Basics of Pharmacology: Pharmacodynamics Flashcards
(115 cards)
1
Q
What is the definition of PHARMACODYNAMICS
A
What the drug does to the body.
2
Q
The pharmacological effect is produced when?
A
When the drug from a complex with the drug receptor.
3
Q
Change in drug effect ______(is or is not) proportional to the change in drug dose or concentration.
A
is not proportional
4
Q
Pharmacodynamics follow the law of
A
Mass action
5
Q
What is mass action
A
The concentration of a ligand plus the concentration of receptors –> Drug -receptor complex change.
6
Q
Receptor theory :LOCK and KEY” hypothesis
A
The drug need to have the key to the receptor (lock). drug need a particular shape to enter lock. (Chemical structure of drug and receptor should match)
7
Q
Lock and key governed by 2 basic concepts
A
Affinity
Intrinsic activtiy.
8
Q
What is Affinity
A
how well a particular compound is drawn into and held a the binding site.
9
Q
What is Intrinsic activity?
A
Describe effect the ligand has when it interacts with a receptor site.
10
Q
What is affinity and intrinsic activity determined by?
A
Chemical structure.
11
Q
Concentration vs response curves
A
relationship between the dose of the drug given and the resulting pharmacologic effect.
12
Q
Concentration vs response curves help described
A
Potency
Slope
Efficacy
Individual responses
13
Q
What is EC 50? What is it a measure of?
A
the concentration associated with 50% of peak drug effect and is a measure of drug POTENCY
14
Q
What is Emax?
A
Maximum possible drug effect and no further increases in drug dose produce a GREATER EFFECT.
15
Q
The smaller EC 50 the (more /less ) ______potent.
A
The MORE POTENT the drug
16
Q
What are the factors affecting POTENCY?
A
Pharmacokinetics (ADME) + affinity to the receptors.
17
Q
Potency refers to :
A
the quantity of drug that must be administered to produce a specific drug effect.
18
Q
Effective Dose (ED) of a drug is
A
The dose required to produce a specific effect
19
Q
The lower the ED the (more/less) potent
A
the more potent
20
Q
What is ED 50?
A
Dose of a drug required to produce a speficic desired in 50% of INDIVIDUALS RECEIVING THE DOSE>
21
Q
What is Median ED 50?
A
Dose of a drug required to produce a speficic desired in 50% of INDIVIDUALS RECEIVING THE DOSE>
22
Q
What is ED 90?
A
Dose of a drug required to produce a specific desired in 90% of INDIVIDUALS RECEIVING THE DOSE
23
Q
Median Lethal dose (LD50)
A
Dose of a drug required to produce DEATH in 50% of INDIVIDUALS RECEIVING THE DOSE
24
Q
The closer the ED and LD are: the more/less dangerous
A
The more diligent you should be with your DOSING
25
Efficacy definition
Measure the INTRINSIC ABILITY of a drug to produce a given physiological effect.
26
Efficacy is more/less ______Important than potency
More
27
What is the Therapeutic index OR
Margin of safety-- the DIFFERENCE between the dose of a drug that produces a desired effect and the dose that produces undesirable effect.
28
What is the TI mathematically?
LD50/ED 50
29
The LARGER THE THERAPEUTIC INDEX, The ______the drug is for administration.
SAFER
30
Therapeutic window
Therapeutic window is the range of steady-state
| concentrations of drug that provides therapeutic efficacy with MINIMAL toxicity
31
INDIVIDUAL VARIATION (meaning)? What can it influence?
Diffrent people have different response, Can influence efficacy and safety of a drug.
32
________lean body mass and ______Body fat tissue increases the Vd of lipid soluble drugs
Decreased: increased
33
****What is decreased in the elderly making them at risk for decrease clearance of opioids, hypnotics and benzo? What consideration should be made?
Decreased CO, liver blood flow and liver metabolic clearance.
Decrease the dose.
34
****A decreased in plasma protein binding does what to the free drug form
Increase the effect of highly protein bound drugs.
35
Classic example of highly drug bound DRUG? What happens with low protein state
Phenytoin; severe phenytoin toxicity may occur.
36
***Myasthenia Travis patients have _______ number of post-synaptic nicotinic receptors on skeletal muscles. They are sensitive to muscle relaxants (e.g. Succynylcholine) that act on the ______ ______ receptors:
Decreased; NICOTINIC ACETYLCHOLINE.
37
****G6PD deficiency-- Certain medication can cause
HEMOLYTIC ANEMIA
38
Warfarin variability --________enzyme and receptor _____
polymorphisms- CYP2C9
39
BRIEF : STEREOCHEMISTRY , what is it
The branch of organic chemistry that describes how molecules ARE STRUCTURED in 3 Dimensions (3D)
40
What is an isomer
compounds with same MOLECULAR formula.
41
StereoISOMER
kind of isomer, different only in the way ATOMS ARE ORIENTED IN SPACE (molecular formula is identical)
42
Enantiomers definition? do they interact the same.
pair of molecules existing in 2 forms that are MIRROR images of another but cannot be SUPERIMPOSED.
43
Drugs may have CHIRAL CARBON, why?
It is where the molecules can move to change the arrangement.
44
Any enatiomers have
CHIRAL CARBON>
45
A drug can have more than ______chiral carbon? examples is________ , it has _____ enantimers, meaning ?
more than 1 enantiomer; Labetalol; you administer 4 enantiomers (4 mechanism actions, same molecular formula, arranged differently--> 4 actions>) with labetalol.
46
Enantiomers naming system: when dissolved in solution , can be distinguished that rotated
POLARIZED Light
47
***d or +
rooted POLARIZED light to the RIGHT (clockwise)
48
*** l or (-)
rooted POLARIZED light to the LEFT (counterclockwise)
49
***What is a racemic mixtures? Does it rotate to polarized light?
50:50 mixtures of 2 isomers; NO
50
All drugs are racemic mixtures
NO
51
A drug with R is _____ and S is _____
Rectus; Sinister
52
The binding of a chemical to a receptor is
STEREOSPECIFIC
53
The majority of drugs has to _______ ____ ____ ______
bind to a receptor
54
Some examples of RACEMIC MIXTURES: ________and ________
Thiopental
| Methohexital
55
All volatile anesthetics are racemic mixtures except:
Sevoflurane (one enantiomer)
56
Ketamine is a racemic mixtures of :
S and R
57
S (+) form in Ketamine
has a greater NMDA receptor affinity ; is MORE POTENT is LESS LIKELY to produce EMERGENCE DELIRIUM
58
R (-) form in Ketamine
form is weaker and PRODUCES emegence and delirium
59
Local anesthetics such as ______ and ______ are racemic mixtures
Bupivacaine and Prilocaine.
60
MEMORIZE: Hyperractive
low doses of medications leads to HIGHER expected effect.
61
MEMORIZE: Hypersensitive
when a patient is allergic (sensitive) to a drug
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MEMORIZE: Hyporeactive
high doses of medication required to evoke desired effect
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Types of hyporeactivity :Tolerance
Hyporeactivity required from chronic exposure to a drug.
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MEMORIZE****Types of hyporeactivity: Cross-tolerance
Tolerance to a drugs through continued used of another drugs /substance, with similar pharm. effects.
65
Example of cross tolerance ; Ask what question
Volatile anesthetics and Alcohol use (ask how much patient drinks)
66
Types of hyporeactivity :Tachyphylaxis
Tolerance that develops rapidly only after a few doses. (loss of drug response after a few doses)
67
3 types of hyporeactive reactions
Tolerance
Cross tolerance
Tachyphylaxis
68
Mechanism of action of TOLERANCE
NEURONAL ADAPTION as a cellular tolerance
Decreased in number of receptors
Enzyme induction
Decrease neurotransmitter release.
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2 Types of HYPERREACTIVITY
immunity
| idiosyncrasy -- Unusual effect (NO IDEA about why and how)
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Drug to drug interactions: additive
Additive effect: 1+1 = 2 (increase predictable
| Ex: anesthetic effect 2 different inhaled anesthetics
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drug to drug interaction : Synergistic
1+1 =4 two drugs interact to produce a much greater effect. ex: mepivacaine + bupivacaine
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Drug to drugs : Antagonistic
Agonist with antagonist (fentanyl and narcan)
73
What is a receptor?
cellular protein macromolecule to which a drug binds to bring about a response.
74
What is an Agonist?
ACTIVATOR; mimics the expected receptor response
75
What is a full agonist
High efficacy or HIGH INTRINSIC activity --> FULL/Maximal response.
76
Agonist can be (examples)
Drug, molecule or neurotransmitter
77
What is a PARTIAL AGONIST
Not as good of a response as a full agonist. LOW INTRINSIC ACTIVITY at the receptor.
78
****What happens when a partial agonist is given with a full agonist?
act as a partial agonist and DECREASES the effects of a full agonist. Ex: Buprenorphine (partial agonist at the Mu receptor) and morphine (Full agonist at the opioid mu receptor)
79
A partial agonist given a alone Does it act an antagonist.?
Does not act as an antagonist
80
What is a antagonist
Bind, doest not activate, and prevent agonist from binding.
81
No intrinsic activity or affinity to the receptor is :
ANTAGONIST
82
Atropine is
Blocks the effects of ACh at a muscarinic receptor
83
Beta blockers
Beta receptor antagonist.
84
Flumanezil does what
Blocks the effect of diazepam at the bentzo site
85
Competitive antagonists (REVERSIBLE)
binds to a receptor at the same binding site as the ENDOGENOUS LIGANTS or agonist, THEY COMPETE
86
The maximal effect can still be achieved if sufficient agonist is given in
Competitive antagonists
87
Competitive antagonists (REVERSIBLE) example
All non-depolarizing NEUROMUSCULAR Blocking agents.
88
NONCOMPETITIVE IRREVERSIBLE ANTAGONIST
binds permanently via COVALENT bond to the active site
89
NONCOMPETITIVE PSEUDO- IRREVERSIBLE ANTAGONIST
Does not bind covalently
90
The log dose effect curve is shifted: agonist in presence of noncompetitive antagonist
DOWNWARD slightly to the right
91
Allosteric (Non-competitive) antagonist
binds to a different sites (different binding site from agonist)
92
Does allosteric compete with agonist at active site.
NO
93
***ALLOSTERIC POTENTIATION
Compound acts at an ALLOSTERIC SITE and enhances the AFFINITY of the normal agonist at its binding site
94
ALL benzo are -_____________
Allosteric potentiators ( they bind to the GABAa complex to increase the affinity of GABA to its binding site)
95
INVERSE AGONIST is
Binds selectively to the INACTIVE STATE of the receptor and shift the equilibrium of the receptors to the inactive ; keep them in the inactive state, THEY HAVE NEGATIVE INTRINSIC ACTIVITY.
96
Clinically: inverse agonist exert ______ effect of pharmacological
exert the OPPOSITE OF THE PHARMACOLOGY EFFECT of a receptor agonist.
97
Examples of inverse Agonist
Antihistamine drugs at histamine-1 receptors.
98
Up-regulation of receptors
Increase in the number of receptors --> Cells become hypersensitive to the receptor agonist
99
Down regulation of receptors
Decreased in the number of receptors.
100
***REMEMBER: if drugs form COVALENT BOND WITH A RECEPTOR...
It is always IRREVERSIBLE>
101
Termination of drugs response: ADME
Metabolism--> inactive --> no longer active
| Excretion -->
102
Redistribution is when -->
drugs distributes from site of action to other tissues
103
Main factor in terminating drugs that are HIGHLY LIPID SOLUBLE (like waking up from anesthesia is )
RESTRIBUTION
104
With regard to drug-receptor binding:
| A competitive antagonist ________intrinsic activity –
A competitive antagonist has no intrinsic activity –
105
A partial agonist:
Has a dose response curve similar to that of a full agonist in the presence of a non-competitive antagonist.
106
A Basic drug with a pKa of 8.7
Will be predominantly ionized at plasma p
107
The CNS effects after bolus injection of an IV anesthetic agent are terminated primarily by__________
REDISTRIBUTION
108
______ is an increase in the number of receptor; Occurs from lack of use of the receptor
Up-regulation
109
Down-regulation – ________ in the number of receptors
decrease
110
Occurs from excessive stimulation from an agonist or overuse of the
receptor
down regulation
111
Receptors have 2 major functions
Ligand Binding
| Signal Transduction – Message Propagation
112
Receptors have 2 functional domains
Ligand-Binding domain
| Effector domain
113
Non-surmountable IRREVERSIBLE ANTAGONIST
PHENOXYBENZAMINE
114
Antagonist Competitive reversible example
i.e.: Non-depolarizing neuromuscular blockers
115
Examples of enantiomeric differences important in anesthesia:
cisatracurium is an atracurium isomer that doesn't cause histamine release
