TDM - THERAPEUTIC DRUG MONITORING Flashcards
Typical Effectiveness of Route of Exposure
intravenous > inhalation > intraperitoneal injection
> intramuscular injection > ingestion > topical
intravenous route of administration is associated with ___ % bioavailability
100
orally administered drug should achieve % bioavailability
70% 0.7 fraction
5 pharmacological parameters that determine serum drug concentration
liberation
absorption
distribution
metabolism
excretion
refers to the release of the drug
liberation
is the transport of drug from the site of administration to the blood
absorption
refers to the delivery of the drug to the tissues
distribution
is the process of chemical modification of the drug by cells
metabolism
is the process by which the drug and its metabolites are excreted from the body
excretion
most drugs are absorbed in what way
passive diffusion
tablets and capsules require dissolution before being absorbed; liquid solutions are rapidly absorbed
true or false
true
weak acids are absorbed in ___ while weak bases are in ___
stomach; intestine
the process wherein the drugs are effective in the body tissues, not generally in the blood
distribution
the relationship between distribution of substances between tissue and blood levels is termed as
distribution space
the rate at which a particular drug is cleared from the circulation is dependent not only on the type of drug itself, but also on a patient’s capacity to metabolize and excrete it
excretion
causes of drug toxicity
elevated concentration of free drug
abnormal response to drug after administration
the presence of active drug metabolites
these drugs are used for treatment of arrhythmias and congestive heart failure
cardioactive drugs
classification of cardioactive drugs
class I (rapid sodium channel blockers)
class II (beta receptor blockers)
class III (potassium channel blockers)
class IV (calcium channel blockers)
class 1 cardioactive drugs example
quinidine, procainamide, lidocaine
class II cardioactive drugs example
PROPANOLOL
class III cardioactive drugs example
AMIODARONE
class IV cardioactive drugs example
VERAPAMIL
is a cardiac glycoside for treatment of atrial arrhythmia and congestive heart failure
digoxin
digoxin, when taken in large doses it inhibits Na-K-ATPase thus it decreases ___
K and Mg, and increase Ca
effect of digoxin to hyperthyroid individuals
resistant
toxic effects of digoxin
nausea, vomiting, visual disturbances, premature ventricular contractions, and atrioventricular bode blockage
therapeutic level of digoxin
0.5-2 ng/ml
toxic level of digoxin
> 2 ng/ml
is used to correct ventricular arrhythmia for treatment of acute myocardial infarction
lidocaine (xylocaine)
it is administered by continuous IV infusion after a loading dose
lidocaine (xylocaine )
lidocaine is also known as
xylocaine
cardioactive drugs that can be used as a local anaesthetic
lidocaine(xylocaine)
lidocaine(xylocaine) is can’t be administered ___ due to almost complete hepatic removal of the absorbed drug
orally
toxic effect of lidocaine(xylocaine)
congestive heart failure and heart block
toxicity level of lidocaine(xylocaine)
> 4 -8 ug/ml
a naturally occurring drug for the treatment of arrhythmia
quinidine
quinidine is almost ___ protein bound
85%
quinidine’s elimination
hepatic metabolism
route of delivery of quinidine
oral administration
quinidine’s common formulation
quinidine sulfate and quinidine gluconate
toxic level of quinidine
> 5 ug/ml
toxic effects of quinidine
cinchonism, blood dyscrasia, hepatitis
procainamide is also called as
pronestyl
describe the absorption of procainamide(pronestyl) in GIT
rapid and complete
elimination of procainamide(pronestyl)
renal filtration
hepatic metabolism
route of delivery of procainamide(pronestyl)
oral
toxic level of procainamide(pronestyl)
> 12 ug/ml
toxic effects of procainamide(pronestyl)
reversible lupus-like syndrome (ANA)
nephrotic syndrome
urticaria
it is used to treat cardiac arrhythmias and used as a substitute for quinidine
disopyramide
route of disopyramide
orally
describe the absorption of disopyramide in GIT
rapid and complete
elimination of disopyramide
renal filtration
toxic level of disopyramide
10 ug/ml
toxic effects of disopyramide
bradychardia and atrioventricular node blockage
a beta-receptor-blocking drug
propanolol
propanolol is used in the treatment of
angina pectoris, hypertension, and coronary artery disease
propanolol’s effect to thyroid hormones
suppresses the conversion of T4 to T3
it is used in the treatment of thyrotoxicosis
propanolol
therapeutic range of propanolol
50-100 ng.ml
toxic effects of propanolol
bradycardia, arterial insufficiency (raynaud’s type), platelet disorder, and pharyngitis
amiodarone is also called as
cordarone
it blocks potassium channel in the cardiac muscle
amiodarone (cordarone)
amiodarone (cordarone) is used for treatment of
ventricular arrhythmia
it is an iodine containing drug which can cause hyperthyroidism or hypothyroidism
amiodarone (cordarone)
toxic level of amiodarone (cordarone)
> 2.5 ug/ml
toxic effects of amiodarone (cordarone)
bradychardia, hepatitis, photodermatitis, and thyroid dysfunction
is used for treatment of angina, hypertension, and supraventricular arrhythmia
verapamil
therapeutic range of verapamil
80-400 ng/ml
verapamil’s toxic effects
hypotension, peripheral edema, and ventricular fibrillation
list down the aminoglycosides antibiotics
gentamicin
tobramycin
amikacin
kanamycin
neomycin
streptomycin
purpose of aminoglycosides
treatment of gram-negative bacterial infections;
route of aminoglycosides
intramuscular or intravenous
absorption of aminoglycosides in GIT
not well absorbed from the GIT
aminoglycosides can cause damage to which cranial nerve
8th cranial nerve (hearing loss )
aminoglycosides’ elimination
renal filtration
toxic effects of aminoglycosides
nephrotoxicity and ototoxicity
toxic levels of amikacin and kanamycin
> 30 ug/ml
toxic levels of gentamicin and tobramycin
12-15 ug/ml
it is the antibiotic and glycopeptide against gram positive cocci and bacilli
vancomycin
vancomycin’s route of administration
IV infusion
describe the oral absorption of vancomycin
poor oral absorption
its toxic side effects occur in the therapeutic range (5-10 ug/ml)
vancomycin
elimination of vancomycin
renal filtration and excretion
toxic effects of vancomycin
“red man syndrome”
nephrotoxicity
ototoxicity
this antibiotic is distributed to all tissues and concentrates in the CSF
chlorampenicol
chlorampenicol is ___% protein bound
50%
describe the GIT absorption of chlorampenicol
rapidly absorbed
toxic level of chlorampenicol
> 25 ug/ml
toxic effects of chlorampenicol
blood dyscrasia and cytoplasmic vacuolation (erythroid and myeloid cells )
it is a long-acting barbiturate that controls grand mal tonic-clonic seizure and focal epileptic
phenobarbital
this anti epileptic drug is not used for petit mal seizure
phenobarbital
used for treating withdrawal symptoms in infant whose mothers are addicted to opiate or barbiturate
phenobarbital
an anti epileptic drug that is used to treat cases of congenital hyperbilirubinemia
phenobarbital
majority of phenobarbital taken is stored in
brain
elimination of phenobarbital
hepatic metabolism
therapeutic level of phenobarbital
20-40 ug/ml
toxic effects of phenobarbital
nystagmus
stupor
ataxia
respiratory depression
phenytoin is also called as
phenytoin (dilantin )
it controls tonic clonic and simple partial seizures
phenytoin (dilantin )
phenytoin (dilantin) is not used for what type of seizure
petit mal and atomic seizures
route of phenytoin (dilantin)
intravenous
describe the GIT absorption of phenytoin (dilantin)
incomplete
elimination of phenytoin (dilantin)
hepatic pathway (zero order kinetics )
major toxicity effect of phenytoin (dilantin)
initiation of seizures
tetragonic action (cleft lip and palate)
nystagmus
therapeutic range of phenytoin (dilantin)
10-20 ug/ml
toxic level of phenytoin (dilantin)
> 20 ug/ml
phenytoin (dilantin) ‘s injectable proform
fosphenytoin
valproic acid is also called as
depakene
used for treatment of petit mal (absence seizure ), atomic, and grand mal seizures
valproic acid (depakene)
valproic acid (depakene)’s route of administration
orally
describe the GIT absorption of valproic acid (depakene)
rapid and complete
valproic acid (depakene) protein bound percentage
93%
why do valproic acid (depakene) needs monit0ring after 6 months of therapy
hepatic dysfunction is observable
valproic acid (depakene)’s elimination
hepatic metabolism
therapeutic level of valproic acid (depakene)
50-100 ug/ml
valproic acid (depakene)
toxic level of > 100 ug/ml will cause
nausea
lethargy
weight gain
valproic acid (depakene)
toxic level of > 200 ug/ml will cause
pancreatitis
hallucinations
hyperammonemia
carbamazepine is also called as
tegretol
a tricyclic compound related to imipramine
carbamazepine (tegretol)
effective for grand mal seizures and for treating seizures accompanied by pain
carbamazepine (tegretol)
route of carbamazepine (tegretol)
orally
elimination of carbamazepine (tegretol)
hepatic metabolism
idiosyncratic effect of carbamazepine (tegretol)
rashes
leukopenia
nausea
vertigo
febrile reactions
therapeutic level of carbamazepine (tegretol)
4-16 ug/ml
toxic level of carbamazepine (tegretol)
> 12 ug/ml
toxic effects of carbamazepine (tegretol)
hematologic dyscrasias
aplastic anemia
irregular pulse
ataxia
this antiepileptic drug has antineuralgic action and is 70-805 protein bound
carbamazepine (tegretol)
drug of choice for controlling petit mal (absence of seizure )
ethosuximinde (zarontin)
route of ethosuximinde (zarontin)
orally administered
how many percent is ethosuximinde (zarontin) protein bound?
free in the serum and not protein bound
toxic level of ethosuximinde (zarontin)
> 100 ug/ml
toxic effects of ethosuximinde (zarontin)
GIT disturbances
ataxia
SLE
aplastic anemia
pancytopenia
this anti epileptic drug is similar to neurotransmitter gamma aminobutyric acid (GABA)
gabapentin (neurontin)
gabapentin (neurontin) is used in
partial seizures and as an adjunctive therapy
route of gabapentin (neurontin)
orally
percent of gabapentin (neurontin) being bound to protein
not bound to plasma proteins
elimination of gabapentin (neurontin)
unchanged in urine and not metabolized in humans
toxic effects of gabapentin (neurontin)
ataxia and somnolence (drowsiness )
other seizure drugs of interest that is used as an adjunct drug for partial seizures
topiramate
lamotrigine (lamictal )
felbamate
psychoactive drug that is used for treatment of manic-depressive illness (bipolar disorders )
lithium
psychoactive drugs that is a drug of choice for the prevention of chronic cluster headache
lithium
effect of psychoactive drugs - lithium, to thyroid hormone
inhibits thyroid hormone synthesis and release, inhibits iodine update causing hypothyroidism
psychoactive drug that is a cationic metal that does not bind to proteins
lithium
lithium’s route of administration
orally and absorption is rapid and complete
psychoactive drug that go along with lithium, together, they inhibit the action of ADH on the kidneys
demeclocycline
elimination of lithium
renal filtration
toxic effects of lithium
severe dehydration
nephrotoxicity
hypothyroidism
toxic effect of lithium if 1.2-2 mmol/l
apathy, lethargy, speech difficulties
toxic effect of lithium if >2 mmol/l
seizures
muscle rigidity
coma
psychoactive drug that is used for the treatment of depression, insomnia, extreme apathy, and loss of libido
tricyclic antidepressants
route of tricyclic antidepressants
orally administered
example of tricyclic antidepressants
imipramine, amitriptyline, doxepin, nortriptyline, trazadone
elimination of tricyclic antidepressants
hepatic metabolism
toxic effects of tricyclic antidepressants
drowsiness
blurred vision
memory loss
seizure
cardiac arrhythmia
Parkinsonsian syndrome
unconsciousness
this psychoactive drug has the ability to block the re-uptake of serotonin in central serotonergic pathways
fluoxetine (prozac)
this psychoactive drug is used for treatment of obsessive-compulsive disorders
fluoxetine (prozac)
toxic effects of fluoxetine (prozac)
attempted suicide, decreased libido, and sexual function
the only bronchodilator in the book of rodriguez
theophylline
theophylline belongs to the ___ class
methylated xanthine
theophylline
its action is specific to the relaxation of ___
bronchial smooth muscle
theophylline is used for the treatment of
asthma and chronic obstructive pulmonary disease
it is therapeutic for primary apnea of prematurity
theophylline
used to treat the absence of respiratory effort in newborn infants
theophylline
effect of theophylline to histamine and proinflammatory agents
inhibitor
route of administration of theophylline
initially administered intravenously then orally
percent of theophylline of protein bound
50%
can theophylline cross placenta?
yes, and teratogenic in pregnant females
theophylline
the best predictor of toxicity is the
the blood level of the drug and not the early signs or symptoms of toxicity
elimination of theophylline
renal filtration and hepatic metabolism
toxic level of theophylline
> 20 ug/ml
toxic effects of theophylline
GI bleeding
seizures
tachycardia
syncope
an immunosuppressive drug that inhibits the cellular immune response by clocking production of interleukin 2
cyclosporine
an immunosuppressive drug that is used to prevent the rejection of allogenic organ transplants
cyclosporine
an immunosuppressive drug that is utilized for suppression of acute graft-versus-host disease
cyclosporine
what are the organs that require high dosage of cyclosporine
heart
liver
pancreas
an immunosuppressive drug that has marked affinity with RBC
cyclosporine
erythrocyte-cyclosporine is ___ dependent
temperature-dependent
cyclosporine’s route of administration
orally with 5-50% absorption
elimination of cyclosporine
hepatic metabolism
best sample of cyclosporine determination
whole blood (with lysis of RBC to yield the total amount )
toxic level of cyclosporine
> 500 ng/ml
toxic effects of cyclosporine
renal tubular and glomerular dysfunction
gi disturbances
hirsutism
hemotologic dyscrasias
an immunosuppressive drug that is 100x more powerful than cyclosporine
tacrolimus ()
tacrolimus is also known as
tacrolimus (prograf/fk-506)
an immunosuppressive drug that is a macrolide lactone antibiotic
tacrolimus (prograf/fk-506)
tacrolimus (prograf/fk-506)
elevated level are observed in
cholestasis
elimination of tacrolimus (prograf/fk-506)
hepatic metabolism
specimen of choice for
whole blood
toxic effects of tacrolimus (prograf/fk-506)
thrombus formation
nephrotoxicity
neurotoxicity
this immunosuppressive drug is similar to tacrolimus (prograf/fk-506)
rapamycin
rapamycin is also known as
rapamycin (sirolimus)
rapamycin (sirolimus)’s major side effects
lipid abnormalities and thrombocytopenia
other immunosuppressive drug that decreases renal allograft rejection
mycophenolate mofetil
other immunosuppressive drug that inhibits lymphocyte proliferation
leflunomide (LFM)
other immunosuppressive drug that is used for treatment of rheumatoid arthritis
leflunomide (LFM)
the 2 antineoplastic drugs in rodriguez book
methotrexate
busulfan
it is an effective therapy for a variety of neoplastic conditions
methotrexate
the antineoplastic drug that works as well as immunosuppressive drug
methotrexate
methotrexate’s effect to DNA synthesis
inhibitory in all cells by blocking dihydrofolate reductase
is used to reverse the action of methotrexate
leucovorin
the reversal of action of methotrexate by leucovorin is known as
leucovorin rescue
toxic level of methotrexate
0.01 umol/l
toxic effects of methotrexate
leicopenia
GI ulceration
thrombocytopenia
cirrhosis
is an alkalyting agent used to treat leukemia and lymphomas prior to bone marrow transplantation
busulfan
busulfan’s overdosage may cause
hepatic occlusive disease
this is a sub item under inflammatory/analgesics
salicylates/aspirin (acetylsalicylic acid)
commonly used analgesic, antipyretic, and anti inflammatory drug
salicylates/aspirin (acetylsalicylic acid)
direct stimulator of the respiratory system and an inhibitor of the kreb’s cycle
salicylates/aspirin (acetylsalicylic acid)
this anti-inflammatory/analgesic has an anticoagulant property (antiplatelet activity by inhibiting the action of cyclooxygenase)
salicylates/aspirin (acetylsalicylic acid)
it decreases thromboxane and prostaglandin formation through inhibition of action of cyclooxygenase
salicylates/aspirin (acetylsalicylic acid)
is the common cause of fatal drug poisoining in children
acute aspirin intoxication
side effects of salicylates/aspirin (acetylsalicylic acid)
gastrointestinal disturbance and interference with plt aggregation
toxic level of salicylates/aspirin (acetylsalicylic acid)
> 30 mg/dl
therapeutic level of salicylates/aspirin (acetylsalicylic acid) for treatment of headache
5 mg/dl
toxic effects of salicylates/aspirin (acetylsalicylic acid)
mixed acid-base disturbance (metabolic acidosis and respiratory alkalosis)
hypoglycemia
reye’s syndrome
an anti-inflammatory/analgesic that is an inhibitor of prostaglandin metabolism
acetaminophen (tylenol)
commonly used analgesic and antipyretic drug
acetaminophen (tylenol)
acetaminophen (tylenol)
overdosage of this drug will leads to
hepatoxicity
toxic effects of acetaminophen (tylenol)
cyanosus due to methemoglobinemia
cns depression
seizure
this has analgesic and anti inflammatory actions
ibuprofen
this anti-inflammatory/analgesic has lower risk of toxicities and salicylates and acetaminophen
ibuprofen
toxic effects of ibuprofen
nausea, vomiting, blurred vision, abdominal pain, edema
toxic level of ibuprofen
> 100 ug/ml
therapeutic level of ibuprofen
10-50 ug/ml
these drugs block the action of dopamine and serotonin in the limbic system
neuroleptics (antipsychotic major tranquilizers)
they are used in the treatment of acute schizoprenia
neuroleptics
monitoring of these drugs in serum is difficult to abundant metabolites for each drug resulting in extensive metabolism in liver
neuroleptics (anti-psychotic major tranquilizers )
it reflects the lowest level of drug in the blood
trough concentration
the best specimen for initial investigation of therapeutic drug toxicity since it is most likely to exceed the upper therapeutic limit
peak concentration
