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Pharmacodynamics

Bodys response to Rx|Rx effect on body


Efficacy|Potency|Affinity|Dose|R#|Genetic

Efficacy How well Rx prod pharmaco resp|y
Agn|full|partial|Antg|C|NC
Relative|full Agn=1|Antg=0
Antg Rev|conf|effect|Endo Agn

Full
Agn
Partial
Agn
C Antg
Reversible
NC Antg
Irreversible
E/NE Pindolol Propranolol Pehnoxybenzamine


Potency Amt Rx needed for desired effect|y
Affinity How tight Rx bind R|left=affinity
Dose EC
50
|CAntg|NCAntg
R# R
max
|NCAntg|y|spare R|
Genetics Quantal DR curve|Cumulative Q-DR
Variability|ED
50
|





























Rx action EC
50
|R
max
|

Agn|CAntg EC
50
|R
max
|right shift
CAntg|Agn Antg EC
50
dep on [Agn]
NCAgtg EC
50
C|R
max
|R#

Spare R Saturate|limited by later step|
Rmax reached before all R occupied
Sm dose NC Antg Rmax

R Regulation Over|reg|mlc|R#|tachyphalaxis
Prolong|reg|dose|rebound phenm
pharmacodynamic tolerance

Quantal Normal curve
% of pop need certain dose to respond
Cum Q Sigmoid|% of pop responding to a dose
Include those that resp to lower dose

Multi-effects Rx bind same R @ other tissue|potency
Rx bind other R|completely selective
R density|diff R isoforms expr

TI Rx safety|TD
50
/ED
50
|LD
50
/ED
50
















Physicochemical properties
Intracellular barrierlipid bilayer mem
Rx specific carriers|not natural meta

PC PC=[Rx]
fat
/[Rx]
H2O

PC=0|soluble in fat
PC=|soluble in H
2
O

Rx N
o
|Weak A/B|Strong A/B
Weak Ionized|Unionized|@equilibrium
HA+BH
+
A
-
+B+H
+
|Ka

***Ionized Rx are trapped in urine & cleared***
Acidic AH|B
+
|Base excreted via urine
Basic A
-
|BH|Acid excreted via urine
Ka [B][H
+
]/[HA]

HH Eq [A]/[B]=10
(pH-pKa)

Weak A Salicylic|ASA|0.01% N
o
|H2O insoluble
Good PC in lipids
Weak B Diphenhydramine|Benadryl|anti-his
1% N
o
|H2O insoluble|Good PC in lipids

Strong A|B Phophate|Sulfate|Poor PC|
NH
4
+
|always |poor PC
Multiple weak A/B|act like strong
Quaternary Ipratropium|inhale|analog of atropine
COPD|deliberate poor PC|
Strong A Heparin|lots SO
4
-
& -OH|sugar
Strong B AG|Tobra|multiple weak bases|NH
3

Sugar=low PC



























Transportation

Diffusion Fav PC|N
o
|E|dissipate gradient|
Rate=k1(C1-C2)|@Eq, C1=C2|trans
wB conjAcross|N
o
B cross|[N
o
] & PC
wA conjBcross|N
o
A cross|[N
o
] & PC

Diff pH Ion Trapping
wB affect N
o
|ratio of B:A|
accum in lower pH than blood
wA affect N
o
|ratio of B:A|
accum in higher pH than blood

Filtration Pores|size|P
hydrostatic
grad|BF
Capillaries|glomerulus|NH
4
+

Liver sinusoid & spleen real endo
Succinylcholine|tubocura|pancuro
Hep too big|trapped in plasma

Active E|up [Rx] grad|SLC|ABC|
Compete|Rx interaction|
Facilitated
Into cells |OCT1,2,3|Uniport
|OAT1,3|Antiport
Grad|Na
+
pump|KG
2-


Out of cells |MATE-1,2|Antiport Rx
+
/H
+

1|Na/K pump|est Grad
2|Na/H|est H
+
Grad
3|Rx/H|dissipate H
+
Grad

ATP driven Kidney|Hepato|GI|Vasc endo brain
Choroid plexus|Testis|Placenta
Rx
+
/Rx
o
P-glycoprot|MDR1|Rx
+
|large Rx
o


Rx- MRP2|BCRP|amphiphilic |Conj
MRP2 Glucuronide|Glutathione|Sulfate
BCRP Rx
o
/Rx
-
|

Pharmacokinetics

Absorption GI|Lungs|Skin (barrier)|Injection sites
SA|Thickness|Perfusion

Oral GI|exclude most Rx|
Passive non-ionic diffusion|
No|PC||wA/B|PC|pK|pH
Fixed charge|poorly abs-but still does
**Abs from GI complexed by the presence of Rx
transporters & Rx meta enz in epithelial cells**
Stomach designed for Abs|wBabs|wA may

Sm Int Lg SA|major abs site|GI & Liver meta
P-gp|Rx back into lumen|HepPortal v
1
st
pass |Rx uneffective

Bioavailability (f)fraction of Rx into Sys circ
Rx w/f=0 still useful if metabolite is active agent
Source of Rx interaction|more important for Rx with
low f as interaction can f

Liver Sublingual|NTG|isosorbide dinitrate
Rectal|unconscious|V|unpredict abs
50% enter sys circ b/f passing liver

Parenteral IV|IM|SubQ|Topical|Inhale|Nasal|Eye

IV Bypass abs|rapid|best control of []
p

Vein dmg|Aq soln|reverse
IM capillary pore|lymphatic|BF|amt fat
Ctrl abs rate|slow but sustained|
use during anticoagulant Tx
SubQ capillary pore|lymphatic|Aq soln~fast
Insoluble Rx slow abs|sustained effect
Solid pellets implant|abs for mo/yr
use for Rx that irritate tissue
Topical Local|minimize sys exposure|patches
Potent & VERY fav PC|tolerance|
Site of admin|scrotum best|sole worst
BF|inflame Abs rate

















Distribution [Rx]
p

BF Heart|Liver|Kidney|Brain|min
Muscle|Skin|Viscera|Fat|min/hr
BloodECF [Rx]
p
=Rx
admin
/(V
p
+V
EF
)|pores|~rapid
ECFCells V
d
=Vp+V
EF
+V
IF
|V
d
=V
app
|ICF|cell
***if Rx lipophilic, Distr limited to ECF***
BBB pores|Cap endo Rx transporter|P-gp
Cap surr by glial cells,ECF|
Very good PC|guarantee|P-gp
Inflame vasc perm|meningitis|PCN
BBB|ChemoR trigger zone|HTh
Choroid plx Blood-CSF|3
rd
& 4
th
Lat Ventricles|CSF
Tight Jxn|enter only thru passive dffsn
1/1000 SA of BBB|active trnsptr|enz
Placenta pores|Lg or charged cross|
Lipophilic crosses readily|simple dffsn
P-gp|pH7-7.2|pH than mom|
***Fetus is exposed to some extent all Rx taken***

Testis/prost sertoli|tight Jxn|pore|limited distr
Synovial pores|perm if inflamed
Lungs large cap SA|Rx meta|*Dapto
Blood from all organs pass thru lungs
Bodily fluid passive non-ionic dffsn|ion trapping

Distr can be limited by prot binding
Albumin|acidic Rx|1-gp|basic Rx
Only free Rx can cross|enz meta|filter
Reversible|buffering
Rx interxn two Rx compete|transient [Rx]|elim
***Duration & significance of effect dep on t
1/2
***

Storage prot bound=storage|accum in tissue
Fat soluble|accum in adipose
Affinity for Ca or |accum bn & teeth

Diseases
plasma prot|Rx bound|free Rx in blood
o synthesis|liver|albumin
o prot excretion|renal neprhititis
plasma prot|Rx bound|free Rx in blood
o Acute phase response|prot syn
o CA|arthritis|Crohns|MI



Elimination H
2
O soluble mlc|Kidneys
MW|Prot bnd|Charge|PC

Glom Filtration|MW<50kDa|20%|bnd
PT Active secretion|charged mlc|[bnd]
Grad|dffsn|peritubular cap|alb bnd
dev in babies|with age b/c GFR
DT Reabsorption|N|wA/B|Fav PC
pH dependent
***1% of filteredurine|2/3 reabsorbed***

Active secretion
Rx
+
|BL Blood|OCT1,3|Import Rx
+
|Pm
Rx
+
|Apical Urine|MATE1,2k|Na
+
/H
+
|H
+
/Rx
+
|P-gp
Metformin OCT2|MATE1|99.9% elim by kidneys

Rx
-
|BL OAT1,3|Ex Rx
-
/KG
2-
|3|
Na/K pump|NaDC3|KG|Rx
-
|
Rx
-
|Apical MRP2,4 (ABC)|ATP hydrolysis|xenoBt
Conj|glucuronate|glutathione|
PCN OAT1,3|MRP4|98% elim by kidneys
Probenecid Rx
-
|Good PC|90%bnd|active secrete
Compete w/PCN to prolong PCN t
1/2

Tx Gout|promote uric acid excretion

Reabsorption
Salt & H
2
O actively reabsorbed|[Rx]
urine
[Rx]
p

creating a grad for Rx reabsorption

pH pH|wA N|pH|wB N|Rx
Rate Reabs PC|pKa|pH
***as urine concentrates, Rx with low water solubility
[Rx] & precipblock tubular flow***

Inulin (Frc)
n
|N|PC=0|bnd|WM=5kDa|
20%filtered|secrete|reabsorbed
Very H2O soluble|GFR dep ONLY
GFR x [Inu]
p
=UFR x [Inu]
u



Biotransformation Chem Mod|Conjugation
Liver|lung|kidney|brain|(blood)

Prob H2O soluble|highly bnd|well reabs
Soln Chem mod H2O solub|lipid solub

Phase I Oxidation|Hydrolysis|CYP
CYP RLS|low selectivity|slow Rxn rate
P450 Pink w/CO|Peak abs @450nm
Oxidize Rx|Heme Fe|O
2
H
2
O|
NADPH-P450 reductase|flavoprot|e
-

Liver meta CYP3A4|50%Rx|CYP2D6|20%

P450 Oxidation
Hydroxylation Ibuprofen|S-warfarin
Deamination (1) -OH-amphetamine|
N-dealkylation Theophylline||1/10 activity
O-dealkylation CodeineMorphine ()
N-oxidation acetaminophenNAPQI (toxic)
S-oxidation Omeprazole sulfone ()

P450 Hydrolysis
Epoxide Hydrolase CYP prod epoxide ()|EH
Carbamazepinediol ()
Esterase EsterAcid+Alcohol
Esmolol|1 selective adr|
Latanoprost|glaucoma Tx|
Amidase LidometaXylidide


Phase II Conj|add H-philic sub|low PC|Rx
Exception: morphine|minoxidil

Glucurondtn Gulcuronate|UDP-glucuronic|UGTs|
ER|microsome|liver|GI|inducible
(UGTs) H
2
O solub|provides neg charge
bnd|filtration|anion pump|reabs
UDP-UGT+AcetaminephRx- ()|65%
UGT1 conj|bilirubin|UGT1A1 mutation
Gilberts|Crigler-Najjar|jaundice
UGT2 endogenous substance|steroids

Sulfation Sulfate|PAPS|SULTs|to Ar-OH
(SULTs) SULT1,2,4,6|liver|GI|skin
Endogenous|hormone|XenoBt|SULT1
Acetaminophen+PAPSmeta()|30%
*Minoxidil ()+PAPSmeta ()|vasoD
Glutathione -carboxyl|Glu-Cys-Gly|Rxt w/e-philic
(GSH) GSHGSSH+NADPH2GSH+NADP
+

Conj mediated by GST|
Microsomal GST|endogenous|LTs
Cytosolic GST|xenoBt|Rx
NAPQI+GSHtox meta|Glu-Gly rmv
Cys N-acetylated|merapturic acid
***Acetaminophen overdose depletes GSH; liver tox
can be minimized with N-Acetyl-Cys Tx***

N-Acetylatn Acetyl|AcCoA|NATs|Rx polarity
NAT1|ubiquitous|NAT2|GI & Liver
Hydralazinemeta ()|
Genetics|fast|16%slow|35%|~SLE Sx

Methylation Methyl|SAM|TPMT|O,N,S|Rx polarity
Epinephrine syn|catecholCOMT|
Azithioprine6-mercatopurinemeta ()
***TPMT catalyze 6-MP to inactive metabolite; TPMT
dfcn due to mutation=severe toxicity when taking 6-
MP derived RxImmSupp|RA|IBD|chemotherapy***


LIVER
HPV & HA to central v|GI Rx|HPV|Rest of body|HA
Liver sinusoid extract Rx via transporters & passive
dffsn
Rx transported out of liver by
1. Into sys circ|kidney excretion
2. Bile canaliculus|GB|bile duct|Sm Int

Sinusoid mb (SLC) OAT|OATP|OCT
Pm|Na/K pump
Canaliculi mb(ABC) P-gp(MDR1)|MRP2|BRCP
ATP hydrolysis
Blood (ABC) via sinusoid mb|MRP1,3,4
ATP hydrolysis


































Enterohepatic cycling


DDI due to t
1/2

Most Rx in the cycle ultimately elim by kidneys
Rxcycle by reabst
1/2
|source of Rx interaction
ABt that kill bacteria in GI
Non-abs polymers|cholestyramine|fiber





Biliary Excretion
Rx
Poor PC
Remain in GI
Stool
Fav PC
Reabs via passive
dffsn
Back to liver
(via blood)
Liver
Conj
w/glucuronic
Very bad PC
Bact in colon rmv
glucuronic
Free Rx w/Fav PC
Back to Liver
Free Rx w/Bad
PC
Stool
Rx Response Variation

Genetic variation Metabolism|Transporters

Rx Meta P450|UGT|NAT|Cholinestease|TPMT
P450 2D6|4 phenotypes|/Rx metabolism
Poor/P|intermed/IM|Extnsv/NL|ultrarpd/UP

Poor allele|CYP2D6*4|Ccsn|Afrc|Asn
Ultrarpd multiple gene copies|13|
Ethiopn|Spaniards|Swedes

Rx Trans ABC|SLC
ABC P-gp|BCRP|MRP2
SLC OCT|OAT|MATE

CYP2D6
Affected Rx Tricyclic|-blocker|||tamoxifen|
Tamoxifen by CYP|poor=poor resp to tamox

MEC & MTC but pts ability to metabolize codeine
influence the effects of the Rx. For instance, P may
not have enough active morphine in blood to reach
MEC for analgesic effects whereas UR would have too
much morphine surpassing MTC to prod toxic effects.

Poor Ultra rapid
Codeine Cmax Cmax
Morphine Cmax Cmax


CYP2C19
1 2,3 4,5,6,7,8
Max activity activity /activity

4 Pheno P|IM|NL|UR
P 2 defective|2% Ccsn|14% Chinese|
Affected Rx Omeprazole|Clopidofrel
Omeprazole Prilosec|f=30-40%|stom acid scr
2C19|demethylation|hydroxylation

Clopidofrel Plavix|2C19 oxi|esterase 40%|Hlysis
3A4 oxi|CES1 esterase 90%|6%
DDI Ome2C19|clop|effective

CYP2C9 1,2,3 metabolic activity
Affected Rx Warfarin

CYP3A4 2,7 Ccsn|16,18 Asn|low clnc signifc
Dual pathway|3A5|diff meta rate

NAT2 2 pheno|rapid|slow|5A,6A,7A
Affected Rx Hydralazine|INH|Carcinognc arylamine
Hydralazine active Rx lvl|SLE-like Sx
INH t1/2|1hr3hr|periph neuropathy
CA arylamine CA risk after prolonged exposure

UGT1A1 glucuronidation|bilirubin|
*6|20%|Jpn|Chn|neonatal jaundice
Crigler-Najjar-I|CrNj-II|Gilberts
CrNj-I conj bilirubin|early childhood death
CrNj-II conj bilirubin|jaundice
Gilberts promoter mutation|expr
**GI & Bn tox to Colorectal CA Rx irinotecan
(proRx|enterohepatic cycling) due to
glucuronidation of active metabolite**


Rx Trans MRP2|BCRP|OAT

MRP2 ABC|Rx- out|hepatocytebile|
Dfcn| transport from liverbile well
GI tox of irinotecan|BM tox though
BCRP Gln141Lys|activity|biliary excretion
30-60% Asn|5-10% Ccsn & AA
Rosuvastatin HMG-CoA reductase|chol syn
90% bile CL|mutation effect & tox
Asn|2xAUC|2xCmax|5mg|Ccsn20mg

OATP1B1 Rx- into|
Simvastatin ProRx|N
0
lactone|fav PC|1
st
pass
Liver|H-lysis|acid|low PC|OAT
Enterohepatic cycle|MRP2
OATP1B1|get in liver well|[Rx]p
[simva acid]
p
|myopathy|efficacy





DDI Physiologic|Pharmacologic
Pharm DDI Rx1 directly aff PharmDyn/Kin of Rx2

Abs pH|trapping|solub|trans|motility|bac meta

Rx that pH Rx affected by pH
Antacid
NaHCO
3

Mg(OH)
2

CaCO
3

H2 Antg|cimetidine
H
+
pump |omep
PCN G
Ketoconazol|itraconazol|amp
Fe supplement (FeSO
4
)
Bisacodyl coated laxative
Digoxin (10% in f)
Atazanavir (protease )

Trapping Rx that interact with another abs
Non-abs Rx|bind other Rx|fiber
Charged polymer|antacids multivalent
Tetra|FQ|Cipro

Transporter P-gpabs & elim
Cyclosporine|quinidine|clarith|itraco
Cyclosporine Target T|immsupp Rx|prev renal rjct
Sirolimus GI abs=limited by P-gp|CSA siro abs
Admin 4hr apart to minize DDI

Motility motilityabs|clnc significant
stom emptying=delay abs

Distr
Liver BF -blocker|hepatic BF|Rx meta
rpd meta Rx|deliv to liver=RLS

Prot bnd compete|transient on free []|warf
Lvl of eff dep on V
d
|clnc signfcnt

BBB Loperamide opioid|cross BBB|
Quinidine coadminCNS eff|P-gp

Elim Biotransformation|Excretion
Biotrans biotrans|compete|Irrev|CYP3A4
Compete Rx meta by same pathway
Irrev Cimetidine|irrev bnd CYP|Rx elim
Wafarin|Diazepam|Chlordiazepoxide

3A4 Inhibitor
Antifungal Ketoconazole
Itraconazole
Immunosuppressant Cyclosporine
Antibiotics Erythromycin
Clarithromycin
HIV protease Inhibitor Ritonavir
Indinavir
Food/drink Grapefruit juice has
furano-coumarins which
intestinal
CYP3A4proteolytic
degradation

Transporter

INDUCTION
***the purpose of biotransformation is to protect the
body against xenoBt and other foreign sub; when you
are exposed to a large amount of xenoBt, its logical
to induce biotransformation***

NR|TFprot syn|p450|RLS
DDI|Low selectivity|induce meta of >1 Rx

Nuclear R Ligands Induces
PXR
Pregnane
Rifamin
Phenobarbital
Carbamazepine
Phenytoin
Ritonavir
Paclitaxel
Statins
CCB
Glitazone
St. Johns Wart
(hyperforin)
CYP3A4
SULTs
UGTs
P-gp
CAR
Constitutive
Pehnobarbital CYP2B6
CYP2C9
CYP3A4
UGTs
SULTs
GSTs
AHR
Aryl hydrocarbon
Omeprazole
Cigarette smoke
(polycyclic AHs)
CYP1A1
CYP1A2
CYP1B1

Pharmacokinetic Tolerancewhen Rx induces its
own metabolism
Carbamazepine Antiepileptic|t1/2|36-8/12hr
Bosentan Endothelin antg|Tx pulm HTN
*even though t1/2 of rosentan is 5hr, it takes 3-5d to
reach steady state when given 62.5mg twice daily*

Renal Excrtn Compete trans|pH
u
|passive reabs

2
nd
Rx elim[1
st
Rx]
p
1
st
Rx dose
2
nd
Rx elim|reabs|Rx meta|[1s Rx]
p
D




Age pharmKin|body fat:H
2
O|
BodFat:H2O with age|/ V
d
|Rx H
2
O or fat solub
V
d
determines D
load
|t
1/2
|oscillation
[Rx]
p
=X
admin
/V
d
|

Peds sens to Rx|immature organ dev
clnc trial|unpredictable abs

Stom acid scrt Stom emptying
& peristalsis
Bile level
Low @ birth
|hrs/d/2yr
Slower
Irregular
Slows abs|
Amt
Low bile
abs or lipid
soluble Rx

Biotrans P450 peak @ 2-6mo|faster than adults
CYP1A2 peak @2yr|@puberty
*P450 can be induced by mom taking phenobarbital*
**Glucuronidation takes 3-4yr to reach adult lvl**
***Bilirubin accumulates in newborns***

Renal excretion in peds
Low renal BF
Neonate GFR=30-40% adult value
3wk GFR=50-60%
6-12mo GFR=100%
GFR of kids continue to above adult values

Geriatrics >75yo|many Rx|SE/DDI|compliance
Nutritional prob|limited $|diff Rx resp
Rx sens|homeostatic mech less effcnt
Diff resp Wt|muscle mass|H
2
O|fat
renal fxn|CO|lung capacity
Abs GI motility|t
empty
|stom scrt|GI BF
Slower abs but extent unaffected
Distr/Elim Alb|fat:H
2
O|/ V
d
dep on Rx solub
live size|BF|CYP450|Rx t
1/2
Renal elim All : BF|GFR|PT secretion|#nephron
Monitor renal fxn via creatinine CL
Rule: use lower doses in geriatric pt

Diseases Impair: p450|Rx excretion|BF to liver


TOLERANCE
Pharmacodynamic Rx resp|[Rx]
p
|tachyphylaxis
Opioids DR right shift|dev rapidly
Benzodiazepine antiepileptic
-adr Agonists bronchodilator|asthma
persistent -R in lungs|reg
Shortterm PKA,-ARK,-arrestin
Longterm R#
-adr Antagonists HTN|Angina|Prolong|R#
Rebound phenomenon| upon Rx w/d

Pharmacokinetic Metabolic|Dispositional
[Rx]
p
due to cont admin

















































Toxicology

Toxicology is governed by the same principles as
pharmacology. HOWEVER, overdose characteristics
may be different from those of therapeutic doses.

Abs rate|extent|stom emptying|bezoar
Distr BPrt saturate|free Rx|%bnd|Vd
pH|distr wA & wB|Rx induced
hypoperfusion|distr|delay elim
Elim f|Rx meta enz saturate|
Elim t
1/2
|1st order|pump saturate
Dmg liver/kidn|blood pH|perfusion

General Tx Principles

1
st
KEEP Pt ALIVE
ABCD airway|breathing|circulation|dextrose

2
nd
Minimize Toxicity
Minimize absorption
(GI decontamination)
Maximize elimination
Induce emesis
Gastric lavage
Activated Charcoal
Cathartics & Laxatives
Whole-bowel irrigation
Renal excretion
Forced diuresis
Elim wA Rx
Elim wB Rx
MDAC
Biotransformation
Hemodialysis|perfusion

Consider WBI if Rx is:
Slowly absorbed
Fe tablet (Fe2+ not abs by charcoal)
Poisons not adsorbed by charcoal
Cocaine-filled condoms






















Enhance Rate of Elimination

Forced diuresis
Give large volume of IV diuretic (furosemide) to
increase urine production. The procedure is obsolete.

Alkalization of urine|Weakly acid Rx
Elimination of weakly acidic drugs by alkalinizing the
urine. As salts and water are reabsorbed in the
tubules, the concentration of drugs in urine increase
to generate a favorable gradient for reabsorption. If
Rx is uncharged and have a favorable PC, it will be
reabsorbed passively. The rate of reabsorption dep
on PC, pKa, and urine pH.
Alkalination of the urine will resulting in ion trapping
thus, inhibiting reabsorption and promoting excretion.
NaHCO
3

o IV|pH7.5-8.5
o Nonionic reabsorption of CO
2

alkalinizes the urine
o pH in blood relatively small due to
greater volume & buffering power
o Useful for ASA & Phenobarbital
Other barbiturates are
metabolized rapidly so Renal
excretion play enough a
role for this to be used
ASA 138Da|80%bound|pKa=3.0|wA|active scrt
Good PC|reabs|
PhBbt CNS depressant|anticonvulsant|antiepileptic
232Da|50%bound|pKa=7.3|wA|active scrt
Very fav PC|almost all uncharged @ urine pH
Extensively & efficiently reabsorbed

Acidification of urine|Weakly basic Rx
Same principle as alkalization for weakly acidic drugs.
Note that this only works if there is significant non-
ionic reabsorption of Rx in DT thus, significant
amount of Rx must 1
st
by filtered or actively secreted.
NH
4
Cl|VitC
o [NH
4
]
u
& [NH
4
]
p
|generate gradient
o Nonionic reabsorption of NH3 acidify
urine
o Enhance elim of MDMA & PCP
Urine is usually acidic anyways & further
acidification can exacerbate renal complications of
rhabdomyolysis often associated with amphetamine
overdose. RARELY USED

Single Dose kinetics
Dose

t
max

t
1/2

C
max

AUC
TOA
DOA
OOA

CL

C
max

t
max

t
1/2

AUC
DOA
TOA

k
abs


t
1/2
AUC

T
max

OOA
TOA
C
max

t
max


Slow/Extended Release Rx


Combined Rapid and Slow Release Rx

ie. Zolpidem (Ambien)

Problem with these extended release Rx is if pt takes
them via a faster absorption method (crushing it, IV)
is toxicity of the Rx.