THERAPEUTIC DRUG

MONITORING
 INTRODUCTION
THERAPEUTIC DRUG MONITORING (TDM)
It involves the analysis, assessment and evaluation of circulating
concentrations of drugs in serum, plasma or whole blood. It allows for the
safe use of drugs that would otherwise be potentially toxic.

DEFINITION OF TERMS:
PHARMACOLOGY is the study of drugs including their origins, history, uses, and
properties. It mainly focuses on the actions of drugs on the body.
DRUG is a substance that is used to treat, cure, or prevent a disease or
otherwise enhance physical or mental health.
Bioavailability is the rate and relative amount at which the intact form of a drug
appears in the systemic circulation following administration.
PRINCIPLES OF PHARMACOLOGY
When prescribing for older patients, it is important to
consider pharmacokinetic and pharmacodynamic
changes observed in normal aging, the likely effects of
the individual's genetics and intercurrent disease, as
well as evidence for therapeutic efficacy, and safety
and the patient's total exposure to medications.

2 Branches of Pharmacology
PHARMACODYNAMICS is how the drugs does to the body
PHARMACOKINETICS is how the body does to the drugs
A. ROLE OF DRUGS IN PATIENT
TREATMENT

SYMPTOMATIC: Used to relieve disease

symptoms
PREVENTIVE: Used to avoid getting disease
DIAGNOSTIC: Used to determine the presence or
absence of disease
CURATIVE: Used to eliminate disease
HEALTH MAINTENANCE: Used to keep body
functioning normally
 B. ADMINISTRATION

(or Absorption) The entry of drug into the systemic circulation from the site
of administration.

1. Surface area of the GIT

Stomach (not an organ for absorption)
Weak acids are absorbed in the stomach
Small Intestine (Most important site for drug absorption)
Large Intestine (Site of absorption for slowly absorbed drugs)

2. Gastric Emptying Rate

Rate at which the drug solution leaves the stomach and enters the
duodenum (small intestine).
Decrease GER = Decrease Absorption = Decrease onset of action
C. TRANSPORT

The drug leaves the bloodstream and distribute

into the interstitial and intracellular fluids.
Drugs from the systemic circulation to organs
and tissues.
Distribution Space- the relationship between
tissue and blood levels.
A large distribution space indicates that much of
the drug moves into the tissues that stays in
D. CELL UPTAKE AND
METABOLISM
Metabolism is an essential pharmacokinetic
process which converts lipid soluble and non-
polar compounds to water soluble and polar
compounds so that they are excreted.
* Liver - is the main site of metabolism
*also includes: Kidney, Liver, Lung, Skin, Brain
E. EXCRETION

It is the process whereby drugs are transferred

from the internal to external environment
Principal organs involve: KIDNEY(main), LUNG,
BILIARY SYSTEM, INTESTINE, SALIVA, MILK
F. GENERIC DRUGS
CARDIOACTIVE DRUGS
ANTIBIOTICS
ANTIEPILEPTIC DRUGS
PSYCHOACTIVE DRUGS
BRONCHODILATOR
IMMUNOSUPRESSIVE DRUGS
ANTINEOPLASTIC DRUGS
ANTI-INFLAMMATORY/ ANALGESICS
NEUROLEPTICS
FUNDAMENTAL CONCEPTS OF
THERAPEUTIC DRUG MONITORING

TDM is based on the principle that for some drugs

there is a close relationship between the plasma
level of the drug and its clinical effect.
If such a relationship does not exit TDM is of little
value.
The clinical value of plasma level monitoring
depends on how precisely the treatment outcome
can be defined.
When a precise therapeutic end point is difficult
to define, monitoring of drug levels may be of
considerable therapeutic assistance.
 A. REASONS FOR THERAPEUTIC DRUG
MONITORING
Toxicity
Diagnosing toxicity when the clinical syndrome is undifferentiated (unexplained
nausea in a patient taking digoxin)
Avoiding toxicity (aminoglycosides, cyclosporin)
Dosing
After dose adjustment (usually after reaching a steady state)
Assessment of adequate loading dose (after starting phenytoin treatment)
Dose forecasting to help predict a patient's dose requirements1 (aminoglycosides)
Monitoring
Assessing compliance (anticonvulsant concentrations in patients having frequent
seizures)
Diagnosing under treatment (particularly important for prophylactic drugs such as
anticonvulsants, immunosuppressants)
Diagnosing failed therapy (therapeutic drug monitoring can help distinguish between
ineffective drug treatment, non-compliance and adverse effects that mimic the
underlying disease).
B. BASIC PRINCIPLES OF
THERAPEUTIC DRUG MONITORING
The following are important considerations to ensure an
optimum TDM service in any setting:
Measurement of patient’s serum or plasma drug concentration
taken at appropriate time after drug administration
Knowledge of pharmacological and pharmacokinetic profiles of
the administered drugs
Knowledge of relevant patient’s profile like demographic data,
clinical status, laboratory and other clinical investigations, and
Interpretation of SDC after taking into consideration all of the
information and individualizing drug regimen according to the
clinical needs of the patient.
C. APPLICATIONS OF THERAPEUTIC
DRUG MONITORING

The circulatory system is convenient route that

can effectively deliver most drugs to its site of
action.
IV – 100% bioavailability
Orally Administered drug should achieved 0.7
bioavailability fraction.
When drugs are IV administered, the
distribution and elimination rates are constant.
D. PRECAUTIONS

Specimen of choice: Serum or Plasma

Whole blood EDTA sample is required for cyclosporine and
tacrolimus tests.
Timing of specimen collection is the single most important factor in
TDM.
TDM samples should not be collected in tubes with gel separators or
SSR – some gels absorb certain drugs causing a falsely low
result.
No changes occurred in Theophylline and salicylates levels when
blood is collected in serum separator tube (SST).
Measurement of serum concentrations should be done only after
steady state has been achieved.
OVERVIEW OF ASSAY
TECHNIQUES

ASSAY
An investigative procedure for
qualitatively assessing or quantitatively
measuring the amount or functional
activity of the target entity.
SPECTROPHOTOMETRIC:
COLORIMETRIC AND FLUOROMETRIC

COLORIMETRIC ASSAY
This uses the quantitative estimation of colors. The
substance binds woth color forming chromogens. The
difference in color results in difference in absorption of
light.
FLUOROMETRIC ASSAY
An analytical technique for characterizing minute
amount of substance by excitation of the substance
with a beam of light and detection and measurement of
the characteristic wavelength of the fluorescent light
emitted.
IMMUNOASSAYS
CHROMATOGRAPHIC
Chromatographic immunoassay
Is a technique in which an antibody or antibody-related
agent is used as part of a chromatographic system for
the isolation or measurement of a specific target.
Are based on the indirect detection of an analyte by
observing how it reacts with labeled binding agent or
prevents a labeled analog of the analyte from
interacting with an antibody.
Various binding agents, detection methods, supports
and assay formats have been developed for this group
of methods, and applications have been reported that
range from drugs, hormones and herbicides to
peptides, proteins and bacteria.
IMMUNOASSAYS
CHROMATOGRAPHIC

Two types of chromatographic

immunoassays:
Competitive binding Immunoassay
Can be used for either large or small analytes

Homogenous Immunoassay
Involves a size separation that restricts their use to
low-mass analytes
AMINOGLYCOSIDES

Contains Amino sugars

Linked by Glycosidic bond
Protein synthesis inhibitors
Bactericidal
Used to treat infectious caused by Gram Negative
Bacteria
Derived from the soil Actinomycetes
Suffix: Mycin and Micin
 PROPERTIES
Pharmacokinetics
Highly polar
No absorption from GIT
Not used orally, but only used orally in surgical prophylaxis
For Meningitis, used parentally I/V, I/M, and I/T
It may cause damage to the 8th cranial nerve at toxic levels
Given combination with other drugs for synergistic effect
Toxic Level:
>30 µg/ml (Amikacin and Kanamycin)
12-15 µg/ml (Gentamicin and Tobramycin)
 PROPERTIES
Genus: Streptomyces
Streptomycin
First drug (Waksman=1944)
To treat a number of bacterial infections such as tuberculosis,
mycobacterium avium complex, rat bit fever and others
Kanamycin
To treat severe infections and tuberculosis orally or injection
Tobramycin
To treat various types of infections especially Gram- negative
infections
Neomycin
Has been used as preventive measure for hepatic
encephalopathy and hypercholesterolemia
PROPERTIES
Genus: Micro-Monospora
Gentamicin
To treat bone infections, pelvic
inflammatory
PROPERTIES
Genus: Semisyn
Amikacin
 To treat bacterial infections such
as joint infections, intra-abdominal
infections, sepsis and urinary tract
infections
 PROPERTIES

Adverse Effect
> 5 days
High doses
Pre- existing renal insufficiency
Elderly

Common Toxic Effects

Nephrotoxicity
Ototoxicity
 PROPERTIES

Nephrotoxicity
Kidney damage
Neomycin
Gentamicin
Tobramycin

Ototoxicity
Disruption of inner ear
Cochlea (Amikacin and Kanamycin)
Vestibule (Gentamicin and Streptomycin)
PROPERTIES
Mechanism Of Action
The overall process consists of two main
steps:
Transport of aminoglycosides into the
cell wall and cytoplasmic membrane
Irreversibly binding of ribosomes
 PROPERTIES
Uses
Aerobic Gram Negative Bacteria
Infections
Complicated Urinary Tract
Infections
Complicated Skin And Soft
Tissue Infections
Infective Endocarditis
Intra-abdominal Infections
Severe Pelvic Inflammatory
Tuberculosis (Streptomycin)
Sepsis
 ASSAY TECHNIQUES
CHROMATOGRAPHY IMMUNOASSAY
The primary methods used for
aminoglycoside determinations
ANTI ARRHYTHMATICS AND
OTHER CARDIOACTIVE DRUG
CARDIOACTIVE DRUGS
 used for treatment of arrhythmias and congestive heart failure

CLASSIFICATION OF CARDIO DRUGS

 Class I - rapidly sodium channel blockers
Example: Quinidine, Procainamide, Lidocaine
 Class II - beta receptor blockers
Example: Propanolol
 Class III - Potassium Channel blockers
Example: Amiodarone
 Class IV - Calcium channel blockers
Example: Verampil
 DIGOXIN
Cardiac glycoside for treatment of Atrial
arrhythmia and CHF
Elimination: Renal filtration of plasma free
form
Peak serum level: 8 hrs after an oral dose
Half-life: 38 hours (average adult)
Therapeutic level: 0.5-2ng/mL
Toxic level: >2ng/mL
 LIDOCAINE (XYLOCAINE)
Used to correct ventricular arrhythmia
for treatment of AMC
Administered by continuous IV
infusion after a loading dose
Can be used as Local anaesthetic
 LIDOCAINE (XYLOCAINE)
Elimination: By hepatic metabolism, changes in renal
function have little effect
Primary product of hepatic metabolism:
Monoethylglycinexylidide (MEGX)
Therapeutic level: 1.5-4.0 ug/mL
Toxicity level: >4.0 ug/mL
CNS depression: >4-8 ug/mL
Seizure and ↓bp and cardiac output: >8ug/mL
Toxic effect: CHF and Heart block
 QUINIDINE
Naturally occurring drug for the treatment of
arrythmias
85% protein bound; GIT absorption is complete and
rapid for the sulfate

Elimination: Hepatic metabolism

Route of delivery: Oral administration
Common formulations: Quinidine sulfate and
quinidine gluconate
Peak serum level: 2 hours after an oral
dose (sulfate); 4-5 hours (gluconate)
Therapeutic level: 2.3-5 ug/mL
Toxic level: >5 ug/mL
Toxic effects: Cinchonism, blood
dyscrasia and hepatitis
PROCAINAMIDE (PRONESTY)
Used to treat ventricular arrythmia
GIT absorption is rapid and complete
20% protein bound; eliminated by renal
filtration and hepatic metabolism

Common route: Oral

Hepatic metabolite: N-acetyl procainamide
(NAPA)
PROCAINAMIDE (PRONESTY)
Peak serum level: One hour after the dose
Therapeutic level: 4-10 ug/mL
Toxic level: >12 ug/mL
Toxic effects: Reversible upus-like
syndrome (ANA), nephrotic syndrome,
urticaria
DISOPYRAMIDE
Used to treat cardiac arrythmias
Used as substitute for Quinidine
Has anticholinergic effects – dry mouth
and constipation (>4.5 ug/mL)
Elimination: Renal filtration
Therapeutic level: 3-5 ug/mL
Toxic level: 10ug/mL
Toxic effects: Bradycardia and
atrioventricular node blockage
 PROPRANOLOL
A beta-receptor blocking drug
Used in the treatment of angina pectoris, hypertension,
coronary artery disease
Suppresses the conversion of T4 to T3 – Used in the
treatment of thyrotoxicosis
Therapeutic range: 50-100 ng/mL
Toxic effects: Bradycardia, arterial insuffiency
(Raynauds type), platelet disorder and pharyngitis
 Anti-neoplastic
drugs are medications used to
treat cancer. Antineoplastic
drugs are also called anticancer,
chemotherapy, chemo, cytotoxic,
or hazardous drugs.
 BUSULFAN
Busulfan is used treat a certain type of
chronic myelogenous leukemia (CML; a
type of cancer of the white blood
cells). Busulfan is in a class of
medications called alkylating agents. It
works by slowing or stopping the growth
of cancer cells in your body.
Common side effects of BUSULFAN include:
•nausea or vomiting (may be severe),
•diarrhea,
•stomach/abdominal pain,
•loss of appetite,
•injection site reactions (redness, pain, or
swelling),
•mouth sores, or.
•temporary hair loss.
 METHOTREXATE
Methotrexate is used to treat certain types of cancer
including cancers that begin in the tissues that
form around a fertilized egg in the uterus, breast
cancer, lung cancer, certain cancers of the head
and neck, certain types of lymphoma, and leukemia
(cancer that begins in the white blood cells).
Methotrexate is in a class of medications called
antimetabolites. Methotrexate treats cancer by
slowing the growth of cancer cells.
Methotrexate may cause very serious, life-threatening side
effects. You should only take methotrexate to treat cancer or
certain other conditions that are very severe and that cannot be
treated with other medications.

It may cause:
• a decrease in the number of blood cells made by your bone
marrow.
• liver damage, especially when it is taken for a long period of
time.
• may cause lung damage.
• damage to the lining of your mouth, stomach, or intestines.
 ANALGESICS
ACETAMINOPHEN, ACETYLSALICYLIC ACID AND MORPHINE

ANALGESICS are medicines that are used to relieve pain.

They are also known as painkillers or pain relievers.
Technically, the term analgesic refers to a medication that
provides relief from pain without putting you to sleep or
making you lose consciousness.
 ACETAMINOPHEN
Acetaminophen is an analgesic used
to temporarily relieve minor aches and
pains due to headache, muscular aches,
backache, minor pain of arthritis, the
common cold, toothache, and
premenstrual and menstrual
cramps. Acetaminophen is also used
to temporarily reduce fever.
 COMMON SIDE EFFECTS OF ACETAMINOPHEN
INCLUDE:
• nausea, • headache,
• stomach pain, • dark urine,
• loss of appetite, • clay-colored
• itching, stools
• rash,
 ACETYLSALICYLIC ACID
Aspirin, or acetylsalicylic acid (ASA), is commonly used as a pain
reliever for minor aches and pains and to reduce fever. It is also
an anti-inflammatory drug and can be used as a blood thinner.
Aspirin is one of the most commonly used drugs for treating mild to
moderate pain, migraines, and fever.
Common uses include headaches, period pains, colds and flu,
sprains and strains, and long-term conditions, such as arthritis.
For mild to moderate pain, it is used alone. For moderate to severe
pain, it is often used along with other opioid analgesic and
NSAIDs.
The most common side effects of aspirin are:
•irritation of the stomach or gut
•indigestion
•nausea

The following adverse effects are possible, but less

common:
•worsening asthma symptoms
•vomiting
•inflammation of the stomach
•stomach bleeding
•bruising

A rare side effect of low-dose aspirin is hemorrhagic

stroke.
 MORPHINE
Morphine is a pain medication of the
opiate family which is found naturally in
a number of plants and animals. It acts
directly on the central nervous system to
decrease the feeling of pain. It can be
taken for both acute pain and chronic
pain.
Opioid medicine can slow or stop your breathing, and death may
occur. A person caring for you should seek emergency medical
attention if you have slow breathing with long pauses, blue
colored lips, or if you are hard to wake up.

Call your doctor at once if you have:

• slow heart rate, sighing, weak or shallow breathing;

• chest pain, fast or pounding heartbeats;
• extreme drowsiness, feeling like you might pass out; or
• nausea, vomiting, loss of appetite, dizziness, worsening
tiredness or weakness.
 BRONCHODILATORS
THEOPHYLLINE AND CAFFEINE

BRONCHODILATORS is a substance that dilates

the bronchi and bronchioles, decreasing
resistance in the respiratory airway and
increasing airflow to the
lungs. Bronchodilators may be endogenous
(originating naturally within the body), or they may
be medications administered for the treatment of
breathing difficulties.
 THEOPHYLLINE
Theophylline is used to prevent and treat
wheezing, shortness of breath, and
chest tightness caused by asthma,
chronic bronchitis, emphysema, and
other lung diseases. It relaxes and
opens air passages in the lungs, making
it easier to breathe.
Theophylline may cause side effects. Tell your doctor if any of these
symptoms are severe or do not go away.
•upset stomach
•stomach pain
•diarrhea
•headache
•restlessness
•insomnia
•Irritability

If you experience any of the following symptoms, call your doctor

immediately:
•vomiting
•increased or rapid heart rate
•irregular heartbeat
•seizures
•skin rash
 CAFFEINE
CAFFEINE CITRATE is a central nervous system stimulant
used to treat breathing problems in premature infants.
It is a central nervous system stimulant. It works by
stimulating the brain.
Caffeine is used to restore mental alertness or
wakefulness during fatigue or drowsiness. Caffeine is
also found in
some headache and migraine medications, in certain
dietary supplements used for weight loss, and in many
popular energy drinks.
Common side effects of Caffeine:
•difficulty sleeping (insomnia)
•nervousness or anxiety
•irritability
•nausea
•headache

Seek medical attention right away if any of these severe side

effects occur:
•serious allergic reactions (difficult breathing, chest tightness,
swelling of the mouth, face, lips, or tongue, rash, hives, or
itching)
•diarrhea
•vomiting
•rapid heart rate or palpitations
•increased blood pressure
•chest pain
 POSOCONAZOLE/VORINAZOLE
ORAL
Clinical use: systemic treatment of common fungal
infection
MOA: inhibit ergosterol production by binding and inhibiting
lanosterol-14alpha-demethylase
Toxic effect:
Posoconazole: nausea, vomiting and hepatoxicity
Voriconazole: liver dysfunction and skin reaction
Factor affecting concentration:

Posconazole- varable absorption from

the guts

Voriconazole- polymorphism In the cyp

2c19 isoenzyme
 AMIODARONE
Oral
Clinical use: treatment arrhythmias when other drug are
ineffective or contraindicated
MOA: prolong phase 3 of cardiac action potential, slows
conduction rate also has beta blocker activity
Factor affecting concentration- very large volume of
distribution, when given orally, days suppress ventricular
tachycardias loading dose required
Toxic effect:

Toxicity related to dosage and duration

of treatment
Pulmunary toxicity is the most serious
adverse effect (cough, dyspenea and
respiratory)
 DISOPYRAMIDE
Clinical use: to control supraventricular and ventricular arrhythmias after
myocardial infractiom
MOA: inhibits conduction by blocking sodium channel
Factor affecting concentration: predominantly renal excretion
Toxic effect:
Gastrointestinal( nausea, vomiting. Diarrhea)
Cardiovascular( decrease cardiac output)
Anticholinergic( dry mouth, blurred vision, urinary retention)
 FLECAINIDE
Clinical use: to control serious symptomatic ventricular
arrhythmias, junctional reentry tachycardia and
paroxysmal atrial fibrillation
MOA: reduces maximun rate of depolarization in heart
muscle and slows conduction
Factor affecting concentration: clearance reduced in
renal failure and heart failure
Toxic effect: dizziness, visual disturbance, nausea and
headache
 LIDOCAINE
Clinical use: to control ventricular arrhythmias after myocardial
infration
MOA: block sodium channel in the cardiac conduction system,
raising depolarization threshold and reducing arrhythmia
Factor affecting concentration: volume of distribution decrease
in congestive heart failure and dosage requirements are
lower
Toxic effect: drowsiness, dizziness, slurred speech and
paresthesia
 DIGOXIN
Clinical use: management of certain supraventricular
arrhythmias, particularly chronic atrial flutter and
fibrillation
MOA: increase the force of cardiac concentration and
increase cardiac output
Factor affecting concentration:
Renal elimination, so extra care needed in part with
impaired renal function and In the elderly.
 Toxic effects:
Gastrointestinal( nausea, vomiting,
diarrhea or constipation, abdominal
pain)
Neurological (headache, fatigue,
insomnia, confusion and vertigo)
 BUPRENORPHINE
BUPRENEX
Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death

ROUTE OF ADMINISTRATION :

It can be used under the tongue, by injection, as a skin patch, or as an implant.

ONSET OF ACTION:
Within 30 min

ELIMINATION HALF-LIFE:
37 hours (range 20–70 hours)
 COMMON SIDE EFFECT

Constipation
Dizziness
Drowsiness
Headache
Nausea
 METHADONE
A narcotic that works by changing the way the brain and nervous
system respond to pain.

ROUTES OF ADMINISTRATION :
By mouth, intravenous, insufflation, sublingual, rectal
ONSET OF ACTION :
Rapid

ELIMINATION HALF-LIFE:
15 to 55 hours
 COMMON SIDE EFFECT
• Constipation • Stomach pain
• Weakness • Sore tongue
• Headache • Dry mouth
• Nausea or vomiting • Sweating
• Loss of appetite
• Weight gain
 ANTIRETROVIRALS
• The Anti-HIV drugs can be classified into

1. Nucleoside reverse transcriptase inhibitors (NRTIs): Zidovudine,

Stavudine, Lamivudine, Abacavir, Zalcitabine, Emtricitabine,
Didanosine.
2. Non nucleoside reverse transcriptase inhibitors (NNRTIs):
Efavirenz, Nevirapine, Delaviridine.
3. Nucleotide reverse transcriptase inhibitors (NTRTIs): Tenofovir
4. Protease inhibitors (PIs): Saquinavir, Indinavir, Nelfinavir,
Amprenavir, Fosamprenavir, Ritonavir, Lopinavir, Atazanavir.
5. Entry/Fusion inhibitors: Enfuvirtide
EXAMPLES:
• Cyclosporine
• Tacrolimus
• Sirolimus
 CYCLOSPORINE
Mode of action
• Inhibits calcineurin phosphatase and limits T-cell
activation
• Usual Dose
• Following transplantation (oral): 10-15 mg/kg daily for 1-2 weeks postoperatively then
reduced gradually to 2-6 mg/kg daily for maintenance in two divided doses

• Route of elimination
• -hepatic metabolism
 TOXIC EFFECTS
• Renal dysfunction is a serious adverse e
ect
• Raised blood pressure and hyperlipidemia
• Adverse cosmetic e ects (gingival
hyperplasia and hypertrichosis)
• Overimmunosuppression associated with
infection and neoplasia
 TACROLIMUS
Mode of action
• Inhibits calcineurin phosphatase
and limits T cell activation
 USUAL DOSE AND DOSE
INTERVAL
Vary with type of transplant and time
post-transplant; oral doses following
kidney transplantation are of the order
of 100-200 mcg/kg daily in two divided
doses Route of Elimination: hepatic
metabolism
 TOXIC EFFECTS:
• Renal dysfunction is a serious adverse e ect
• Hematological (anemia, leucopenia,
thrombocytopenia)
• Hypertriglyceridemia and hypercholesterolemia
• Lymphocele formation and impaired wound
healing
• Overimmunosuppression associated with
infection and neoplasia
 AMINOGLYCOSIDES
Aminoglycosides are a group of
chemically related antibiotics used
for the treatment of infectious with
Gram-negative bacteria that are
resistant to less toxic antibiotics
 AMINOGLYCOSIDES
• AMIKACIN
• GENTAMICIN
• TOBRAMYCIN
 AMIKACIN
Broad spectrum antibiotic active against
aerobic Gram-negative organisms including
Pesudomonas aeruginosa and
Mycobacteria
Used in treatment of serious infections
caused by gentamicin-resistant Gram-
negative bacili as more resistant to enzyme
inactivation.
 MODE OF ACTION
Disruption of protein synthesis by
irreversible binding to the 30s
ribosomal subunit of susceptible
organisms.
 DOSE AND DOSE INTERVAL
Once-daily dosing by intravenous
infusion: initially 15 mg/kg daily
(maximum 1.5g)
Child: 15mg/kg daily in two divided
doses
Dosing should generally not exceed 7
days
 FACTORS AFFECTING
CONCENTRATION
• Large, highly polar molecule
• Very poor oral bioavailability –
must be given parenterally
• Not metabolized, excreted renally
• Short plasma half life (2-3 hours)
 TOXIC EFFECTS
• Vestibular and auditory damage
• Nephrotoxicity
 GENTAMICIN
Broad spectrum antibiotic active against
aerobic Gram-negative organisms including
Pesudomonas aeruginosa and some Gram-
positive organisms such as Staphylococcus
aureus
Used in treatment of serious infections
sometimes with a penicillin or
metronidazole
 MODE OF ACTION
Disruption of protein synthesis irreversible
binding to the 30s ribosomal subunit of
susceptible organisms
DOSE AND DOSE INTERVAL
Once-daily/extended dosing interval regimes
Once-daily 5-7mg/kg, then just according to serum gentamicin
concentration
 FACTORS AFFECTING
CONCENTRATION
• Large, highly polar molecule
• Very poor oral bioavailability – must be given
parenterally
• Not metabolized, excreted renally
• Short plasma half life (2-3 hours)
 TOXIC EFFECTS
• Vestibular and auditory damage
• Nephrotoxicity
 TOBRAMYCIN
Broad spectrum antibiotic active against
aerobic Gram-negative organisms including
Pesudomonas aeruginosa and some Gram-
positive organisms such as Staphylococcus
aureus
Used in treatment of serious infections
sometimes with a penicillin or
metronidazole
 MODE OF ACTION
Disruption of protein synthesis irreversible
binding to the 30s ribosomal subunit of
susceptible organisms

DOSAGE AND DOSE INTERVAL

3mg/kg daily
Once-daily in severe infection up to 5mg/kg daily divided dose every 6-8 hrs
Child: 2.0-2.5 mg/kg every 8 hrs
FACTORS AFFECTING CONCETRATION
• Large, highly polar molecule
• Very poor oral bioavailability
• Short plasma half life (2-3 hours)

TOXIC EFFECTS
• Vestibular and auditory damage
• Nephrotoxicity
 OTHER ANTIBIOTICS
• VANCOMYCIN
• TEICOPLANIN
 VANCOMYCIN
Is a glycopeptide antibiotic that is effective
against gram-positive cocci and bacilli
Used in prophylaxis and treatment of
endocarditis and other serious infections
caused by Gram-positive cocci
 MODE OF ACTION
Inhibits cell wall synthesis in susceptible
organisms.

DOSE AND DOSAGE INTERVAL

By intravenous infusion:
1.0-1.5 g every 12 hrs (over 65 year, 500mg every 12 hrs or 1 g once daily)
Child: 15mg/kg every 8hrs, maximum 2 g daily
 FACTORS AFFECTING
CONCENTRATION
• Large, highly polar molecule
• Very poor oral bioavailability
• Short plasma half life (4-6 hours)

TOXIC EFFECTS
• Neutropenia, thrombocytopenia
• Nephrotoxicity and ototoxicity rare
• Rashes including toxic epidermal necrolysis
 TEICOPLANIN
Glycopeptide antibiotic with bactericidal activity
against aerobic and anaerobic Gram-positive
bacilli including multiresistant Staphylococci
(MRSA)
 MODE OF ACTION
Inhibits cell wall synthesis in susceptible organisms
DOSE AND DOSE INTERVAL
By intravenous injection or infusion: initially 400 mg
minimum or 6 mg/kg, whichever is greater, every 12
hrs for three doses
Streptococcal or enterococcal endocarditis: initially 10
mg/kg every 12 hrs for three doses
Child by intravenous injection or infusion: initially 10
mg/kg every 12 hrs for three doses
 FACTORS AFFECTING
CONCENTRATION
• Large, highly polar molecule
• Very poor oral bioavailability – must be given parenterally
• Not metabolized, excreted renally
• Terminal Half life (>100hours)

TOXIC EFFECTS
• Neutropnia, Thrombocytopenia
• Nephrotoxicity and ototoxicity rare
 PHENOBARBITAL
Type of Slow acting barbiturate
drug
Used for Control Seizures
Half life : 4 days
Therapeu 15-40
tic range
inactive Primidone
form. •Rapidly converted to
active form when
absorbed
Eliminate Hepatic metabolism
d by
 PHENYTOIN (DILANTIN)
Used for Seizure disorders

Prophylactic agent for

brain injury
Route Oral
Therapeutic 1-2 ug/ml
range

Half life ; 1 day

Inactive: fosphenytoin
Proform • usually injected
Major toxicity Initiates seizures , brain
: injuries
 VALPROIC ACID
Function To treat
•petit-mal
seizures
•Absence
seizures
Therapeutic 50-120ug/ml
ranges
Half-life : 15 hrs
Adverse Nausea,
effects Lethargy
Weight gain
 CARBAMAZEPINE {TEGRETOL }
Function Also for seizures
•But less frequently used
•Due to toxic effects
•Only used when patients fails to
respond to other drugs
Therapeutic 4-12 ug/ml
range
Half life 27hrs
Monitors hematologic hepatic and renal
Toxicity Leukopenia
Nausea
Vertigo
 ETHOSUXIMIDE
used for controlling petitmal seizure.
therapeutic range is 40 to 100 μg/mL
TDM of ethosuximide is done to
ensure that serum concentrations
are in the therapeutic range.
 FELBAMATE
orally administered drug that is nearly
completely absorbed by the gastrointestinal tract, and peak
serum concentrations are reached within 1 to 4 hours.
known for its toxicity and is primarily
indicated in severe epilepsies such as in children with the
mixed seizure disorder Lennox-Gastaut syndrome and in
adults with refractory epilepsy.
Adverse side effects have been documented and include fatal
aplastic anemia and hepatic failure
 GABAPENTIN
This drug may be indicated
as monotherapy or in conjunction with other
AEDs in patients suffering from complex partial
seizures with or without generalized seizures
most likely treatment consideration in
patients with liver disease and in treating partial-
onset seizures in patients with acute intermittent
porphyria
 LAMOTRIGINE

Effective first-line anticonvulsant

Partial and generalized tonic-clonic seizures
Use alone or in combination with other anticonvulsants
TOXIC EFFECTS
• Life-threatening skin reactions such as Stevens-Johnson syndrome and toxic
epidermal necrolysis may occur, usually within the first 8 weeks; may be
associated with Antiepileptic Hypersensitivity Syndrome; combination with
valproate increases the risk
• Neurological side-effects (e.g., weakness, visual disturbance, dizziness)
• Gastrointestinal disturbances
 LEVETIRACETAM
indicated in partial and generalized seizures.
Levetiracetam’s rate of clearance correlates
well with glomerular filtration rate, which
may be of use in monitoring patients with
renal impairment.
may be useful in monitoring compliance and
fluctuating levels during pregnancy.
 OXCARBAZEPINE
• Monotherapy and adjunctive therapy of partial seizures with
or without secondary generalization
• Pain relief in trigeminal neuralgia
Toxic effects
• Similar neurological side-effect profile to carbamazepine
• High incidence (~25%) of hyponatremia (<125 mmol/L)
• Patients need to be warned of the risk of blood, hepatic and
skin disorders
 TOPIRAMATE
• Monotherapy or adjunctive therapy for generalized, tonic-
clonic or partial seizures
• Adjunctive therapy for seizures in Lennox-Gastaut syndrome
• Migraine prophylaxis
Toxic effects
• Need adequate hydration to avoid nephrolithiasis as makes
urine alkaline favoring calcium phosphate stones
• Avoid in porphyria
 TIAGABINE
CLINICAL USE
• Adjunct therapy where other antiepileptics have been
unsatisfactory for focal seizures with and without
secondary generalization
TOXIC EFFECTS
• Tremor
• Psychosis
• Emotional lability
 ZONISAMIDE
CLINICAL USE
• Focal seizures with or without secondary generalization
• Adjunctive therapy for refractory focal seizures
TOXIC EFFECTS
• Sensitivity to sulfonamides (zonisamide is a sulfonamide
derivative)
• Nephrolithiasis (incidence ~1%)
• Hyperthermia
• Metabolic acidosis
 CYCLOSPRINE
Feature Cyclic peptide

Use Suppression of host- versus graft

rejection in transplanted organs
Circulating cyclosporine sequesters in
cells
Specimen of Whole blood
choice
Method of Hepatic metabolism
elimination
Cardiac, Liver and pancreas
transplants have the highest
requirement
 TACROLIMUS
Route Oral

Feature 100x more potent

than cyclosporine
•Has less dosage
Conc. Above Thrombus formation
therapeutic range leads
to
Eliminated by Hepatic metabolism

Measured by HPLC
 SIROLIMUS ( RAPAMYCIN)
Use Antifungal agents

Approved for Kidney transplant patients

Adverse Anemia, throbocytopenia, leukopenia

effects Infections

Can be used with cyclosporine and

tacrolimus
 MYCOPHENOLIC ACID

Inactive form Mycophenolate mofetil ( inactive)

Transformed by the liver

Function Lymphocyte proliferation inhibitor

Supplemental therapy in renal

transplant )
Route Oral

Plasma