Pharmacology Flashcards
1
Q
Give 3 protein targets for drug action
A
- ) Receptors
- ) Ion channels
- ) Enzymes
- ) Transporters
2
Q
What are ion channels?
A
Gateways in cell membranes that selectively allow ion passage
3
Q
What are ligand gated ion channels?
A
Channels that open when an agonist molecule binds
4
Q
What are voltage gated ion channels?
A
Open when transmembrane potential changes
5
Q
How can drugs affect ion channel function?
A
By binding to the orthosteric (primary) site and blocking the allosteric (non-primary) site, and changing the configuration for that the ligand cannot bind
6
Q
What are 2 types of inhibitors?
A
Competitive and non-competitive
7
Q
What are G protein coupled receptors?
A
Receptors coupled to intracellular effector systems by G proteins
8
Q
Give an example of a G protein coupled receptor (GPCR)
A
Beta adrenoreceptors
9
Q
What are G proteins?
A
Membrane proteins which function to recognise activated GPCRs and pass on the message to intracellular effectors
10
Q
Give an example of an intracellular effector
A
CAMP
11
Q
What do kinase linked and related receptors mainly respond to?
A
Protein mediators
12
Q
Give an example of a kinase linked receptor
A
Growth factor receptor
13
Q
What do nuclear receptors do?
A
Regulate gene transcription and recognise foreign molecules
14
Q
Give an example of a nuclear receptor
A
Steroid receptor
15
Q
What is an agonist?
A
Binds to receptor and activates it
16
Q
What is an antagonist?
A
Binds to receptor and reduces its effect by reversing its action
17
Q
What is Emax?
A
Describes the maximum response for a given agonist - full agonists give maximal responses
18
Q
What is affinity?
A
How well a ligand binds to a receptor - agonists and antagonists
19
Q
What is efficacy?
A
How well a ligand activates a receptor - agonists only
20
Q
What is potency?
A
How much of a drug needs to be given, binding affinity
21
Q
What is the equation for intrinsic activity?
A
Emax of partial agonist/ Emax of full agonist
22
Q
What is EC50?
A
The concentration of a drug that gives half of the maximal response
23
Q
How can we find out the EC50?
A
From a potency (sigmoidal shaped) curve
24
Q
What 2 things can we compare drugs by?
A
Potency (how much is needed for it to work)
Efficacy (maximal response)
25
What are the 2 main types of cholinergic receptors?
Nicotinic and muscarinic
26
Where are the 4 types of histamine receptors found?
H1 - allergic conditions
H2 - gastric acid secretion
H3 - mostly in CNS disorders
H4 - immune system and inflammatory conditions
27
Is histamine an agonist or antagonist?
Agonist
28
What does histamine do?
Causes contraction of the ileum and acid secretion from parietal cells (H2)
29
What causes reversed contraction of the ileum?
Mepyramine, antagonist
30
What is allosteric modulation?
A second ligand has the capacity to modify the response whilst not being in the agonist site
31
What is the difference between an antagonist and an inverse agonist?
Antagonist usually just neutralises the effects of an agonist, whereas an inverse agonist has the capacity to repress the response to the receptor - do the opposite
32
What is an enzyme inhibitor?
A molecule that binds to an enzyme and (normally) decreases its activity
33
How does an enzyme inhibitor work?
By preventing the substate from entering the enzyme's active site and thus preventing it from catalysing its reaction
34
What are the 2 main type of enzyme inhibitors?
Irreversible and reversible
35
How do irreversible inhibitors usually work?
Bind via a covalent bond and change enzyme chemically
36
What ways can an inhibitor bind to the enzyme?
Enzyme or enzyme-substrate complex
37
How do statins work?
By blocking the rate limiting step in the cholesterol pathway
38
How does aspirin work?
Irreversible inactivation of cyclooxygenase (COX)
39
How does ibuprofen work?
Completely inhibiting arachidonic acid at the active site of COX
40
How does penicillin work?
Inhibits transpeptidases, preventing cross linking and inhibiting bacterial wall synthesis
41
How do PPIs work?
Inhibit gastric acid secretion from parietal cells by irreversibly inactivating proton pumps
42
How do (some) diuretics work?
Inhibit symporters in areas of the kidney nephron so that there is a reduced reabsorption of salt from the filtrate
43
What does xenobiotic mean?
Compounds foreign to an organism's normal biochemistry
44
What are the 3 main types of protein port?
- ) Uniporter
- ) Symporter
- ) Antipoter
45
How do uniporters work?
Uses energy from ATP
46
How do symporters work?
Use movement of one molecule to pull another molecular in against its concentration gradient
47
How do antiporters work?
One substance moves against its gradient using energy from the second substance moving down its gradient
48
What are the 4 phases of pharmacokinetics?
- ) Absorption
- ) Distribution
- ) Metabolism
- ) Elimination
49
What is absorption?
The process of transferring the drug from the site of administration into the general or systemic circulation
50
Give 3 methods of administration of a drug
- ) Oral
- ) IV
- ) Intra-arterial
- ) IM
- ) SC
- ) Inhaled
- ) Topical
- ) Sublingual
- ) Rectal
- ) Intrathecal
51
Give 3 ways in which drugs move around the body
- ) Blood
- ) Lymphatics
- ) CSF
- ) Diffusion
52
Give 3 methods of transport for molecules
- ) Simple diffusion
- ) Facilitated diffusion
- ) Active transport
- ) Through extracellular spaces
- ) Via aquaporins
- ) Pinocytosis
53
What sort of pH is aspirin?
Weak acid
54
What sort of pH is propranolol?
Weak base
55
How do drugs with ionisable groups exist?
In equilibrium between charged (ionised) and uncharged forms
56
What are the most water soluble types of drugs?
Ionised
57
Define pKa of a drug
Dissociation or ionisation constant
58
What does pKa of a drug mean?
The pH at which half of the substance is ionised and half is unionised
59
Where are weak acids best absorbed?
Stomach
60
Where are weak bases best absorbed?
Intestine
61
What does bioavailability mean?
The amount of drug taken up as a proportion of the amount administered
62
What do drugs commonly bind to?
Albumin (plasma protein)
63
What does binding of a drug to protein cause?
Lowers the free concentration of the drug, and can act as a source by releasing the drug
64
What is irreversible binding of a drug to a protein equivalent to?
Elimination
65
What is the volume of distribution? (Vd)
The volume the drug would occupy if it was distributed through all of the components
66
What does a higher Vd mean?
The drug is more lipid soluble
67
What Vd will a drug have if it has a low plasma concentration?
High Vd
68
Where fo lipophilic drugs adhere to?
Hydrophobic areas of plasma proteins
69
How do we calculate Vd?
The total amount of drug in the body (dose)/ plasma concentration
70
What is the Vd if we give 50mg of a drug and find that the plasma concentration is 1mg/L?
50L
| 50mg/1mg/L = 50L
71
What is metabolism?
Transformation of the drug molecule into a different molecule
72
What do high hepatic/renal extraction ratio drugs have?
A high first pass metabolism
73
What does a high first pass metabolism also mean?
The bioavailability is limited
74
What is phase I metabolism?
Hepatic metabolism
75
What does phase I hepatic metabolism include?
Non-specific reactions that remove functional groups of side chains and add -OH or =O to make the molecule soluble
76
What catalyses phase I hepatic metabolism?
Cytochrome P450 catalyses oxidative hydroxylation
77
What does enterohepatic circulation do?
Prolongs some drug actions by liberating phase I metabolites to rediffuse into the blood
78
What is phase II metabolism?
Coagulation reactions
79
What does phase II coagulation reactions metabolism include?
Conjugating drugs with an OH group and glucuronic acid to make a glucuronide
80
How is a glucuronide made in a phase II reaction?
Formation of a covalent bond between the drug/phase I metabolite and an endogenous substance
81
Give 2 examples of endogenous substances
- ) Glucuronic acid
- ) Sulfate
- ) Acetyl group
- ) Methyl group
82
What are the resulting products of phase II reactions like?
Less active and readily excreted by kidneys
83
What is clearance?
Removal of the drug from the plasma by the liver or kidneys
84
How do we calculate clearance?
The volume of plasma that can be completely cleared of drug per unit time
85
What can reduce clearance?
Kidney or liver damage
86
What is the clearance if 10% od a drug carrier to the liver is cleared at a flow rate of 1000ml/min?
100ml/min
87
Give 3 states of matter and an example of a different form of excretion for each
Liquid - urine, bile, sweat, tears, breast milk
Solid - faeces, hair
Gas - expired air
88
How can we measure the fall in plasma concentration of a drug with time?
Taking repeat plasma samples
89
What is first order kinetics?
A constant fraction of the drug is eliminated per unit of time, exponential decline in plasma concentration of drug
90
What is zero order kinetics?
Rate of removal of drug is constant decline, unaffected by increase in concentration, enzyme system that removes drug is saturated
91
What order of kinetics does ethanol follow once alcohol dehydrogenase has been saturated?
Zero order
92
What does the graph look like for first order kinetics?
Exponential decline
93
What does the graph look like for zero order kinetics?
Constant gradient decline
94
What is half life?
The time taken for a concentration of a drug to reduce by a half
95
How do we calculate bioavailability?
As the fraction of the administered drug that reaches the systemic circulation unaltered (F)
96
What is the bioavailability of IV drugs?
F=1
97
What is the bioavailability of oral drugs?
F<1
98
How much larger will the dose need to be for a drug with an oral bioavailability of 0.1 compared to its IV dose?
10x
99
How do we measure the bioavailability on a graph?
Measure the areas under the curve (AUC)
100
How do we compare IV and oral plasma concentrations?
AUC oral/ AUC IV
101
What is the rate of elimination inversely proportional to?
Vd
102
What is the rate constant factor of elimination?
K
103
What is the equation relating clearance, elimination and volume of distribution?
K = CL/Vd
104
What is the calculation for clearance of an IV drug?
CL = dose/AUC
105
What is the calculation for clearance of an oral drug with F<1?
CL = dose x F/AUC
106
What is Css?
Steady state, balance between drug input and elimination
107
How do we get to Css?
Repeat drug administration
108
Give 2 things that will delay Css
- ) Slow elimination of drug
| - ) High Vd
109
What is the calculation for when the rate of elimination equals the rate of infusion? (In IV infusions)
CL x Css
110
What is the equation for Css for oral administration?
D x F/t = CL x Css
| t is the time interval between doses
111
Give 2 ways in which we can alter the plasma Css
- ) Change dose
| - ) Change interval
112
What is the equation for the loading dose?
Css x Vd
113
What is the loading dose?
A high initial dose which shortens the time to a steady state
114
Define synergy
2 drugs working towards the same effect
115
What does inhibition mean in the term of drug interactions?
Drug A blocks the metabolism of drug B thus leaving more free drug B in the plasma to have more of an effect
116
What does induction mean in the term of drug interactions?
Drug C induces an enzyme, leading to increased drug D metabolism so there is less of an effect
117
What does a narrow therapeutic index mean?
There is a small range between the drug not working and it being toxic
118
Define adverse event
Any unintended outcome
119
Define adverse drug reaction (ADR)
Unwanted or harmful reaction following administration of a drug/combination of drugs under normal conditions of use, and is suspected to be related to the drug
120
What are the 5 classes of ADRs?
```
Type A - augmented pharmacological
Type B - bizarre or idiosyncratic
Type C - chronic
Type D - delayed
Type E - end of treatment
```
121
Describe a type A ADR
Predictable, dose dependent, common (constipation and morphine)
122
Describe a type B ADR
Consider hypersensitivity types, not predictable, not dose dependent (anaphylaxis and penicillin)
123
Give an example of a type C ADR
Osteoporosis and steroids
124
Give an example of a type D ADR
Malignancies after immunosuppression
125
Describe a type E ADR
Occurs after abrupt drug withdrawal
126
Give 3 causes for an ADR
- ) Pharmaceutical variation
- ) Receptor abnormality
- ) Abnormal biological system unmasked by drug
- ) Abnormalities in drug metabolism
- ) Immunological
- ) Drug-drug interactions
- ) Multifactorial
127
Give 2 instances when we should suspect an ADR
- ) Symptoms after starting a new drug
- ) Symptoms after increased dose
- ) Symptoms disappearing/reappearing when drug stopped/restarted
128
What is the scheme for reporting ADRs?
Yellow card scheme
129
What is substance use?
The ingestion of a substance that affects the CNS which then leads to behavioural and psychological changes
130
What does dependence refer to?
The effects of withdrawal (cravings, euphoria)
131
What does addiction refer to?
Physical and psychological dependence
132
What does tolerance mean?
The body needs more of the drug for the same effect
133
Give 3 factors that influence drug response
- ) Food
- ) Alcohol
- ) Smoking
- ) Complementary medicines
- ) Medial herbalism
- ) OTC medicines
134
What is homeopathy?
Using small doses of natural substances that would produce symptoms of the illness in large amounts
135
What is the placebo effect?
Beneficial effect produced by positive expectation of homeopathic therapy, not by the therapy itself
136
What is allopathy?
The treatment leads to opposite effects of the symptoms (coughing to no coughing)
137
Which opioid does not have the desired effect in everyone?
Codeine
138
How do opioids work? (3)
- ) Inhibit release of pain transmitters at the spinal cord and midbrain
- ) Modulate pain perception in higher centres
- ) Change emotional perception of pain
139
What drug to we give to reverse an opioid overdose?
Naloxone
140
What is a pro-drug?
A drug that doesn't work until it is metabolised
141
Give an example of a pro-drug
Codeine
142
What do the names of corticosteroids usually end in?
Sone
| Dexamethasone
143
What do the names of monoclonal antibodies usually end in?
Mab
| Reslizumab
144
What do the names of bronchodilators usually end in?
Terol
| Salmeterol
145
What do the names of kinase inhibitors usually end in?
Nib
| Nintendanib
