Pharmacokinetics and pharmacodynamics Flashcards

Question 1

Q

what is pharmacology?

Answer

A

the study of the effects of drugs

Question 2

Q

what is pharmacokinetics?

Answer

A

how the body affects the drug; Absorption, Distribution, Metabolism and Excretion (ADME)

Question 3

Q

what is pharmacodynamics?

Answer

A

how the drug affects the body

Question 4

Q

what is the role of zinc fingers in cytosolic/nuclear receptors?

Answer

A

can recognise discrete regions of DNA

Question 5

Q

what is potency?

Answer

A

measure of how well a drug works

Question 6

Q

what is EC50?

Answer

A

concentration (M) that gives half of the maximal response

Question 7

Q

what is an agonist?

Answer

A

a compound that binds to a receptor and activates it

Question 8

Q

what are types of normal response curves?

Answer

A

linear (normal scale) and sigmoidal (log scale)

Question 9

Q

what is a full vs partial agonist?

Answer

A

full agonist can get a maximal response

- partial agonist cannot get maximal response when binding to receptor

Question 10

Q

what is Emax?

Answer

A

maximal response of a drug

Question 11

Q

what is intrinsic activity/efficacy? how is it calculated?

Answer

A

the relative ability of a drug-receptor complex to produce a maximum functional response
Emax of partial agonist ÷ Emax of full agonist

Question 12

Q

what is affinity?

Answer

A

how well a drug binds to a receptor

Question 13

Q

what is potency?

Answer

A

a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity
highly potent drug evokes a given response at low concentrations
lower potent drug evokes same response only at higher concentrations

Question 14

Q

what is an antagonist?

Answer

A

a compound that reduces the effect of an agonist
does not activate receptors
affinity of the antagonist for the receptor affects its activity

Question 15

Q

what is a competitive antagonist? what is its effect on the dose-response curve?

Answer

A

bind to receptors at same binding site as the endogenous ligand or agonist, but without activating the receptor
competes for same binding site with agonist
sufficient concentrations of an antagonist will displace the agonist from the binding sites
dose-response curve shifts to the right; more agonist is required to elicit the same response; decreased potency

Question 16

Q

what are the types of competitive antagonists?

Answer

A

reversible (surmountable)

- irreversible (insurmountable)

Question 17

Q

what are reversible (surmountable) competitive antagonists?

Answer

A

bind via noncovalent intermolecular forces

- will eventually dissociate from the receptor, freeing it to be bound again

Question 18

Q

what are irreversible (insurmountable) competitive antagonists?

Answer

A

bind via covalent intermolecular forces
there is not enough free energy to break covalent bones in the local environment, so the bond is essentially permanent, so the complex will never dissociate
receptor remains permanently antagonised until it is ubiquinated and destroyed

Question 19

Q

what is a non-competitive antagonist? what effect does it have on the dose-response curve?

Answer

A

type of insurmountable antagonist that binds to an allosteric (other) site of the receptor, or by irreversibly binding to the active site of the receptor
reduce maximum response that can be attained by any amount of agonist
effects cannot be negated, no matter how much agonist is present
shift right and down of the dose-response curve

Question 20

Q

what is the agonist and antagonist of the mAChR receptor?

Answer

A

muscarinic ACh receptor

agonist: muscarine
antagonist: atropine

Question 21

Q

what is the agonist and antagonist of the nAChR receptor?

Answer

A

nicotinic ACh receptor

agonist: nicotine
antagonist: curare

Question 22

Q

what is the agonist for the histamine receptor? what are its effects?

Answer

A

agonist: histamine
- contraction of the ileum
- acid secretion from parietal cells

Question 23

Q

what is the antagonist for the histamine receptor? what are its effects?

Answer

A

antagonist: mepyramine
- reversed contraction of the ileum
- no effect on acid secretion

Question 24

Q

what is efficacy?

Answer

A

how well a ligand activates the receptor

Question 25

Q

what shows affinity?

Answer

A

shown by both antagonists and agonists

Question 26

Q

what shows efficacy?

Answer

A

only agonists show efficacy

- antagonists show zero efficacy

Question 27

Q

what are factors governing drug action?

Answer

A

affinity
efficacy
number of receptors at tissue
signal amplification

Question 28

Q

how does the number of receptors at the tissue affect drug action?

Answer

A

the less number of receptors at a tissue will result in more drug being required to illicit the same effect and vice versa
in most cases it is possible to still get maximum response despite a reduction in receptor numbers meaning you only need a small number of receptors to get a full response
example of drug that will inactivate a receptor is: bromoacetyl alprenolol menthane (BAAM) which is an
irreversible B-adrenoceptor antagonist
an equation called the Furchgott equation is used to calculate how many receptors are available
receptor reserve/Spare receptors:
• many tissues have holds for a full agonist, this reserve can be large or small depending on the tissue
• there is no receptor reserve for a partial agonist

Question 29

Q

what is the Furchgott equation? what does it calculate?

Answer

A

used to calculate how many receptors are available in a tissue

Question 30

Q

what is signal amplification? how does it affect drug action?

Answer

A

when a ligand binds to a receptor it sets off a signalling cascade
signal amplification determines how powerful the response will be
determined by the type of tissue the receptor is based in

Question 31

Q

what is allosteric modulation?

Answer

A

substance binds to a receptor to change the receptor’s response to stimulus
bind to allosteric site
affinity modulation: change in EC50
efficacy modulation: change in Emax
modulation can be positive-allosteric or negative-orthosteric

Question 32

Q

what is an example of an allosteric ligand?

Answer

A

benzodiazepine

Question 33

Q

what is an inverse agonist?

Answer

A

a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist; <0% efficacy

Question 34

Q

what is a neutral antagonist?

Answer

A

has no activity in the absence of an agonist or inverse agonist but can block the activity of either; 0% efficacy

Question 35

Q

what is tolerance?

Answer

A

the diminishing effect of a drug resulting from repeated administration at a given dose
seen with continuous, repeated high concentration of drug over time

Question 36

Q

what is desensitisation of receptors?

Answer

A

uncoupled - receptor can’t interact with G-protein
receptor is internalised in vesicle of cell
receptor becomes degraded

Question 37

Q

what is specificity?

Answer

A

the ability of a protein’s binding site to bind specific ligands
the fewer ligands a protein can bind, the greater its specificity
describes the strength of binding between a given protein and ligand

Question 38

Q

what is selectivity?

Answer

A

how a ligand may bind more preferentially to one receptor than another
defined with respect to the binding of ligands to a substrate forming a complex

Question 39

Q

what are examples of selectivity in beta-adrenoceptors?

Answer

A

isoprenaline is a non-selective B-adrenoceptor agonist so it activates both B1 (heart) & B2 (lungs) receptors
whereas salbutamol is a selective B2-adrenoceptor agonist, but at very high concentrations it loses its specificity so will activate both B1 and B2

Question 40

Q

what catalyses the conversion of membrane phospholipid to arachidonic acid?

Answer

A

phospholipase A2

Question 41

Q

what is the action of phospholipase A2?

Answer

A

converts membrane phospholipid to arachidonic acid

Question 42

Q

what catalyses the conversion of arachidonic acid to prostaglandin H2?

Answer

A

cyclooxygenase

Question 43

Q

what is the action of cyclooxygenase?

Answer

A

converts arachidonic acid to prostaglandin H2

Question 44

Q

what are examples of NSAIDs?

Answer

A

include aspirin and ibuprofen but there are about 50

Question 45

Q

what are the actions of NSAIDs?

Answer

A

• analgesic
• anti-pyretic (reduces fever)
• anti-inflammatory
• they inhibit the enzyme
cyclooxygenase (COX) which is responsible for the breakdown of arachidonic acid to prostaglandin H2 (PGH2)
• NSAIDs work by preventing arachidonic acid from reaching the active site of the COX enzyme and thus from being broken down into prostaglandin H2 - this is achieved by competitive inhibition

Question 46

Q

what is PGH2 acted on? what does this generate?

Answer

A

PGH2 is acted on by specific synthases to generate prostanoids:
• Prostaglandin D2 (PGD2)
• Prostaglandin E2 (PGE2)
• Prostaglandin I2 (PGI2)
• Thromboxane A2 (TXA2)

Question 47

Q

what are some examples of prostanoids?

Answer

A

Prostaglandin D2 (PGD2)
Prostaglandin E2 (PGE2)
Prostaglandin I2 (PGI2)
Thromboxane A2 (TXA2)

Question 48

Q

what produces the different prostanoids?

Answer

A

Prostaglandin D2 - mast cells
Prostaglandin I2 - vascular endothelial cells
Thromboxane A2 - platelets
Prostaglandin E2 - macrophages (most widely found and mediates largest number of effects in the body)

Question 49

Q

what is the action of aspirin?

Answer

A

prevents arachidonic acid from reaching the active site of the COX enzyme and thus from being broken down into prostaglandin H2 (competitive inhibition)
irreversibly blocks the active site resulting in irreversible inactivation of the COX enzyme

Question 50

Q

what are the two isoforms of COX?

Answer

A

COX-1: found normally and widely around the body (normal physiology)
COX-2: this is induced and found mainly in inflammation only

Question 51

Q

what are examples of selective and non-selective drugs for COX?

Answer

A

aspirin is non-selective so acts on both COX-1 and COX-2

* whereas celecoxib for example is COX-2 selective

Question 52

Q

what are examples of ACE inhibitors?

Answer

A

captopril and enalapril

Question 53

Q

what are actions of ACE inhibitors?

Answer

A

anti-hypertensives
work by inhibiting ACE thereby preventing the conversion of angiotensin I to
angiotensin II meaning there is less angiotensin II so less bind to angiotensin receptors (AT1) resulting in reduced vasoconstriction and thus
hypertension as well as less aldosterone release further reducing hypertension

Question 54

Q

what is the mechanism of action of ACE inhibitors?

Answer

A

Captopril - mimic dipeptides; His and Leu
Enalapril - mimic tripeptides; Phe, His and Leu
both captopril and enalapril work by binding to ACE active site thereby meaning it is unable to convert angiotensin I to angiotensin II

Question 55

Q

what are examples of beta-lactam antibiotics?

Answer

A

penicillins, amoxicillin and cephalosporins

Question 56

Q

what is the action of beta-lactam antibiotics?

Answer

A

work by inhibiting cell wall biosynthesis of peptidoglycan bacterial cell walls by inhibiting the activity of certain enzymes

Question 57

Q

what is the enzymatic inactivation of drugs?

Answer

A

most drugs are excreted by the kidneys but lipophilic drugs are not effectively
removed as they are passively absorbed because they can diffuse through cell membranes easily
in these cases Cytochrome P450 is required to introduce a hydroxyl (OH) group into the drug to enable it to be excreted more easily by the kidneys
note: some drugs act to either inhibit or induce CYP450s to either make drugs remain in the system for longer or to be excreted quickly (e.g. quite toxic drugs)

Question 58

Q

what are examples of proton pump inhibitors?

Answer

A

omeprazole, lansoprazole, pantoprazole and rabeprazole

Question 59

Q

what are the actions of proton pump inhibitors?

Answer

A

they are all activated in acidic (i.e. stomach) environments
they act to inhibit acid secretion
when prostaglandin E2 (PGE2) released from chromaffin cells, it binds to EP3 receptors on parietal cells, this causes a reduction in the concentration of H+ and thus acidity of the stomach by reducing the activity of the H+/K+ ATPase pump - PGE2
inhibits parietal cells
when histamine released from histaminocytes, binds to H2 receptors on parietal cells, this causes the H+/K+ ATPase pump to increase activity
resulting in a higher concentration of H+ being pumped into the gastric lumen thereby increasing acidity - histamine activates parietal cells
PPIs act to irreversibly inactivate the proton pump (H+/K+ ATPase) resulting in a marked reduction in acidity of the stomach, thereby helping with reflux etc.

Question 60

Q

what is the action of diuretics?

Answer

A

act to inhibit symporters
the increased excretion of water is useful for the treatment of hypertension and heart failure since the removal of water from the blood will reduce its volume and thus blood pressure

Question 61

Q

what is the action of furosemide?

Answer

A

furosemide can inhibit the NKCC2 pump on the thick ascending part of the loop of Henle thereby reducing the amount of Na+,Cl- and K+ ions able to enter the medullary interstitium thereby reducing hyperosomolarity meaning
that less water will diffuse out of the collecting ducts into the blood, resulting in more water loss in the urine and thus dehydration

Question 62

Q

what is the action of thiazides?

Answer

A

act to inhibit the Na/Cl cotransporter on the distal tubule of the nephron; this results in increased water loss

Question 63

Q

what neurotransmitters are subject to uptake?

Answer

A

dopamine, noradrenaline, serotonin and GABA

Question 64

Q

what do uptake inhibitors do?

Answer

A

cause an increased concentration of neurotransmitter in the synapse by preventing their re-uptake

Answer 65

A

tri-cyclic anti-depressant that mostly inhibits the reuptake of noradrenaline (majority) and serotonin

Answer 66

A

inhibits reuptake of dopamine

Answer 67

A

inhibits the reuptake of GABA (the inhibitory transmitter in CNS) thus useful for the treatment of panic disorders

Answer 68

A

lidocaine and procaine

Answer 69

A

these local anaesthetics work by interrupting axonal neurotransmission in the sensory nerves
they do this by blocking voltage dependent sodium channels thereby preventing the neurones from depolarising, meaning the threshold isn’t met and thus no action potential is developed to be propagated
this rests in pain relief since pain isn’t transmitted to the brain to be perceived
local anaesthetics can diffuse through mucus membranes easily thus
sometimes can act on muscles too

Answer 70

A

any compound that is administered with an intended therapeutic effect

Answer 71

A

uptake into the plasma
distribution from the plasma
elimination from the plasma

Answer 72

A

rate of diffusion is directly proportional to the concentration gradient - it is a first order process
an increase in concentration will result in a higher rate of diffusion from plasma to tissue
rate of diffusion is directly proportional to temperature (most drugs won’t work outside normal physiological temperature)
rate is influenced by chemical reactions between the drug and solute (i.e. plasma)

Answer 73

A

rate is directly proportional to the concentration of drug (rate ∝ [drug])

Answer 74

A

rate is directly proportional to the square of the concentration of the drug (rate ∝ [drug]^2)

Answer 75

A

rate is directly proportional to the cube of the

concentration of the drug (rate ∝ [drug]^3)

Answer 76

A

rate is unrelated to the concentration of the drug

rate ∝ [drug]0

Answer 77

A

first order

Answer 78

A

where the rate of reaction is governed by one of the components involved in the reaction whose quantity or
magnitude is changing

Answer 79

A

• the plasma is the fluid fraction or aqueous solution that remains when cells are
removed from the blood
• proteins (including antibodies) are found in the plasma as a result of their polar amino acid side chains
• the pH of the interstitium is reflected in the plasma
• plasma has a slightly higher pH than interstitium due to diffusion gradient

Answer 80

A

pharmacokinetic theory considers the body as 3 main compartments divided by tissue lipid rich barriers

Answer 81

A

plasma (5 litres)
interstitial (15 litres)
intracellular (45 litres)

Answer 82

A

vessel rich viscera: muscle tissue

- vessel poor: fat stores/subcutaneous tissue

Answer 83

A

simple diffusion
facilitated diffusion
active transport
through extracellular spaces
non-ionic diffusion

Answer 84

A

• movement of solutes from a region of their high
concentration to a region of
their low concentration through a lipid barrier
• first order process

Answer 85

A

• movement of solutes from a
region of their high
concentration to a region of
their low concentration through protein channels
• no energy required

Answer 86

A

• movement of solutes from a
region of their low
concentration to a region of
their high concentration using
protein carriers
• require energy
• goes against the concentration gradient
• first order reaction initially but when saturated it becomes zero order

Answer 87

A

movement of solutes through pores in cell membrane

* protein typically cannot enter through these pores

Answer 88

A

• the movement of ionic molecules (which find it difficult to diffuse across a lipid membrane) across a lipid
membrane (such as that found in a cell) into the cell
• ionised molecules are water soluble
• un-ionised molecules are
freely diffusable and lipid
soluble
• the mechanism of action of
non-ionic diffusion is that an
ionic molecule becomes less
ionic and thus more non-
ionic to enable it to cross the
lipid membrane and enter the
cell

Answer 89

A

• ionised molecules are water soluble
• un-ionised molecules are
freely diffusable and lipid
soluble

Answer 90

A

• the degree of ionisation of
weak acids and weak bases is influenced by pH
• non-ionic diffusion is enhanced if adjacent compartments have a pH difference

Answer 91

A

weak acid: more ionised

weak base: less ionised

Answer 92

A

weak acid: less ionised

weak base: more ionised

Answer 93

A

amount of drug taken up as a proportion of the amount administered

Answer 94

A

has the greatest variability due to different factors involved; surface area of gut, diarrhoea (bioavailability is greatly decreased) and pH of
gut (alkaline at duodenum)

Answer 95

A

simple diffusion of the lipid

soluble freely diffusible non ionised fraction

Answer 96

A

has the greatest variability due to different factors involved; surface area of gut, diarrhoea (bioavailability is greatly decreased) and pH of
gut (alkaline at duodenum)
unpredictable
movement across the gut membrane is simple diffusion of the lipid soluble freely diffusible non ionised fraction
most tablets are either weak acids or weak bases
water soluble tablets will not pass across the membranes of cells unless there is carrier mediated transport

Answer 97

A

close to 1

Answer 98

A

should be 1

Answer 99

A

such as a skin patch

- has a lower bioavailability than I.V.

Answer 100

A

oral
intramuscular
IV
transcutaneous
intrathecal (into CSF)
sublingual
inhalation
topical
rectal

Answer 101

A

aspirin is acidic
in the stomach the acidic tablet dissolves but it then becomes less ionised due to the fact that a weak acid (such as aspirin) becomes less ionised in lower pH
movement of the un-ionised aspirin across the gut is rapid
in the plasma, aspirin is more ionised due to the higher pH
gastric pH affects the amount of aspirin uptake

Answer 102

A

due to higher pH

Answer 103

A

in the plasma aspirin is more ionised due to the higher pH

* gastric pH affects the amount of aspirin uptake

Answer 104

A

in the stomach the acidic tablet dissolves but it then becomes less ionised due to the fact that a weak acid (such as aspirin) becomes less ionised in lower pH
movement of the un-ionised aspirin across the gut is rapid

Answer 105

A

antacids act to increase pH e.g. treatment of ulcer
omeprazole (PPI) and ranitidine (H2 blocker) acts to reduce acid secretion in stomach and thus increase pH
ingesting alkali foods results in an increased pH
a raised pH results in the reduced uptake of aspirin from the stomach and thus a reduction in bioavailability

Answer 106

A

a raised pH results in the reduced uptake of aspirin from the stomach and thus a reduction in bioavailability

Answer 107

A

a drug is distributed in the plasma according to its chemical properties and
molecular size

Answer 108

A

dissolved gases and small ionic molecules

Answer 109

A

hydrophobic areas of plasma proteins

Answer 110

A

proteins/large molecules are only active in the plasma compartment (5L)
water soluble molecules are active in plasma and interstitial compartment
(5L + 15L)
lipid soluble molecules are only active in the intracellular fluid (45L)

Answer 111

A

plasma compartment (5L)

Answer 112

A

plasma and interstitial compartments (5L + 15L)

Answer 113

A

intracellular fluid (45L)

Answer 114

A

derived value from steady state (where drug intake is in equilibrium with its
elimination) plasma level studies

Answer 115

A

volume of distribution = total amount of drug in body ÷ concentration of drug in plasma
it is the volume (litres) that the drug would occupy if it was distributed through all the compartments as if they were all plasma

Answer 116

A

the volume of distribution can appear to be larger than it actually is, this is because when calculating volume of distribution, concentration and volume is taken from the plasma (blood)
however, when a drug is injected it can be taken up by organ systems (such as the liver, lungs and kidney etc.) this will mean its concentration in the blood will decrease
thus when you calculate the volume of distribution after the drug has been partly taken up then the value you get can be much larger than it physically is
drugs that are highly lipid soluble, enter the CNS and have a high volume of distribution

Answer 117

A

drugs that are highly lipid soluble, enter the CNS and have a high volume of distribution

Answer 118

A

plasma expanders
immunoglobulin
warfarin

Answer 119

A

aspirin/ other NSAIDs
antibiotics
muscle relaxants

Answer 120

A

steroids
local anaesthetics
opioids
CNS drugs
paracetamol
amiodarone (has a volume of distribution of 450L i.e. very easily taken up by tissue)

Answer 121

A

assumes plasma is in equilibrium
shows plasma concentration against time during the distribution of drug phase
line of best fit to 1,2 or 3 compartment models of distribution

Answer 122

A

C = C0 e^-kt

Answer 123

A

C = C0 e^-kαt + C0 e^-kβt

Answer 124

A

C = C0 e^-kαt + C0 e^-kβt + C0 e^-kλt

Answer 125

A

for every compartment you
add to the model you add
another “C0 e-kt”

Answer 126

A

most lipid soluble drugs have 3 compartment models - this suggests that the movement between the compartments is plasma > viscera > adipose
tissue

Answer 127

A

plasma compartment

Answer 128

A

renal and/or hepatic elimination are the route for the vast majority of drugs
in renal failure, a patient will not be able to eliminate for up to a week

Answer 129

A

first order process

Answer 130

A

the volume of plasma that can be completely cleared of drug per unit time (mls minute^-1 (ml/min))
the rate at which plasma drug is eliminated per unit plasma concentration (mls minute^-1 (ml/min))

Answer 131

A

the removal of drug from the plasma by either liver or kidney is clearance
both definitions are measures of efficiency
can influence the rate of elimination depending on plasma concentration of drug

Answer 132

A

the rate at which plasma drug is eliminated = mg per minute
per unit plasma concentration = mg per ml
total = mg per minute ➗ mg per ml
cancel out the “mg”
results in = mls minute^-1 (ml/min)
thus the units of clearance are mls minute-1 (ml/min)

Answer 133

A

• all of the factors affecting renal blood flow affect clearance most notably
blood pressure
• water soluble molecules which pass through the glomerular endothelial gap are eliminated by glomerular filtration
• larger water soluble molecules can be eliminated by active tubular secretion

Answer 134

A

the calculation assumes; rate of elimination = rate of appearance in urine
plasma concentration measured during the clearance process is assumed to be constant
clearance = rate of appearance in urine ➗ plasma concentration
creatinine is used as a marker substance in kidney

Answer 135

A

creatinine

Answer 136

A

renal blood flow is 18% of cardiac output = 1L/min

Answer 137

A

renal plasma flow is 60% of blood flow = 600mls/min

Answer 138

A

glomerular filtration is 12% of renal blood flow = 130mls/min

Answer 139

A

many drugs are eliminated by the kidney either by glomerular filtration e.g digoxin and gentamicin or via active secretion e.g. penicillin, frusemide and thiazides
many highly lipid soluble drugs metabolised to water soluble glucuronic acid conjugates are eliminated by active secretion e.g.
morphine 3 & 6 glucuronides
only free plasma is cleared
highly protein bound drugs have little exposure to renal clearance
most drugs eliminated by the kidney are water soluble and small molecules

Answer 140

A

water soluble and small molecules

Answer 141

A

reduced pre-renal perfusion

Answer 142

A

diabetes and hypertension

Answer 143

A

reduced clearance and prolonged elimination of a large number of drugs

Answer 144

A

for patients with renal impairment, choose drugs that are eliminated by the liver instead
hypoalbuniaemia means lipid soluble drugs in the plasma have highly freely diffusable fractions and greater effects
elevated plasma creatinine and urea compete for lipid binding sites on protein and displace more lipid soluble free drug
patients with renal impairment have unpredictable reactions to drugs due to oedema in compartments

Answer 145

A

choose alternatives not eliminated by the kidney
avoid nephrotoxic drugs
make corrections based on plasma creatinine which estimated the percentage reduction in clearance and then alter dose
measure plasma concentrations if there is a toxicity risk

Answer 146

A

has no equivalent to glomerular filtration
all hepatic clearance involves active transport
there is active secretion (if water soluble) from the liver into the bile duct

Answer 147

A

hepatic blood flow is 24% of cardiac output (3/4 from portal vein and 1/4 from hepatic artery)

Answer 148

A

the proportion of drug removed by one passage through the liver

Answer 149

A

can be so high that clearance is only limited by hepatic blood flow - perfusion limited

Answer 150

A

the process is slow and not efficient with a low amount

removed - diffusion limited

Answer 151

A

liver enzymes can alter the HER
if the liver is exposed to a low HER drug then it will produce more enzymes to enable it to increase clearance
high HER drugs have little effect on the number of new enzymes produced

Answer 152

A

drugs with a high HER are described as having a high first pass metabolism and thus have limited uptake from oral administration since they will first go to the liver before it can reach its target but by
that time most of it will have been eliminated - ineffective

Answer 153

A

some large water soluble molecules are secreted unchanged in bile
most large lipid soluble drugs are metabolised to increase their water solubility so that they may be excreted more easily by the kidney
pro-drugs are activated in the liver, whereby the pro-drug is cleaved into the active drug via metabolism e.g hydrocortisone is broken down into the active drug cortisol

Answer 154

A

95% of phase I reactions are in liver smooth endoplasmic

reticulum

Answer 155

A

aim is to make the drug more hydrophilic so that it can be excreted by the kidneys - it does this by adding a hydroxyl group to the drug

Answer 156

A

they introduce or expose hydroxyl (-OH) groups or other reactive sites that can be used for conjugation reactions (the Phase II reactions)
introduces reactive group to drug - attack point for conjugation
hydrophilic molecules usually do not reach the metabolising enzymes since they are excreted easily
oxidation
reduction: add hydrogen (saturate unsaturated bonds)
hydrolysis: split amide (peptide bond (between a carboxyl (COOH) and amino (NH) group) O=C-NH) and ester (the H from a COOH
(carboxylic acid) is replaced by some sort of hydrocarbon) bonds

Answer 157

A

hydroxylation (add -OH)
dealkylation (remove -CH side chains)
deamination (remove -NH)
hydrogen removal

Answer 158

A

add hydrogen (saturate unsaturated bonds)

Answer 159

A

split amide (peptide bond (between a carboxyl (COOH)
and amino (NH) group) O=C-NH) and ester (the H from a COOH
(carboxylic acid) is replaced by some sort of hydrocarbon) bonds

Answer 160

A

introduces reactive group to drug
includes adding or exposing; -OH,-SH,-NH2,-COOH
the product of the reaction is usually more reactive
there is a small increase in hydrophilicity

Answer 161

A

mainly occur in the liver

- mainly catalysed by cytochrome P450 enzymes

Answer 162

A

type of microsomal enzyme i.e. found on liver smooth
endoplasmic reticulum
involved in Phase I reactions

Answer 163

A

uses heme group (Fe2+) to oxidise substances
products of P450 enzymes are more water soluble
requires energy and molecular oxygen

Answer 164

A

some drugs act to inhibit cytochrome P450 such as amiodarone and cimetidine resulting in drugs lasting longer/not being eliminated as fast

Answer 165

A

also known as glucuronidation, used if drug is very hydrophobic
essentially adding a glucuronic acid group (glucuronide) to the drug to make it more hydrophilic
process forms covalent bonds

Answer 166

A

enzyme: glucuronosyltransferase (Uridine 5’-diphospho-
glucuronosyltransferase) (UGT) - microsomal enzyme, used in
phase II reactions, catalyses reaction
uridine diphospho-glucuronic acid (UDPGA) - essentially a co-
enzyme/donor compound required to conjugate glucuronic acid

Answer 167

A

UDPGA + drug -> uridine diphosphate + drug-glucoronide

- catalysed by UGT

Answer 168

A

phase I water soluble metabolites and phase 2 glucuronides enter the bile and then enter the gut via the cystic duct
some phase I metabolites and phase 2 glucuronides also enter the blood and are actively excreted into the urine
during cholestasis (stoppage of bile flow), increased amounts are excreted by the kidneys
conversely biliary secretion may increase if renal function is reduced

Answer 169

A

large bowel flora tend to metabolise the glucuronic acid group on the phase 2 glucuronide
this results in the liberation of the drug from the glucuronic acid
the drug is then able to re-diffuse from the gut into the blood and then have a prolonged effect before going back to the liver to be re-conjugated and excreted again
thus the enterohepatic circulation can prolong the action of some drugs

Answer 170

A

isolated liver failure with no effects on other organs is unusual
there is minimal effect on drug metabolism until at least 70% of functioning liver is lost

Answer 171

A

the prolonged duration of the action of a drug comes with the risk of drug accumulation and thus toxicity

Answer 172

A

the prolonged duration of the action of a drug comes with the risk of drug accumulation and thus toxicity
hypoalbuminaemia means an increased free plasma levels of freely diffusable lipid soluble drugs
pharmacodynamic (how drug affects body) alterations are often secondary to disease
the nitrogen containing substances that are cleared by the liver contribute to toxicity

Answer 173

A

Prednisone
Isosorbide dinitrate
Codeine
Diamorphine
L-dopa
Cortisone
Morphine

Answer 174

A

Insulin
Heparin
Antibiotics
Frusemide
Anti-arrhythmics
Sedation anaesthsia

Answer 175

A

enables steady state plasma (where drug intake is in equilibrium with its elimination) levels to be maintained for as long as possible
enables highly accurate drug delivery
useful for drugs that are ineffective administered by other routes or those who cannot absorb oral medication
is the quickest administration route
guarantees 100% bioavailability (the gold standard)

Answer 176

A

much less accurate drug delivery since bioavailability can be highly variable resulting in uncertainty or effectiveness of treatment
however it does have excellent patient compliance with one tablet a day

Answer 177

A

requires constant monitoring of patency of IV access, replenishing of drug delivery and observation of response to therapy
has the potential for serious calculation errors
limited by the number of places a cannula can be inserted

Answer 178

A

patency of IV access, replenishing of drug delivery and observation of response to therapy

Answer 179

A

IV regimes lack standardisation of prescription
units are mg hour-1 (mg/hour)
drug dosage is based on body weight - problematic with extreme body weights
monitoring necessary to look at therapeutic response

Answer 180

A

high volume of distribution means that there will be a small fraction in the plasma so it will take a long time to reach a steady state
with high volume of distribution drugs, adjusting infusions rate takes ages to change the plasma concentration
thus a ‘loading’ bolus dose is often recommended to speed up saturation of all the components
steady state means that infusion dosage = rate of elimination from plasma
increasing infusion rate aims to raise plasma level and maintain equilibrium
if elimination becomes saturated then this will lead to the accumulation of the drug and thus toxicity

Answer 181

A

high volume of distribution means that there will be a small fraction in the plasma so it will take a long time to reach a steady state
with high volume of distribution drugs, adjusting infusions rate takes ages to change the plasma concentration
thus a ‘loading’ bolus dose is often recommended to speed up saturation of all the components

Answer 182

A

steady state means that infusion dosage = rate of elimination from plasma

Answer 183

A

increasing infusion rate aims to raise plasma level and maintain equilibrium

Answer 184

A

if elimination becomes saturated then this will lead to the accumulation of the drug and thus toxicity

Answer 185

A

one with a small volume of distribution so it is easy to reach steady state and so that the plasma concentration is responsive to dose rate
one which is broken down by tissue/plasma enzymes irrespective of liver and renal function
one with an obvious and predictable dose to response relationship
one with a low risk of toxicity and that is easy to determine the concentration of it in the plasma

Answer 186

A

insulin is infused with 10% dextrose for managing a diabetic who is nil by mouth
there is a danger of hypoglycaemia if the insulin is not given alongside dextrose since plasma glucose can change rapidly

Answer 187

A

type of antibiotic
requires plasma level monitoring of peak (sample hour after drug given) and trough (sample hour before next dose) level after three doses

Answer 188

A

• anti arrhythmic drug
• has problem of returning arrhythmia when the infusion is turned off
• is a high volume of distribution drug and thus often steady state is not
achieved after 48hrs of IV infusion

Answer 189

A

for emergency anticoagulation if at high risk of thrombosis
chemical reaction works in minutes

Answer 190

A

alpha-1 agonist
used as a vasoconstrictor
given for the treatment of septic shock

Answer 191

A

GnRH (pituitary) when given in continuos infusion results in a contraceptive
effect
pulsatile GnRH however is a physiological fertility treatment
desensitisation occurs with many agonist drug infusions, perhaps pulsatile delivery could avoid this

Answer 192

A

intermittent/pulsatile IV gentamicin results in a higher peak level than steady state infusion and thus has higher bactericidal activity

Answer 193

A

patient controlled morphine analgesia only requires a 1/3 of the normal IV dose if given as intermittent IM injections, this is very beneficial since there is less respiratory depression than with IV infusion

Answer 194

A

somatic (NMJ) = voluntary = acetylcholine (ACh)

* autonomic = involuntary = ACh and Noradrenaline (NAd)

Answer 195

A

parasympathetic - ACh

* sympathetic - NAd

Answer 196

A

nicotinic (nAChR) - ion channel receptors

* muscarinic (mAChR) - G-protein coupled receptor

Answer 197

A

muscarinic ACh receptors (M1, M2, M3 - most common)

Answer 198

A

ACh mediates the release of adrenaline (Ad) and

noradrenaline (NAd)

Answer 199

A

nicotinic receptors (nAChR) mediate the response of ACh in the somatic system at the neuromuscular junction

Answer 200

A

nicotinic ACh receptors (nAChR)

Answer 201

A

choline acetyl transferase enzyme is required to make ACh from acetyl CoA and choline (substrate) in the neurone
ACh is then packaged into a vesicle ready to be released when the neurone is stimulated
after ACh has been used it is broken down in the synaptic cleft by acetylcholinesterase AChE into choline and acetate
choline is taken up into the neurone where it can be used to make more ACh

Answer 202

A

choline acetyl transferase enzyme makes ACh from acetyl CoA and choline (substrate) in the neurone

Answer 203

A

after ACh is used, it’s broken down in the synaptic cleft by acetylcholinesterase into choline and acetate

Answer 204

A

lethal toxin

* inhibits ACh release into the neuromuscular junction resulting in paralysis

Answer 205

A

uses protease to degrade vesicle proteins

* thereby preventing vesicle fusion and thus the release of ACh into the synaptic cleft

Answer 206

A

cosmetic and spasticity

Answer 207

A

competitive nAChR antagonist
nAChR found at the neuromuscular junction
arrow poison known as tubocurarine
acts as a neuromuscular blockade by binding to the 2
nicotinic binding sites on the nAChR thereby preventing the
binding of ACh

Answer 208

A

results in a muscle relaxant effect

- can result in being conscious but aware of pain and paralysed

Answer 209

A

can reverse the block using sugammadex which is a selective relaxant binding agent that encapsulates the blocker thereby preventing it from binding

Answer 210

A

suxamethonium is essentially 2 ACh stuck together
acts to desensitise the receptor resulting in paralysis of skeletal muscle
action is fast and short duration (less than 10 mins)

Answer 211

A

remains in the NMJ for a while since it is a poor substrate for acetylcholinesterase; can only be broken down by plasma cholinesterase, not synaptic acetylcholinesterase

Answer 212

A

neostigmine

Answer 213

A

blocks cholinesterase reversibly
resulting in an increase of ACh at the synaptic cleft since it isn’t broken down
thus ACh remains for longer and thus signal stimulated
for longer

Answer 214

A

reversible cholinesterase inhibitor

Answer 215

A

useful in treatment of myasthenia gravis whereby the immune system produces antibodies against nAChR, resulting in less receptors and thus a weak skeletal muscle response - thus having ACh remain longer will result in stronger responses

Answer 216

A

organophosphates:

insecticides (diazinon)
nerve gas (sarin)

Answer 217

A

irreversibly inhibit acetylcholinesterase, meaning ACh remains indefinitely, leading to huge accumulation

Answer 218

A

insecticides (diazinon) and nerve gas (sarin)

Answer 219

A

twitching, severe weakness and paralysis

Answer 220

A

salivation, defectation, urination, bradycardia and hypotension

Answer 221

A

confusion, loss of reflexes, convulsions and coma

Answer 222

A

normal physiological conditions

* rest and digest

Answer 223

A

stress

* fight or flight

Answer 224

A

eye agonists
lungs
bladder
GI tract

Answer 225

A

pilocarpine (stimulates saliva (dry mouth)) is a partial agonist of the muscarinic 3 receptor (M3)
constrictor muscle and ciliary muscle contract, resulting in miosis (excessive constriction of pupil)
leads to improved filtration of aqueous fluid
lowers intraocular pressure (to treat glaucoma) which is associated with optic nerve damage

Answer 226

A

• the intrinsic tone of the airways is governed by the
parasympathetic system
• mediated by cholinergic (ACh) muscarinic M3 receptors
• excessive parasympathetic activation can result in
bronchoconstriction mediated via the M3 receptor
• seen in COPD and asthma
• antagonists either short-acting (ipratropium) or long-acting (tiotropium) act as bronchodilators

Answer 227

A

pilocarpine

Answer 228

A

muscarinic 3 receptor

Answer 229

A

leads to contraction of the constrictor muscle and the ciliary muscle, resulting in miosis (excessive constriction)
leads to improved filtration of aqueous fluid
lowers intraocular pressure in glaucoma, which would lead to optic nerve damage

Answer 230

A

parasympathetic system via cholinergic (ACh) muscarinic M3 receptors

Answer 231

A

excessive parasympathetic activation of the M3 receptors in the lungs can lead to bronchoconstriction

Answer 232

A

ipratropium

- acts as a bronchodilator

Answer 233

A

tiotropium

- acts as a bronchodilator

Answer 234

A

short-acting antagonist of the M3 receptors in the lungs

- is a bronchodilator

Answer 235

A

long-acting antagonist of the M3 receptors in the lungs

- is a bronchodilator

Answer 236

A

causes contraction of the bladder

Answer 237

A

a bladder agonist results in more contraction e.g. bethanechol - useful in urinary retention

Answer 238

A

a bladder antagonist is used to relax the bladder e.g.

oxybutinin - useful in urinary frequency

Answer 239

A

acts to increase GI motility

Answer 240

A

GI antagonist such as mebeverine and scopolamine are useful at decreasing GI motility - especially useful in Irritable Bowel Syndrome (IBS)

Answer 241

A

Diarrhoea
Urination
Miosis (excessive pupil constriction)
Bradycardia
Emesis (vomiting)
Lacrimation (tears)
Salivation/sweating
Remember by DUMBELS!

Answer 242

A

competitive antagonist at the nAChR at autonomic ganglia
blocks both parasympathetic and sympathetic divisions of the
autonomic nervous system
has no effect on the neuromuscular junction

Answer 243

A

secretions reduced
constipation
urinary retention
blurred vision

Answer 244

A

marked hypotension

Answer 245

A

the first antihypertensive drug

Answer 246

A

ACh stimulates the vomiting centre in the brain

* scopolamine (anti-muscarinic) used for motion sickness treatment

Answer 247

A

dopamine is low in Parkinsons sufferers
ACh stimulates the reuptake of dopamine
benzatropine blocks the reuptake and thus increases the amount of dopamine at cleft

Answer 248

A

• there is a lack of cholinergic neurones and thus a reduction
in ACh
• donepezil acts to inhibit acetylcholinesterase and is specific to the CNS resulting in increased ACh in the CNS

Answer 249

A

NAd is a neurotransmitter and Ad is a hormone

Answer 250

A

acetylcholine
• rest and digest
• constricts pupils
• stimulates tears
• stimulates salivation
• lowers heart rate
• reduces respiration
• constricts blood vessels
• stimulates digestion
• contracts bladder
• erection

Answer 251

A

noradrenaline
• fight or flight
• dilates pupil
• inhibits tears
• inhibits salivation
• activates sweat glands
• increases heart rate
• increases respiration
• inhibits digestion
• release of adrenaline
• relaxes bladder
• ejaculation in males

Answer 252

A

noradrenaline (20%) and adrenaline (80%)

Answer 253

A

monoamine neurotransmitter, an organic compound that has a catechol and a side chain amine
noradrenaline, adrenaline, DOPA and dopamine

Answer 254

A

tyrosine -> DOPA -> dopamine -> noradrenaline -> adrenaline

Answer 255

A

tyrosine hydroxylase

Answer 256

A

DOPA decarboxylase

Answer 257

A

dopamine beta-hydroxylase

Answer 258

A

phenylethanolamine N-methyltransferase

Answer 259

A

monoamine oxidase and catechol-O-methyl transferase inactivate noradrenaline release by metabolising it thus reducing its stimulant effect
- metabolise other catecholamines too

Answer 260

A

alpha-1 and alpha-2
beta-1, beta-2 and beta-3
all are GPCRs

Answer 261

A

coupled with Gq protein and phospholipase C
phosphatidylinositol is converted into DAG and IP3
DAG activates protein kinase C
IP3 triggers release of Ca2+ -> contraction

Answer 262

A

coupled with Gi protein

- Gi protein inhibits adenylyl cyclase, which would usually produce cAMP which would activate protein kinase A

Answer 263

A

vasoconstriction
pupil dilation
bladder contraction

Answer 264

A

presynaptic inhibition of noradrenaline (negative
feedback) i.e. when blood sugar is low then alpha-2 in
pancreas will be stimulated to reduce noradrenaline
release thereby reducing insulin levels being released
from the pancreas

Answer 265

A

Gs protein and adenylyl cyclase
converts ATP to cAMP
cAMP activates protein kinase A

Answer 266

A

increased force of heart contraction (positive inotropic effect)
increased heart rate
increased electrical conduction in heart
increased renin release from the kidney
increased blood pressure

Answer 267

A

bronchodilation
vasodilation
reduced GI motility

Answer 268

A

increased lipolysis

- relaxation of bladder

Answer 269

A

non-selective agonist

- non-selective since it works at any alpha or beta adrenoceptor

Answer 270

A

• anaphylaxis - reduced blood pressure and increased
bronchoconstriction
• cardiac arrest
• acute hypotension

Answer 271

A

blood vessels (Alpha-1)
heart (Beta-1)
bronchial smooth muscle (Beta-2)

Answer 272

A

vasoconstriction (Alpha-1)
positive inotropic effect (Beta-1)
bronchodilation (Beta-2)

Answer 273

A

blood vessels and bladder

- phenylephrine and oxymetazoline

Answer 274

A

results in vasoconstriction

* useful as a nasal decongestant since vasoconstriction results in less fluid leakage from vessels

Answer 275

A

pre-synaptic neurone

- clonidine

Answer 276

A

it inhibits noradrenaline release therefore is useful as an anti-hypertensive

Answer 277

A

heart

- dobutamine

Answer 278

A

has a positive inotropic effect in the heart thus increases force of heart contraction

Answer 279

A

lungs

- salbutamol

Answer 280

A

bronchodilation

Answer 281

A

bladder

- mirabegron

Answer 282

A

relaxation of the bladder

Answer 283

A

adrenaline (works on all alpha and beta receptors)

Answer 284

A

amphetamines and cocaine

- MAO and COMT inhibition

Answer 285

A

work by inhibiting the noradrenaline transporter on the pre-synaptic neurone thereby resulting in a build up of catecholamines, especially noradrenaline but dopamine too, in the synapse
results in CNS overstimulation

Answer 286

A

this results in the build up of noradrenaline as well as other catecholamines such as dopamine
useful in the treatment of Parkinson’s and depression

Answer 287

A

doxazosin and tamsulosin

Answer 288

A

alpha-1 adrenergic antagonist

- vasodilator; reduces blood pressure; is a anti-hypertensive

Answer 289

A

alpha-1 adrenergic antagonist
relaxes bladder neck and aids in urination
useful in men with enlarged prostates who find it difficult to urinate

Answer 290

A

yohimbine

Answer 291

A

alpha-2 adrenergic antagonist
blocks alpha-2 receptor
noradrenaline inhibition does not occur, leading to an increase in noradrenaline and other catecholamines e.g. dopamine

Answer 292

A

results in a reduction in cardiac output as well as a reduction in renin thus a reduction in blood pressure
useful in treating hypertension, angina and arrhythmia

Answer 293

A

propanolol; works on all beta receptors

Answer 294

A

atenolol, metoprolol, bisoprolol, betaxolol

Answer 295

A

non-selective beta and alpha-1 antagonist which affects the heart and causes vasodilation

Answer 296

A

partial agonists: intrinsic sympathomimetic activity

- membrane stabilising activity

Answer 297

A

beta-blockers that are able to stimulate beta-adrenergic
receptors (agonist effect) as well as acting like antagonists too
- e.g. penbutolol and acebutolol

Answer 298

A

• can inhibit the propagation of action potentials across a
membrane
• useful in the treatment of arrhythmias
• propranolol and betaxolol

Answer 299

A

vasoconstriction and bladder contraction

Answer 300

A

presynaptic inhibition

Answer 301

A

increased cardiac effects

Answer 302

A

bronchodilation

Answer 303

A

bladder relaxation and increased lipolysis

Answer 304

A

“to treat like with like”
quite possible there is a placebo effect
one advantage is that there are unlikely to be any drug interactions with homeopathic treatments

Answer 305

A

medicine from plants
can be medically effective
but the industry is unregulated e.g. heavy metals found in asian herbal
products
also these medicines can interfere and interact with normal medication

Answer 306

A

digitalis from foxglove plant - for heart failure treatment
morphine from poppy - analgesic
atropine from deadly nightshade - scarlet fever treatment
vincristine from periwinkle - cancer treatment

Answer 307

A

digitalis from foxglove plant

Answer 308

A

morphine from poppy

Answer 309

A

atropine for deadly nightshade

Answer 310

A

vincristine from periwinkle

Answer 311

A

chance and rational drug design

Answer 312

A

penicillin and sildenafil

Answer 313

A

propanolol and ritonavir

Answer 314

A

using fermentation

- led to discovery of other antibiotics e.g. streptomycin

Answer 315

A

lovastatin (statin)
cyclosporine (immunosuppressant)
ivermectin (broad spectrum antibiotic)

Answer 316

A

asymmetry; an object is chiral if it’s distinguishable from its mirror image; it cannot be superimposed onto it

D (S form) or L (R form)
may influence drug action
some drugs have chiral centres (asymmetric carbon) e.g. salbutamol

Answer 317

A

L-amino acids (R form)

Answer 318

A

rational drug design
developer undertook physiochemical considerations such as solubility, electrostatic and bulk
was developed as a antagonist to counter the agonist noradrenaline
is a Beta-antagonist used in treatment of hypertension

Answer 319

A

was developed under rational drug design
developed as a antagonist to counter the agonist histamine
is a H2-antagonist used in the treatment of peptic ulcers

Answer 320

A

extracted from beef/pork pancreas first
then eventually engineered insulin analogues was developed
second generation insulin analogues

Answer 321

A

Lispro
Aspart
Glulisine

Answer 322

A

Degludec
Detemir
Glargine

Answer 323

A

insulin (recombinant human protein)
erythropoetin
growth hormone
interleukin 2
gamma interferon
interleukin 1 receptor antagonist

Answer 324

A

mAb (monoclonal antibody) technology

Answer 325

A

• mouse is immunised against the antigen of interest
• B cells are isolated to check they are producing antibodies against the antigen
• if desired antibody is being produced then the mouse spleen is removed
• B cells in the spleen are removed and then cultured along with myeloma tumour cells (these cells can divide indefinitely but cannot produce antibodies)
• solution is added to fuse the B cells with the tumour cells to produce hybridomas (fused cells) that can divide indefinitely and produce
antibodies
• the hybridomas are then cloned and undergo clonal expansion
• then the monoclonal antibodies produced are extracted and then used for clinical purposes

Answer 326

A

these were mouse derived and thus tended to illicit immune responses against themselves since the human immune system recognised the antibodies as foreign
also these antibodies had a poor half-life

Answer 327

A

chimeric antibodies

- humanised antibodies

Answer 328

A

have a mix of human and mouse antibody

- but since mouse antibody is still present still can illicit immune response

Answer 329

A

have 3 hypervariable regions (cutting edge of antigen recognition) and are less likely to illicit immune response
reason why mAbs and humanised mABs recognise the same target e.g. TNF is due to similarities in hypervariable regions

Answer 330

A

infliximab
adalimumab
trastuzumab
omalizumab

Answer 331

A

type: chimeric
target: TNF
use: RA, Crohn’s

Answer 332

A

type: humanised
target: TNF
use: RA

Answer 333

A

type: humanised
target: HER2 (EGFR)
use: breast cancer

Answer 334

A

type: humanised
target: IgE
use: asthma

Answer 335

A

adalimumab, trastuzumab, omalizumab

Answer 336

A

infliximab

Answer 337

A

delivery of nucleic acid polymer to cell
DNA is delivered using a viral vector
therapeutic gene administered to treat effects of mutated gene
suppresses mutated gene gene expression

Answer 338

A

biochemical modification of natural products
tropical rain forest and the sea are important sources of natural products
note: chemical modifications of natural products may be very difficult

Answer 339

A

Penicillin
Cyclosporine
Quinine
Morphine

Answer 340

A

large enzyme complexes generate natural products

- then manipulate biosynthetic machinery to generate structural analogues

Answer 341

A

combinatoral chemistry and biosynthesis
huge library of compounds
high throughput screening -> hits -> leads

Answer 342

A

can screen around 50,000 compounds a day, roughly 2.5 million a year

Answer 343

A

looks a biological activity of compounds
computers collate and retrieve data and analyse whether any compound has
clinical efficacy
rapid way to identify ‘hits’

Answer 344

A

bioavailability
pharmacokinetics
toxicology

these still need to be tested for using traditional methods

Answer 345

A

the path from a lead to a drug is very long, expensive and has a high attrition rate

Answer 346

A

unpleasant sensory and emotional experience associated with actual or
potential tissue damage

Answer 347

A

sensory
emotional
actual/potential tissue damage

Answer 348

A

warning of tissue damage
immobilisation for healing
protection of the species: establishment of memory

Answer 349

A

increased heart rate
increased blood pressure
increased respiratory rate

Answer 350

A

acute pain
cancer pain
chronic non cancer pain
nociceptive
neuropathic

Answer 351

A

post-op pain and non-surgical causes (most common)

Answer 352

A

palliative pain

Answer 353

A

visceral and MSK pain

Answer 354

A

inflammatory chemicals reach nerves to stimulate pain

Answer 355

A

where the nerve is directly injured - pain originates in nervous system

Answer 356

A

generally lasts less than a week

* results from the activation of sensory nerve fibres called nociceptors

Answer 357

A

the nerve endings of the peripheral nervous system
myelinated A delta fibres
unmyelinated C afferent fibres
located is most body tissues except the brain

Answer 358

A

complex mix of activation of different afferent fibres types

Answer 359

A

noxious stimulus
nociceptors
spinal cord (ascending pathway)
spinal cord modulation
thalamus
cortical areas, somatosensory cortex and prefrontal cortex
pain experience and memory

Answer 360

A

glutamate

Answer 361

A

mechanical
thermal
chemical

Answer 362

A

the breakdown of membrane lipids leads to the formation of arachidonic acid under the action of the enzyme phospholipase A2
arachidonic acid is then converted to prostaglandins under the action of the enzyme cyclooxygenase (COX)
prostaglandins are irritants to nerve fibres and stimulate pain

Answer 363

A

prostaglandins
act directly on the nociceptors (peripheral terminals of A delta and c fibres) and lower their threshold to thermal stimuli
results in a sensation of burning at room temperature

Answer 364

A

C fibres and A delta fibres

Answer 365

A

unmyelinated

- characterised by diffuse dull intense pain

Answer 366

A

small and myelinated

- conduct localised sharp sensation

Answer 367

A

A beta fibres

Answer 368

A

A delta fibres and C fibres

Answer 369

A

there is a balance of activity between large (A beta fibres) and small (A delta fibres and C fibres) fibres
interneurons of the substansia gelatinosa regulate this input in Lamina V (dorsal horn of spinal cord)
if A beta fibres are not stimulated by nociceptive stimulus then the pain signal goes through to the brain and is perceived
if A beta fibres are stimulated then the pain signal is halted and does not reach the brain and is thus not perceived
this means that low intensity stimulation of the skin or peripheral nerves or vibration in order to stimulate the A beta fibres will generate analgesia

Answer 370

A

interneurons of the substantia gelatinosa regulate the input in Lamina V (dorsal horn of the spinal cord)

Answer 371

A

if A beta fibres are not stimulated by nociceptive stimulus then the pain signal goes through to the brain and is perceived

Answer 372

A

if A beta fibres are stimulated then the pain signal is halted and does not reach the brain and is thus not perceived

Answer 373

A

low intensity stimulation of the skin or peripheral nerves or vibration which stimulates the A beta fibres will generate analgesia

Answer 374

A

rubbing site of injury
application of heat
TENS - trans cutaneous nerve stimulation of A beta fibres
spinal cord stimulation

Answer 375

A

higher centre inputs

Answer 376

A

various neurotransmitters

Answer 377

A

play key role in endogenous pain system
they inhibit the firing of the dorsal horn neutron that
responds to noxious stimulus (gate control theory)
changing the levels of neurotransmitters at the level of synapses meaning less pain is transmitted

Answer 378

A

contains a high concentration of opiod receptors and endogenous opioids
under situations of extreme stress this pathway can be
activated, resulting in the modulation of afferent noxious transmission
it projects to the dorsal horn
once the dorsal horn is activated, opioid receptors are activated resulting in a reduction in pre-synaptic neuronal sensitivity (thereby reducing Substance P release) which in turn results in reduced pain sensation
meaning less impulses travel up the first, second and third order neurones to the somatosensory cortex, meaning less pain is felt

Answer 379

A

once the dorsal horn is activated, opioid receptors are activated resulting in a reduction in pre-synaptic neuronal sensitivity (thereby reducing Substance P release) which in turn results in reduced pain sensation

Answer 380

A

release increases pain

Answer 381

A

once the dorsal horn is activated, opioid receptors are activated resulting in a reduction in pre-synaptic neuronal sensitivity (thereby reducing Substance P release) which in turn results in reduced pain sensation
meaning less impulses travel up the first, second and third order neurones to the somatosensory cortex, meaning less pain is felt

Answer 382

A

Enkephalin
Dynorphine
Beta endorphine: effect similar to morphine

Answer 383

A

opioids such as morphine, methadone, codeine and
oxycodone mimic this effect by binding to the opioid
receptors in the periaqueductal grey thereby conferring profound analgesia

Answer 384

A

reducing excitatory neurotransmitters (glutamate) and excitation of the nerve (with respect to pain transmission)
enhancing inhibitory neurotransmitters

Answer 385

A

basis for using anti epileptics

- local anaesthetics are Na+ channel blockers

Answer 386

A

GABA is the main inhibitory neurotransmitter

- noradrenaline and serotonin are also inhibitory; used as basis for anti depressants

Answer 387

A

GABA is the main inhibitory neurotransmitter

- noradrenaline and serotonin are also inhibitory; used as basis for anti depressants

Answer 388

A

in presence of pain

Answer 389

A

acupuncture - bearable pain
placebo
psychological modulation of pain

Answer 390

A

• prostaglandins act directly on the nociceptors and reduce their threshold meaning normal stimuli can activate them resulting in a
sensation of pain (peripheral sensitisation)
• opioids
• local anaesthetics

Answer 391

A

block the conduction of the nerve by blocking Na+ channels thereby preventing the depolarisation of the nerve and the propagation of an action potential

Answer 392

A

ongoing persistent pain greater than 3-6 months

Answer 393

A

beyond the usual course of an acute disease

- after healing/cure has taken place

Answer 394

A

ongoing persistent pain greater than 3-6 months
recurs at intervals for months or years
due to persisting stimulation in areas of ongoing tissue damage
serve no useful biological function, but has profound effects on the patient and their family

Answer 395

A

physical: immobility
emotional: distress
social: little social interaction leading to isolation
economical: job issues
day to day activity is severely affected

Answer 396

A

improve pain perception
improve function/mobility
improve sleep
improve emotional and psychological consequences of pain
improve quality of life

Answer 397

A

a response to a drug which is noxious and unintended

Answer 398

A

occur in 10-20% of hospital patients
cost the NHS £1 billion a year
recognised as being associated with drug

Answer 399

A

Type A - augmented:
• commonest
• an extension of the clinical effect
• predictable
• dose related
• self-limiting

Answer 400

A

diuretic causing dehydration
anticoagulant causing bleeding
drug for hypertension causing hypotension

Answer 401

A

those with renal or hepatic impairment are at a higher risk of ADR due to elimination difficulties i.e. have high blood plasma levels of the drug for longer
also the elderly (above 65) are at higher risk since as you get older there is decreased glomerular filtration and hepatic impairment etc.

Answer 402

A

type B - bizarre
• unexpected
• unrelated to dosage and not expected from known pharmacological action
• unpredictable
• mostly immunological mechanisms
• hypersensitivity
• genetically linked

Answer 403

A

heparin causing hair loss

Answer 404

A

those with predisposing factors such as; history of allergy, asthmatics and some family history are at greater risk
can be seen in drugs that inhibit certain metabolic pathways

Answer 405

A

type C - chronic:
• occurs after long term therapy
• may not be immediately obvious with new medicines

Answer 406

A

steroids predispose to hypoglycaemia - may result in diabetes

Answer 407

A

type D - delayed:
• also occurs after a long period of time after treatment (many years)
• common to see patient having treatment, then after 20-30 years they suffer an ADR

Answer 408

A

type E - end of use:
• relatively long term use (days/weeks)
• withdrawal reactions
• serious complication of stopping related to clinical effect

Answer 409

A

A - Augmented
B - Bizarre
C - Chronic
D - Delayed
E - End of Use

Answer 410

A

is there a history of allergy? - Type B (Bizarre)
is it predictable from the mechanism of action? does it seem dose-related? - Type A (Augmented)
has the patient been using the medication for a long time? - Type C (Chronic)
is the patient withdrawing from a medicine? - Type E (End of Use)
has the patient uses a drug in the past that could be causing a problem now? - Type D (Delayed)

Answer 411

A

history of allergy

Answer 412

A

reaction is predictable from mechanism of action and it seems dose-related

Answer 413

A

patient has been using medication for a long time

Answer 414

A

if patient is withdrawing from a medicine

Answer 415

A

if patient used a drug in the past that could be causing a problem now

Answer 416

A

age - elderly
gender - more common in females
pregnancy - negative effect on baby etc.
disease - liver or renal in particular
drug interactions
diet or alcohol intake changes
genetics
hypersensitivity

Answer 417

A

type 1: IgE-mediated drug hypersensitivity; anaphylaxis
type 2: IgG-mediated cytotoxicity - some drugs can cause renal failure through this type
type 3: immune-complex deposition; reacts with antibiotics
type 4: T-cell mediated; usually substance containing metals

Answer 418

A

prior exposure to antigen (drug)
virgin B lymphocyte activation to IgE producing plasma cells
IgE becomes attached to mast cells, expressed as cell surface receptors

Answer 419

A

monocyte in skin, sub mucosal, around blood vessels
dormant indefinitely
many are found in bronchial mucosa
see a lot of mast cell activity beneath the skin, around lungs and blood vessels

Answer 420

A

cross linking of IgE receptors releasing:

histamine
thromboxanes, prostaglandins
Tumour Necrosis Factor (TNF)
all of above are acute inflammatory mediators

Answer 421

A

histamine
thromboxanes, prostaglandins
Tumour Necrosis Factor (TNF)
all of above are acute inflammatory mediators

Answer 422

A

not caused by any IgE antibodies
due to direct mast cell degranulation
previously called anaphylactoid reactions
some drugs are recognised to cause this
no prior exposure
clinically identical to immune anaphylaxis

Answer 423

A

exposure to drug, immediate rapid onset
rash with characteristic blotches
swelling of lips, face, oedema, central cyanosis (go blue/purple)
wheeze
hypotension (Anaphylactic shock)
cardiac arrest

Answer 424

A

cardiorespiratory arrest

- no skin changes

Answer 425

A

commence basic life support: A (airway), B (breathing), C (circulation)
specific/drug treatment
effect of adrenaline

Answer 426

A

stop drug if infusion
adrenaline 1mg (10mls of 1:10,000 (IV)) 1ml IV increments - note: if cardiac arrest then may need to give cardiac massage in order to get drugs circulating
IV anti-histamine (Chlorphenamine 10mg)
IV Hydrocortisone (100 to 200mg) - note: unlikely to cause harm in excess so can’t really give too much

Answer 427

A

vasoconstriction, bronchodilation and increased cardiac output

Answer 428

A

protein or polysaccharide base macro molecules e.g. penicillin
mono-clonal antibodies (proteins) can cause reactions

Answer 429

A

more common in females compared to males

* immunosuppression

Answer 430

A

certain HLA groups (gene that encodes major histocompatibility complex (MHC))

Answer 431

A

drug allergy is a highly specific term clinically; local rash, local swelling - specific
GI upset (from NSAIDs) is not allergy
type A (Augmented) is not allergy, but some people can be more sensitive e.g. more likely to develop hypotension with anti-hypertensives

Answer 432

A

elicit a full medication history and previous reactions
check useful sources to find if ADR is described e.g BNF, eMC, Medicine Information Centres and MHRA (medical health regulation agency)
identify markers

Answer 433

A

serum concentration - plasma monitoring

Answer 434

A

tryptase - released from only mast cells; best test to confirm allergy based ADR
urine methylhistamine; breakdown product of histamine

Answer 435

A

continue the drug and manage the ADR by other means
reduce the dose of the drug
stop the drug

Answer 436

A

dose-related
may respond to dose-reduction or temporary withdrawal
severe reactions may require active treatment

Answer 437

A

not usually dose-related
should usually withdraw the medicine immediately
give supportive treatment if the reaction is severe e.g. anaphylaxis

Answer 438

A

MHRA Yellow-card scheme is the main method of surveillance of ADRs
can complete it; online, by post or by telephone

Answer 439

A

all suspected ADRs for new medicines
all ADRs in children
all serious reactions, even if well-documented to include

Answer 440

A

fatal
life threatening
disabling
incapacitation or resulting in prolonged hospitalisation

Answer 441

A

where the actions of 2 drugs combine

Answer 442

A

clavulanic acid and amoxil to make augmentin

* paracetamol and codeine to increase analgesic effect

Answer 443

A

where one drug blocks the action of the other

Answer 444

A

polypharmacy - on many different drugs
old age
genetics - e.g. slow/fast metabolism
hepatic disease
renal disease

Answer 445

A

narrow therapeutic index
steep dose/response curve
saturable metabolism - e.g. paracetamol and alcohol are metabolised at a set rate

Answer 446

A

motility
acidity
solubility
non-absorbed complex formation
direct action on enterocytes

Answer 447

A

erythromycin increases gut motility

- oral contraceptive pill and antibiotics have the commonest interaction causing motility changes

Answer 448

A

often with antacids and proton pump inhibitors - these change the pH of the stomach so if taking with other medication it can alter absorption of the drug

Answer 449

A

eating avocado (high in fat) and taking a fat soluble drug e.g. anti-coagulant then will dissolve the drug meaning there will be little or no drug absorption

Answer 450

A

large complexes in intestinal lumen - cholestyramine and thyroxin, warfarin or digoxin

Answer 451

A

grapefruit juice inhibits P-glycoprotein resulting in the

increased uptake of certain drugs

Answer 452

A

affects drug concentration in plasma thus reduces distribution thus less available to have effect
occurs with sulphonamide antibiotics and warfarin

Answer 453

A

drug A (inhibits CYP450) blocks metabolism of drug B, leaving more free drug B in the plasma - increase effects
note: in pro-drugs if metabolism is blocked then will be a decreased effect

Answer 454

A

drug C induces CYP450 isoenzyme, leading to increased metabolism of drug D resulting in decreased therapeutic effects
note: in pro-drugs if metabolism is increased then there will be increased therapeutic effects

Answer 455

A

affects CYP3A4 resulting in increased bioavailability thus this can make a drug more effective

Answer 456

A

renal and biliary

Answer 457

A

renal excretion is pH dependent
weak bases - cleared faster if urine is acidic
weak acids - cleared faster if urine is alkali
can alter pH of urine to alter excretion

Answer 458

A

aspirin - try to alkalinise urine to help increase excretion with aspirin overdose
ibuprofen
paracetamol
warfarin

Answer 459

A

amphetamine
atropine
propranolol
salbutamol

Answer 460

A

receptor based
signal transduction
physiological systems

Answer 461

A

bind to receptor

- for example, alcohol and benzodiazepine at GABA A receptor

Answer 462

A

partially bind/activation at receptor

- for example buprenorphine for opioid addiction

Answer 463

A

block receptor
can be competitive and non-competitive
for example beta-blockers and asthma (competitive)
never give beta-blockers to asthmatics since they will be on beta-agonists to help with bronchodilation, if using beta-blockers then will cause bronchoconstriction and increased risk of asthma attack

Answer 464

A

rarer but examples exist
commencing beta-blockers in a diabetic resulting in action at beta3 receptors in adipose tissues which normally detect and alter blood glucose, but action at B2 receptors can suppress hypoglycaemic awareness so they will not detect fall in glucose as well

Answer 465

A

different drugs that effect different receptors, but in the same physiological system
Ca2+ channel antagonists and beta-blockers
ACE inhibitors and NSAIDs have a degree of nephrotoxicity

Answer 466

A

digoxin works on cardiac fibres and its effect is increased if there are low levels of potassium in blood plasma
furosemide is a diuretic that lowers arterial pressure but
favours the loss of potassium
this could lead to hypokalaemia, which could increase the toxicity of digoxin

Answer 467

A

prescribe rationally
BNF
medicines information service

Answer 468

A

amiodarone

Answer 469

A

terfenadine, diphenhydramine

Answer 470

A

felodipine, nifedipine, nimodipine, nicardipine

Answer 471

A

simvastatin

Answer 472

A

atorvastatin

Answer 473

A

cyclosporin, tacrolimus

Answer 474

A

amiodarone
terenadine, diphenhydramine
simvastatin

Answer 475

A

felodipine, nifedipine, nimodipine, nicardipine
atorvastatin
cyclosporin, tacrolimus

Answer 476

A

rhabdomyolysis (muscle pain/breakdown)

Answer 477

A

itraconazole, erythromycin, clarithromycin, diltiazem, verapamil, amiodarone

Answer 478

A

20-200x increase in plasma concentrations

Answer 479

A

erythromycin, clarithromycin, tramadol, amiodarone

Answer 480

A

monitor INR at day 3, then weekly, up to 4 weeks post commencement

Answer 481

A

serotonin syndrome

Answer 482

A

tricyclic antidepressants, tramodol

Answer 483

A

renal failure

Answer 484

A

NSAID or COX2 inhibitor, plus ACEi, plus dehydration or furosemide

Answer 485

A

avocado reduces effectiveness of warfarin; could increase risk of blood
clots
grapefruit juice increases effectiveness of calcium channel blockers and anti-rejection medication
garlic increases anti-platelet activity so can increase risk of bleeding
soya increases effectiveness of NSAIDs and warfarin so can increase risk of bleeding
ginger reduces effectiveness of anticoagulants so increases risk of bleeding

Answer 486

A

diagnosis
drug treatment
indications and contraindications
peculiar properties of either the diagnosis or drugs:
• does it require plasma monitoring?
• is there a risk of drug interaction?
patient name
dose
route
frequency
duration
total number of tablets
drug name
date and signature

Answer 487

A

home: current medications, self prescribing?
hospital admission: continue home meds, investigation, diagnosis
inpatient: new treatment?
discharge from hospital: pre-admission drugs, new prescription

Answer 488

A

home: drug history and pharmacy printout
hospital admission: inpatient prescription chart
inpatient: multi-disciplinary prescribing
discharge from hospital: take home medication or not and discharge summary to GP

Answer 489

A

the number of different times the same information is translated or transposed
information on admission
duplication; paper, different teams
clerical/legibility/ administration errors
emergency situations

Answer 490

A

are avoidable; is classed as neglect
carelessness since staff generally have the appropriate knowledge but do not use it at the time
ward pharmacists check prescriptions carefully but only do daily checks - not continuous
specify whether IV or intrathecal (spinal cord); can be confused easily leading to spinal cord damage

Answer 491

A

beware that drugs with co-something-amol actually contain paracetamol, so inform patients of this because they might supplement this with more
paracetamol leading to a potential paracetamol overdose - need to be
careful

Answer 492

A

tazocin and augmentin

Answer 493

A

withdrawal reactions if stopping most long term drugs; analgesics, anti
hypertensives and anti depressants
the vast majority of drugs should be continued unless there is a specific reason related to the presenting complaint

Answer 494

A

nil by mouth policy for fluids is 2 hours, due to fear of aspiration under anaesthesia
a sip of water with tablets is OK; can safely have a small drop of water for the taking of medications prior to surgery

Answer 495

A

ACE inhibitors, losartan (angiotensin receptor blocker)
warfarin should be bridged to heparin (easier to manage dosage since injected)
diabetes drugs - a detailed guidance proforma for this exists

Answer 496

A

opioid receptor agonist
• the oral bioavailability of morphine is about 50% due to liver metabolism
• in 10% of the population codeine won’t work and in 10% it works too well

Answer 497

A

naturally occurring opioids from the opium poppy (contains both morphine and codeine)
simple chemical modifications
synthetic opioids
synthetic partial agonists
antagonists

Answer 498

A

morphine

* codeine (weak)

Answer 499

A

diamorphine (heroin)
oxycodone
dihydrocodeine (more predictable than codeine)

Answer 500

A

pethidine
fentanyl (very potent)
alfentanil (very potent)
remifentanil (very potent)

Answer 501

A

buprenorphine - if overdose there is no respiratory depression

Answer 502

A

naloxone - give to reverse overdose

Answer 503

A

oral (simplest route)
10mg orally is equivalent to 5mg parenterally (subcutaneous, intramuscular and IV)
single dose of morphine lasts 3-4 hours
subcutaneous
IV

Answer 504

A

• 50% of oral morphine is metabolised by first pass metabolism in the liver
• give half the dose if giving parenterally (sub-cutaneous,
intramuscular and intravenous (IV))

Answer 505

A

3-4 hours

Answer 506

A

• fastest mode of administration, once given it will go around the whole
body in one minute
• will take 5 minutes for morphine to reach brain

Answer 507

A

dose can be self-administered by patient every 5 minutes with lockout
safe since the patient will sleep before the onset of respiratory depression
danger if somebody else presses the button for delivery e.g. grandchildren

Answer 508

A

more potent and faster acting (crosses BBB quickly)

Answer 509

A

opioid drugs simply use the existing pain modulation system - natural endorphins (endogenous morphine) and enkephalins
G protein coupled receptors act via second messengers
they inhibit the release of pain transmitters at spinal cord and midbrain and modulate pain perception in higher centres - euphoria - to change the emotional perception of pain
opioids block descending pain transmission
they were never designed for sustained activation; designed only to be used for 30 minutes or so
sustained activation leads to tolerance and addiction

Answer 510

A

greek letter μ for morphine (MOP)
soon after delta (DOP) and kappa (KOP) receptors were identified
more recently the nociceptin opioid-like (NOP) receptor was identified

Answer 511

A

aim of opioid development is to develop opioid analgesic without the side effects of respiratory depression or addiction

Answer 512

A

mental depression instead of euphoria

Answer 513

A

midbrain
spine
GI tract - can get constipated with opioid use
breathing centre - it communicates using opioid receptors, opioid use can cause respiratory depression

Answer 514

A

whether a drug is ‘strong’ or ‘weak’ - relates to how well the drug binds to the receptor - the binding affinity

Answer 515

A

diamorphine - 5mg (twice as potent as morphine)
morphine - 10mg
pethidine - 100mg (10 times weaker than morphine)

Answer 516

A

• is it possible to get a maximal response with the drug or not?
• or if all the receptor sites are occupied, do you get a ceiling
response?
• the concept of full or partial agonists (e.g. buprenorphine)

Answer 517

A

• down-regulation of the receptors with prolonged use
• need higher doses to achieve the same effect
• can develop with continued morphine use due to the
desensitisation of μ receptors

Answer 518

A

• morphine given with
naloxone (antagonist) will
reduce the efficacy of
morphine since naloxone is a
competitive receptor
antagonist
• given to correct morphine overdose

Answer 519

A

psychological - craving of euphoria

* can be physical

Answer 520

A

begins within 24 hours, lasts about 72 hours - can give methadone to provide a slower and thus safer reduction in opioid

Answer 521

A

opioid receptors exist outside the pain system e.g. digestive tract and respiratory control centre
respiratory depression
sedation
nausea and vomiting
constipation
itching
immune suppression
endocrine effects
different patients have quite a range of sensitivity to opioids - start with small dose and titrate up as necessary

Answer 522

A

A (airway), B (breathing), C (circulation)
administer naloxone - IV is fastest route - 400 micrograms per ml
titrate to effect - don’t give all at once - once a drug has been injected you cannot get it back! - dilute 1ml in 10ml saline
naloxone has a short half-life so give a depot of naloxone, some IV and some subcutaneous - so if the naloxone wears off then the depot will maintain levels

Answer 523

A

opioids for non-cancer pain start to lose effectiveness fairly quickly (within weeks)
addiction to the drug leads to manipulative behaviour - easy to start but can be very difficult to get patient off them

Answer 524

A

codeine is a prodrug; it needs to be metabolised by cytochrome CYP2D6 to work
CYP2D6 activity is decreased in 10-15% of the caucasian population, so
codeine will not be as effective
CYP2D6 activity is absent in 10% of the caucasian population meaning
codeine will have no effect
CYP2D6 is overactive in 5% of the caucasian population - these individuals may be at increased risk of respiratory depression with codeine; this is the reason why codeine is banned from children and breast feeding mothers in case they are in the 5%

Answer 525

A

morphine is metabolised to morphine-6-glucuronide which is more potent than morphine
morphine-6-glucuronide is renally excreted and will build up and cause respiratory depression in renal failure

Answer 526

A

pethidine is metabolised to norpethidine which is epileptogenic and will build up and cause fits in renal failure

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Pharmacokinetics and pharmacodynamics Flashcards

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