Lecture 1 Flashcards
(109 cards)
1
Q
What is pharmacology?
A
the study of substances that interact with living systems through chemical processes (what drug does to body)
2
Q
binding to regulatory molecules does what?
A
activates/inhibits normal physiological process
3
Q
these substances includes what?
A
chemicals administered to achieve a beneficial therapeutic effect on some process within the patient
4
Q
What is a drug?
A
any substance that
1) affects living processes
2)inhibits or stimulates a physiological process
3) is used in the prevention, diagnoses, alleviation, treatment, or cure of a disease
5
Q
What is Medical Pharmacology?
A
the science of substances used to PREVENT, DIAGNOSE, and TREAT disease
6
Q
What is Toxicology?
A
the branch of pharmacology that deals with the UNDESIRABLE effects of chemicals on living systems, from individual cells to complex ecosystems
7
Q
what are the 3 branches of pharmacology?
A
-pharmacodynamics
-pharmacokinetics
-pharmacotherapeutics
8
Q
what is pharmacodynamics?
A
the study of the biochemical and physiological effects of drugs
9
Q
what is pharmacokinetics?
A
the study of ADME of drugs or the disposition of drugs in the body
10
Q
what is pharmacotherapeutics?
A
the use of drugs to prevent and treat diseases
11
Q
what is a receptor?
A
a drug molecule interacts with a specific molecule in the biologic system that plays a regulatory role
12
Q
Endogenous means
A
-hormones
drugs may be SYNTHESIZED within the body
ex: insulin, epinephrine,norepinephrine
13
Q
Exogenous means
A
- may be chemicals NOt made by the body
14
Q
Poisons are drugs that have ___ effects
A
harmful
15
Q
what are toxins?
A
POISONS or biologic origin synthesized by plants or animals
16
Q
what are examples of inorganic poisons?
A
cyanide, lead, arsenic
17
Q
where is a drug often administered?
A
at a location distant from its intended site of action
18
Q
Practical Drugs ***
A
should be INACTIVATED OR EXCRETED from the body at a reasonable rate so that it’s actions will be of appropriate duration
19
Q
what does a drug need in order to interact chemically with its receptors?
A
appropriate
-size
-electrical charge
-shape
-atomic composition
20
Q
at room temperature drugs may be
A
-solid ( aspirin, atropine)
-liquid (nicotine, ethanol)
-gas (nitrous oxide)
THESE ROUTES INFLUENCE THE BEST ROUTE OF ADMINISTRATION
21
Q
what are the various classes of organic compounds?
A
-carbohydrates
-proteins
-lipids
22
Q
T/F: Many drugs are weak acids or bases
A
True
23
Q
what are the 3 types of forces or bonds?
A
-covalent (irreversible)
-ionic (electrostatic, hydrogen)
-hydrophobic
24
Q
T/F: Covalent bonds are very strong
A
True
25
what are covalent bonds?
DNA alkylating agents used in chemotherapy to disrupt cell division in neoplastic tissue
26
what are electrostatic bonding?
-much more common than covalent bonding in drug-receptor interactions
can be:
1) relatively strong linkages between permanently charged ionic molecules to
2) weaker hydrogen bonds
3) very weak induced-dipole interactions such sd vsn der waals forces and simialr phenomena
27
T/F: electrostatic bonds are stronger than covalent bonds
false
28
what are hydrophobic bonds?
they are quite weak and are important in the interactions of highly lipid-soluble drugs with the lipids of cell membranes and in the interaction of drugs with the internal walls of receptor 'pockets'
29
the drug's shape is _____ to that of the receptor site
complementary
30
Chirality (stereoisomerism)
-refers to a molecule with a center of three-dimensional asymmetry
31
Enantiomers are chemically identical BUT
not necessarily pharmacology identical
32
Enantiomers
-molecules having opposite shapes
-pairs of molecules existing in forms that are mirror images to each other but cannot be superimposed
33
enantiomers have....
-same physical property (except optical)
-same chemical property (except rxn with other enantiomers)
-Differing pharmacological properties (bc of drug shape)
34
EX: Ketamine is an intravenous anesthetic, so the (+) enantiomer is a more _____ anesthetics and less ____ than the (-) enantiomer
potent, toxic
35
T/F: one drug enantiomer is often more susceptible than the other to drug-metabolizing enzymes
TRUE
bc enzymes are usually stereospecific
36
Rational drug designs
implies the ability to predict the appropriate molecular structure of a drug on the basis of information about its biologic receptor
37
pharmacodynamic processes
- the actions of the drug on the body
-these properties determine the group in which the drug is classified -plays a major role in deciding whether that group is that group is the appropriate therapy for a system or disease
38
know this slide ig
39
Agonist
-bind to and activate the receptor in some fashion
-this directly or indirectly brings about an effect
-increase blood
40
Antagonist
-binds to the receptor but do not activate it
-can't produce effects on its own
-decrease blood
41
Chemical antagonists
-chemical interactions
-may directly interact with other drugs
42
a few drugs known as ______ agents interact almost exclusively with water molecules
osmotic
43
know this slide
44
Agonist drugs do what?
-bind to and activate the receptor in some fashion
45
Antagonist drugs do what?
-bind to a receptor and prevent (agonist) binding by other molecules
-decreases effect of antagonist
46
what is the antagonist of acetylcholine?
atropine
-reduces the effects of Ach and similar drugs in the body
47
how do some drugs mimic agonist drugs?
by inhibiting the molecules responsible for terminating the action of an endogenous agonist
ex: ach inhibitors slow the destruction of endogenous ach
48
what are partial agonists?
-kind of acts like antagonist in presence of a full agonist
-50% less effect
49
when a agonists is bound it does what?
it stabilizes
50
inverse agonist
-the inactive drug will stabilize the inactive drug conformation (opposite effect)
-has a different pathway
51
when the drug effects lasts only as long as the drug occupies the receptor....
dissociation of the drug from the receptor automatically terminates the effect (for drugs that are reversible & have dissociation)
52
when the action of the drug persists after the drug has dissociated....
some coupling molecule is still present in activated form
53
when a drug binds covalently to the receptor, the effect....
may persist until the DRUG-RECEPTOR COMPLEX IS DESTROYED AND THE NEW RECEPTORS ARE SYNTHESIZED
- we basically have to have degradation and synthesize the drug so the activity stops
54
many receptor-effector systems incorporate _______ mechanisms for preventing excessive activation when drug molecules continue to be present for long periods of time
desensitization
-basically you keep on giving a drug, some get drunk easily, but if your body is used to it doesn't produce same effect, body has mechanism to say stop and not acting anymore, so ur body desensitize the receptor
55
To function as a receptor, you need to be
-selective
-functional and effective
56
T/F: not all these endogenous molecules are regulatory molecules
True
basically not all are receptors
57
Plasma albumin is an INERT binding site, what is its significance?
it affects the distribution of drug within the body and will determine the amount of free drug in the circulation
*both of these factors have pharmacokinetic importance
58
A drug should be able to reach its intended site of action after administration by which route?
convenient route
59
if a drug is given intravenously (iv), what happens?
It circulates in the blood directly to target blood vessels in another part of the body where they bring about useful effects
60
what happens when you insert a drug from it's site of administration?
the drug gets ABSORBED into the blood and DISTRIBUTED to its site of action
it can also get ELIMINATED at a reasonable rate by metabolic inactivation, by excretion from the body, or by a combination of these processes
61
what are the 4 primary mechanisms proceeded by drug permeation?
1) Aqueous Diffusion
2) Lipid Diffusion
3) Special carriers
4) Endocytosis and exocytosis
62
T/F: Passive diffusion in an aqueous or lipid medium is common
True
63
_____ play a role in the movement of many drugs, especially with molecules that are too large to diffuse readily
Active Processes
64
what is lipid diffusion?
lipid permeation is the most important limiting factor for drug permeation because of the large number of lipid barriers that separate the compartments of the body
65
what is lipid:aqueous coefficient
determines how readily the molecule moves between aqueous and lipid media
66
the ability to move from aqueous to lipid does what?
varies with the pH of the medium because charged molecules attract water
67
T/F: Lipophilic is passive diffusion
true
68
Fick's Law of diffusion
The passive flux of molecules down a concentration gradient
FLUX= (c1-c2) x [ Area x Permeability coefficient] / Thickness
Flux= the number of molecules per unit time
Area= the area across which diffusion is occurring
C1= the higher concentration
C2= the lower concentration
*the thickness is the thickness of the diffusion path
69
Facilitated Special Carriers exist for certain substances that are
important for cell function and too large or too insoluble in lipid to diffuse passively through members
ex: peptides, amino acids, glucose
70
Special carriers bring about movement by _______ transport or ______ diffusion , and unlike passive diffusion, are _____ and _____
active, facilitated
saturable, inhibitable
71
Permeation
Endocytosis & Exocytosis
Endocytosis: the process by which the substance is engulfed by the cell membrane and carried into the cell by pinching off the newly formed vesicle inside the membrane
*this is basically passive diffusion*
Exocytosis: secretion of many cells
ex: many neurotransmitter substances are stored in membrane-bound vesicles in nerve endings to protect them
from metabolic destruction in the cytoplasm
72
Henderson-Hasselbalch Equation
the electrostatic charge of an ionized molecule attracts water dipoles and results in a polar, relatively water-soluble and lipid-insoluble complex
-charged: hydrophilic
-uncharged: lipophilic
*basically tells you about lipophilicity & permeation
73
since lipid diffusion depends on relatively high lipid solubility, what happens to the ionization of drugs?
ionization of drugs may markedly reduce their ability to permeate membranes
74
a weak acid is a neutral molecule that can reversibly dissociate into what?
an anion (a negatively charged molecule) and a proton ( a hydrogen ion)
75
a weak base can be defined as what?
a neutral molecule that can form a cation ( a positively-charged molecule) by combining with a proton.
R + H+ --> RH+
76
the law of mass action requires what?
The law of mass action requires that this reaction moves to the left in an acid environment (low pH, excess protons available) and to the right in an alkaline environment).
RH ---> R- + H+ RH+ ---> R + H+
77
log [protonated]/[unprotonated] = pKa – pH
The equation applies to both acidic and basic drugs. confirms that the lower the pH relative to the pKa, the greater will be the fraction of drug in the protonated form
78
since the uncharged form of a weak acid is the more lipid-soluble, what happens?
more of a weak acid will be lipid soluble at acidic pH
79
what happens to more of a basic drug in lipid soluble form?
will be lipid soluble @ alkaline pH
80
know these equations
81
manipulation of drug excretion occurs where?
at the kidney
82
almost all drugs are filtered where?
glomerulus
83
If a drug is in a lipid-soluble form during its passage down the renal tubule, what happens?
a significant fraction will be reabsorbed by simple passive diffusion
84
if you want to accelerate excretion of the drug, what should happen
it is important to prevent its reabsorption from the tubule this can often be accomplished by adjusting urine pH to make certain most of the drug is in the ionized state
*noncharged= excreted
*charged= very hydrophilic
* highly lipophilic don't get eliminated quickly
85
weak acids are excreted faster where?
alkaline urine
86
weak bases are usually excreted faster where?
acidic urine
87
know this chart ig
88
how many drug groups are there?
70
89
Structure Activity Relationships
Understanding the relationship between drug structures and biological activities forms the basis of rational drug design
90
what are prototype drugs?
identify the most important characteristics of the group
91
types of FDA applications?
Investigational New Drug (IND)
New Drug Application (NDA) - clinical trials are done
Abbreviated New Drug Application (ANDA)- just do a single study
Over-the-counter (OTC) - more extensive studies
Biologic License Application (BLA)- basically shows the activity
92
Preclinical phase includes what?
Target discovery
Synthesis of lead compound
Rational drug design
Chemical libraries (natural products, chemical banks)
Derivatives and analogs
93
In Vitro drug screening
Cells, enzyme assays, isolated tissues,
P450 studies
test tubes
94
In vivo drug screening
Effect on organ systems, disease models
Efficacy testing, study of adverse effects
animals
95
LD50 means what?
half of the population
96
Acute toxicity
Usually two species, two routes. Determine the no-effect dose and the maximum tolerated dose. In some cases, determine the acute dose that is lethal in approximately 50% of animals.
97
Subacute or subchronic toxicity
Three doses, two species. Two weeks to 3 months of testing may be required before clinical trials. The longer the duration of expected clinical use, the longer the subacute test. Determine biochemical, physiologic effects
98
Chronic toxicity
Rodent and at least one nonrodent species for ≥ 6 months. Required when drug is intended to be used in humans for prolonged periods. Usually run concurrently with clinical trials. Determine same end points as subacute toxicity tests.
99
Effect on reproductive performance
Two species, usually one rodent and rabbits. Test effects on animal mating behavior, reproduction, parturition, progeny, birth defects, postnatal development.
100
Carcinogenic potential
Two years, two species. Required when drug is intended to be used in humans for prolonged periods. Determine gross and histologic pathology.
*does it cost cancer ----> mutation
101
Mutagenic potential
Test effects on genetic stability and mutations in bacteria (Ames test) or mammalian cells in culture; dominant lethal test and clastogenicity in mice.
*bacteria
102
what are the limitations of preclinical testing?
Time consuming, expensive
Large number of animals needed
Extrapolation of data to human diseases predictive for many but not for all
Rare adverse effect identification unlikely (statistical reason)
103
Confounding Factors in Clinical Trials
The variable nature and history of diseases.
Presence of other diseases/ risk factors
Subject and observer bias
Placebo effect
Single bind study, double blind study
Adherence to medication
104
Crossover Design
Alternative treatment with test drug, placebo, and standard treatment.
105
Meta analysis
Rigorous evaluation and grouping of similar studies to increase number of subjects and statistical power.
106
Phase 1
Small no. (20-100) healthy volunteers.
If drug has significant toxicity, then volunteer patients with the disease
Safe range of drugs
Detect predictable toxicities
107
Phase 2
Target disease patients (100-200)
Single-blinded placebo design
Special clinical centers
High rate of drug failure (~75%)
108
Phase 3
Larger number of patients with target disease
Double-blinded and crossover technique
Specialists in disease carry out studies
Drugs used are in same format as for marketing
Immunologic effects are noted
109
