Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Mpharm > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What is pharmacology?

A

Explains what drugs are, what effect they have on the body and the effect the body has on the drug.
Explains why side effects may occur and why different people may react differently to drugs.

The science of the interaction of chemical agents with living systems. It encompasses the study of biochemical and physiological aspects of drug effects, including absorption, distribution, metabolism, elimination, toxicity and specific mechanisms of drug actions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is a drug?

A

A substance that affects a biological system. Used in prevention, diagnosis, treatment of a disease.
Once the chemicals are absorbed into systemic circulation they bind with a target to change the function of the cell.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is an active ingredient?

A

The chemical in the drug that affects physiological functioning

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is an inactive ingredient?

A

They have no effect on the cells. Act as a filler to bind the drug together, make it taste or smell pleasant, to lubricate the drug.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Where do drugs come from?

A 
Plants- aspirin, opiates
Microbes- penicillin, chloramphenicol 
Animals- heparin, insulin (usually now made synthetically or by genetic engineering)
Minerals- calcium, magnesium 
Can be synthesised by chemists
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Advantages of synthetic drugs?

A 
Easier quality control 
Process easier and cheaper 
Safer 
Large scale production 
Drugs can be modified to improve properties
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How are biological drugs made?

A

A product that is formed from living organisms or contain components of living organisms
These drugs are often large and difficult to generate synthetically

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Types of drug names:

A

1) chemical: includes information on molecular structure
2) trivial: a common name, sometimes arising from historical uses
3) generic: non-proprietary drug name adopted by an officially recognised organisation in a country. E.g. BAN (British approved name) from the British Pharmacopeia or USP (United states pharmacopeia)
4) trade names: owned by a company

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Reasons why adverse affects may occur?

A

Drug has additional effects on the body due to lack of specificity
Patient is sensitive to the drug given
Patient is not taking the prescribed dose
Dose incorrectly proscribed
Drug-drug interactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Why so drugs effect people differently?

A 
Age
Genes 
Disease state 
Tolerance
Dependence
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is a poison?

A

Any chemical agent that produces harmful effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is a toxin?

A

A poison of biological origin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What did Paul Ehrlich say?

A

A drug will not work unless bound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Types of drug targets?

A

Proteins- most common
Nucleic acids- some drugs bind to DNA, such as cancer therapies that interfere with DNA replication, e.g. doxorubicin
Others- such as protons, e.g. antacids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Types of drug target proteins?

A

Receptors, e.g. GPCRs
Enzymes
Ion channels
Transporters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Receptor definition?

A

A protein that, when bound to an agonist, transmits a signal which turns on or off a specific biological/physiological response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the name of the endogenous molecule that binds to a receptor?

A

Ligand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Examples of endogenous ligands?

A 
Hormones
Neurotransmitters 
Growth factors
Cytokines
Metabolites
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Different classes of receptors?

A 
Cell surface receptors
Intracellular receptors (nuclear receptors)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Cell surface receptors?

A

G protein-coupled receptors (GPCR) (metabotropic): ligand binding to receptor activates a G-protein which then activates or inhibits an enzyme or ion channel
Ligand gated ion channels (ionotropic): ligand binding to the ion channel causes opening or closing of the channel and modulates passage of ions
Enzyme-coupled receptors: ligand binding activates the enzyme activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Intracellular receptors?

A

Either cytoplasmic or nucleolus.

Binding of ligand activates receptor and alters gene expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does an agonist work?

A

Bind to and activates the receptor to produce biological response
They have affinity and efficacy
They often mimic or are the endogenous ligand

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Examples of agonists

A

Salbutamol: beta 2 adrenergic receptor agonists (GPCR). Very similar chemical structure to adrenaline

Insulin: insulin receptor agonist (enzyme-linked receptor)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

How does an antagonist work?

A

Binds to the receptor and prevents the agonist from producing a biological response
They have affinity but not efficacy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Types of antagonist?

A

Competitive: bind with the same site as the agonist
Non-competitive: binds to allosteric site on receptor to stop agonist from being able to bind
Can be reversible or irreversible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Example of antagonists?

A

Propranolol: antagonist of beta adrenergic receptors (GPCR)

Tamoxifen: antagonist of the oestrogen receptor (intracellular receptor)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

How do ion channels blockers work?

A

The blocker sits in the channel to affect permeation (passage of ions)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Example of ion channel blocker?

A

Tetrodoxin: blocks voltage gated sodium channel. A poison isolated from Japanese puffer fish but in trials for analgesia purposes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How do ion channel modulators work?

A

Bind to the channel proteins to affect gating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Example of ion channel modulator?

A

Sulfonylureas: target ATP-sensitive potassium channel and promote insulin release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

How do enzyme inhibitors work?

A

Bind to substrate binding site to inhibit normal reactions
Can be competitive or non-competitive
Can be reversible or irreversible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Examples of enzyme inhibitors?

A

Aspirin: a non-competitive inhibitor of cyclooxyrgenase

Sildenafil: a competitive inhibitor of cGMP phosphodiesterase type 5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

How do pro-drugs work?

A

Drugs that first require modification by an enzyme before being active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Example of a pro-drug?

A

Enalapril: ACE inhibitor that needs to first be activated by an enzyme to enalaprilat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

How do false substrates work?

A

Drugs that bind to the substrate binding site and are converted to an abnormal product by the enzyme. The product then subverts the normal metabolic pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

False substrate example?

A

Methyldopa: catalysed by DOPA decarboxylase to methylnorepinephrine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

How do transporter inhibitors work?

A

Block the channel or inhibit the activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Example of transporter inhibitors?

A

SSRIs: they block the transporters responsible for the reuptake of serotonin meaning more is available to pass further messages to nerve cells

Amphetamines: compete with noradrenaline for NA-uptake 1 transporter. Meaning more noradrenaline is available to bind to receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Drug binding to a receptor is determined by what forces?

A

Hydrogen bonds
Van der Waals forces
Ionic bonds
Covalent bonds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Affinity meaning in pharmacology?

A

The strength of attraction between the drug and its receptor

It’s the ability to associate and dissociate from the receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What type of bond causes irreversible competition?

A

Covalent

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Two most common types of forces between receptors and ligands?

A

Hydrogen bonds

Van der Waals forces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

In terms of affinity, at equilibrium, the rate of associate is equal to?

A

Rate of dissociation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Drug binding to receptor formula?

A

[drug/receptor complex]

Which is equal to
K dissociation
———————-
K association

Which is equal to Kd

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What is Kd?

A

The dissociation constant.

This is when 50% of the receptors are occupied

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What does Kd measure?

A

Affinity

50% occupancy of receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What does a low Kd mean?

A

High affinity, so smaller concentrations of the drug are needed
Implying a strong binding of the receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What does a high Kd mean?

A

Low affinity, so higher drug concentrations are needed

Implying a weak binding of the receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What is a radioligand assay used for?

A

To measure affinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

How does a radioligand assay work?

A

1) conducted in vitro
2) cells in the dish have the receptors you are interested in
3) radiolabelled ligand is added to the dish
4) watch binding over time and record the steady-state at different concentrations
5) plot this against time
6) add excess non-radioactive ligands to complete and remove labelled ligands from the receptors; this measures the nonspecific binding
7) minus the nonspecific binding from the total binding to work out the specific binding of that drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What does occupancy mean?

A

The proportion of receptors bound or occupied by the drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

What is Bmax?

A

The maximum number of receptors bound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

When plotted on a linear scale a concentration-occupancy relationship is?

A

Hyperbolic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

When plotted on a log scale a concentration-occupancy relationship is?

A

Sigmoidal (S-shaped)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What is Ka?

A

The reciprocal of Kd; 1/Kd
Measure of the affinity of the drug for the receptor
Low Kd would mean high Ka

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

How can efficacy be determined?

A

Plotting the concentration of a drug against its response
Usually in vitro as in humans the concentration at the site of action would not be the same as the concentration administered

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

When plotted on a linear scale a concentration-response relationship is?

A

Hyperbolic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

When plotted on a log scale a concentration-response relationship is?

A

Sigmoidal (S-shaped)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Why do drug responses saturate?

A

Amplification of signals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

What is Emax?

A

The maximum effect which can be expected from the drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

What is EC50?

A

The effective concentration that produces 50% of the maximal effect/response
It is a measure of potency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

What is ED50?

A

The effective dose of a drug producing 50% of a maximal effort OR the dose required to produce a therapeutic response in 50% of the population

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

What is the difference between EC50 and ED50?

A

EC is measured in vitro as we can measure specific concentrations
ED is measured in vivo as we cannot measure the concentration of the drug at the site of action, but we can give a dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What is TD50?

A

The dose required to produce a toxic effect in 50% of the population

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

What is therapeutic index?

A

Measurement of drug safety

The relationship between the therapeutic and the toxic dose of a drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

How to calculate the therapeutic index?

A

TD50/ED50

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

A drug with a high therapeutic index is?

A

Usually safer- maximal benefit with minimal risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

A drug with a low therapeutic index is?

A

More dangerous. May require regular monitoring of drug levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

What is the therapeutic window?

A

The range of doses between efficacy and toxicity. Achieving the greatest benefit without resulting in toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

What do full agonists do?

A

Produce a 100% response

Have high efficacy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

What do partial agonists do?

A

Produces less than a full response when fully occupying their receptors
Have a lower efficacy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

What values can efficacy take?

A

Between 0 and 1
1 being a maximum response
0 being no response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Potency meaning?

A

The amount of drug required to produce an effect of given intensity
The product of both affinity and efficacy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

How to compare drug potency?

A

Using the EC/ED50 values

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

What does a low ED/EC 50 mean?

A

High potency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

What does a high ED/EC50 show?

A

Low potency

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Why is EC50 usually much lower than Kd?

A

Signal amplification

Drugs can produce a full response without full occupancy; some receptors are spare

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Where do competitive antagonists bind?

A

Reversibly or irreversibly to the orthosteric site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Where do non-competitive antagonists bind?

A

Irreversible to the orthosteric site or to an allosteric site

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

The majority of clinically used drugs are what type?

A

Reversible competitive antagonists

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

What happens if you add more agonist to a reversible competitive antagonist?

A

No change in efficacy
A rightward shift of the concentration-response for the agonists (increased EC50)
The higher the affinity of the antagonist, the greater the shift

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

Can be inhibitory effects of an antagonist be surmounted by the addition of the agonist?

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

What happens if you add more agonist to an irreversible competitive antagonist?

A

The action of an irreversible antagonist cannot be surmounted
A reduction in efficacy- Emax
It may or may not affect EC50

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

What are the barriers to oral/dermal/pulmonary absorption?

A

Mainly the epithelium as cells are tightly packed; plasma membranes are lipid based
Effux proteins
Mucosal enzymes that may degrade the drug
Highly viscous layers that cover the epithelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

How can drugs cross the epithelium?

A

Passive diffusion

Active transport

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

How are most oral drugs absorbed?

A

Passive diffusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

Which kind of drugs can absorb by passive diffusion?

A

Small

lipophilic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

What kind of drugs can enter cells by carrier proteins?

A

Small and hydrophilic molecules or ions

It may be passive or active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

What is intracellular diffusion?

A

The movement of small (<600 Da) hydrophilic molecules through the right junction of cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

What is transcytosis?

A

How larger hydrophilic molecules may penetrate the epithelium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

What is the pKa of a substance?

A

The pH at which ionised and unionised forms are equal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

Why is pKa important in drug absorption?

A

So you can predict ionisation behaviour in different parts of the body that have different pHs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

What happens if the pH is lower than the pKa?

A

In acids: the unionised form will dominate

In bases: the ionised form will dominate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

What happens if the pH is higher than the pKa?

A

In acids: the ionised form will dominate

In bases: the unionised form will dominate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

What happens if the pH is the same as the pKa?

A

50% will be ionised, and 50% will be unionised irrespective if acid or base

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

What does the partition coefficient measure?

A

Tests the hydrophilic/phobic properties

To what degree the molecule prefers to be in octanol or water

97
Q

How is the partition coefficient measured?

A

Drug placed in a flask of octanol and water
Shaken
Analyse the amount of substance in each layer

98
Q

What is log-P?

A

The partition coefficient is when none of the substance is ionised. The ratio of the concentrations of unionised compounds in octanol and water at equilibrium

99
Q

Log-P equation?

A

P= [drug] octanol
——————–
[drug] water

100
Q

What does log-P of 0 show?

A

50/50 in octanol and water

101
Q

What does log-P of 1 show?

A

10x more in octanol

102
Q

What does log-P of 2 show?

A

100x more in octanol

103
Q

What does log-P of 3 show?

A

1000x more in octanol

104
Q

What does log-P of -1 show?

A

10x more in water

105
Q

What does log-P of -2 show?

A

100x more in water

106
Q

What does log-P of -3 show?

A

1000x more in water

107
Q

What is log-D?

A

Distribution coefficient
Includes the amount of ionised compound in the aqueous stage
The partition changes with pH

108
Q

Weak bases are mainly absorbed at…… pH’s?

A

Higher

109
Q

Weak acids are mainly absorbed at…… pH’s?

A

Lower

110
Q

What is the pH of the stomach?

A

1-2

around 4 in neonates

111
Q

What is the pH of the duodenum?

A

5-6

112
Q

What is the pH of the jejunum/ileum?

A

6.5-7.6

113
Q

What is the pH of the colon?

A

8

114
Q

If the pKa of aspirin is 3.5 where will it be absorbed?

A

Stomach

115
Q

If the pKa of morphine is 8 where will it be absorbed?

A

Duodenum

116
Q

Why are ionised drugs not absorbed?

A

There are surrounded with a water sphere and therefore no lipophilic

117
Q

What is faster passive diffusion or facilitated diffusion?

A

Facilitated diffusion

118
Q

What is transported by facilitated diffusion?

A

Charged molecules

Polar substances

119
Q

What are the two types of membrane transporters?

A

ATP-binding cassette (ABC)

Solute carrier transporters (SLC)

120
Q

Which type of membrane transporters use energy from ATP?

A

ABCs

SLCs do not but after often couples to other energy-dependent mechanisms

121
Q

What does the Biopharmaceutical Classification System do?

A

Categorises drug molecules based on intestinal permeability and aqueous solubility
Four possible categories

122
Q

Barriers for oral absorption?

A

Rate of gastric emptying
The acidic environment of the stomach
Presence of enzymes

123
Q

Advantages of the pulmonary administration route?

A 
Non-invasive 
Delivers to a large surface area
Thin alveolar epithelial cells 
Avoidance of first-pass metabolism 
Minimal enzymatic activity in the lungs
124
Q

Factors that may limit the use of pulmonary administration?

A

Lung disease
Smoking
Necessity to control the breathing rate

125
Q

How are drugs transported through the skin?

A

Passive diffusion

1) via hair follicles with their associated sebaceous glands
2) through sweat ducts
3) across the continuous stratum corneum between these appendages

126
Q

What kinds of molecules are absorbed well by the dermal route?

A

High log-P, so lipophilic

Low molecular weight

127
Q

Types of plasma proteins?

A

Albumin
Immunoglobulin
Fibrinogen

128
Q

Why are plasma proteins important in drug distribution?

A

All drugs bind to plasma proteins to some degree, meaning only a certain amount can enter cells
Warfarin 99% bound
Digoxin less than 10% bound

129
Q

What is extracellular fluid?

A

Blood plasma
Interstitial fluid
Lymph
22% total body weight

130
Q

What is intracellular fluid?

A

Total fluid contents of all cells

30-40% of total body weight

131
Q

What is transcellular fluid?

A 
Cerebrospinal
Intraocular
Peritoneal
Pleural
Synovial 
Digestive secretions
Around 2.5% of total body weight
132
Q

What factors can affect distribution?

A 
LogP
Blood flow to organ/tissue
Binding to blood and plasma proteins 
Size of molecules 
Membrane transporters
133
Q

Volume of distribution definition?

A

The volume of fluid required to contain the total amount of drug throughout the body, at the same concentration as that present in the plasma
It provides a measure of the extent of distribution

134
Q

What does a low volume of distribution indicate?

A

Distribution is restricted to a particular compartment such as the plasma

135
Q

What could cause a low volume of distribution?

A

Large molecular weight drugs

High levels of protein binding 

136
Q

What kind of drugs can have a high volume of distribution?

A

Lipid soluble or bind extensively to tissues

137
Q

What is the blood brain barrier?

A

It functions as a physical, metabolic and immunological barrier maintaining the homoeostasis of the brain

138
Q

What is the main type of cell in the blood brain barrier?

A

Brain capillary endothelial cells, these limit the movement of material from the blood to the brain

139
Q

What kind of drugs can cross the blood brain barrier?

A

Highly lipid soluble

Molecules less than 400 Da and that form less than eight hydrogen bonds can pass via passive diffusion

140
Q

Formula for protein binding?

A

Fu=Cu/C

Fu fraction unbound
Cu concentration unbound in plasma
C total plasma drug concentration

141
Q

How can plasma proteins cause drug interactions?

A

Some drugs can push other drugs off the proteins.

142
Q

What is metabolism?

A

Biotransformation of xenobiotics to more water-soluble compounds to facilitate excretion

143
Q

What happens in phase 1 metabolism?

A

Low molecular weight functional groups are added

144
Q

What happens in phase 2 metabolism?

A

Xenobiotic is conjugated with higher molecular weight adducts

145
Q

What happens in phase 3 metabolism?

A

Further processing of phase 2 products

146
Q

What part of the bloodstream does a drug enter?

A

The hepatic portal vein

147
Q

What are the there most important conjugates? 

A

Glucuronides, glutathione and sulfate

148
Q

What type of reactions are involved in phase 1 metabolism?

A

Oxidation, reduction, hydration, hydrolysis and other reactions

149
Q

What enzymes are involved in oxidation reactions?

A 
Cytochrome p450 enzymes (CYPs)
Flavin monooxygenases
Monoamine oxidases
Alcohol dehydrogenase
Xanthine oxidase
150
Q

What enzymes are involved in reduction reactions?

A

DT-diaphorase

Cytochrome p450 (CYPs)

151
Q

What kind of enzymes are involved in hydrolysis reactions?

A

Peptidases, carboxylesterases

152
Q

What type of enzymes are involved in hydration reactions?

A

Epoxide hydrolase

153
Q

What is the most common type of phase 1 metabolism reaction?

A

Oxidation

154
Q

How do flavin monooxygenases work?

A

Tertiary amines to N-oxides
Secondary amines to hydroxylamines or N–oxides
Primary amines to hydroxylamine or oximes
sulfur atoms oxidised to disulfides or S-oxides

155
Q

How do monoamine oxidase work?

A

They catalyse the oxidative deamination is monoamines

156
Q

What is the most common CYP enzyme?

A

CYP3A4

157
Q

What is the naming system for CYP enzymes?

A

The first number is the family.
The letter is the subfamily.
The second number is the isoform

158
Q

How do CYP enzymes work?

A

A substrate binds to the active site.
This reduces redox potential.
this leads to a flow of electrons from NADPH to FAD to FMN and then into cytochrome
 oxygen binds to heme, which reacts with solvent hydrogen forming water and a Fe03 complex
Followed by the transfer of the oxygen to the substrate

159
Q

Where are CYPs found?

A

All over the body but concentrated in SER of hepatocytes

160
Q

How many CYPs are there?

A

57 in humans, 15 implicated in xenobiotic transformation

161
Q

Are CYPs always expressed?

A

No, some are but not all

Some are induced/inhibited by food or drugs

162
Q

How can CYPs be involved in drug interactions?

A

For example hyperforin in St johns wort can induce CYP3A4 leading to an increase in metabolism wheres ketoconazole can inhibit CYP3A4 leading to a decrease in metabolism

163
Q

What are CYP polymorphisms?

A

Genetics from person to person

Some people have higher activity CYPs than others

164
Q

What type of function group does histamine have?

A

Amine

165
Q

Where is histamine most concentrated?

A

In the lungs, skin, and gastrointestinal tract

166
Q

How is calcium involved with made cells?

A

When the antibodies of the mast cell bind to an antigen this caused an influx of calcium causing release of the histamine

167
Q

What is the triple response?

A

Red
Flare
Wheal

168
Q

What happens at a histamine plasma concentration of 0-1ng/ml?

A

Nothing

169
Q

What happens at a histamine plasma concentration of 1-2ng/ml?

A

Enhanced gastric acid secretion

170
Q

What happens at a histamine plasma concentration of 3-5ng/ml?

A

Tachycardia

Skin reactions

171
Q

What happens at a histamine plasma concentration of 6-8ng/ml?

A

Decreased arterial pressure

172
Q

What happens at a histamine plasma concentration of 7-12ng/ml?

A

Bronchospasm

173
Q

What happens at a histamine plasma concentration of ~100ng/ml?

A

Cardiac arrest

Death

174
Q

Examples of localised histamine release?

A

Urticaria/ angioedema
Allergic rhinitis
Allergic conjunctivitis

175
Q

What to use in an anaphylactic emergency?

A

Adrenaline as it is a physiological reversal of histamine

176
Q

What does of adrenaline to use for anaphylaxis?

A

0.5ml of 1:1000 (0.5mg)

Or 0.3ml if selfadminstered

177
Q

How many types of histamine receptor?

A

4

But only 1 and 2 are therapeutically important

178
Q

What type of receptors are histamine receptors?

A

G-protein couples receptors

179
Q

Transduction mechanism of H1 receptors?

A

Two second messengers, IP3 and diacyglycerol (DAG)

180
Q

Transduction mechanism of H2 receptors?

A

Stimulates production of cAMP from ATP by stimulating adenylate cyclase. cAMP activates protein kinase A

181
Q

Transduction mechanism of H3 receptors?

A

Inhibits the productions of cAMP from ATP

182
Q

First H2 receptor antagonist and who discovered it?

A

Cimetidine and James Black

183
Q

Antihistamine drug therapy problems?

A 
Hepatic disease
Sometimes renal impairment
Some can have CNS effects
Anticholinergic burden- especially in elderly
Urinary retention
Long QT syndrome
Interactions with CNS medications
184
Q

Where are the adrenal glands?

A

Top of the kidneys

185
Q

What are the parts of the adrenal gland?

A

Adrenal medulla and adrenal cortex

186
Q

What does the adrenal medulla secrets?

A

Noradrenaline and adrenaline

187
Q

What does the adrenal cortex release?

A

Corticosteroids

188
Q

What are the three main corticosteroids secreted by the adrenal cortex?

A

Cortisol (hydrocortisone) a glucocorticoid for carbohydrate and protein metabolism
Aldosterone a mineralocorticoid for water and electrolyte balance
Dihydroepiandrostone (DHEA) for sexual development

189
Q

Therapeutic uses of corticosteroids?

A 
Replacement (in Addison’s disease)
Asthma
IBD
Rheumatoid arthritis
Eczema
Post transplant
190
Q

What controls secretion from the adrenal cortex?

A

Hypothalamic-pituitary axis which secretes adrenocoricotropin (ACTH)

191
Q

What factors can influence the level of circulating cortisol?

A

Time of day (circadian rhythm) levels drop when you go to bed and is highest when you wake up in the morning
Stress such as hypoglycaemia, trauma, infection, extensive exercise, anxiety and fear

192
Q

Cortisol secretion pathway?

A

Stress/circadian rhythm -> hypothalamus -> corticosteroid releasing hormone (CRH) -> anterior pituitary-> andrenocorticotrophic hormone (ACTH) -> adrenal cortex-> cortisol

193
Q

Molecular action of glucocorticoids?

A

Easily crossed cell membrane
Attaches to cytoplasmic receptor which induces conformation change
Steroid/receptor complex enters nucleus
Binds to DNA and affects transcription and therefore translation

194
Q

Pharmacological affects of mineralocorticoids?

A

Increase Na reabsorption in kidney
Increase K and H excretion
Increase water retention
Increase blood volume

195
Q

Physiological affects of glucocorticoids?

A

Decrease the uptake and utilisation of glucose
Increase gluconeogenesis
Increase glycogen synthesis and storage
Decrease protein synthesis
Increase protein breakdown
Increase lipolysis and redistribution of fat

196
Q

Pharmacological affects of therapeutic concentrations of corticosteroids?

A

Anti-inflammatory
Immunosuppressive
Mineralocorticoid activity and K loss
Effect on a a balance and bone metabolism
Atrophy of adrenal cortex (so treatment must not be stopped suddenly)

197
Q

What causes cushing’s disease?

A

Excessive production of glucocorticoids usually due to a pituitary tumour which increases production of ACTH

198
Q

What causes Addison’s disease?

A

Deficiency of glucocorticoids and mineralocorticoids due to atrophy of the adrenal cortex

199
Q

Symptoms of Addison’s disease?

A

Hypoglycaemia
Hypotension
Weight loss
Muscular weakness

200
Q

What causes Conn’s disease?

A

Excess of mineralocorticoids usually due to a tumour

201
Q

Symptoms of Conn’s disease?

A

Oedema
Hypokalaemia
Alkalosis
Hypertension

202
Q

Symptoms of cushings disease?

A 
Same as corticosteroid side effects
Hyperglycaemia
Diabetes
Muscle weakness
Thin skin
Fat redistribution to face and torso
Poor wound healing
Infection
Infection of growth in children
Hypertension
203
Q

What is a polymorphism?

A

A gene mutation that occurs in more than 1% of the population

204
Q

Benefits of pharmacogenomics?

A

maximise drug effectiveness
Minimise drug toxicity
Minimise PD and PK variability
Avoid unnecessary treatment

205
Q

what is an SNP?

A

single nucleotide polymorphism

206
Q

What does *1 in genetics mean?

A

wild-type (normal)

207
Q

Types of polymorphism?

A

SNP
Variable number tandem repeat
Gene deletion
Copy number variant

208
Q

What drug, according to the BNF, requires a patient’s DPD gene to be tested?

A

Fluorouracil

209
Q

What drugs, according to the BNF, requires a patient’s TPMT gene to be tested?

A

Azathioprine
Mercaptopurine
Thioguanine

210
Q

What is the HLA complex?

A

Human Leukocyte Antigen system. Can cause idiosyncratic drug reactions if gene mutations.

211
Q

What drugs require HLA-B*1502 allele tests and why?

A

Carbamazepine and phenytoin in patients of Han Chinese or Thai origin due to the risk of Stevens-johnson syndrome

212
Q

What drug requires HLA-B*5701 allele tests?

A

Abacavir

213
Q

What are barriers to implementing pharmacogenomics?

A 
Test issues
IT
Educational 
Ethical
Legal
Social
Cost-effectiveness 
Clinical utility
214
Q

What is zero order elimination?

A

A constant amount of drug is eliminated per unit time independent of drug concentration

215
Q

What is first order elimination?

A

A constant fraction of the drug is eliminated per unit time which is dependent upon the drug concentration

216
Q

What shape is a first order drug elimination on a graph?

A

Curved

217
Q

What shape is a first order drug elimination on a semi-log graph?

A

Straight line

218
Q

Examples of drugs cleared via zero order?

A

Ethanol

Phenytoin

219
Q

What is Cmax?

A

The maximum concentration after a single oral dose

220
Q

What is Tmax?

A

The time Cmax occurs

221
Q

What does Kel stand for?

A

Elimination rage constant

222
Q

What is Kel?

A

The fraction of drug eliminated per hour, with first order elimination

223
Q

How to calculate Kel?

A

use the terminal data from a concentration-time plot

224
Q

What is half-life?

A

The time it takes for drug concentration to half

225
Q

What does t1/2 stand for?

A

half-life

226
Q

Equation to work out half-life?

A

t1/2 = 0.693
———
Kel

227
Q

What does area under the curve show?

A

The exposure to the drug

228
Q

How to calculate AUC?

A

Use the trapezoid rules

229
Q

What does F stand for?

A

Absolute oral bioavailability

230
Q

What is absolute oral bioavailability?

A

The fraction of the drug that reaches the system circulation

231
Q

What to calculate absolute oral bioavailability?

A

Compare AUCs from an oral dose and an IV dose
AUC oral
————-
AUC IV

232
Q

What does V stand for?

A

Volume of distribution

233
Q

How to calculate volume of distribution?

A

the total amount of drug in body/ plasma concentration

234
Q

Volume of distribution definition?

A

the volume of distribution is the volume of plasma that would be necessary to account for the total amount of drug in the patient’s body, if that drug were present throughout the body at the same concentration as found in the plasma.

235
Q

What PK parameters can only be determined by an IV dose?

A

Volume of distribution

Clearance

236
Q

What does CL stand for?

A

Clearance

237
Q

Clearance definition?

A

The efficiency that a drug is eliminated from the circulation. The volume of blood cleared of drug per unit time.

238
Q

How to calculate clearance?

A

Does/ AUC

Mpharm (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions