Pharmacology Flashcards
(238 cards)
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
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.
3
Q
What is an active ingredient?
A
The chemical in the drug that affects physiological functioning
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.
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
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
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
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
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
10
Q
Why so drugs effect people differently?
A
Age Genes Disease state Tolerance Dependence
11
Q
What is a poison?
A
Any chemical agent that produces harmful effects
12
Q
What is a toxin?
A
A poison of biological origin
13
Q
What did Paul Ehrlich say?
A
A drug will not work unless bound
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
15
Q
Types of drug target proteins?
A
Receptors, e.g. GPCRs
Enzymes
Ion channels
Transporters
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
17
Q
What is the name of the endogenous molecule that binds to a receptor?
A
Ligand
18
Q
Examples of endogenous ligands?
A
Hormones Neurotransmitters Growth factors Cytokines Metabolites
19
Q
Different classes of receptors?
A
Cell surface receptors Intracellular receptors (nuclear receptors)
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
21
Q
Intracellular receptors?
A
Either cytoplasmic or nucleolus.
Binding of ligand activates receptor and alters gene expression
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
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)
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
25
Types of antagonist?
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
26
Example of antagonists?
Propranolol: antagonist of beta adrenergic receptors (GPCR)
Tamoxifen: antagonist of the oestrogen receptor (intracellular receptor)
27
How do ion channels blockers work?
The blocker sits in the channel to affect permeation (passage of ions)
28
Example of ion channel blocker?
Tetrodoxin: blocks voltage gated sodium channel. A poison isolated from Japanese puffer fish but in trials for analgesia purposes
29
How do ion channel modulators work?
Bind to the channel proteins to affect gating
30
Example of ion channel modulator?
Sulfonylureas: target ATP-sensitive potassium channel and promote insulin release
31
How do enzyme inhibitors work?
Bind to substrate binding site to inhibit normal reactions
Can be competitive or non-competitive
Can be reversible or irreversible
32
Examples of enzyme inhibitors?
Aspirin: a non-competitive inhibitor of cyclooxyrgenase
Sildenafil: a competitive inhibitor of cGMP phosphodiesterase type 5
33
How do pro-drugs work?
Drugs that first require modification by an enzyme before being active
34
Example of a pro-drug?
Enalapril: ACE inhibitor that needs to first be activated by an enzyme to enalaprilat
35
How do false substrates work?
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
36
False substrate example?
Methyldopa: catalysed by DOPA decarboxylase to methylnorepinephrine
37
How do transporter inhibitors work?
Block the channel or inhibit the activity
38
Example of transporter inhibitors?
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
39
Drug binding to a receptor is determined by what forces?
Hydrogen bonds
Van der Waals forces
Ionic bonds
Covalent bonds
40
Affinity meaning in pharmacology?
The strength of attraction between the drug and its receptor
| It's the ability to associate and dissociate from the receptor
41
What type of bond causes irreversible competition?
Covalent
42
Two most common types of forces between receptors and ligands?
Hydrogen bonds
| Van der Waals forces
43
In terms of affinity, at equilibrium, the rate of associate is equal to?
Rate of dissociation
44
Drug binding to receptor formula?
[drug] x [receptor]
------------------------------------
[drug/receptor complex]
Which is equal to
K dissociation
----------------------
K association
Which is equal to Kd
45
What is Kd?
The dissociation constant.
| This is when 50% of the receptors are occupied
46
What does Kd measure?
Affinity
| 50% occupancy of receptors
47
What does a low Kd mean?
High affinity, so smaller concentrations of the drug are needed
Implying a strong binding of the receptors
48
What does a high Kd mean?
Low affinity, so higher drug concentrations are needed
| Implying a weak binding of the receptors
49
What is a radioligand assay used for?
To measure affinity
50
How does a radioligand assay work?
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
51
What does occupancy mean?
The proportion of receptors bound or occupied by the drug
52
What is Bmax?
The maximum number of receptors bound
53
When plotted on a linear scale a concentration-occupancy relationship is?
Hyperbolic
54
When plotted on a log scale a concentration-occupancy relationship is?
Sigmoidal (S-shaped)
55
What is Ka?
The reciprocal of Kd; 1/Kd
Measure of the affinity of the drug for the receptor
Low Kd would mean high Ka
56
How can efficacy be determined?
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
57
When plotted on a linear scale a concentration-response relationship is?
Hyperbolic
58
When plotted on a log scale a concentration-response relationship is?
Sigmoidal (S-shaped)
59
Why do drug responses saturate?
Amplification of signals
60
What is Emax?
The maximum effect which can be expected from the drug
61
What is EC50?
The effective concentration that produces 50% of the maximal effect/response
It is a measure of potency
62
What is ED50?
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
63
What is the difference between EC50 and ED50?
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
64
What is TD50?
The dose required to produce a toxic effect in 50% of the population
65
What is therapeutic index?
Measurement of drug safety
| The relationship between the therapeutic and the toxic dose of a drug
66
How to calculate the therapeutic index?
TD50/ED50
67
A drug with a high therapeutic index is?
Usually safer- maximal benefit with minimal risk
68
A drug with a low therapeutic index is?
More dangerous. May require regular monitoring of drug levels
69
What is the therapeutic window?
The range of doses between efficacy and toxicity. Achieving the greatest benefit without resulting in toxicity
70
What do full agonists do?
Produce a 100% response
| Have high efficacy
71
What do partial agonists do?
Produces less than a full response when fully occupying their receptors
Have a lower efficacy
72
What values can efficacy take?
Between 0 and 1
1 being a maximum response
0 being no response
73
Potency meaning?
The amount of drug required to produce an effect of given intensity
The product of both affinity and efficacy
74
How to compare drug potency?
Using the EC/ED50 values
75
What does a low ED/EC 50 mean?
High potency
76
What does a high ED/EC50 show?
Low potency
77
Why is EC50 usually much lower than Kd?
Signal amplification
| Drugs can produce a full response without full occupancy; some receptors are spare
78
Where do competitive antagonists bind?
Reversibly or irreversibly to the orthosteric site
79
Where do non-competitive antagonists bind?
Irreversible to the orthosteric site or to an allosteric site
80
The majority of clinically used drugs are what type?
Reversible competitive antagonists
81
What happens if you add more agonist to a reversible competitive antagonist?
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
82
Can be inhibitory effects of an antagonist be surmounted by the addition of the agonist?
Yes
83
What happens if you add more agonist to an irreversible competitive antagonist?
The action of an irreversible antagonist cannot be surmounted
A reduction in efficacy- Emax
It may or may not affect EC50
84
What are the barriers to oral/dermal/pulmonary absorption?
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
85
How can drugs cross the epithelium?
Passive diffusion
| Active transport
86
How are most oral drugs absorbed?
Passive diffusion
87
Which kind of drugs can absorb by passive diffusion?
Small
| lipophilic
88
What kind of drugs can enter cells by carrier proteins?
Small and hydrophilic molecules or ions
| It may be passive or active
89
What is intracellular diffusion?
The movement of small (<600 Da) hydrophilic molecules through the right junction of cells
90
What is transcytosis?
How larger hydrophilic molecules may penetrate the epithelium
91
What is the pKa of a substance?
The pH at which ionised and unionised forms are equal
92
Why is pKa important in drug absorption?
So you can predict ionisation behaviour in different parts of the body that have different pHs
93
What happens if the pH is lower than the pKa?
In acids: the unionised form will dominate
| In bases: the ionised form will dominate
94
What happens if the pH is higher than the pKa?
In acids: the ionised form will dominate
| In bases: the unionised form will dominate
95
What happens if the pH is the same as the pKa?
50% will be ionised, and 50% will be unionised irrespective if acid or base
96
What does the partition coefficient measure?
Tests the hydrophilic/phobic properties
| To what degree the molecule prefers to be in octanol or water
97
How is the partition coefficient measured?
Drug placed in a flask of octanol and water
Shaken
Analyse the amount of substance in each layer
98
What is log-P?
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
Log-P equation?
P= [drug] octanol
--------------------
[drug] water
100
What does log-P of 0 show?
50/50 in octanol and water
101
What does log-P of 1 show?
10x more in octanol
102
What does log-P of 2 show?
100x more in octanol
103
What does log-P of 3 show?
1000x more in octanol
104
What does log-P of -1 show?
10x more in water
105
What does log-P of -2 show?
100x more in water
106
What does log-P of -3 show?
1000x more in water
107
What is log-D?
Distribution coefficient
Includes the amount of ionised compound in the aqueous stage
The partition changes with pH
108
Weak bases are mainly absorbed at...... pH's?
Higher
109
Weak acids are mainly absorbed at...... pH's?
Lower
110
What is the pH of the stomach?
1-2
| around 4 in neonates
111
What is the pH of the duodenum?
5-6
112
What is the pH of the jejunum/ileum?
6.5-7.6
113
What is the pH of the colon?
8
114
If the pKa of aspirin is 3.5 where will it be absorbed?
Stomach
115
If the pKa of morphine is 8 where will it be absorbed?
Duodenum
116
Why are ionised drugs not absorbed?
There are surrounded with a water sphere and therefore no lipophilic
117
What is faster passive diffusion or facilitated diffusion?
Facilitated diffusion
118
What is transported by facilitated diffusion?
Charged molecules
| Polar substances
119
What are the two types of membrane transporters?
ATP-binding cassette (ABC)
| Solute carrier transporters (SLC)
120
Which type of membrane transporters use energy from ATP?
ABCs
| SLCs do not but after often couples to other energy-dependent mechanisms
121
What does the Biopharmaceutical Classification System do?
Categorises drug molecules based on intestinal permeability and aqueous solubility
Four possible categories
122
Barriers for oral absorption?
Rate of gastric emptying
The acidic environment of the stomach
Presence of enzymes
123
Advantages of the pulmonary administration route?
```
Non-invasive
Delivers to a large surface area
Thin alveolar epithelial cells
Avoidance of first-pass metabolism
Minimal enzymatic activity in the lungs
```
124
Factors that may limit the use of pulmonary administration?
Lung disease
Smoking
Necessity to control the breathing rate
125
How are drugs transported through the skin?
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
What kinds of molecules are absorbed well by the dermal route?
High log-P, so lipophilic
| Low molecular weight
127
Types of plasma proteins?
Albumin
Immunoglobulin
Fibrinogen
128
Why are plasma proteins important in drug distribution?
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
What is extracellular fluid?
Blood plasma
Interstitial fluid
Lymph
22% total body weight
130
What is intracellular fluid?
Total fluid contents of all cells
| 30-40% of total body weight
131
What is transcellular fluid?
```
Cerebrospinal
Intraocular
Peritoneal
Pleural
Synovial
Digestive secretions
Around 2.5% of total body weight
```
132
What factors can affect distribution?
```
LogP
Blood flow to organ/tissue
Binding to blood and plasma proteins
Size of molecules
Membrane transporters
```
133
Volume of distribution definition?
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
What does a low volume of distribution indicate?
Distribution is restricted to a particular compartment such as the plasma
135
What could cause a low volume of distribution?
Large molecular weight drugs
| High levels of protein binding 
136
What kind of drugs can have a high volume of distribution?
Lipid soluble or bind extensively to tissues
137
What is the blood brain barrier?
It functions as a physical, metabolic and immunological barrier maintaining the homoeostasis of the brain
138
What is the main type of cell in the blood brain barrier?
Brain capillary endothelial cells, these limit the movement of material from the blood to the brain
139
What kind of drugs can cross the blood brain barrier?
Highly lipid soluble
| Molecules less than 400 Da and that form less than eight hydrogen bonds can pass via passive diffusion
140
Formula for protein binding?
Fu=Cu/C
Fu fraction unbound
Cu concentration unbound in plasma
C total plasma drug concentration
141
How can plasma proteins cause drug interactions?
Some drugs can push other drugs off the proteins.
142
What is metabolism?
Biotransformation of xenobiotics to more water-soluble compounds to facilitate excretion
143
What happens in phase 1 metabolism?
Low molecular weight functional groups are added
144
What happens in phase 2 metabolism?
Xenobiotic is conjugated with higher molecular weight adducts
145
What happens in phase 3 metabolism?
Further processing of phase 2 products
146
What part of the bloodstream does a drug enter?
The hepatic portal vein
147
What are the there most important conjugates? 
Glucuronides, glutathione and sulfate
148
What type of reactions are involved in phase 1 metabolism?
Oxidation, reduction, hydration, hydrolysis and other reactions
149
What enzymes are involved in oxidation reactions?
```
Cytochrome p450 enzymes (CYPs)
Flavin monooxygenases
Monoamine oxidases
Alcohol dehydrogenase
Xanthine oxidase
```
150
What enzymes are involved in reduction reactions?
DT-diaphorase
| Cytochrome p450 (CYPs)
151
What kind of enzymes are involved in hydrolysis reactions?
Peptidases, carboxylesterases
152
What type of enzymes are involved in hydration reactions?
Epoxide hydrolase
153
What is the most common type of phase 1 metabolism reaction?
Oxidation
154
How do flavin monooxygenases work?
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
How do monoamine oxidase work?
They catalyse the oxidative deamination is monoamines
156
What is the most common CYP enzyme?
CYP3A4
157
What is the naming system for CYP enzymes?
The first number is the family.
The letter is the subfamily.
The second number is the isoform
158
How do CYP enzymes work?
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
Where are CYPs found?
All over the body but concentrated in SER of hepatocytes
160
How many CYPs are there?
57 in humans, 15 implicated in xenobiotic transformation
161
Are CYPs always expressed?
No, some are but not all
| Some are induced/inhibited by food or drugs
162
How can CYPs be involved in drug interactions?
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
What are CYP polymorphisms?
Genetics from person to person
| Some people have higher activity CYPs than others
164
What type of function group does histamine have?
Amine
165
Where is histamine most concentrated?
In the lungs, skin, and gastrointestinal tract
166
How is calcium involved with made cells?
When the antibodies of the mast cell bind to an antigen this caused an influx of calcium causing release of the histamine
167
What is the triple response?
Red
Flare
Wheal
168
What happens at a histamine plasma concentration of 0-1ng/ml?
Nothing
169
What happens at a histamine plasma concentration of 1-2ng/ml?
Enhanced gastric acid secretion
170
What happens at a histamine plasma concentration of 3-5ng/ml?
Tachycardia
| Skin reactions
171
What happens at a histamine plasma concentration of 6-8ng/ml?
Decreased arterial pressure
172
What happens at a histamine plasma concentration of 7-12ng/ml?
Bronchospasm
173
What happens at a histamine plasma concentration of ~100ng/ml?
Cardiac arrest
| Death
174
Examples of localised histamine release?
Urticaria/ angioedema
Allergic rhinitis
Allergic conjunctivitis
175
What to use in an anaphylactic emergency?
Adrenaline as it is a physiological reversal of histamine
176
What does of adrenaline to use for anaphylaxis?
0.5ml of 1:1000 (0.5mg)
| Or 0.3ml if selfadminstered
177
How many types of histamine receptor?
4
| But only 1 and 2 are therapeutically important
178
What type of receptors are histamine receptors?
G-protein couples receptors
179
Transduction mechanism of H1 receptors?
Two second messengers, IP3 and diacyglycerol (DAG)
180
Transduction mechanism of H2 receptors?
Stimulates production of cAMP from ATP by stimulating adenylate cyclase. cAMP activates protein kinase A
181
Transduction mechanism of H3 receptors?
Inhibits the productions of cAMP from ATP
182
First H2 receptor antagonist and who discovered it?
Cimetidine and James Black
183
Antihistamine drug therapy problems?
```
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
Where are the adrenal glands?
Top of the kidneys
185
What are the parts of the adrenal gland?
Adrenal medulla and adrenal cortex
186
What does the adrenal medulla secrets?
Noradrenaline and adrenaline
187
What does the adrenal cortex release?
Corticosteroids
188
What are the three main corticosteroids secreted by the adrenal cortex?
Cortisol (hydrocortisone) a glucocorticoid for carbohydrate and protein metabolism
Aldosterone a mineralocorticoid for water and electrolyte balance
Dihydroepiandrostone (DHEA) for sexual development
189
Therapeutic uses of corticosteroids?
```
Replacement (in Addison’s disease)
Asthma
IBD
Rheumatoid arthritis
Eczema
Post transplant
```
190
What controls secretion from the adrenal cortex?
Hypothalamic-pituitary axis which secretes adrenocoricotropin (ACTH)
191
What factors can influence the level of circulating cortisol?
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
Cortisol secretion pathway?
Stress/circadian rhythm -> hypothalamus -> corticosteroid releasing hormone (CRH) -> anterior pituitary-> andrenocorticotrophic hormone (ACTH) -> adrenal cortex-> cortisol
193
Molecular action of glucocorticoids?
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
Pharmacological affects of mineralocorticoids?
Increase Na reabsorption in kidney
Increase K and H excretion
Increase water retention
Increase blood volume
195
Physiological affects of glucocorticoids?
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
Pharmacological affects of therapeutic concentrations of corticosteroids?
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
What causes cushing’s disease?
Excessive production of glucocorticoids usually due to a pituitary tumour which increases production of ACTH
198
What causes Addison’s disease?
Deficiency of glucocorticoids and mineralocorticoids due to atrophy of the adrenal cortex
199
Symptoms of Addison’s disease?
Hypoglycaemia
Hypotension
Weight loss
Muscular weakness
200
What causes Conn’s disease?
Excess of mineralocorticoids usually due to a tumour
201
Symptoms of Conn’s disease?
Oedema
Hypokalaemia
Alkalosis
Hypertension
202
Symptoms of cushings disease?
```
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
What is a polymorphism?
A gene mutation that occurs in more than 1% of the population
204
Benefits of pharmacogenomics?
maximise drug effectiveness
Minimise drug toxicity
Minimise PD and PK variability
Avoid unnecessary treatment
205
what is an SNP?
single nucleotide polymorphism
206
What does *1 in genetics mean?
wild-type (normal)
207
Types of polymorphism?
SNP
Variable number tandem repeat
Gene deletion
Copy number variant
208
What drug, according to the BNF, requires a patient's DPD gene to be tested?
Fluorouracil
209
What drugs, according to the BNF, requires a patient's TPMT gene to be tested?
Azathioprine
Mercaptopurine
Thioguanine
210
What is the HLA complex?
Human Leukocyte Antigen system. Can cause idiosyncratic drug reactions if gene mutations.
211
What drugs require HLA-B*1502 allele tests and why?
Carbamazepine and phenytoin in patients of Han Chinese or Thai origin due to the risk of Stevens-johnson syndrome
212
What drug requires HLA-B*5701 allele tests?
Abacavir
213
What are barriers to implementing pharmacogenomics?
```
Test issues
IT
Educational
Ethical
Legal
Social
Cost-effectiveness
Clinical utility
```
214
What is zero order elimination?
A constant amount of drug is eliminated per unit time independent of drug concentration
215
What is first order elimination?
A constant fraction of the drug is eliminated per unit time which is dependent upon the drug concentration
216
What shape is a first order drug elimination on a graph?
Curved
217
What shape is a first order drug elimination on a semi-log graph?
Straight line
218
Examples of drugs cleared via zero order?
Ethanol
| Phenytoin
219
What is Cmax?
The maximum concentration after a single oral dose
220
What is Tmax?
The time Cmax occurs
221
What does Kel stand for?
Elimination rage constant
222
What is Kel?
The fraction of drug eliminated per hour, with first order elimination
223
How to calculate Kel?
use the terminal data from a concentration-time plot
224
What is half-life?
The time it takes for drug concentration to half
225
What does t1/2 stand for?
half-life
226
Equation to work out half-life?
t1/2 = 0.693
---------
Kel
227
What does area under the curve show?
The exposure to the drug
228
How to calculate AUC?
Use the trapezoid rules
229
What does F stand for?
Absolute oral bioavailability
230
What is absolute oral bioavailability?
The fraction of the drug that reaches the system circulation
231
What to calculate absolute oral bioavailability?
Compare AUCs from an oral dose and an IV dose
AUC oral
-------------
AUC IV
232
What does V stand for?
Volume of distribution
233
How to calculate volume of distribution?
the total amount of drug in body/ plasma concentration
234
Volume of distribution definition?
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
What PK parameters can only be determined by an IV dose?
Volume of distribution
| Clearance
236
What does CL stand for?
Clearance
237
Clearance definition?
The efficiency that a drug is eliminated from the circulation. The volume of blood cleared of drug per unit time.
238
How to calculate clearance?
Does/ AUC
