THERAPEUTIC DRUG MONITORING

- involves the analysis, assessment, and evaluation of circulating

concentrations of drugs in serum, plasma, or whole blood.
- ensure that a given drug dosage produces maximal therapeutic beneft and minimal
toxic adverse efects.
- provides a basis for establishing a rational dosage regimen to ft individual situations.
- the quantitative evaluation of circulating concentrations of drugs
Terminologies:
. !ioavailable fraction " fraction of dose that reaches blood
#. $irst pass metabolism " drugs that are transporeted to the liver,lost a fraction of
its bioavailability
%. $irst order elimination " representation of relationship between the amount of
drug eliminated per hour and blood level of drug.
&. 'ea( concentration " highest concentartion of drug obtain in the dosing interval
). 'harmacogenomics " study of genes that afects the performance of drug in an
individual
*. 'harmacodynamics- relationship between the drug concentration at the target
site and response of the tissues
+. 'harmaco(inetics " mathematical expression of the relationship between drug
dose and drug blood level.
,. Therapeutic index " ratio between minimum and maximum therapeutic serum
concentration
-. Therapeutic range " diference between highest and lowest efective dosages
.. Trough concentration " lowest concentration of a drug obtain in the dosing
interval.
The following are the common indications for T/0:
. The consequences of overdosing and underdosing are serious.
#. There is a small diference between a therapeutic and a toxic dose.
%. There is a poor relationship between the dose of drug and circulating
concentrations but a good correlation between circulating concentrations and
therapeutic or toxic efects.
&. There is a change in the patient1s physiologic state that may unpredictably afect
circulating drug concentrations.
). 2 drug interaction is or may be occurring.
*. 3elps in monitoring patient compliance.
Route of Aministration:
- in4ected directly into the circulation 5intravenous 6789:
- into muscles 5intramuscular 6709:
- under the s(in 5subcutaneous 6;<9:
- inhaled or absorbed through the s(in 5transcutaneous:.
- rectal delivery 5suppository:
Absorption:
- the traansport of drug from the site of administration to the blood.
- 'roper concentration at its site of action
- '2;;78= /7$$>;7?@ " hydrophoic state A non ioniBed
- Cea( acids " stomach
- Cea( base " intestine
- <hanges may due to age, pregnancy, pathologic condition
- $actors afecting absorption:
o 7ntestinal movement
o p3
o inDammation
o presence of food or other drugs
Distribution:
- refers to the delivery of drugs to the tissue
- Eange
o Eelationship between tissue and blood levels
o 7nc " more drugs moves into tissues that circulation
Excretion:
- 'rocess by which the drugs and its metabolites are excreted from the body
- Eate depends on the type of drug and the patients capacity to metaboliBe and
excrete it
- 8ia >E7@= " unchanged or as metabolites of the parent drug
AMP!E CO!!ECTION
- Trough concentration " before the next dose
- 'ea( concentration " hour after an orally administered dose
- ;erum and plasma - the specimen of choice for the determination of circulating
concentrations of most drugs
- 3epariniBed plasma
o is suitable for most drug analysis.
- =/T2, citrated and oxalated plasma
o not usually acceptable specimen
2. <2E/7?2<T78= /E>F
o <lass 7 " rapid sodium channel bloc(ers
o <lass 77 " beta receptor bloc(er
o <lass 777 " 'otassium channel bloc(er
o <lass 78 " <alcium channel bloc(er
. /7F?G7@
2 cardiac glycoside for treating congestive heart failure
functions by inhibiting membrane @a-H-2T'ase, dec. in H I inc. in <a 5cardiac
contractility: ..,"# ngAmJ
Hyperthyroid patients - resistance to digoxin actionsK hypothyroid patients - more
sensitive.
greater than # ngAmJ
o nausea, vomiting, and visual disturbances
o premature ventricular contractions 5'8<s: and atrioventricular node bloc(age
=limination: renal fltration
3alf life: %, hours
'ea( level: ,-. hours after an oral dose
#. L>7@7/7@=
a naturally occurring drug that can be used to treat various cardiac arrhythmic
situations
0ost common formulation: quinidine sulfate 5rapid git absorption: and quinidine
gluconate
Eoute of delivery: oral
'ea( level: ;ulfate 5 # hours: , Fluconate 5& " ) hours:
Therapeutic range: #.% " ) ugAmJ
=limination: hepatic metabolism
Toxic range: M) ugAmJ
o Toxic adverse efect:
nausea, vomiting, and abdominal discomfort.
Twice upper limit : premature ventricular contractions 5'8<s:
%. 'E?<27@207/=
Treat cardiac arrythmias
Eoute of delivery: oral 5git- apid and complete:
'ea( concentration: after hour of dose
=limination: renal fltration and hepatic metabolism
0etabolite: N-2cetyl procainamide 5@2'2:
Toxic efect:
o myocardial depression and arrhythmia
&. /7;?'NE207/=
drug used to treat cardiac arrhythmias
commonly used as a quinidine substitute
Eoute of delivery: oral
'ea( concentration: after hour to # hours of dose
Therapeutic range: % " +.) ugAmJ
=limination: renal fltration and hepatic metabolism 5lesser extent:
Toxic range:
o M&.) ugAmJ
Toxic adverse efect:
2nticholinergic efect : dry mouth and constipation
o M. ugAmJ
Toxic adverse efect: bradycardia and atrioventricular node bloc(age
). J7/?<27@=
>sed to correct ventricular arrhythmia and to prevent ventricular fbrillation.
Eoute of delivery: continous 78 infusion
=limination: complete hepatic removal
0etabolite: monoethylglycinexylidide 50=FG:
Therapeutic range: .) " &.. ugAmJ
Toxic range: M &.. ugAmJ
o <@; depression: M & - , ugAmJ
o ;eiBure and decrease !' and cardiac output: M, ugAmJ
*. 'E?'E2@?J?J
>sed in the treatment of angina pectoris, hypertension, coronary artery disease
Toxic efect: bradycardia, arterial insuOciency, pharyngitis
+. 207/2E?@=
$or ventricular arrhythmia treatment
7odine containing drug which can cause hyperAhypothyroidism
Toxic efect: bradycardia, hepatitis, photodermatitis
,. 8=E2'207J
2ngina, hypertension and supraventricular arrythmias treatment
Therapeutic range: ,. -&.. ngAmJ
o Toxic efects: hypotension, peripheral edema, ventricular fbrillation
!. 2@T7!7?T7<
. 207@?FJN<?;7/=;
treatment of infections with gram-negative bacteria that are resistant to less toxic
antibiotics
gentamicin, tobramycin, ami(acin, and (anamycin
Eoute of delivery: 78 and 70 infusionK not well absorbed by F7T
=limination: renal fltration
Toxic range: M %. ugAmJ 52mi(acin, Hanamycin: , # -) ugAmJ 5Fentamicin,
Tobramycin:
Toxic efect
o @ephrotoxicity
impair the function of proximal tubules of the (idney
electrolyte imbalance and possible proteinuria
o ?totoxicity
disruption of inner ear cochlear and vestibular membrane
hearing and balance impairment
#. 82@<?0N<7@
is a glycopeptide antibiotic that is efective against gram-positive cocci and bacilli.
Eoute of delivery: 78 infusion
Therapeutic range: ) " . ugAmJ
=limination: renal fltration
Toxic efect: red-man syndrome
Toxic levels: M. ugAmJ " nephrotoxicity , M&. ugAmJ " ototoxicity
<. ';N<3?2<T78=
. J7T37>0
drug used to treat manic depression 5bipolar disorder:
Eoute of delivery: oral
=limination: renal fltration
Therapeutic range: ..)".# mmolAJ
Toxic levels:
o .)"# mmolAJ
apathy, lethargy, speech diOculties, muscle wea(ness
o M # mmolAJ
muscle rigidity, seiBures, and possible coma
#. Tricyclic 2ntidepressant
used to treat depression, insomnia, extreme apathy, and loss of libido
imipramine, amitriptyline, and doxepin
0etabolites: /esipramine 5imipramine: and nortriptyline 5amitriptyline:
Eoute of delivery: oral
'ea( level: # " # hours
=limination:hepatic metabolism
Therapeutic level: .. " %.. ngAmJ
Toxic level: twice the upper limit
o drowsiness, constipation, blurred vision, and memory loss
o seiBure, cardiac arrhythmia, and unconsciousness
%. <J?P='7@=
atypical antipsychotic for treatment of schiBophrenia
o suicidal tendencies, cognitive defciencies associated
Therapeutic level:
o %). " &#. ngAmJ
&. ?J2@P2'7@=
thienobenBodiaBapine derivative
efectively treats schiBophrenia, acute manic episodes, and the recurrence of bipolar
disorders
Eoute of delivery:
o 7ntramuscular in4ection at a dose of #.)". mg per in4ection
o ?rally " most common
Toxic level: #."). ngAmJ
). $J>?G=T7@=
>sed for treatment of obsessive-compulsive disorders
Therapeutic level: -. " %.. ngAmJ
Toxic efect: attempted suicide, dec. libido, and sexual function
/. 700>@?;>''E=;;78= /rugs
used to prevent re4ection 5Transplantation medicine:
. <N<J?;'?E7@=
a cyclic polypeptide that has potent immunosuppressive activity
primary clinical use is suppression of host-versus-graft re4ection of heterotopic
transplanted organs
Eoute of delivery: oral
Therapeutic level: %.. ngAmJ - <ardiac, liver, and pancreas transplants
Toxic level: %)."&.. ngAmJ
o renal tubular and glomerular dysfunction
hypertension
#. T2<E?J70>;