Module 1 Flashcards
1
Q
Science of substances used to prevent, diagnose, and treat disease.
A
Medical pharmacology
2
Q
Ancient Hindu text describes 760 medicinal herbs.
A
Susruta
3
Q
Wrote “Kitab Al Shifa “ which considered 760 drugs and is the chief guide to medical sciences from the 12th century to the 16th century.
A
Avicenna/ Abu Ali Al Hussain Ibn Sina (980-1037)
4
Q
The science of drug preparation and the medical use of drugs - developed as the precursor to pharmacology.
A
Materia Medica
5
Q
Developed methods of experimental physiology and pharmacology.
A
Francois Magendie
6
Q
Investigated the plant extract Curare(muscle relaxant) and proposed site of action of this agent.
A
Claude Bernard
7
Q
Proposed: Corpora non agunt nisi fixate = “Agents do not act unless they are bound” (drug-receptor binding)
A
Paul Ehrlich
8
Q
Any substance that produces a change in biologic function through its chemical actions.
A
Drugs
9
Q
Single, active chemical entity that is used for diagnosis, prevention and treatment of diseases.
A
Drug
10
Q
Drug that acts as an activator
A
Agonist
11
Q
Drug that acts as an inhibitor
A
Antagonist
12
Q
A specific molecule in the biologic system that plays a regulatory role. Drug molecules interact with this molecule.
A
Receptor
13
Q
Drugs synthesized within the body
A
Hormones
14
Q
Chemicals not synthesized in the body
A
Xenobiotic (Greek: Xenos = stranger)
15
Q
Drugs that are exclusively harmful
A
Poison
16
Q
Defined as poisons of biologic origin,ie, synthesized by plants or animals, in contrast to inorganic poisons such as lead and arsenic
A
Toxins
17
Q
Nature of drug that determines the best route of administration
A
Physical nature: solid, liquid, gas
18
Q
Nature of drug that determines specificity of action
A
Drug size: MW 100 - MW 1000
19
Q
Bond that is very strong and in many cases not reversible under biologic conditions
A
Covalent bond
20
Q
Bonds that are usually quite weak and are probably important in the interactions of highly lipid-soluble drugs.
A
Hydrophobic bond
21
Q
The actions of the drug on the body
A
Pharmacodynamics
22
Q
The actions the body on the drug
A
Pharmacokinetics
23
Q
When drugs bind to the same receptor molecule but do not prevent binding of the agonist.
A
Allosteric inhibition
24
Q
Effect in which even in the absence of any agonist, some receptor pool must exist in the activated form some of the time and may produce the same physiologic effect as agonist-induced activity
A
Constitutive activity
25
The study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body process.
Pharmacology
26
Largely determine the quantitative relations between dose or concentration of drug and pharmacologic effects
Receptor
27
The specific binding region of the receptor macromolecule has a relatively high and selective affinity for the drug molecule
Receptor site
28
Molecules that translate the drug-receptor interaction into a change in cellular activity. This include your secondary messenger system, protein kinases, etc.
Effector
29
Graph of the response versus the drug concentration. Response of a particular receptor-effector system is measured against increasing concentrations of a drug
Graded dose-response relationship
30
Concentration of drug required to bind 50% of the receptor sites. Useful measure of the affinity of a drug molecule for its binding site on the receptor molecule.
Kd
31
A maximum amount of drug or radiology do which can bind specifically to the receptors in a membrane preparation. Can be used to measure density of the receptors in a particular preparation
Bmax
32
Ability of drug to bind to receptor
Affinity
33
Greatest effect an agonist can produce if the dose is taken to the highest tolerated level
Emax
34
Emax is determined mainly by:
Nature of the drug
Receptor
Associated effector
35
Amount of drug needed to produce a given effect
Potency
36
Effective concentration in specific person
EC50
37
Effective dose in the population
ED50
38
Potency is determined mainly by:
Affinity of the receptor to the drug
| Number of receptors available
39
Defined as the minimum dose required to produce a specified response determined in each member of the population.
Quantal - dose response
40
The dose that produces a quantal effect (all or nothing) in 50% of the population that takes it
Median effective dose (ED50)
41
Dosage of the drug where side effects starts to manifest
Median toxic dose (TD50)
42
Dosage there there is death of the population
Median lethal dose (LD50)
43
Exist if the maximal drug response (Emax) is obtained at less than 100% occupation of the receptors (Bmax)
Spare receptor
44
A drug capable of fully activating the effector system when it binds to the receptor conformation
Full agonist
45
Drug that produces less than the full effect, even when it has saturated the receptors. In the presence of a full agonist, it acts as an inhibitor
Partial agonist
46
Bind with equal affinity of the activated and inactivated states. Prevents deviation from the level of constitutive activity
Neutral agonist
47
Have a much higher affinity for the inactive state than for the active state. It decreases or abolishes any constitutive activity
Inverse agonist
48
The property of increasing doses of a given medication to have progressively smaller incremental effect. The phenomenon in which a drug reaches a maximum effect, so that increasing the drug dosage does not increase its effectiveness
Ceiling effect
49
Drugs that bind to, or very close to, the agonist receptor site. Does exactly not activate the effector system for that receptor
Competitive antagonist
50
Bind the receptor without shifting the activated and inactivated equilibrium. Retains the status quo
Neutral antagonists
51
Appear to decrease the efficacy of the agonist. It causes a downward shift of the maximum
Irreversible antagonist
52
Drugs that act at the aldosterone site of the receptor may bind reversible or irreversibly. They do not compete with agonists for binding at the active site
Non-competitive antagnonist
53
Binds to a different receptor molecule. Produces an effect opposite to that produced by the drug it antagonizes
Physiologic antagonists
54
Determined from quantal-dose response curve. It represents an estimate of the safety of a drug
Therapeutic index
55
Measure the clinical drug effectiveness for a patient. Describes the dosage range between the minimum effective therapeutic concentration or dose and the minimum toxic concentration or dose.
Therapeutic window
56
5 tea of signaling mechanism
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Transmembrane diffusion
Transmembrane enzyme receptor
JAK-STAT
Gated transmembrane channels
G-protein coupled receptors
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57
Complexes translocate to the nucleus, where they interact with response elements in spacer DNA. slower in onset but longer in duration. (e.g steroid hormones)
Intracellular receptors
58
Mimic or antagonize the actions of endogenous Logan's. Regulate flow of ions through excitable membranes. (e.g nicotine, ach)
Membrane receptors directly coupled to ion channels
59
Typically serpentine. Seven transmembrane spanning domains, the third of which is coupled to the G-protein effector mechanism
Receptors linked via coupling proteins to intravenous are effectors
60
Binding of agonists to receptors linked to this protein increases cAMP production
Gs protein
61
Binding to receptors linked with this protein decreases cAMP production
Gi protein
62
Activates phospholipids C. Releases the second messengers IP3 and DAG
Gq protein
63
Receptors for cytokines
Janus kinases (JAKs)
64
Frequent or continuous exposure to agonists often results in short term diminution of the receptor response
Tachyphylaxis
65
The rate at which a drug reaches its site of action depends on two rates:
Absorption and distribution
66
Passage of the drug from its site of administration into the blood
Absorption
67
Delivery of the drug to the tissues
Distribution
68
Most important transport mechanism for foreign molecules. It passes from a region of higher to lower concentration
Passive diffusion
69
Passage to different pores of membrane (i.e via fenestrations)
Filtration
70
Mechanism of drug transfer against a concentration gradient. It is energy-dependent, saturable and selective-carrier mediated
Active transport
71
Mechanism of drug transfer down a concentration gradient. It does not require energy, it is saturable and selective-carrier mediated
Facilitated diffusion
72
Four parameters that influence the rate of diffusion of drugs
Concentration gradient
Surface area
Permeability coefficient
Thickness
73
Expression of the ability of a drug to diffuse across membranes. Ratio of concentration of a drug in two phases: oil and water
Lipid-water partition coefficient
74
In this area of absorption, weak bases will be ionized resulting to poor absorption while weak acids will be un-ionized and are absorbed well
Gastric absorption
75
In this area of absorption, weak acids will be ionized resulting to poor absorption while weak bases will be un-ionized and are absorbed well
Intestinal absorption
76
Fraction of the drug which is available in the systemic circulation and obtained by comparing the area under the curve of drugs with dose that of IV
Bioavailability
77
Rate and availability of two products after administration are similar in the same doses.
Bioequivalence
78
Implies the same amount of same active substance, in the same dosage for. For that same route of administration and is identical in strength and concentration
Pharmaceutical equivalence
79
Criteria for both bioequivalence and pharmaceutical equivalence are met
Therapeutic equivalence
80
General principle: speed of effect of the different routes of drug administration
IV > IM > SC > Oral
81
The extent of distribution of a drug is quantified by this parameter. The volume of fluid required to dissolve the amount of drug in the body to give the same concentration as that in the plasma at the same time.
Apparent volume of distribution (Vd)
82
Factors affecting the rate of distribution
Lipids solubility
Degree of ionization
Molecular weight
Blood flow
83
Factors affecting the extent of distribution
Lipid solubility
Protein binding
Tissue binding
84
What are the processes involved in pharmacokinetics?
Absorption
Distribution
Metabolism
Excretion
85
What are the phases of metabolism?
Phase I - REDOX
| Phase II - CONJUGATION
86
Examples of phase I reactions
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Hydrolysis
Methylation
Dealkylation
Hydroxylation
Desulfuration
Reduction
Oxidation
Deamination
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87
Reactions that are hallmarks of Phase II metabolism
Glucoronidation
Sulfation
Methylation
Acetylation
88
Most important of phase II conjugation reactions. Requires the activated form of glucoronic acid - glucoronic acid uridine diphosphate
Glucoronidation
89
This antibiotic should not be given to infants as this can lead to Grey Baby Syndrome
Chloramphenicol
90
Site of cellular metabolism
Endoplasmic reticulum, specifically smooth ER
91
Primary phase I enzyme system
Cytochrome P450 family
92
Most abundantly expressed cytochrome
CYP3A4
93
Cytochrome expressed only in the fetus
CYP3A7
94
Second most common cytochrome. Known for its propensity to exhibit polymorphisms
CYP2D6
95
Metabolizes several clinically important drugs with narrow T.I (eg Phenytoin, Warfarin)
CYP2C9
96
Inhibitor of CYP2C19
Cimetidine, Ketaconazole
97
Inducer of CYP2A6
Phenobarbital, dexamethasone
98
Primary organ of removal of most drugs
Kidney
99
3 principal processes that determine the urinary excretion of a drug
Glomerular filtration
Tubular secretion
Tubular reabsorption
100
True or False: Almost all drugs that a mother take can be expressed in the milk
True
101
Which of the following is true about the drug concentration time profiles of a drug X when given PO and SL?
A. PO formulation would have a faster rate of absorption.
B. SL formulation would have a longer Tmax
C. Bioavailability of PO > SL
D.
102
Time needed to reach Cmax
Tmax
103
Maximum concentration achieved in the blood
Cmax
104
Used to asses the person's overall exposure to a drug. Also useful in calculating clearance
Area under the Curve (AUC)
105
The time it takes for the drug to be eliminated from the body.
Half-life
106
When the rate of drug entering the body is equal to the rate of drug leaving the body
Steady state
107
How many half-lives does it take to remove 97% of the drug from the body?
Five
108
How many half-lives does it take to reach a steady state?
Five
109
Fraction of administered drug that reaches the systemic circulation
Bioavailability
110
This mechanism limits the efficacy of many drugs when orally taken.
First-pass hepatic metabolism
111
Kinetics resulting from saturable drug transfer, leading to variation of the standard kinetic parameters with drug concentration
Michaelis-Menten kinetics
112
The rate of elimination is independent of the concentration of the drug.
Zero order kinetics
113
The rate of elimination is directly proportional to the drug concentration.
First order kinetic
114
Examples of drugs that undergo zero order kinetic
"PPWHEATS"
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Phenytoin
Phenylbutazone
Warfarin
Heparin
Ethanol
Aspirin
Theophylline
Salicylates
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