Intro to Pharmacology Flashcards
(135 cards)
1
Q
A molecule on the surface of the cell (or inside it) that receives an external signal and produces some type of cellular response is known as a ________-__________ interaction.
A
drug-receptor
2
Q
A protein recognition molecule for a chemical mediator
A
Receptor
3
Q
“Ligand-binding theory” describes how the right molecule binds to the receptor, which leads to a conformational change in the ________, leading to cellular changes.
A
protein
4
Q
Drugs can change the ________ and _________ of body functions
A
amplitutde and speed
5
Q
___________ prevent the binding of endogenous compounds.
A
Antagonists
6
Q
The site on a receptor where a non-competitive antagonist binds is called an
A
allosteric binding site or allosteric effect
7
Q
Name some examples of competitive reversible antagonists
A
Beta blockers, atropine, naloxone, and Prazosin
8
Q
Drugs that have opposing physiological actions at different receptors
A
Functional or physiological antagonists
9
Q
The effect of adrenaline on histamine produced in anaphylaxis is what type of antagonism?
A
Functional or physiological
10
Q
What is a chemical antagonist?
A
A substance that binds to and inactivates the agonist itself (as opposed to something that binds to an inactivates a receptor)
11
Q
This describes how tightly a ligand binds to a receptor
A
Affinity
12
Q
The probability that a drug molecule will bind to an available receptor at any given instant in time is expressed numerically as the _______ ________ (__)
A
dissociation constant (Kd)
13
Q
The dissociation constant is the concentration of ________ required to occupy ____% of the available receptors.
A
agonist, 50%
14
Q
The lower the dissociation constant (Kd), the _________ the affinity.
A
higher
15
Q
The ability of an agonist to produce a biological effect
A
Drug efficacy
16
Q
Drug efficacy is expressed numerically as
A
R Max (maximum response)
17
Q
What numerical expression is used to compare whether one drug is as effective as another?
A
R Max
18
Q
A measure of drug activity expressed in terms of the amount required to produce an effect of given intensity
A
Drug potency
19
Q
Drug potency depends on both _______ and ________.
A
affinity, efficacy
20
Q
One measure used to look at drug potency is _____
A
EC 50
21
Q
Half maximal effective concentration is represented as .
A
EC 50
22
Q
This is the concentration of a drug, anitbody, or toxicant which induces a response halfway between the baseline and maximum after a specified exposure time
A
EC 50
23
Q
The ________ the EC50, the _________ the potency.
A
lower, higher
24
Q
How can drugs be classified? (List 3 ways)
A
- Site or mode of action
- Therapeutic use
- Chemical structure
25
"What the body does to the drug"
Pharmacokinetics
26
"What the drug does to the body"
Pharmacodynamics
27
List the four main phases of pharmakokinetics (ADME)
Absorption
Distribution
Metabolism
Excretion
28
This is the process of transfer of the drug from the site of administration into the general/systemic circulation.
Absorption
29
How much of the drug, if taken orally, reaches the systemic circulation after first-pass metabolism?
20%
30
The process by which a compound is transferred from the general circulation to other parts of the body and into the tissues is known as
Distribution
31
The process by which a drug is chemically altered in a way that facilitates its action or enhances its elimination from the body
Metabolism
32
The main site of drug metabolism in the body
the liver
33
Name the sites of drug metabolism in the body
```
Liver
Kidneys
GI tract
Lungs
Skin
```
34
The superfamily of enzymes that metabolise >75% of drugs used in medicine
Cytochrome p450
35
What is the effect on the drug in the body with enzymatic induction?
Faster clearance
36
What is the effect on the drug in the body in cases of enzymatic inhibition?
Accumulation of drug in the system
37
The process by which drugs or their metabolites are removed from the body
Excretion
38
What are routes of drug excretion?
Renal, biliary, respiratory, dermal, faecal
39
Pharmacodynamics mainly has to do with the interaction of the drug with rthe body's _______
proteins
40
What occurs when the drug interacts with the same type of receptor at different sites around the body, and/or interacts with more than 1 type of receptor?
Side effects
41
True or false: No drug is free of side effects
True
42
Individual drug response can be influenced by
```
Age
Gender
Genetics
Previous exposure
Disease
Interactions
Body composition
Variability in PK and PD
```
43
Briefly list the key stages of drug development
```
Non-clinical testing
Phase I, II, and III clinical studies
Registration with MHRA
Launch phase
Post-launch research and development
```
44
What is "2 species toxicology" in the non-clinical testing phase?
Testing on 1 rodent species and 1 non-rodent species for a minimum of 14 days to determine PK and ADME
45
What does the non-clinical testing phase look for?
```
Effects on:
Pharmacokinetics
ADME
Pharmacodynamics
Local tolerance/phototoxicity/immunotoxicity
Genotoxicity
```
46
This phase of clinical trials tests a new drug on a small group of humans- usually multiples of 10, in healthy volunteers or patients affected with the particular disease.
Phase I clinical trials
47
Phase I trials look for:
```
*SAFETY/TOLERABILITY*
Data on PK/PD
Guide to therapeutic dose
Drug/food interactions
Drug/Drug interactions
QT prolongation potential
```
48
Why would ECG's be performed on volunteers in Phase I clinical trials?
To look for QT prolongation- abnormal heart rhythm
49
How long do Phase I trials typically last?
1-4 months
50
Distribution of phase I clinical trials?
Single centre, one country
51
This phase of clinical trials involves several hundred partipants (multiples of 100) who are living with the condition the new medication is meant to treat.
Phase II clinical trial
52
These are randomised clinical trials to show that the candidate drug results in a biological and/or clinical change associated with the disease or mechanism of action.
Phase II clinical trial
53
This phase of clinical trial enables dose selection (most effecacious dose) for the next phase
Phase II clinical trial
54
How long do phase II clinical trials typically last?
3-6 months
55
This phase of clinical trials is known as the "therapeutic exploratory" phase
Phase II
56
This phase of clinical trials usually involves multiples of 1000 patients who have the condition that the new medication is meant to treat
Phase III
57
Trials in phase III can last for __________
several years
58
The main purpose of this phase of clinical trials is to evaluate how the new medication works in comparison to existing medications for the same condition.
Phase III
59
How many randomised controlled trials take place in Phase III?
At least two
60
What are the end points of Phase III clinical trials?
*Safety is essential!*
Regulatory acceptance
Patient reported outcomes for QOL
61
In phase III clinical trials, the safety and efficacy of the new drug is compared to
the current standard of care
62
Distribution of phase III clinical trials?
>10 centres, multinational
63
This is the phase where further scientific data is collected on efficacy or safety objectives. Can look for new disease indications.
Phase IIIb or phase IV
64
Prior to the invention of antibiotics, _________ __________ were the leading cause of death.
infectious diseases
65
What are the three ideal characteristics of antiobiotic therapies?
1. Selective toxicity
2. Slow emergence of resistance
3. No interference with other drugs
66
Name some of the PATIENT FACTORS to consider that might affect either the PK or the patient response to treatment
Decreased liver or kidney function
| Whether they are immunocompromised
67
List the six principal mechanisms of antiobiotic actions
1. Cell wall
2. DNA replication
3. RNA synthesis
4. Antimetabolites
5. Protein synthesis against Rb 50
6. Protein synthesis against Rb 30
68
What is the mneumonic for remembering protein synthesis ihibitors?
Ma life AT cell
Macrolides- Lincosamides (clindamycin)- Aminoglycoside, Tetracyclines- Clindamycin, Erythromycin
50s 30s 50s
69
NITu MET SULtan in CEPtember with a FLUid PEN and a CAR
```
Nitrofurans = DNA synthesis inhibitor
Metronidazole= DNA replication inhibitor
Sulfonamides = Antimetabolites
Cephalosporin = cell wall inhibition
Fluoroquinolone = DNA replication
Penicillin= cell wall inhibition
Carbapenem= cell wall inhibition
```
70
Name the two types of drugs affecting the bacterial cell wall
1. Beta lactams
| 2. Glycopeptides
71
Beta lactams bind bacterial _____________
transpeptidases
72
What are the enzymes that are essential for peptidoglycan synthesis?
Transpeptidases
73
Beta lactams prevent the cross-linking peptides from binding to the
tetrapeptide side chains
74
Are beta lactam drugs bactericidal or bacteristatic?
Bactericidal
75
The two main classes of beta lactams commonly used in practice include:
1. Penicillins
| 2. Cephalosporins (Cephalexin, Cefuroxime)
76
The beta lactam drugs generally reserved for difficult to treat infections include
Carbapenems and monobactams
77
Vancomycin, Teicoplanin, and Telavancin are in what type pf drug class?
Glycopeptides (inhibit cell wall synthesis)
78
When are glycopeptides used?
Only for Gram + bacteria, in serious infections where bacteria is producing beta-lactamase. Generally administered IV.
79
What is the treatment for C.Difficile infection?
Oral Vancomycin
80
What is the main adverse effect associated with glycopeptides?
Nephrotoxicity
81
Ciprofloxacin, Nalidixic acid, Norfloxacin, and Ofloxacin are what class of drugs?
Quinolones
82
Mechanism of action for this drug class: Inhibits DNA gyrases needed for DNA supercoiling, replication and separation
Quinolones
83
What types of infections are quinolones used for?
UTI (not first line), pseudomonal infection, GI infections, STI's
Gram negative, Gram positive, anaerobes, mycoplasma, chlamydia
84
Metronidazole is a pro-drug. This means that only _________ organisms can metabolise it into its active form. Metabolites that are produced are toxic to the DNA.
anaerobic
85
List some of the potential adverse effects associated with extended use of metronidazole
Mutagenic, carcinogenic, teratogenic
86
Drug that inhibits RNA synthesis
Rifampicin
87
Which drug is bactericidal in mycobacteria?
Rifampicin
88
How does Rifampicin inhibit mRNA synthesis?
By binding to RNA polymerase
89
Rifampicin is a strong inducer of which enzyme?
Cytochrome p450
90
Which drug produces an unusual side effect of orange-coloured saliva, tears, sweat, and urine?
Rifampicin
91
Trimethoprim and sulfonamides are what type of drugs? (MOA?)
Anti-metabolites
92
Trimethoprim and sulfonamides-
| bacteriocidal or bacteriostatic?
Bacteriostatic
93
Co-trimoxazole (Trimethoprim combibned with sulfamethoxazole)- Bacteriocidal or bacteriostatic?
Bacteriocidal
94
Which group of drugs work by inhibiting synthesis of tetrahydrofolate?
Anti-metabolites:
| Trimethoprim & sulfonamides
95
What are the classes of drugs that inhibit the 30s subunit of the bacterial ribosome?
AT
Aminoglycosides
Tetracyclines
96
What is the class of drugs that inhibit the 50s subunit of the bacterial ribosome?
Macrolides
97
What type of drug is gentamycin?
Aminoglycoside
98
Aminoglycosides like gentamycin- bactericidal or bacteristatic?
Bactericidal
99
Side effects associated with gentamycin (aminoglycosides)?
Nephrotoxicity and ototoxicity
100
Are Tetracyclines bactericidal or bacteriostatic?
Bacteriostatic
101
Which type of drug has the following side effects: Phototoxicity, chelation of metal ions leading to discolouration of teeth, bone growth inhibition?
Tetracyclines
102
Erythromycin, Azithromycin, and Clarithromycin belong to which drug class?
Macrolides
103
What is the MOA of macrolide antibiotics?
Inhibit protein synthesis at the 50s subunit of bacterial ribosomes (70s)
104
Which class of broad-spectrum antibiotic is often prescribed in cases of penicillin allergy
Macrolides
105
What types of bacteria are macrolides effective against?
Both gram positive and gram negative- broad spectrum
106
The ability of bacteria and other microorganisms to resist the effects of an antibiotic to which they were once sensitve.
Antiobiotic resistance
107
Bacteria produce _____ _____________ which catalyse the hyrolysis of the beta lactam ring, inactivating beta lactam antibiotics.
beta lactamases
108
Describe the ways in which bacteria can develop resistance to antibiotics
```
Mutations in cell genes
Gene transfer (vertical or horizontal)
Inactivation or modification of the antibiotic
Alteration of microbial enzymes
Alteration of the target
Reduced uptake of the antibiotic
Development of alternative pathways
```
109
Drug class of amoxicillin
Beta lactam (chemically modified penicillin)
110
MOA of Amoxicillin
Inhibition of cell wall synthesis
111
Activty of Amoxicillin
Broad spectrum. Used to treat sore throat, skin infections, respiratory infections, UTI's
112
Half life of Amoxicillin
One hour
113
Excretion of Amoxicillin
Urine
114
Interactions with Amoxicillin
Can increase levels of other protein-bound drugs
115
Adverse effects of Amoxicillin
ALLERGY.
| Damage to commensal microflora (GI disturbance, thrush)
116
Clarithromycin drug class
Macrolide
117
Clarithromycin MOA
Inhibition of protein synthesis in the 50s subunit of bacterial ribosome
118
Activity of Clarithromycin
Broad spectrum. Similar to penicillin. Used in cases of Penicillin allergy
119
Clinical uses of Clarithromycin
Similar to amoxicillin (sore throat, skin infections, resp infections, UTI) also used in CHLAMYDIA
120
Protein binding of Clarithromycin
High
121
Metabolism of Clarithromycin
Hepatic
122
Half life of Clarithromycin
1-6 hours
123
Excretion of Clarithromycin
Metabolites in bile
124
Adverse effects of Clarithromycin
Nausea and diarrhea. May alter cardiac conduction (arrythmias)
125
Vancomycin drug class
Glycopeptide
126
MOA of Vancomycin
Inhibition of cell wall (peptidoglycans)
127
Activity of Vancomycin
ONLY GRAM POSITIVE BACTERIA
128
Vancomycin has a ___________ therapeutic window.
narrow
129
GI absorption of Vancomycin
Very low
130
Protein binding of Vancomycin
50%
131
Metabolism of Vancomycin
None
132
Half life of Vancomycin
4-8 hours
133
Excretion of Vancomycin
Urine
134
Major adverse effects of Vancomycin
Nephrotoxicity and ototoxicity
135
Interactions of Vancomycin
Other ototoxic or nephrotoxic drugs
