Michael Jackson's Cause of

Death
ETATUTWUNI
0911013101

Sudden death was caused by an

overdose of propofol - an
anesthetic that is normally used in
the operation - which injected a
personal physician, Dr.. Conrad
Murray

DESCRIPTION
DIPRIVAN (propofol) Injectable Emulsion is a
sterile, nonpyrogenic emulsion containing 10
mg/mL of propofol suitable for intravenous
administration.
Propofol is chemically described as 2,6diisopropylphenol and has a molecular weight of
178.27.

CLINICAL PHARMACOLOGY
General
DIPRIVAN Injectable Emulsion is an intravenous
sedative-hypnotic agent for use in the induction and
maintenance of anesthesia or sedation. Intravenous
injection of a therapeutic dose of propofol produces
hypnosis rapidly with minimal excitation, usually
within 40 seconds from the start of an injection (the
time for one arm-brain circulation). As with other
rapidly acting intravenous anesthetic agents, the
half-time of the blood-brain equilibration is
approximately 1 to 3 minutes, and this accounts for
the rapid induction of anesthesia.

Pharmacodynamics
Pharmacodynamic properties of propofol are
dependent upon the therapeutic blood propofol
concentrations. Steady state propofol blood
concentrations are generally proportional to
infusion rates, especially within an individual
patient.
Undesirable side effects such as cardiorespiratory
depression are likely to occur at higher blood
concentrations which result from bolus dosing or
rapid increase in infusion rate. An adequate interval
(3 to 5 minutes) must be allowed between clinical
dosage adjustments in order to assess drug effects.

 The hemodynamic effects of DIPRIVAN Injectable

Emulsion during induction of anesthesia vary. If
spontaneous ventilation is maintained, the major
cardiovascular effects are arterial hypotension
(sometimes greater than a 30% decrease) with little
or no change in heart rate and no appreciable
decrease in cardiac output.
If ventilation is assisted or controlled (positive
pressure ventilation), the degree and incidence of
decrease in cardiac output are accentuated.
Addition of a potent opioid (e.g., fentanyl) when
used as a premedicant further decreases cardiac
output and respiratory drive.

Pharmacokinetics
The proper use of DIPRIVAN Injectable
Emulsion requires an understanding of the
disposition and elimination characteristics of
propofol.
The pharmacokinetics of propofol are well
described by a three compartment linear model
with compartments representing the plasma,
rapidly equilibrating tissues, and slowly
equilibrating tissues.

 Following an IV bolus dose, there is rapid

equilibration between the plasma and the highly
perfused tissue of the brain, thus accounting for
the rapid onsetof anesthesia. Plasma levels
initially decline rapidly as a result of both rapid
distribution and high metabolic clearance.
Distribution accounts for about half of this
decline following a bolus of propofol.

 However, distribution is not constant over time, but

decreases as body tissues equilibrate with plasma and
become saturated. The rate at which equilibration occurs is a
function of the rate and duration of the infusion. When
equilibration occurs there is no longer a net transfer of
propofol between tissues and plasma.
Discontinuation of the recommended doses of DIPRIVAN
Injectable Emulsion after the maintenance of anesthesia for
approximately one-hour, or for sedation in the ICU for oneday, results in a prompt decrease in blood propofol
concentrations and rapid awakening. Longer infusions (10
days of ICU sedation) result in accumulation of significant
tissue stores of propofol, such that the reduction in
circulating propofol is slowed and the time to awakening is
increased.

Michael Jackson Battled

Demerol Addiction

Demerol Dosage and Administration

General
Give the smallest effective dose and as
infrequently as possible to minimize the
development of tolerance and physical
dependence.
Reduced dosage is indicated initially in poor-risk
patients, in geriatric and very young patients, in
patients with renal (particularly) or hepatic
impairment, and in patients receiving other CNS
depressants.

Reduce meperidine dose by 2550% when used in

conjunction with other CNS depressants (e.g.,
phenothiazines, other tranquilizers); dosage
adjustment for the concomitantly administered drug
also may be necessary.
Orally, 300 mg is approximately equianalgesic with 30
mg morphine sulfate.c 245 248 Parenterally, 75100
mg is approximately equianalgesic with 10 mg
morphine sulfate.c 245 248 (For specific patient
dosages, see dosage recommendations in Dosage and
also see Prescribing Limits under Dosage and
Administration.)

Generally limit to short-term use (a few days)

because of risk of accumulation of toxic
normeperidine metabolite with repeated or large
doses

Administration
Oral Administration
Least effective when given orally.b 246 247 245
Higher dosages may be necessary for pain relief, but
the risk of toxicity from metabolite normeperidine is
increased.247 248
Oral therapy is discouraged because of extensive firstpass metabolism in the liver and resultant increased
formation of the toxic metabolite (normeperidine).

IV Administration
Administer by direct IV injection, IV infusion, or IV via a
controlled-delivery device for patient-controlled analgesi
If IV administration is required, decrease dosage and administer
injections very slowly, preferably as a 10-mg/mL injection.
Alternatively, may use the commercially available injection
containing 10 mg/mL intended for use with a compatible
infusion device (does not require further dilution); this 10mg/mL injection is for single use only, and unused portions
should be discarded appropriately.
When given parenterally, especially by the IV route, the patient
should be lying down.
During and immediately following IV administration, an opiate
antagonist and facilities for administration of oxygen and control
of respiration should be available

Demerol Pharmacokinetics
Absorption
Bioavailability
Oral: Undergoes extensive first-pass metabolism
in the liver, with approximately 5060% of a
dose reaching systemic circulation unchanged.
Oral: Bioavailability increases to approximately
8090% in patients with hepatic impairment.
Less than half as effective when given orally as
when given parenterally.
IM: Approximately 8085% of a dose of the drug
is absorbed within 6 hours after intragluteal
injection.

Onset
Oral, peak analgesia: Within 1 hour and declines
gradually over 24 hours.
Sub-Q, peak analgesia: In about 4060.
IM, peak analgesia: In about 3050 minutes.
Duration
Sub-Q or IM: Analgesia is maintained for 24
hours.
Plasma Concentrations
Oral, peak: About 1 hour.
IM, peak: Within 515 minutes.

distribution
Extent
Crosses the placenta; may accumulate in fetus.
Distributes into breast milk
Plasma Protein Binding
Approximately 6080%;246 212 principally
albumin and 1-acid glycoprotein

Elimination
Metabolism
Principally in the liver.
Normeperidine is the active metabolite and exhibits
about half the analgesic potency of meperidine but
twice the CNS stimulant (e.g., seizure-inducing)
potency.
Various toxic effects secondary to CNS stimulation
(e.g., seizures, agitation, irritability, nervousness,
tremors, twitches, myoclonus) have been attributed
to accumulation of normeperidine.

Elimination Route
Excreted in urine as metabolites and unchanged
drug.
Acidifying the urine enhances excretion of the
unchanged drug and normeperidine.
Half-life
Distribution phase half-life, meperidine: 211
minutes
Terminal elimination half-life, meperidine: 35
hours.
Terminal elimination half-life, normeperidine:
Approximately 821 hours

 Special Populations
Elimination half-life in hepatic dysfunction,
meperidine: Prolonged.
Cirrhosis207 213 215 or active viral hepatitis:207
216 Averages about 711 hours.
Terminal elimination half-life in renal impairment,
normeperidine: May be prolonged (e.g., 3040
hours).
Renal or hepatic impairment: Accumulation of
normeperidine may occur with repeated, high doses
of the drug

CONTRAINDICATIONS
Hypersensitivity to meperidine(demerol).
Patients who are receiving MAO inhibitors or
those who have received MAO inhibitors in the
past 14 days (ex. selegline, carbex, eldepryl, and
others).
Patients with renal insufficiency (creatine
clearance less than 50 mL/min).
Patients with untreated hypothyroidism,
Addisons disease, benign prostatic hypertrophy,
or urethral stricture.

List medicine which MJ use before he died

Dilaudid
Vicodin
ZOLOFT

dilaudid

difinition
Dilaudid (hydromorphone) belongs to a group of
drugs called narcotic pain relievers, also called
opioids. It is similar to morphine.
Dilaudid is prescribed for the relief of moderate to
severe pain. It works by binding to certain
receptors in the brain and nervous system to
reduce pain.
Dilaudid may also be used for other purposes not
listed in this medication guide.

structure

Pharmacokinetics and Metabolism

The analgesic activity of DILAUDID (hydromorphone hydrochloride)
is due to the parent drug, hydromorphone. Hydromorphone is
rapidly absorbed from the gastrointestinal tract after oral
administration and undergoes extensive first-pass metabolism.
Exposure of hydromorphone (Cmax and AUC0-24) is doseproportional at a dose range of 2 and 8 mg.
In vivo bioavailability following single-dose administration of the 8
mg tablet is approximately 24% (coefficient of variation 21%).
Bioequivalence between the DILAUDID 8 mg TABLET and an
equivalent dose of DILAUDID ORAL LIQUID has been
demonstrated.

Absorption
After oral administration of DILAUDID 8 mg
liquid or tablets, peak plasma
hydromorphone concentrations are
generally attained within to 1-hour

Distribution
At therapeutic plasma levels, hydromorphone is
approximately 8-19% bound to plasma proteins. After an
intravenous bolus dose, the steady state of volume
distribution [mean (%cv)] is 302.9 (32%) liters.

 Metabolism

Hydromorphone is extensively metabolized via

glucuronidation in the liver, with greater than 95%
of the dose metabolized to hydromorphone-3glucuronide along with minor amounts of 6hydroxy reduction metabolites.

Elimination

Only a small amount of the hydromorphone dose

is excreted unchanged in the urine. Most of the
dose is excreted as hydromorphone-3-glucuronide
along with minor amounts of 6-hydroxy reduction
metabolites. The systemic clearance is
approximately 1.96 (20%) liters/minute. The
terminal elimination half-life of hydromorphone
after an intravenous dose is about 2.3 hours.

vicodin

structure

CLINICAL PHARMACOLOGY
Hydrocodone is a semisynthetic narcotic
analgesic and antitussive with multiple actions
qualitatively similar to those of codeine. Most of
these involve the central nervous system and
smooth muscle. The precise mechanism of action
of hydrocodone and other opiates is not known,
although it is believed to relate to the existence of
opiate receptors in the central nervous system. In
addition to analgesia, narcotics may produce
drowsiness, changes in mood and mental
clouding.

Pharmacokinetics

The behavior of the individual components is

described below.
Hydrocodone
Following a 10 mg oral dose of hydrocodone
administered to five adult male subjects, the mean
peak concentration was 23.6 5.2 ng/mL.
Maximum serum levels were achieved at 1.3 0.3
hours and the half-life was determined to be 3.8
0.3 hours. Hydrocodone exhibits a complex pattern
of metabolism including O-demethylation, Ndemethylation and 6-keto reduction to the
corresponding 6-- and 6--hydroxy-metabolites.
See OVERDOSAGE for toxicity information.

 Acetaminophen
Acetaminophen is rapidly absorbed from the
gastrointestinal tract and is distributed throughout
most body tissues. The plasma half-life is 1.25 to 3
hours, but may be increased by liver damage and
following overdosage. Elimination of
acetaminophen is principally by liver metabolism
(conjugation) and subsequent renal excretion of
metabolites. Approximately 85% of an oral dose
appears in the urine within 24 hours of
administration, most as the glucuronide conjugate,
with small amounts of other conjugates and
unchanged drug. See OVERDOSAGE for toxicity
information.

 INDICATIONS AND USAGE

VICODIN tablets are indicated for the relief of
moderate to moderately severe pain.
CONTRAINDICATIONS
This product should not be administered to patients
who have previously exhibited hypersensitivity to
hydrocodone or acetaminophen.
Patients known to be hypersensitive to other opioids
may exhibit cross-sensitivity to hydrocodone.

ZOLOFT
Pfizer
Sertraline HCl
Antidepressant - Antipanic Antiobsessional Agent

Action And Clinical Pharmacology:

The mechanism of action of sertraline is
presumed to be linked to its ability to inhibit
the neuronal reuptake of serotonin. It has only
very weak effects on norepinephrine and
dopamine neuronal reuptake. At clinical doses,
sertraline blocks the uptake of serotonin into
human platelets.
Like most clinically effective antidepressants,
sertraline downregulates brain norepinephrine
and serotonin receptors in animals. In receptor
binding studies, sertraline has no significant
affinity for adrenergic (alpha1, alpha2 and
beta), cholinergic, GABA, dopaminergic,
histaminergic, serotonergic (5-HT1A, 5-HT1B,
5-HT2) or benzodiazepine binding sites.

Pharmacokinetics
Following multiple oral once-daily doses of 200
mg, the mean peak plasma concentration (Cmax)
of sertraline is 0.19 g/mL occurring between 6 to
8 hours post-dose. The area under the plasma
concentration time curve is 2.8 mg h/L.
For desmethylsertraline, Cmax is 0.14 g/mL, the
half-life 65 hours and the area under the curve 2.3
mg h/L. Following single or multiple oral once-daily
doses of 50 to 400 mg/day the average terminal
elimination half-life is approximately 26 hours.
Linear dose proportionality has been
demonstrated over the clinical dose range of 50 to
200 mg/day.

Contra-Indications
In patients with known hypersensitivity to
the drug.
MAO Inhibitors: Cases of serious, sometimes
fatal, reactions have been reported in
patients receiving sertraline in combination
with an MAO inhibitor, including the
selective MAO inhibitor, selegiline and the
reversible MAO inhibitor (reversible
inhibitor of MAO-RIMA), moclobemide.