pharmacodynamics pacific
TRANSCRIPT
-
8/8/2019 Pharmacodynamics PACIFIC
1/119
Principles ofPrinciples of
Pharmacology:Pharmacology:
PharmacodynamicsPharmacodynamics
Dennis Rosete, M.D.Dennis Rosete, M.D.
Philippine Society ofPhilippine Society of
Experimental and ClinicalExperimental and Clinical
PharmacologyPharmacology
-
8/8/2019 Pharmacodynamics PACIFIC
2/119
Learning Objectives:Learning Objectives:
Understand the theoretical basis of drug-Understand the theoretical basis of drug-receptor interactions.receptor interactions.
Understand the determinants and types ofUnderstand the determinants and types of
responses to drug-receptor interactionsresponses to drug-receptor interactionsincluding the graded dose-response curve.including the graded dose-response curve.
Define potency and efficacy.Define potency and efficacy. Understand how to compare drug potencyUnderstand how to compare drug potency
and efficacy.and efficacy. Understand measures of drug safety.Understand measures of drug safety. Understand the consequences of receptorUnderstand the consequences of receptor
regulationregulation
-
8/8/2019 Pharmacodynamics PACIFIC
3/119
DRUGDRUG MANMAN
TwoTwoINTERACTIONINTERACTION WayWay
RelationshipRelationship
PHARMACODYNAMICS:PHARMACODYNAMICS:ActionActionEffectEffect
PHARMACOKINETICSPHARMACOKINETICS
AbsorptionAbsorptionDistributionDistributionMetabolismMetabolismEliminationEliminationExcretionExcretion
-
8/8/2019 Pharmacodynamics PACIFIC
4/119
A. PharmacodynamicsA. Pharmacodynamics
Study of the biochemical andStudy of the biochemical andphysiological effects of drugs andphysiological effects of drugs and
their mechanism of action.their mechanism of action.
Refers to the actions of a drug onRefers to the actions of a drug on
the body.the body.
What a drug does to the bodyWhat a drug does to the body
-
8/8/2019 Pharmacodynamics PACIFIC
5/119
PharmacodynamicsPharmacodynamics
drug-receptor interactionsdrug-receptor interactions
dose-response phenomenadose-response phenomena
mechanisms of therapeutic andmechanisms of therapeutic and
toxic actiontoxic action
-
8/8/2019 Pharmacodynamics PACIFIC
6/119
A drug receptor is a . . .A drug receptor is a . . .
. . . macromolecular. . . macromolecularcomponent of the cellcomponent of the cellwith stereospecificitywith stereospecificity
and with which a drugand with which a druginteracts in a lock-and-interacts in a lock-and-key fashion initiating akey fashion initiating achain of events that leadchain of events that lead
to a pharmacologicalto a pharmacologicalresponse.response.
http://opt/scribd/conversion/tmp/scratch500/C:/Documents%20and%20Settings/dennis.rosete/My%20Documents/Teveten/Eprosartan.exe -
8/8/2019 Pharmacodynamics PACIFIC
7/119
-
8/8/2019 Pharmacodynamics PACIFIC
8/119
Cell Membrane has protruding receptors waiting for a drug
The Cell Membrane
-
8/8/2019 Pharmacodynamics PACIFIC
9/119
Ligand-gated IonLigand-gated Ion
ChannelsChannels
-
8/8/2019 Pharmacodynamics PACIFIC
10/119
G-protein coupledG-protein coupled
receptorsreceptors
-
8/8/2019 Pharmacodynamics PACIFIC
11/119
G-protein coupledG-protein coupled
receptorsreceptors
Membran
e
-
8/8/2019 Pharmacodynamics PACIFIC
12/119
G-protein coupledG-protein coupled
receptorsreceptors
-
8/8/2019 Pharmacodynamics PACIFIC
13/119
Receptor-enzymeReceptor-enzyme
Catalyticsite
Binding site
-
8/8/2019 Pharmacodynamics PACIFIC
14/119
Cytosolic-NuclearCytosolic-Nuclear
receptorsreceptors
-
8/8/2019 Pharmacodynamics PACIFIC
15/119
Terminologies
Receptor affinity - tendency of adrug to combine with a receptor
Receptor specificity - tendency ofa drug to combine with a specific
type of receptor and none other.
-
8/8/2019 Pharmacodynamics PACIFIC
16/119
ReceptorsReceptors
Receptors are responsible forReceptors are responsible for
selectivity of drug actionselectivity of drug action
Beta receptors (B1 vs B2)Beta receptors (B1 vs B2) Histamine receptors (H1 vs others)Histamine receptors (H1 vs others)
Angiotensin receptors (AT1, AT2)Angiotensin receptors (AT1, AT2)
Cycloxygenase enzyme receptorsCycloxygenase enzyme receptors(COX1, COX2)(COX1, COX2)
-
8/8/2019 Pharmacodynamics PACIFIC
17/119
Active vs InactiveActive vs Inactive
statesstates Active states initiate cellActive states initiate cell
signaling.signaling.
For any cell, there is anFor any cell, there is anequilibrium between active anequilibrium between active an
inactive states. The inactiveinactive states. The inactive
state usually predominates.state usually predominates. Each state has its own affinity.Each state has its own affinity.
-
8/8/2019 Pharmacodynamics PACIFIC
18/119
PharmacodynamicsPharmacodynamics
Onset of action-time it takes to reachOnset of action-time it takes to reach
minimum effective concentration (MEC)minimum effective concentration (MEC)
Peak action occurs when drug reaches itsPeak action occurs when drug reaches its
highest blood/plasma concentrationhighest blood/plasma concentration
Duration of action-length of time drug has aDuration of action-length of time drug has a
pharmacologic effectpharmacologic effect
-
8/8/2019 Pharmacodynamics PACIFIC
19/119
-
8/8/2019 Pharmacodynamics PACIFIC
20/119
AGONIST /
ANTAGONIST
AGONIST a drug thatbinds to receptors and
produce an effect.
ANTAGONIST a drugthat binds to receptors
and prevent an agonistfrom producing aneffect.
-
8/8/2019 Pharmacodynamics PACIFIC
21/119
ReceptorsReceptors
Receptors mediate the actions ofReceptors mediate the actions ofpharmacologic antagonistspharmacologic antagonists
Mimics the chemical configurationMimics the chemical configurationof the natural chemical in the bodyof the natural chemical in the body
May displace the usual partnersMay displace the usual partnerswhen in excessive quantities or withwhen in excessive quantities or withincreased affinityincreased affinity
http://opt/scribd/conversion/tmp/scratch500/C:/Documents%20and%20Settings/dennis.rosete/My%20Documents/Teveten/Eprosartan.exe -
8/8/2019 Pharmacodynamics PACIFIC
22/119
PharmacodynamicsPharmacodynamics
Refers to the actions of aRefers to the actions of a
drug on the bodydrug on the body
drug-receptor interactionsdrug-receptor interactions dose-response phenomenadose-response phenomena
mechanisms of therapeuticmechanisms of therapeuticand toxic actionand toxic action
-
8/8/2019 Pharmacodynamics PACIFIC
23/119
Definitions and ConceptsDefinitions and Concepts
SelectivitySelectivity: differential: differential
responsiveness among the drugsresponsiveness among the drugs
multiple effectsmultiple effects
DoseDose: amount administered: amount administered
Posology: concerned with thedosage or amount of a druggiven in the treatment of
disease. EfficacyEfficacy: the property of a drug to: the property of a drug to
achieve the desired responseachieve the desired response
-
8/8/2019 Pharmacodynamics PACIFIC
24/119
EfficacyEfficacy
-
8/8/2019 Pharmacodynamics PACIFIC
25/119
Graded dose-responseGraded dose-response
curvescurves Individual responses to varying dosesIndividual responses to varying doses
Concepts to remember:Concepts to remember:
Threshold:Threshold: Dose that produces a just-Dose that produces a just-noticeable effect.noticeable effect.
EDED5050 :: Dose that produces a 50% ofDose that produces a 50% of
maximum response.maximum response.
Ceiling:Ceiling: Lowest dose that produces aLowest dose that produces a
maximal effect.maximal effect.
-
8/8/2019 Pharmacodynamics PACIFIC
26/119
Dose-response curveDose-response curve
Dose
R
espon
s
e 0
20
40
60
80
100
0 200 400 600 800 1000
-
8/8/2019 Pharmacodynamics PACIFIC
27/119
Dose-response curveDose-response curve
Dose
R
espon
s
e
0
20
40
60
80
100
0.1 1 10 100 1000 10000
10 0
-
8/8/2019 Pharmacodynamics PACIFIC
28/119
= Agonist
0
20
40
60
80
10 0
0 . 1 1 1 0 10 0 1 0 0 0 1
10 0
-
8/8/2019 Pharmacodynamics PACIFIC
29/119
= Agonist
0
20
40
60
80
10 0
0.1 1 10 100 10 00 1
100
-
8/8/2019 Pharmacodynamics PACIFIC
30/119
= Agonist
0
20
40
60
80
100
0.1 1 10 100 1000 10
100
-
8/8/2019 Pharmacodynamics PACIFIC
31/119
= Agonist
0
20
40
60
80
0.1 1 10 100 1000 10
100
-
8/8/2019 Pharmacodynamics PACIFIC
32/119
= Agonist
0
20
40
60
80
0.1 1 10 100 1000 10
100
-
8/8/2019 Pharmacodynamics PACIFIC
33/119
= Agonist
0
20
40
60
80
0.1 1 10 100 1000 10
100
-
8/8/2019 Pharmacodynamics PACIFIC
34/119
= Agonist
0
20
40
60
80
0.1 1 10 100 1000 10
-
8/8/2019 Pharmacodynamics PACIFIC
35/119
Dose-response curveDose-response curve
Dose
R
espon
s
e 0
20
40
60
80
100
0.1 1 10 100 1000 10000
Ceiling
ED50
Threshold
ED50
-
8/8/2019 Pharmacodynamics PACIFIC
36/119
Determinants ofDeterminants of
ResponseResponse Intrinsic EfficacyIntrinsic Efficacy
((): Power of a drug): Power of a drug
to induce a response.to induce a response. Number of receptorsNumber of receptors
in the target tissue.in the target tissue.
-
8/8/2019 Pharmacodynamics PACIFIC
37/119
Full vs Partial agonistsFull vs Partial agonists
These terms are tissue dependentThese terms are tissue dependent
Receptor densityReceptor density
Cell signaling apparatusCell signaling apparatus Other receptors that are presentOther receptors that are present
Drug historyDrug history
-
8/8/2019 Pharmacodynamics PACIFIC
38/119
Full vs Partial agonistsFull vs Partial agonists
0
20
40
60
80
100
0.1 1 10 100 1000 10000
Full Agonist
Partial Agonist
Dos
%
Effe
ct
-
8/8/2019 Pharmacodynamics PACIFIC
39/119
Two types ofTwo types of
antagonismantagonismcompetitive (reversible) antagonistcompetitive (reversible) antagonist drug molecule that will compete with andrug molecule that will compete with an
agonist for binding to the receptoragonist for binding to the receptor
response is abolished or diminished as longresponse is abolished or diminished as long
as the antagonist can successfully competeas the antagonist can successfully compete
with the agonist for the receptor sitewith the agonist for the receptor site
competition can be overcome by floodingcompetition can be overcome by flooding
the receptor site with a very largethe receptor site with a very large
concentration of agonist and full responseconcentration of agonist and full response
can be restoredcan be restored
-
8/8/2019 Pharmacodynamics PACIFIC
40/119
Two types ofTwo types of
antagonismantagonismnoncompetitive (irreversible)noncompetitive (irreversible) a drug molecule which binds to thea drug molecule which binds to the
receptor and does not dissociatereceptor and does not dissociate
and cannot be displaced byand cannot be displaced byincreasing agonist concentrationincreasing agonist concentration
Effectively, some of the receptorsEffectively, some of the receptors
become inactivated and the fullbecome inactivated and the fullresponse cannot occur, althoughresponse cannot occur, although
some pharmacologic activity of thesome pharmacologic activity of the
agonist is usually still present.agonist is usually still present.
120
-
8/8/2019 Pharmacodynamics PACIFIC
41/119
= Agonist =
0
2 0
4 0
6 0
8 0
100
- 10 .5 - 10 - 9 .5 - 9 - 8 .5 - 8 - 7 .5 - 7 - 6 .5
12 0
-
8/8/2019 Pharmacodynamics PACIFIC
42/119
= Agonist =
0
20
40
60
80
10 0
-11 -10 -9 -8 -7
12 0
-
8/8/2019 Pharmacodynamics PACIFIC
43/119
= Agonist =
0
20
40
60
80
10 0
-11 -10 -9 -8 -7
120
-
8/8/2019 Pharmacodynamics PACIFIC
44/119
= Agonist =
0
20
40
60
80
100
-11 -10 -9 -8 -7
12 0
-
8/8/2019 Pharmacodynamics PACIFIC
45/119
= Agonist =
0
20
40
60
80
10 0
-1 1 -1 0 -9 -8 -7
120
-
8/8/2019 Pharmacodynamics PACIFIC
46/119
= Agonist =
0
20
40
60
80
100
-11 -10 -9 -8 -7
100
120
-
8/8/2019 Pharmacodynamics PACIFIC
47/119
= Agonist =
0
20
40
60
80
100
-11 -10 -9 -8 -7
-
8/8/2019 Pharmacodynamics PACIFIC
48/119
CompetitiveCompetitive
0
200
400
600
800
1000
1200
-11 -10 -9 -8 -7
IC50
log [antagonist]
Eff
e
ct
-
8/8/2019 Pharmacodynamics PACIFIC
49/119
= Agonist =
-
8/8/2019 Pharmacodynamics PACIFIC
50/119
= Agonist =
-
8/8/2019 Pharmacodynamics PACIFIC
51/119
= Agonist =
-
8/8/2019 Pharmacodynamics PACIFIC
52/119
= Agonist =
-
8/8/2019 Pharmacodynamics PACIFIC
53/119
= Agonist =
-
8/8/2019 Pharmacodynamics PACIFIC
54/119
= Agonist =
-
8/8/2019 Pharmacodynamics PACIFIC
55/119
= Agonist =
-
8/8/2019 Pharmacodynamics PACIFIC
56/119
CompetitiveCompetitive
antagonistsantagonists
0
20
40
60
80
100
0.1 1 10 100 1000 10000
A CB
Dos
Respon s
e
-
8/8/2019 Pharmacodynamics PACIFIC
57/119
NoncompetitiveNoncompetitive
antagonistsantagonists
Dos
Respon s
e
0
20
40
60
80
100
0.1 1 10 100 1000 10000
A
C
B
Chemical andChemical and
-
8/8/2019 Pharmacodynamics PACIFIC
58/119
Chemical andChemical and
PhysiologicPhysiologic
antagonistsantagonists
Physiologic:Physiologic: Two drugs haveTwo drugs have
opposite effects through differingopposite effects through differingmechanismsmechanisms
Response can be irregularResponse can be irregular
Chemical:Chemical: No receptors areNo receptors areinvolvedinvolved
-
8/8/2019 Pharmacodynamics PACIFIC
59/119
Allosteric AntagonismAllosteric Antagonism
-
8/8/2019 Pharmacodynamics PACIFIC
60/119
Allosteric AntagonismAllosteric Antagonism
-
8/8/2019 Pharmacodynamics PACIFIC
61/119
Allosteric AntagonismAllosteric Antagonism
-
8/8/2019 Pharmacodynamics PACIFIC
62/119
Allosteric AntagonismAllosteric Antagonism
ll i iAll t i t i t
-
8/8/2019 Pharmacodynamics PACIFIC
63/119
Allosteric antagonistsAllosteric antagonists
11
0
20
40
60
80
100
0.1 1 10 100 1000 10000
A
Dos
Respon s
e
-
8/8/2019 Pharmacodynamics PACIFIC
64/119
-
8/8/2019 Pharmacodynamics PACIFIC
65/119
Receptor regulationReceptor regulation
Reduced responsivity: ChronicReduced responsivity: Chronicuse of an agonist can result in theuse of an agonist can result in thereceptor-effector systemreceptor-effector systembecoming less responsivebecoming less responsive
Increased responsivity: ChronicIncreased responsivity: Chronicdisuse of a receptor-effectordisuse of a receptor-effector
system can result in an increasedsystem can result in an increasedresponsiveness upon re-exposureresponsiveness upon re-exposureto an agonist.to an agonist.
-
8/8/2019 Pharmacodynamics PACIFIC
66/119
THREE MOST IMPORTANTTHREE MOST IMPORTANTPROPERTIES OF A DRUG:PROPERTIES OF A DRUG:
EFFICACYEFFICACY
SAFETYSAFETY
QUALITYQUALITY
P ti fP ti f
-
8/8/2019 Pharmacodynamics PACIFIC
67/119
Properties of aProperties of a
biological systembiological system
Potency:Potency: Dose of drugDose of drug
necessary to produce a specifiednecessary to produce a specified
effect.effect. Dependent upon receptor density,Dependent upon receptor density,
efficiency of the stimulus-responseefficiency of the stimulus-response
mechanism, affinity and efficacy.mechanism, affinity and efficacy.
Magnitude of effect:Magnitude of effect: EfficacyEfficacy
-
8/8/2019 Pharmacodynamics PACIFIC
68/119
-
8/8/2019 Pharmacodynamics PACIFIC
69/119
Relative PotencyRelative Potency
Dos
Effe c
t
0
20
40
60
80
100
0.1 1 10 100 1000 10000
A B
-
8/8/2019 Pharmacodynamics PACIFIC
70/119
Relative EfficacyRelative Efficacy
0
20
40
60
80
100
0.1 1 10 100 1000 10000
Relative
Efficacy
-
8/8/2019 Pharmacodynamics PACIFIC
71/119
PotencyPotency- biological activity of a drug per unit of weigh- biological activity of a drug per unit of weight
Example 1:Example 1:
drug Adrug A drug Bdrug B drug Cdrug C
1 ng1 ng 100 mg100 mg 1 g1 g
These 3 drugs differ in potency butThese 3 drugs differ in potency but
have identical or similar effects.have identical or similar effects.
Definitions andDefinitions and
-
8/8/2019 Pharmacodynamics PACIFIC
72/119
Definitions andDefinitions and
ConceptsConcepts Dose intensity relationshipDose intensity relationship::
manner in which the intensity ofmanner in which the intensity ofthe effect in the individualthe effect in the individual
recipient relates to doserecipient relates to dose
Dose frequency relationshipDose frequency relationship::manner in which the number ofmanner in which the number of
responders among a populationresponders among a population
of recipients relates to dose.of recipients relates to dose.
-
8/8/2019 Pharmacodynamics PACIFIC
73/119
FIGURE A.
DOSE-FREQUENCY CURVE
-
8/8/2019 Pharmacodynamics PACIFIC
74/119
-
8/8/2019 Pharmacodynamics PACIFIC
75/119
THREE MOST IMPORTANTTHREE MOST IMPORTANTPROPERTIES OF A DRUG:PROPERTIES OF A DRUG:
EFFICACYEFFICACY
SAFETYSAFETY
QUALITYQUALITY
-
8/8/2019 Pharmacodynamics PACIFIC
76/119
Therapeutic IndexTherapeutic Index
TI = LD50 / ED50TI = LD50 / ED50
LD Lethal DoseLD Lethal Dose
(lethal in 50% of animals)(lethal in 50% of animals) ED Effective DoseED Effective Dose
(therapeutic effect in 50%)(therapeutic effect in 50%)
Closer Ratio is to 1 = GreaterCloser Ratio is to 1 = GreaterDanger ToxicityDanger Toxicity
-
8/8/2019 Pharmacodynamics PACIFIC
77/119
-
8/8/2019 Pharmacodynamics PACIFIC
78/119
Safety index: LDSafety index: LD11/ED/ED9999
-20
0
20
40
60
80
100
0.00
01
0.00
10.
01 0. 1 110 10
01K 10
K10
0K
Sleep Death
LDLD11
EDED9999
Therapeutic index:Therapeutic index:
-
8/8/2019 Pharmacodynamics PACIFIC
79/119
Therapeutic index:Therapeutic index:
LDLD5050 /ED/ED5050
-20
0
20
40
60
80
100
0.00
01
0.00
10.
01 0. 1 110 10
01K 10
K10
0K
Sleep Death
d ff
-
8/8/2019 Pharmacodynamics PACIFIC
80/119
PHARMACOLOGYisdefined as:
from the Greek word
pharmakon poison
Adverse effects
T i l i
-
8/8/2019 Pharmacodynamics PACIFIC
81/119
Terminologies
Toxicology: deals with the toxic orpoisonous effects produced by drugs
Side Effects - other effects of drugs(may be positive or negative)
-
8/8/2019 Pharmacodynamics PACIFIC
82/119
According to the WHO definition,According to the WHO definition,
-
8/8/2019 Pharmacodynamics PACIFIC
83/119
According to the WHO definition,cco d g o e O de o ,anan adverse reactionadverse reaction is anyis anyuntoward medical occurrence in auntoward medical occurrence in a
patient:patient:
1. that is harmful or noxious to1. that is harmful or noxious tothethe bodybody
2.2. unintendedunintended
3.3. may arise even from themay arise even from theadministration of the usualadministration of the usualrecommended dose range of therecommended dose range of the
drug.drug.
-
8/8/2019 Pharmacodynamics PACIFIC
84/119
Excluding
-
8/8/2019 Pharmacodynamics PACIFIC
85/119
Serious adverse eventSerious adverse event
DeathDeath
DisabilityDisability Prolonged hospitalizationProlonged hospitalization
Congenital defectCongenital defect Life threatening conditionLife threatening condition
-
8/8/2019 Pharmacodynamics PACIFIC
86/119
Type A (augmented/predictable) reactions
Expected extensions of an individual drugs known
pharmacologic properties and are responsible for the
bulk of ADEs encountered.
Even though their incidence and morbidity is high,
they are rarely life-threatening, although they can
produce significant disability.
Drug Allergy
-
8/8/2019 Pharmacodynamics PACIFIC
87/119
Causes of Type A reactions
-
8/8/2019 Pharmacodynamics PACIFIC
88/119
Causes of Type A reactions
1. Pharmaceutical causes
- Drug quantity
- Drug release
2. Pharmacokinetic causes
- Drug absorption - Drug elimination
- Drug distribution - Drug metabolism
3. Pharmacodynamic causes
- Drug receptors
- Homeostatic mechanisms
- Disease
-
8/8/2019 Pharmacodynamics PACIFIC
89/119
Type B (bizarre/unpredictable) reactions
Type B reactions include idiosyncratic reactions,
immunologic or allergic reactions (e.g.anaphylaxis),
and carcinogenic/teratogenic events.
While uncommon, are often among the most
serious and potentially life-threatening of all
ADEs, and are a major cause of important
drug-induced disease.
Adverse
-
8/8/2019 Pharmacodynamics PACIFIC
90/119
Adverse
reactions which
only occur with
long term use
Special Groups ofSpecial Groups of
-
8/8/2019 Pharmacodynamics PACIFIC
91/119
patientspatients
Pediatric patientsPediatric patientsGeriatric patientsGeriatric patients
Patients with hepatic insufficiencyPatients with hepatic insufficiency
Patients with renal insufficiencyPatients with renal insufficiency Pregnant patientsPregnant patients
Nursing mothersNursing mothers
FDA Classification of DrugFDA Classification of DrugS f tS f t
-
8/8/2019 Pharmacodynamics PACIFIC
92/119
SafetySafety
era ogen c ecera ogen c ec --adversely affect fetaladversely affect fetal
-
8/8/2019 Pharmacodynamics PACIFIC
93/119
adversely affect fetaladversely affect fetal
development.development.
Probably the mostrenowned isPhocomelia, thename given to theflipper-like limbswhich appeared on
the children ofwomen who tookthalidomide
era ogen c ecera ogen c ec --adversely affect fetaladversely affect fetal
-
8/8/2019 Pharmacodynamics PACIFIC
94/119
adversely affect fetaladversely affect fetal
development.development.
Pediatric and Geriatric patientsPediatric and Geriatric patients possible dose adjustments;possible dose adjustments;
-
8/8/2019 Pharmacodynamics PACIFIC
95/119
possible dose adjustments;possible dose adjustments;
safetysafety
Hepatic and renal insufficiencyHepatic and renal insufficiencyibl dpossible dose
-
8/8/2019 Pharmacodynamics PACIFIC
96/119
possible dosepossible dose
adjustments; dialysabilityadjustments; dialysability
Hepatic failureHepatic failure
-
8/8/2019 Pharmacodynamics PACIFIC
97/119
Hepatic failureHepatic failure
urs ng mo ersurs ng mo ers somesomedrugs are excreted indrugs are excreted in
-
8/8/2019 Pharmacodynamics PACIFIC
98/119
drugs are excreted indrugs are excreted in
breastmilkbreastmilk
-
8/8/2019 Pharmacodynamics PACIFIC
99/119
OverdoseOverdose
Beyond theBeyond the
maximum dosagemaximum dosage
Could beCould be
intentionalintentional(suicidal) or(suicidal) or
accidentalaccidental
(medication error)(medication error)
Antidote?Antidote?
i
-
8/8/2019 Pharmacodynamics PACIFIC
100/119
Precautions
Ability to operateAbility to operate
machinerymachinery
Are there sedatingAre there sedating
effects?effects?
Drug Abuse/ Misuse/Drug Abuse/ Misuse/
-
8/8/2019 Pharmacodynamics PACIFIC
101/119
Drug Abuse/ Misuse/Drug Abuse/ Misuse/
AddictionAddiction
Misuse indiscriminate use of drugsMisuse indiscriminate use of drugs
(recreational purpose)(recreational purpose)
Abuse continual non-therapeutic use ofAbuse continual non-therapeutic use of
drug with resulting physical ordrug with resulting physical or
psychological dependencepsychological dependence
Addiction presence of tolerance,Addiction presence of tolerance,withdrawal, increasing dosage andwithdrawal, increasing dosage and
uncontrollable useuncontrollable use
-
8/8/2019 Pharmacodynamics PACIFIC
102/119
-
8/8/2019 Pharmacodynamics PACIFIC
103/119
Drug Abuse/ Misuse/Drug Abuse/ Misuse/
Addi tiAddi ti
-
8/8/2019 Pharmacodynamics PACIFIC
104/119
AddictionAddiction
What is Tolerance?What is Tolerance?
-
8/8/2019 Pharmacodynamics PACIFIC
105/119
What is Tolerance?What is Tolerance?
Tolerance is theneed to increasethe dose ofa drug over time
in order tomaintain a givenpharmacologicaleffect
Withd lWithd l
-
8/8/2019 Pharmacodynamics PACIFIC
106/119
WithdrawalWithdrawal
PhysiologicalPhysiological
PsychologicalPsychological
H bit f i dH bit f i d
-
8/8/2019 Pharmacodynamics PACIFIC
107/119
Habit forming drugsHabit forming drugs
Categories of ControlledCategories of Controlled
SubstancesSubstances
-
8/8/2019 Pharmacodynamics PACIFIC
108/119
SubstancesSubstances Schedule I - not approved for medical useSchedule I - not approved for medical use
and have high abuse potentialand have high abuse potential Schedule II - used medically and haveSchedule II - used medically and have
high abuse potentialhigh abuse potential
Schedule III - less potential for abuse butSchedule III - less potential for abuse but
may lead to physical or psychologicalmay lead to physical or psychologicaldependencedependence
Schedule IV - some potential for abuseSchedule IV - some potential for abuse
Schedule V - contain mod. amounts ofSchedule V - contain mod. amounts ofcontrolled substances, limited abusecontrolled substances, limited abuse
potentialpotential
-
8/8/2019 Pharmacodynamics PACIFIC
109/119
DRUG INTERACTIONDRUG INTERACTION
A pharmacologic phenomenon that occursA pharmacologic phenomenon that occurswhen the action and/or effect of a given drugwhen the action and/or effect of a given drugis modified or altered significantly by anotheris modified or altered significantly by anotherdrug when these are administereddrug when these are administeredconcomitantly or sequentially.concomitantly or sequentially.
A.A. Pharmacodynamic Drug-DrugPharmacodynamic Drug-DrugInteractionsInteractions
B.B. Pharmacokinetic Drug-Drug InteractionsPharmacokinetic Drug-Drug Interactions
-
8/8/2019 Pharmacodynamics PACIFIC
110/119
Pharmacodynamic DrugPharmacodynamic DrugInteractionInteraction
-
8/8/2019 Pharmacodynamics PACIFIC
111/119
InteractionInteraction
Additi itAdditivity
-
8/8/2019 Pharmacodynamics PACIFIC
112/119
AdditivityAdditivity
Administration of the dose of AAdministration of the dose of A
and B simultaneously gives anand B simultaneously gives an
effect equal to 20 unitseffect equal to 20 units
-
8/8/2019 Pharmacodynamics PACIFIC
113/119
SynergismSynergism
-
8/8/2019 Pharmacodynamics PACIFIC
114/119
SynergismSynergism
A certain dose of Drug A aloneA certain dose of Drug A alone
produces an effect equal to 10produces an effect equal to 10
units. A certain dose of Drug Bunits. A certain dose of Drug Balone produces an effect equal toalone produces an effect equal to
10 units. Administration of the10 units. Administration of the
same doses of A and Bsame doses of A and B
simultaneously produces an effectsimultaneously produces an effect
equal to 50 unitsequal to 50 units
-
8/8/2019 Pharmacodynamics PACIFIC
115/119
AntagonisticAntagonistic
-
8/8/2019 Pharmacodynamics PACIFIC
116/119
AntagonisticAntagonistic
AdministrationAdministration
of the dose of Aof the dose of A
and Band Bsimultaneouslysimultaneously
negates thenegates the
effect of eacheffect of each
drugdrug
P-K DrugP-K DrugInteractionInteraction
-
8/8/2019 Pharmacodynamics PACIFIC
117/119
InteractionInteraction
-- due to drugdue to druginteraction at anyinteraction at anypoint during theirpoint during theirabsorption,absorption,
distribution,distribution,metabolism, ormetabolism, orexcretion resultingexcretion resultingeither in increaseeither in increaseor decrease in theor decrease in thedrugdrugconcentration atconcentration atthe site of action.the site of action.
-
8/8/2019 Pharmacodynamics PACIFIC
118/119
-
8/8/2019 Pharmacodynamics PACIFIC
119/119
Thank you.Thank you.