists

A

they both prevented from reaching max asymptote

188
Q

examples of competitive antagonists (most common)

A

cimetidine at the H2 receptor

tamoxifen at the oestrogen receptor

189
Q

example of irreversible antagonism (less common)

A

phenoxybenzamine at the a1 adrenoceptor

190
Q

what effect does the non competitive antagonist have

A

blocks signal transduction events- stop receptor from having effect
E.g. Nifedipine bocks Ca2+ influx

191
Q

what shift on the agonist-response curve does non competitive antagonism cause and why

A

reduces the slope and the maximal effect

looks same as irreversible antagonist

192
Q

what does the therapeutic index tell us

A

measure of risk benefit of drug

193
Q

what is meant by a large therapeutic index

A

large range between the benefit of drug and its side effect

194
Q

example of drug with large therapeutic index

A

penicillin

195
Q

example of drug with small therapeutic index

A

warfarin

196
Q

explain how warfarin has a small therapeutic index

A

Concentration range for anticoagulation is very close to the concentration range where you get side effects and the risk of bleeding.

197
Q

why can the therapeutic index not be determined from a dose response curve alone

A

both the therapeutic effect and the toxic effect must be shown

198
Q

why might a compound a compound show reasonable binding an then no result on the tissue response curve

A

its an antagonist- binds but has no effect

199
Q

why might a large therapeutic index be beneficial

A

Clinicians can adjust the dose depending on the mass of the patient
Greater ability to manipulate drugs

200
Q

how can you work out the potency from a binding graph and response graph

A

binding –> Ec50

response–> lowest conc at which max response is achieved

201
Q

what is the importance of being able to calculate pharmacokinetics parameters

A

can work out how much drug to give to patient
ensures dosage regimen results in correct plasma conc in all patients
indvidualise medication

202
Q

how does a drug enter the plasma

A

Absorption

Distribution (Tissues)

203
Q

what does the absorption of drug involve

A
  • transfer of exogenous compound (i.e. drug) from site of administration into system circulation
  • crossing of cell membranes (passive and active)
204
Q

what affects how rapidly compounds cross cell membranes

A

must be in solution
degree of ionisation (unionised absorbed better)
particle size/charge/solubility

205
Q

what are the enteral routes of drug administration

A

oral
sublingual
rectal
vaginal

206
Q

what are the parenteral routes of drug administration

A 
Intravenous
Intramuscular
Subcutaneous
Transdermal
Inhaled
Intrathecal
207
Q

where does the drug pass when its taken orally

A

stomach then small intestine

208
Q

why is the oral route of absorption poor

A

stomach has thick membranes

low pH so drugs destroyed

209
Q

what drugs are absorbed in the Stomach

A

many drugs DO NOT get absorbed here
mainly weak acids
small amounts of aspirin, NSAIDS, alcohol

210
Q

what controls the rate delivery of compounds to the SI (via sphincter muscles)

A

rate of gastric emptying

211
Q

what is the site of absorption for the most exogenous compounds taken orally

A

small intestine

212
Q

what compounds are best absorbed in the SI

A

preferentially weal bases

213
Q

why are drugs more easily absorbed in the small intestine

A

large, highly permeable, vascularised surface area

214
Q

what are the pH ranges in the SI

A

6(duodenum)

7.4 (terminal ileum)

215
Q

what do the enterocytes of the SI contain

A

drug metabolising enzymes and transporters

216
Q

what are the advantages of oral administration

A

safe
convenient
economical

217
Q

what are the disadvantages of oral administration

A 
irritant drugs cause sickness 
not possible 
vomiting patients 
some drugs destroyed by gut acid/flora
intestinal absorption can be erratic
218
Q

what factors affect GI absorption

A

gut motility
gut pH
physio-chemical interactions
particle size and formulation

219
Q

how does gut motility affect GI absorption

A

decreased motility > decreased absorption (constipation )

220
Q

how does gut pH affect GI absorption

A

poor absorption of strong acids and bases

221
Q

how do physico-chemical interactions affect GI absorption

A

tetracycline binds to Ca rich foods
bile-acid binding resins may bind other drugs and inhibit absorption
another chemical to bind to a drug and prevent it reaching desired location (collate)

222
Q

how does particle size and formulation affect GI absorption

A

slow or fast releasing

resistant to coating

223
Q

what is bioavailability

A

fraction of the administered dose which enters systemic circulation

224
Q

what is first pass metabolism

A

occurs in both intestine and liver before drug reaches systemic circulation (drug can potentially degraded before it enters the systemic circulation

225
Q

how can you measure the parameter of absorption

A

measure the area under the curve (AUC) with respect to time

226
Q

what does the parameter of absorption estimate

A

biovavailability

227
Q

what is the trapezoidal rule

A

area under each trapezoid multiplied by time then divided by the number of trapezoids

228
Q

what is the bioavailability (f) for an IV drug and why

A

1

it enters straight into the bloodstream

229
Q

what is the bioavailability (f) for an extra-vascular dose e.g. oral

A

F<1

230
Q

what are the limitations when using bioavailability

A

it does not consider individual variations (enzyme activity, gastric pH, intestinal motility
it does not consider rate of absorption

231
Q

what are the parameters of absorption

A

Cmax and Tmax

232
Q

what is Cmax

A

the maximum concentration of compound after administration

233
Q

what is Tmax

A

time at which Cmax is reached

234
Q

what is the advantage of sublingual administration

A

fast/rapid response
utilises venous drainage from the mouth to superior vena cava
avoids first pass metabolism

235
Q

what are the advantages of rectal/ vaginal route

A

bypasses GI/hepatic first pass effects
rich blood supply
absorption may be rapid and extensive
useful when drug causes nasusea and vomiting or if patient is already vomiting

236
Q

what is involved in the drainage from the rectum

A

middle and inferior rectal veins to systemic circulation

superior rectal vein to portal

237
Q

what are the advantages of intravenous administration

A

predictable, very rapid action
alternative route for drugs which are irritant by (im)
iv infusion for ill

238
Q

what are the disadvantages for intravenous administration

A

difficult/pain
risk of infection
cost and safety
immediate adverse effects

239
Q

what are the adv of subcutaneous/intramuscular administration

A

faster systemic effect than oral administration or local effect
kept within the peripheral tissue - more local effect

240
Q

what is an ex of subcutaneous administration

A

local anaesthetic

241
Q

when is absorption of a drug important

A

for all routes of administration except IV

242
Q

what are the most important way drugs can cross cell membranes

A

passive diffusion through lipid
diffusion through aqueous channel
carrier mediated transport
pinocytosis- membrane invaginates something

243
Q

what is an important determinant of absorption

A

lipid solubility

244
Q

why do many drugs exist in ionised and unionised forms

A

they’re weak acids(proton donor) or bases (proton acceptor)

245
Q

what is the ratio of ionised: unionised determined by

A

pH

246
Q

what does the degree of ionisation change with respect to

A

the pH of the solution - dependant on the pKa of the drug

247
Q

what is meant by the pKa of the drug

A

measure of the strength of an acid/base

248
Q

what happens when the pH of the drug = pKa

A

50% of the drug is ionised and 50% isn’t

249
Q

in what solution(pH) will an acidic drug need to be in to move across membranes easily and why

A

low pH as it will be unionised (if it was a high pH solution it would get ionised so not move across easily

250
Q

how do you work out ionisation

A

do the pH minus pKa then read of the table

251
Q

what is pH partitioning

A

acidic drugs accumulate in basic fluid compartments and vice versa

252
Q

what is ion trapping

A

an acidic drug trapped in a basic environment so is too ionised to passively diffuse through the bilayer

253
Q

what does distribution of a drug from the plasma into other tissues depend on

A

ability to cross cell membranes
blood flow to individual tissues
extent of its plasma protein binding

254
Q

what happens equilibrium is reached between the systemic circulation and tissue

A

elimination process lower blood concs this lowering tissue conc

255
Q

what is the half life in plasma also equal to

A

elimination half life from tissues

256
Q

what is meant by drug distribution

A

the reversible transfer of drug from one location to another within the body

257
Q

what physical structures does the drug have to pass to be distributed into the tissues

A

away from plasma proteins through the endothelium and into the interstitium and out into the tissues

258
Q

what can slow down the drug distribution process into the tissues

A

plasma proteins and chelating agents can bind ot the drug slowing it down

259
Q

what factors affect the rate of distribution

A

membrane permeability

blood perfusion

260
Q

what factors affect the extent of the distribution

A

lipid solubility
pH-Pka
plasma binding proteins
tissue binding protiens

261
Q

how does a high molecular weight/high degree of binding to plasma proteins affect distribution

A

they tend to stay in the systemic circulation rather than distribute into tissues/organs

262
Q

what are the key drug binding proteins in the plasma

A

albumin (HSA)

Alpha 1 acid glycoprotein (AAG)

263
Q

albumin is decreased in cirrhosis and malnutrition, why is this significant

A

can get a massive effect of the drug

264
Q

what is the normal range of albumin

A

3.5-5 g/dL

265
Q

when is Alpha 1 acid glycoprotein (AAG) elevated

A

cancer, inflammation

266
Q

what is the normal range of - Alpha 1 acid glycoprotein (AAG)

A

0.4-1.1 mg/mL

267
Q

which drugs are pharmacologically active

A

free (unbound drugs)

268
Q

what does plasma protein binding do

A

increases difficulty of blood to get into the blood stream (drug bind reversibly though)

269
Q

what does extensive plasma protein binding do and what are the therapeutic effects of this

A

slows drug action and elimination, prolonged therapeutic effects

270
Q

how can tissues bind drugs

A

due to composition (lipid soluble drugs will accumulate in fat )
binding to cellular components (proteins, pigments, minerals)

271
Q

why shouldn’t tetracylines be used in children

A

they accumulate slowly in bones and teeth , have a high affinity for calcium

272
Q

why does Chloroquine (an antimalarial drug) have high ocular toxicity

A

has a high affinity for melanin and is taken up by the retina, which is rich in melanin granules

273
Q

what does volume of distribution do

A

Measure of the extent of distribution of drug, where in the body has that drug gone to in comparison to the volume of plasma that we have.

274
Q

what does the dilution factor in Vd represent

A

relationship between the amount of compound in the body and the plasma concentration

275
Q

how is Vd calculated

A

total amount of drug in the body/ drug blood plasma concentration

276
Q

when will the Vd be small

A

when drugs are confined to plasma

277
Q

when will the Vd be large

A

drugs accumulate outside the plasma e.g. by being stored in fat,

278
Q

how does Vd help us calculate drug dose

A

plasma conc of a drug defines dose

279
Q

how is plasma conc affected by Vd

A

low Vd- confined to plasma so high plasma conc

high Vd- in peripheral tissues so low plasma conc

280
Q

why do drugs distributed throughout body water readily cross cell membranes (high Vd)

A

they’re lipid soluble e.g. phenytoin ethanol

281
Q

why do drugs distributed in the extracellular compartment not easily enter cells (low Vd)

A

they have low lipid solubility e.g. gentamicin

282
Q

why do drugs that are confined to the plasma compartment not cross capillary wall easily (low Vd)

A

too large e.g. heparin

283
Q

why do drugs that accumulate outside of the plasma compartment easily cross cells (high Vd)

A

bound to tissues or stored in fat e.g. chloriquine, tricyclic antidepressants

284
Q

what is enterohepatic recirculation (HER)

A

drugs that are eliminated in the bile can be absorbed in the GI tract

285
Q

what are some drugs that undergo some degree of EHR

A

morphine, erythromycin, oral contraceptives, lorazepam

286
Q

when a drug get back through the bile where does it go

A

stored in gall bladder and released into duodenum, can get metabolised again (enterohepatically recircualted)

287
Q

how is HER shown graphically

A

as a smaller secondary peak

288
Q

what is bioavailability

A

fraction of the administered dose which enters the systemic circulation

289
Q

what is elimination

A

metabolism + excretion

290
Q

what are the major excretory organs

A

kidneys
hepato-billiary system
lungs

291
Q

what happens to lipophilic drugs prior to elimination

A

must be made more water soluble (this is the opposite of the drug getting into the body where its better if its more lipophilic!!)

292
Q

what is metabolism

A

making the drug more hydrophilic so it will be removed more easily

293
Q

what is the major site of metabolism for most drugs

A

the liver

294
Q

what is involved in phase 1 of drug metabolism

A

activation of the drug- increasing the pharmacological activity of that product by adding on functional groups making it more hydrophilic

295
Q

what is involved in phase 2 of drug metabolism

A

adding on by conjugating with another chemical/compound making the drug more hydrophilic

296
Q

what chemical reactions do phase I reactions usually consist of

A

oxidation (most common)
reduction
hydrolysis

297
Q

what are the cytochrome P450 enzyme family (CYPs)

A

a family of enzymes containing heme as a cofactor

298
Q

what do P450s usually do

A

introduce/expose a functional group e.g. OH and decrease lipid solubility (which may in turn increase pharmacological/toxicological activity

299
Q

what are phase 1 reactions important for

A

activation of pro-drug

300
Q

what does the iron in the heme in CYPs allow for

A

allows group of enzymes to have a REDOX reaction

301
Q

what are individual members of CYPs referred to as

A

isozymes

302
Q

what are the main locations for CYPs

A

intestinal enterocytes and liver hepatocytes

303
Q

where are there a small amount of CYPs

A

in the kidney, white blood cells and nasal passages

304
Q

regardless of the organ/tissue, where in the cell are CYPs located

A

in the endoplasmic reticulum

305
Q

what is involved in the basic reaction of a CYP

A

the addition of O2 and NADPH giving an oxidised form of the drug

306
Q

what are most drugs in phase 1 metabolised by

A

CYPs

307
Q

what compound is the exception to CYPs metabolising phase 1 reactions

A

ethanol metabolism

308
Q

what is ethanol metabolised by (2 steps)

A

alcohol dehydrogenase to acetaldehyde

acetaldehyde to acetic acid by aldehyde dehydrogenase

309
Q

how can consumption of alcohol when on antibiotics cause hepatocyte damage

A

aldehyde dehydrogenase cannot be properly broken down so there is an accumulation of acetaldehyde

310
Q

what is first order kinetics in drug metabolism

A

when the rate of elimination of drug is proportional to how much drug is in the body

311
Q

what is involved in phase II metabolism

A

conjugation reactions where functional groups serve as a point of attack

312
Q

what does adding of conjugate do

A

decreases pharmacological activity

313
Q

what are the groups that can be conjugated in phase II reactions

A

glucuronyl, sulphate, acetyl

314
Q

what is the most common conjugation reaction

A

glucuronidation reaction

315
Q

what enzyme does glucuronidation require the addition of

A

transferase

- UDP glucuronyl transferases

316
Q

why are glucuronides usually pharmacologically inactive/rapidly excrete

A

due to their polar nature

317
Q

how is paracetamol metabolised

A

mainly by conjugation with sulfate and glucuronic acid

only a small portion by CYP450 to a toxic metabolite (NAPQI)

318
Q

how is the toxic metabolite of paracetamol detoxified

A

by glutathione (another phase 2 reaction)

319
Q

what does NAPQI do

A

binds to hepatocytes and cause oxidative damage to cells

320
Q

how is NAPQI removed

A

it is conjugated to eliminate the mercapturic acid from the body

321
Q

how does alcohol affect NAPQI

A

it increases the amount of enzyme working to produce NAPQ

322
Q

what happens in a paracetamol overdose

A

pathways of conjugation are saturated and co-factors are depleted, much more paracetamol is metabolised via CYP450

323
Q

what happens to glucornic acid stores in paracetamol overdose

A

they’re depleted

less sulfation occurs

324
Q

how does hepatic necrosis occur in paracetamol overdose

A

more paracetamol is metabolised by CYP450 due to depletion of glucornic acid. this route of metabolism produces more NAPQ which is toxic causing tissue damage leading to hepatic necrosis

325
Q

what is excreted via renal excretion

A

urine, bile, lung, milk and sweat

326
Q

what drugs are rapidly cleared from the blood (1 nephron transit)

A

penicillin

327
Q

what drugs are slowly cleared from the blood

A

diazepam

328
Q

what are the 3 major processes of renal excretion

A

glomerular filtration
tubular resorption
tubular secretion

329
Q

how are water soluble drugs/metabolites excreted

A

excreted unchanged through the kidneys

330
Q

how are lipid soluble drugs excreted in the kidneys

A 
reabsorbed by bowmen's capsule 
filtered in the glomeruli
reabsorbed on the distal portion of nephron 
metabolised to more polar compounds 
excretion in urine
331
Q

what is the rate limiting step in glomerular filtration

A

size

332
Q

what molecular weight drugs diffuse into glomerular filtrate

A

<20,000

333
Q

why is plasma albumin completely held back from glomerular filtrate

A

68,000

334
Q

why are highly protein drugs found at lower concs in the filtrate than plasma

A

because they have a high molecular weight so do not diffuse into the filtrate e.g. warfarin 98% ppb conc in filtrate and 2% in plasma

335
Q

how do high molecular weight drugs enter the filtrate

A

have to undergo more metabolism

336
Q

what factors do not affect GF

A

lipid solubility and pH

337
Q

what does the rate of entry into the GF depend on

A

conc of drug in plasma

molecular weight

338
Q

where does active tubular secretion take place

A

proximal convoluted tube

339
Q

what are the 2 carrier systems that can transport against an electrochemical gradient

A

acidic drugs and endogenous acids (penicillins and uric), organic bases e.g. morphine

340
Q

how can active tubular secretion lead to competition between drugs

A

many drugs share the same transporter which can lead to competition

341
Q

what does the volume of urine roughly equate to

A

1% of the filtrate

342
Q

what occurs in passive diffusion

A

drug conc increases as water is reabsorbed
highly lipid soluble drugs have high tubular permeability and slowly excreted
high water soluble drugs have low tubular permeability and concentrate in urine (become trapped in the collecting duct)

343
Q

what does the extent of absorption depend on

A 
drug solubility (i.e. pKa)
pH of tubular fluid
344
Q

what happens to the drug if the fluid becomes more alkaline

A

acidic drug ionises - less lipid soluble and reabsorption diminishes
basic drug un-ionises - more lipid soluble and reabsorption increases

345
Q

what does it mean for the drug if it is reabsorbed more

A

it is held in the body for longer

346
Q

for weak bases when is ionisation greatest

A

at acid pH

347
Q

for weak acids when is ionisation greatest

A

at alkaline pH

348
Q

what does pH partition impact

A

the rate at which drugs permeate membranes and distribution of drug between aqueous compartments

349
Q

where do weak acids accumulate

A

accumulate in compartments of relatively high pH, whereas weak bases tend do the reverse

350
Q

what conditions is a compound more rapidly excreted

A

in alkaline urine

351
Q

what will urinary acidification do

A

accelerate excretion of weak bases and vice versa (important in overdose) - ion trapping

352
Q

what does elimination mechanisms depend on

A

physiochemical properties of the compound

353
Q

how are volatile gases eliminated

A

exhalation

354
Q

how are water soluble compounds eliminated

A

urine

maybe in bile

355
Q

when will elimination mechanisms be saturated at a therapeutic dose

A

phenytoin

356
Q

why does saturable elimination occur

A

increasing the dose will disproportionately increase concentration

357
Q

what is clearance (CL)

A

elimination parameter

-Ability of eliminating organs to remove a compound from the body per unit time

358
Q

what is total body CL

A

sum of all organ CL processes

i.e. Total CL = Hepatic CL + Renal CL + all other CL

359
Q

what may CL be defined as

A

the volume of plasma (or blood) cleared of the compound per unit of time (typically expressed as L/hr in clinical pharmacokinetics, but can be any volume/time)

360
Q

equations for CL - iv dose

A

L=IV Dose/〖IV AUC〗_(0→∞)

361
Q

eq for CL- oral dose

A

L=(Oral dose×F)/〖Oral AUC〗_(0→∞)

362
Q

how else can CL be calculated

A

CL = Ke x Vd

363
Q

what does zero order kinetic mean

A

straight line - independent of how much you have e.g. alcohol

364
Q

what does first order kinetic mean

A

depending on how much drug you give you will get a curve deepening on how much you give

365
Q

how can Ke be determined

A

the slope of the line

366
Q

how can elimination be calculated graphically

A

steepness of curve

367
Q

what is the half life

A

Time it takes for concentration of drug in body to half

• Units are time

368
Q

what is the rule of thumb for the half life

A

It takes 5 half-lives for a compound to reach steady-state (rate in=rate out) after chronic exposure (no therapeutic drug present in the body) – its at the right concentration in the body

369
Q

what do additives include

A 
o	pharmaceutical products
o	cosmetics
o	food additives
o	industrial chemicals
o	pesticides
o	smoking
o	alcohol
370
Q

how do chemicals affect drugs

A

theyre an important factor in the pertubation of drug metabolising enzymes

371
Q

what are 2 important mechanisms by which drug interactions occur

A

induction and inhibition

372
Q

what is involved in the induction of drug metabolising enzymes

A

increased synthesis of enzymes (phase I and II)

resulting in increased metabolism of inducing agent and/or other drugs

373
Q

what are examples of drugs that act as inducers

A

rifampicin, carbamazepine and ethanol

374
Q

what are enviro factors that can act as inducers

A

smoking and ethanol

375
Q

what are the implications of induction

A

decreased drug effectiveness on chronic exposure
need to increase drug dose
multiple drug therapy - may be problems when inducer is withdrawn from regimen

376
Q

how can inhibition occur

A

through inhibition of CYP system by drugs

377
Q

what does inhibition result in

A

reduced rate of metabolism and increased pharmacological effect

378
Q

does alcohol act as an inhibitor or inducer

A

both depending on the CYP

ethanol act acutely to inhibit drug metabolism however

379
Q

what is an adverse drug reaction

A

a harmful or seriously unpleasant event occurring at a dose intended for therapeutic effect and that calls for a reduction of the dose or withdrawal of the drug (not the same as a side effect)

380
Q

what must drug safety take into account

A

the severity of the drug reaction
the disease
the therapeutic alternatives

381
Q

what are the features that suggest a cause and effect relationship between drug administration and adverse drug reaction (e.g. if the drug causes the adverse d.r or its the patient

A

time sequence between taking the drug and adverse reaction

the reaction corresponds to the known pharmacology of the drug

the reaction stops on cessation of the drug

the reaction returns on restarting the drug

382
Q

how can adverse drug reactions be monitored

A

MHRA- Medicines and Healthcare products Regulatory Agency

Yellow card filled out when suspected adverse reaction occurs in a patient

accumulate the evidence for/against adverse reaction

MHRA analyses this data

383
Q

what is a side effect and why is different from an adverse reaction

A

They are not adverse drug reactions
Happens in a therapeutic way- the more drug, the more the side effect
Unavoidable consequence of drug administration

384
Q

what occurs in a secondary adverse effect

A

Side effect that’s indirect- the original drug has caused something happening in the body with has caused an increased effect of something else in the body

385
Q

what are risk factors that increase the chances of ADRs

A 
Age 
Sex
Medical history
Disease
Current medication 
Ethnicity
386
Q

how does age increase the chances of ADR

A

more expression of p450s
elderly have increased medication
pharmacokinetic factors
drop in GFR

387
Q

how are younger children susceptible to difference in pharmacokinetic factors thus increased chances of ADR

A

neonates -below 6 months old- have poor glomerular filtration rate

Children above 6 months does not have many phase 2 enzymes (conjugating enzymes) are not able to change the drug. Drugs aren’t made hydrophilic so cannot be removed as easily.

388
Q

how does sex increase ADR

A

Females more susceptible -pharmacokinetic factors and hormonal influences

389
Q

how does medical history increase ADR

A

If ADR to one drug will be more likely to experience ADR to another drug.

If you’ve had one adverse drug reaction you’re likely to have another

390
Q

how does disease increase ADR

A

Pharmacokinetic factors e.g. liver disease that influences with metabolic process increases risk

391
Q

how does ethnicity increase ADR

A

intrinsic

  • pharmocokinetic factors (metabolism)
  • pharmacodynamic- expression of drug in the body

extrinsic
-alcohol, diet and smoking

392
Q

what are the classification of adverse

A

augmented pharmacological effect- adverse effect that is known to occur from the primary pharmacology of the drug and is usually dose depend.

bizzare effects- adverse effect that are unpredictable from the pharmacology of the drug

chronic effects- occur as a result of chronic treatment of the drug

delayed effects- occur remote from treatment, either in the children of the treated patients or in the patient themselves

end of treatment effects- adverse effect occur as a result of stopping the treatment

393
Q

what is augmented pharmacological effect

A

heightened response based on what you would have expected based on the pharmacology of that drug

Increased, more severe (augmented) form of physiological response than predicted

394
Q

what are examples of augmented pharmacological effect

A

Bradycardia from propanol treatment with Beta blocker
- -The primary pharmacology of the B-blocker is to decrease heart rate, however if the dose is too high they can cause life threatening bradycardia (heart rate too low)

Hypoglycaemia from insulin injection

Tachycardia from muscarinic antagonist ipratropium

Common/low mortality - recoverable, withdraw of drug typically will removed adverse drug reaction

395
Q

what are muscarinic antagonists known as

A

parasympatholytic

396
Q

how does Tachycardia from muscarinic antagonist ipratropium (used for asthma- brown inhaler) occur

A

Tachycardia from muscarinic antagonist ipratropium (used for asthma- brown inhaler)

  • Ipratropium - non-specific antagonist
  • Not expecting the drug to get into the systemic circulation - if it does because it ca bind to all Muscarinic receptor’s it can bind to receptors on heart and give you tachycardia
397
Q

what are the effect of parasympathetic activation

A

pupils constrict

lens of eye readjust for closer vision

airways in the lungs
constrict

heart rate decreases

blood vessels to limb muscles constrict

blood vessels to visceral organs more dilated

salivary secretions normalise

398
Q

what is the effect of muscarinic antagonists on pupils

A

pupils dilate (relax of constrictor papillary muscle blurred vision)

increase in focal length of the lens (relax of ciliary muscle)

bronchodialation

increase in cardiac output

decrease in GI motility

decrease in exocrine gland secretion

399
Q

what drugs cause the adverse drug reaction and/OR therapeutic effects shown below

  • pupil dialtion
  • bronchodialtion
  • increased heart rate
  • decreased gut motility
  • decreased exocrine secretions
A

pupil dialtion

  • ADR-atropine
  • TE-tropicamide

bronchodilation
-TE-ipratropium

IHR
-ADR- ipratropium

DGM
-TE- hyoscine

DES

  • ADR- iprapropium
  • TE- atropine
400
Q

what is type 2 ADR and what are examples

A

Unpredictable, usually have caused patient death

Examples;
•Anaphylaxis due to penicillin (beta-lactan antibiotic- breaks down structural wall of bacteria, no association with the immune system)
•Bone marrow suppression due to chloramphenicol

401
Q

what is Northwick park clinical trial

A

•Phase 1 clinical trial – autoimmune, thought to be effective for leukaemia treatment

•ADR’s included:  
­Decreased blood pressure
­	nausea
­	pain
­	soft tissue damage (gangrene)
­	multi-organ failure
  • Excess cytokine release – ‘cytokine storm’
  • Super agonist- stimulated immune system so much that it effect every cell in the body
  • Indiscriminate immune response
402
Q

what is type C ADR and examples

A

Chronic effects (occur after prolonged treatment)
Examples
-latrogenic Cushing syndrome from chronic glucocorticoid therapy

403
Q

what is type D ADR and examples

A

effects occur remote from treatment or in child of treated patient)

Examples
•Diethylstilbestrol given to pregnant mother (1940-70) results in a high incidence of vaginal cancers in offspring in their 20s
•Isotretinoin (accutane) causes birth defects
Vitamin A is a key teratogen in bone malformations of the baby
•Second cancers in response to Hodgkin’s disease treatment

404
Q

what is type E ADR and examples

A

End of treatment effects (withdrawal)- should normally be different from normal course of the disease

examples
•Adrenal insufficiency after glucocorticoid therapy
•adrenal gland shrink  cannot produce as much cortisol

405
Q

what is Adrenal atrophy in response to glucocorticoid treatment

A

• Exogenous glucocorticoids used for anti-inflammatory or immunosuppressive therapy act on the HPA axis negative feedback system and over a period of time cause adrenal atrophy (cant switch off anymore)

On termination of treatment the atrophied adrenals cannot produce enough cortisol so this results in adrenal insufficiency

406
Q

what is adverse drug interactions (ADI)

A

When one drug modifies the action of another drug.

The modification can take the form of potentiation or attenuation

407
Q

what the types of ADI

A

Pharmacodynamic interaction

Pharmacokinetic interaction

408
Q

what is Pharmacodynamic interaction and example

A

similar or opposing pharmacological effects

-Ethanol increasing the sedative effect of antihistamine drugs or certain antidepressants

409
Q

what is Pharmacokinetic interaction and examples

A

one drug interferes with disposition (e.g. metabolism or excretion of drug) of the other

  • Monoamine oxidase inhibitors blocking metabolism of dietary amine,
  • Many drugs can inhibit CYP450 (e.g. fluvoxamine) so can interfere with metabolism of other drugs
410
Q

what is carbamazepine metabolism

A

•anticonvulsive drug which needs to be metabolised into its active drug
Many drugs increase and decrease the activity of the active drug

411
Q

why would there be different half lives for the same drug given to two different people

A

different metabolisms

412
Q

why would there be different half lives for the same drug given to the same person just on separate occasions

A

other interactive agents (drugs) may have been taken. its acts as an INHIBITOR (inhibits drug metabolising enzymes)

413
Q

what is meant when there is a biomodal distribution of pharmacokinetic parameters within a population

A

there are fast and slow metabolisers in the population

414
Q

what are the characteristics of fast metabolisers

A

normal enzyme activity

lower plasma concentrations of the parent drug, higher concentrations of the metabolite

generally normal therapeutic response (therapeutic effect)

415
Q

what are the characteristics of slow metabolisers

A

low enzyme activity

higher plasma concentrations of the parent drug, lower concentrations of the metabolite

may lead to exaggerated therapeutic response at normal doses

416
Q

how do neonates have a reduced ability to metabolise drugs

A

have a low activity with regards to:

  • CYPs, glucornyl transferase, N-acetyltransferase
  • lack of conjugating activity is most important (lack of use of morphine labour)
417
Q

how do the elderly have a reduced ability to metabolise drugs

A

activity declines slowly with age

  • more variability in half-life of many drugs
  • issues for drug development
  • increased half-half of diazepam (memory impairment)
418
Q

how to patient characteristics affect half life

A

Difference in CYP expression

Difference in phase 2 enzyme expression e.g. acetyl transferase

419
Q

is the following statement correct:

Drug A is said to have a greater affinity than drug B if drug A’s maximal effect is greater than that of drug B.

A

no. this is efficacy not affinity

efficacy is determined by Emax

420
Q

is the following statement correct:

Drug A is said to be more efficacious than drug B if drug A produces its maximal effect at a lower concentration than drug B.

A

no this is affinity no efficacy

421
Q

for which drugs is The intravenous route of administration is used

A

those Which may be easily altered in the acidic pH of the stomach.

Stage 2 (16 decks)

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