LAS 1

Lesson Title:
Pharmacokinetics

Group 1:
Bascar, Christine
Cuares, Li Reinae
Dayondon, Alyssa
Estomo, Loury Anne
Roflo, Jovito
OBJECTIVES:
Explain the principles of drug
absorption, distribution, metabolism
and excretion, as well as factors
influencing these processes

Apply knowledge of basic

pharmacokinetic principles on
practice- based case stud
QUICK REVIEW:
PHARMACOLOGY

PHARMACOKINETICS PHARMACODYNAMICS

ADME MOA

B ---> D D ---> B
Activity 1: Drug Absorption
Activity 1: Drug Absorption

1.1 Case study.

A 20-year-old female patient is brought to the emergency
department due to heroin overdose. What is the most
desirable route of administration for administering the
antidote naloxone? Explain.
Activity 1: Drug Absorption

In relation to the given case, the most desirable route of

administration for administering naloxone as an antidote to opioid
overdose is through intravenous or IV route. This is because drugs
given intravenously do have 100% bioavailability, thereby having
the capability to generate the most rapid onset of action in reversing
opioid overdose and resuscitate individuals who otherwise might
have died in the absence of treatment.
Activity 1: Drug Absorption
1.2 Phenytoin is a weakly acidic drug with a pKa of 8.3. If
administered orally, at which of the following sites of
absorption will the drug be able to readily pass through the
membrane?

A. Mouth (pH approximately 7.0).

B. Stomach (pH of 2.5).
C. Duodenum (pH approximately 6.1).
D. Jejunum (pH approximately 8.0).
E. Ileum (pH approximately 7.0).
Activity 1: Drug Absorption

Weakly acidic drugs are easily absorbed in a low pH

medium such as in the stomach. In consideration that
Phenytoin is a weakly acidic drug, when administered
orally, it is more likely to be absorbed in the stomach
which has a pH of 2.5 since weakly acidic drugs are
best absorbed in an acidic environment.
Activity 1: Drug Absorption

1.3 Case Study.

A 28- year- old female was given tetracycline
to treat her UTI. What are the foods that the
patient should avoid? Why?
Activity 1: Drug Absorption

When treated with Tetracycline for a urinary track infection, the

foods that the patient should avoid while taking the indicated drug
are dairy products such as milk, yogurt, cheese and ice cream. It
should also be noted not to intake calcium containing products and
other minerals along with tetracycline. It is because tetracycline is an
antibiotic drug which is not suitable to be taken with the mentioned
foods and drinks as those were most likely to inhibit the effects or
actions of the antibiotic.
Activity 1: Drug Absorption

1.4 Explain the term “First- pass effect”. How does it

affect bioavailability? Give examples of 3 drugs that
undergo significant first- pass effect.
Activity 1: Drug Absorption

First-pass effect refers to a phenomenon in which a drug

gets metabolized at a specific location in the body that
results in a reduced concentration of the active drug
upon reaching its site of action or the systemic
circulation.

It does affect bioavailability in a sense that when a drug

is administered orally, it enters the liver, and undergoes
extensive biotransformation to such an extent that the
bioavailability is drastically reduced.
Activity 1: Drug Absorption

Examples of drugs that undergo significant first-pass effect:

• Propranolol
• Morphine
• Nitroglycerin
Activity 1: Drug Absorption

1.5 Identify at least three routes of drug administration

that avoid first- pass hepatic effects.
Activity 1: Drug Absorption

Transdermal Topical Nasal Inhalation

Activity 2: Drug Distribution
Activity II: Drug Distribution

2.1 If a drug’s volume of

distribution is significantly
larger than normal human
body volume, what does that
mean?
 Activity II: Drug Distribution
The volume of distribution of individual drug varies. Either, remain in the
plasma or is being redistributed to other tissue compartments.

Two scenarios:
A. A drug with a higher VD has the tendency to leave the plasma and enter
extravascular compartments of the body.
HIGH VD = MORE DISTRIBUTION TO OTHER TISSUES

B. A drug with a low VD conversely to a higher VD it is likely to remain in the

plasma.
LOW VD = LESS DISTRIBUTION TO OTHER TISSUES

Therefore, if the drug’s volume of distribution is significantly larger than normal

body volume, meaning the drug is easily distributed throughout the body.
Activity II: Drug Distribution

What is drug plasma protein

binding? How does it affect
volume of distribution of
drug?
Activity II: Drug Distribution
Plasma protein binding refers to the degree when certain
drugs attach to blood proteins within the blood plasma.
Drugs can bind to various proteins, including plasma and
tissue proteins, either specifically or non-specifically. This
can affect drug distribution, as the drug may be trapped in
particular tissues.

Unionized drugs cross cell membranes more readily, to

distribute to the action site. Changes in environmental pH
may therefore alter distribution, due to changes in the
Ionization of a drug. Ex. Lidocaine (a weak base) may be less
effective in the acidic environment of infected tissue.
Activity II: Drug Distribution

2.3 Explain why 1 st generation

antihistamines are more sedating
than 2 nd generation
antihistamines whicharenon-
sedating/ mildly sedating. Give
examples of each class of
antihistamines.
 Activity II: Drug Distribution

The First-generation antihistamines are more sedating than the

2nd generation because of its ability to cross the blood-brain
barrier which then blocks both histaminic and muscarinic
receptors. As for the 2nd-generation it mainly blocks histaminic
receptors and do not pass the BBB.
Activity 3. Drug
Metabolism:
3.1 Why is chloramphenicol
not given to neonates?
 ANS: Neonates have a diminished ability to
conjugate chloramphenicol and inability to
metabolize the drug chloramphenicol results in
Gray Baby Syndrome, which is a potential side
effect of the antibiotic chloramphenicol. Neonates
don't have the liver enzymes needed to metabolize
the large doses of chloramphenicol as this can
result in a high toxic level of antibiotics build up on
their bloodstreams.
3.2 CASE STUDY.

A 52- year old patient with heart failure who

has been taking digoxin presented to hospital
with a recent history of fatigue, dyspnea on
exertion, cough, nausea, vomiting & diarrhea,
loss of appetite, and blurred vision. Three days
prior to his presentation, the patient had been
started on clarithromycin 500 mg PO twice daily
for the treatment of possible pneumonia.
A. What are the symptoms experienced
by the patient?

ANS: The symptoms experienced by the

patient include recent history of
fatigue, dyspnea on exertion, cough,
nausea, vomiting, diarrhea, loss of
appetite, and blurred vision.
 B. What are the medications taken by
the patient for the past three days prior
to hospital visit? What is the
possible interaction between these
drugs?
ANS: The old patient with heart failure has been
taking digoxin and clarithromycin 500 mg orally
three days prior to his hospital visit. Possible
interaction results by the clarithromycin may
inhibit the growth of E.lentum (found in human
colon and feces, can cause ulcerative colitis,
liver and anal absences), which can lead to an
increase in the digoxin bioavailability and blood
concentrations in patients.
C. What can be given to the patient to
alleviate the symptoms he is currently
experiencing?
ANS: To alleviate symptoms that the patient is
currently experiencing, large doses of activated
charcoal can be given as this prevents further
absorption of digoxin and decreases serum levels
by intestinal binding of digoxin. In addition,
digoxin immune fab or digoxin-specific antibody is
also an option in alleviating the symptoms of the
patient as well as lessening the dosage of digoxin
or finding an alternative antibiotic drug that does
not cause any drug-drug interaction with digoxin.
3.3 CASE STUDY

A 62-year-old male has been receiving simvastatin for

approximately six months. About three weeks ago, he started
suffering from pharyngitis and was prescribed the macrolide
antibiotic erythromycin to control the infection. However, he
was admitted to the hospital later with diffuse muscle pain
and severe muscle weakness. Dark-coloured urine was noted.
His creatinine kinase was found to be elevated and over the
next few days the serum creatinine increased to 156
micromol/l (usual baseline for this patient was 90
micromol/l). A diagnosis of rhabdomyolysis was made. It was
suspected that this was related to statin toxicity.
A. What are the symptoms of statin toxicity?

ANS: Symptoms of statin toxicity explicitly shows diffuse

muscle pain, severe weakness, dark-colored
urine, elevation of creatinine kinase, increased of serum
creatinine, and an occurrence of
rhabdomyolysis. Other symptoms of statin toxicity
include headache, sleep disorders, dyspepsia, nausea,
rash, alopecia, erectile dysfunction, gynecomastia and
rarely cause liver damage.
B. What most likely the reason for statin toxicity?

ANS: Most likely reason for statin toxicity in this case

scenario is drug-drug interaction of simvastatin and
macrolide antibiotic erythromycin. Interaction between
these two medications has led into patient being
diagnosed with rhabdomyolysis and such interaction
may significantly increase the blood levels of
simvastatin. Therefore, increasing the risk of side effects
such as liver damage in rare but serious condition of
rhabdomyolysis that involves the breakdown of skeletal
muscle tissue.
C. What is the major enzyme involved in the
metabolism of simvastatin?

ANS: Most of the statins are metabolized

through the cytochrome P450 (CYP)
metabolic pathway. In the metabolism of
simvastatin, the major enzyme involved is
CYP3A4 isoenzyme.
D. What is the potential interaction
between macrolide antibiotics and statins?

ANS: The potential interaction between

macrolide antibiotics and statins results to
an increased exposure to statins due to
macrolides' inhibition of CYP3A4 isoenzyme
and OAT1B transporter.
3.4 Case study. A 65-year-old female patient (60 kg) with a
history of ischemic stroke was prescribed clopidogrel for
stroke prevention. She was hospitalized again after 6
months due to recurrent ischemic stroke. Which of the
following is a likely reason she did not respond to
clopidogrel therapy? She is a:

A. Poor CYP2D6 metabolizer.

B. Fast CYP1A2 metabolizer.
C. Poor CYP2E1 metabolizer.
D. Fast CYP3A4 metabolizer.
E. Poor CYP2C19 metabolizer
Activity 4 . Drug Excretion
4.1 Alkalization of urine by giving bicarbonate is
used to treat patients presenting with
phenobarbital (weakacid) overdose. Which of
the following best describes the rationale for
alkalization of urine in this setting?

A. To reduce tubular reabsorption of phenobarbital.

B. To decrease ionization of phenobarbital.
C. To increase glomerular filtration of phenobarbital.
D. To decrease proximal tubular secretion.
E. To increase tubular reabsorption of phenobarbital.
Answer:
A. To reduce tubular reabsorption of phenobarbital.

Weak acids such Phenobarbital can be eliminated

more quickly by alkalinizing the urine. Bicarbonate
alkalinizes urine and keeps phenobarbital ionized,
which reduces reabsorption.

Weak Acid in alkalinized urine = EXCRETION

Weak Base in acidic urine = EXCRETION

4.2. Explain biliary recycling
(enterohepatic recirculation).
How does it affect the
elimination half- life of
drugs?
Answer:
Biliary recycling (enterohepatic recirculation) is the
phenomenon that drugs emptied via bile into the
small intestines can be reabsorbed from the intestinal
lumen into the systemic circulation. The recycling
process may continue until the drug either undergoes
metabolic changes in the liver, excreted in the
kidneys, or both.

Enterohepatic recirculation prolongs the action of

many medications by increasing their elimination
half-life.
Thank you.
GOD BLESS US ALL!