Professional Documents
Culture Documents
Estole-Casanova, MD
Associate Professor 2
Department of Pharmacology and Toxicology
May 25, 2010
Prepare yourself
Review from your notes and favorite
text
PRAY .
PRAY .
PRAY .
Leonila A. Estole-Casanova, MD
Associate Professor 2
Department of Pharmacology and Toxicology
May 25, 2010
mechanisms of action
what the
Molecular
/ Cellular
level
Organism
Receptors
Affinity
Dissociation
constant (Kd)
Agonist,
antagonist
Population
Vd = D / C
D = C (Vd)
= 5ug/ml (50,000ml)
= 250,000ug or
250mg
FIRST-ORDER
rate is directly
proportional to the
concentration of
free drug
constant
FRACTION of drug
is metabolized per
unit time
linear kinetics
half-life is
constant
ZERO-ORDER
rate remains
constant over
time, e.g. ASA ,
Ethanol,
Phenytoin
constant
AMOUNT of drug
is metabolized per
unit time
non-linear
kinetics
half-life increases
with dose
PHASE I
t functions to
convert lipophilic
materials into
more polar
molecules
PHASE II
t
consists of
conjugation
reactions that
result in polar,
usually water
soluble
compounds that
are
therapeutically
inactive
PHASE I
P450-dependent
oxidations
P450
independent
oxidations (alcohol
or aldehyde
dehydrogenation
deamination,
decarboxylation)
Hydrolysis
Reductions
PHASE II
glucuronidation
acetylation
glycine conj.
sulfate conj.
glutathione conj
N- or Omethylation
Not
For
drugs induce
P450
Increased rate of
metabolism
potentiate the
actions of other
drugs
Phenytoin
omeprazole
carbamazepine
barbiturates
rifampicin
ritonavir
griseofulvin
chronic ethanol
toxicity
DISULFIRAM
erythromycin
valproic acid
isoniazid
cimetidine
ciprofloxacin
acute ethanol
toxicity
Molecular
/ Cellular
level
Organism
Receptors
Affinity
Dissociation
constant (Kd)
Agonist,
antagonist
Population
Kd
A
Molecular
/ Cellular
level
Organism
Receptors
Affinity
Dissociation
constant (Kd)
Agonist,
antagonist
Population
Emax
maximal
response
produced by the
drug
Refers
to the
concentration
(EC50) or dose
(ED50) of a drug
required to
produce 50% of
the drugs
maximal effect
Molecular
/ Cellular
level
Organism
Receptors
Affinity
Dissociation
constant (Kd)
Agonist,
antagonist
Population
e. Effector
Sometimes,
e. Effector
Competes with
agonist for receptor
Surmountable with
increasing agonist
concentration
Agonist affinity is
lower because a
higher dose of
agonist is required,
in the presence of
antagonist, to
achieve receptor
occupancy
Ex: Propranolol
drug binds to
receptor and
stays bound
irreversible does
not let go of
receptor
ex.
Phenoxybenzamin
e
t
inactivate an agonist
before it has the
opportunity to act
Ex Protamine (+)
charged is used to
counteract the effects
of HEPARIN, (-)
charged
acts by IONIC binding
to make heparin
unavailable for
interactions with
proteins involved in
blood clotting
Cause a
physiologic effect
opposite to that
induced by the
agonist
t
Ex. glucocorticoid
increases blood
sugar
insulin decreases
blood sugar
About
Henderson-Hasselbalch equation
pKaspirin = pHstomach + log HA (protonated)
A(deprotonated)
Henderson-Hasselbalch equation
pKaspirin = pHstomach + log HA
A3.5 2.5 = log HA / A1 = log HA / Aantilog of 1 = HA / A10 = HA /AProtonated = 10 / 11 = 90%
defined as
the amount of
time required
for the drug
concentration
to decrease
by 50%
volume of distribution of 80 L
clearance of 1.386 L/h
?? the half-life
Antichol
Sedating
b.Amitriptyline (TCA)
+3
c.Nortriptyline (TCA)
+3
+1
+1
substances such as
epinephrine reduce systemic absorption
of LA from the injection site by
decreasing the blood flow in these areas
Typical antipsychotics
dopamine 2 receptor antagonists
ex. Haloperidol
Chlorpromazine
Atypical antipsychotics
Dopamine 2 receptor antagonists
serotonin 5-HT receptor antagonists
ex. Clozapine
mehylenedioxymetamphetamine- facilitate
interpersonal communication and act as
sexual enhancer)
Congener of amphetamine: Promotes the
release of NE from nerve endings; blocks the
reuptake of norepinephrine
acute effects: feelings of high energy,
altered sense of time and pleasant sensory
experiences
side (negative) effects: tachycardia, dry
mouth
higher doses: visual hallucinations, agitation,
hyperthermia, panic attacks
Spectinomycin
Chloramphenicol
Aminoglycoside
gentamicin
amikacin
streptomycin
Macrolides
erythromycin
azithromycin
clarithromycin
Tetracyclines
Lincosamides
clindamycin
Streptogramins
dalfopristin
Oxazolidones (linezolid)
ACUTE GOUT
CHRONIC GOUT
Leukocyte inhibitors
NSAIDs
Colchicine
Glucocorticoids
Allopurinol
e.Norgestrel
e.Norgestrel
Cell cycle
Antineoplastic
Drugs
M (mitosis)
Inhibitors of
microtubule
function
G1 (gap 1)
Active
glucocorticoids
metabolism in the
absence of DNA
sythesis)
S (synthesis)
Cell replication
Antimetabolites
Folate pathway
inhibitors
Topoisomerase
inhibitors
G2 (gap 2)
Cell preparation
for mitosis
Antitumor
antibiotics
Topoisomerase
inhibitors
e.Losartan
e.Losartan
Bulk-formers
Stool softeners
Stimulant laxative
2 therapeutic goals:
Heal the ulcer Eradicate the organisms
Combination of 2 antibiotics
Proton pump inhibitor raise
intragastric pH lowering the MIC
against H pylori
10-14 day regimen
d.Tetracycline
Rate
Ex: Aminoglycosides
Quinolones
Bacitracin
Beta-lactams
vancomycin
Polmyxins
Pyrazinamide
Isoniazid
Rifampin
Metronidazole
Alkylating agents
ex cyclophosphamide
melphalan
platinum compounds
ex cisplatin
carboplatin
t
bleomycin
A concentration
effect curve applies
only to a single
individual at one
time or to an
average individual
The curve
represents the
effects and dose of
a drug within an
individual animal or
tissue rather in a
population
Pharmacodynamic
variability in a
population may
be analyzed by
constructing a
QUANTAL
CONCENTRATION
EFFECT CURVE
PRAY .
PRAY .
PRAY .
Principles
of Pharmacology: The
Pathophysiologic Basis of Drug
Therapy
Golan et al