(F) Lec 3: Therapeutic Drug Monitoring (Part 2) Flashcards
(84 cards)
1
Q
TOF: Not all drugs will be part of the TDM procedure
A
True (only involves drugs with known serious/life-threatening side effects)
2
Q
Refers to the procedure by which any substance when inhaled, injected, smoked, consumed, absorbed via a patch of skin, or dissolved in the mouth causes a temporary physiological change in the body
A
Therapeutic Drug Monitoring
3
Q
Familiarize yourself with the types of medication tackled in the lecture
A
- Anti-inflammatory
- Antibiotics
- Anti-epileptics
- Psychoactives
- Bronchodilators
- Immunosuppressants
- Anti-neoplastics
4
Q
- Aka “analgesics” wherein the majority are under the NSAIDs groups
- Relieves pain, reduces inflammation, and brings down high temperatures
A
Anti-Inflammatory Drugs
5
Q
Anti-Inflammatory Drugs
- An inhibitor of prostaglandin metabolism (prostaglandin induces inflammation)
- An overdosage leads to hepatotoxicity (liver damage)
- The therapeutic range is 25µg/mL
- Toxic levels include: >50µg/mL and 100-300µg/mL which causes hepatic necrosis
- The reference method for testing is HPLC
A
Acetaminophen
6
Q
Anti-Inflammatory Drugs
What are the ff. ranges for acetaminophen?
1. Therapeutic dose
2. Initial toxic dose
3. Toxic dose which leads to hepatic necrosis
A
- 25µg/mL
- > 50µg/mL
- 100-300µg/mL
7
Q
Anti-Inflammatory Drugs
What is the reference method for detecting acetaminophen levels?
A
HPLC
8
Q
Anti-Inflammatory Drugs
- Has both the analgesic and anti-inflammatory action
- Toxic effects include: nausea, vomiting, blurred vision, abdominal pain, and edema
- The therapeutic range is 10-50µg/mL
- Toxic level is >100µg/mL
A
Ibuprofen
9
Q
Anti-Inflammatory Drugs
What are the ff. ranges for ibuprofen?
1. Therapeutic dose
2. Toxic dose
A
- 10-50µg/mL
- > 100µg/mL
10
Q
- A classification of the anti-microbial agents (against bacteria, viruses, parasites, and fungi)
- Specifically targets bacteria
- Must be selectively toxic to the target infectious organism without causing excessive damage to human cells
A
Antibiotics
11
Q
Antibiotics
- Treats infections caused by Gram(-) bacteria
- Administered via IV or IM but not orally because GIT absorption is poor
- Elimination is via kidney filtration
- Measured using Chromatography and Immunoassays
A
Aminoglycosides (e.g. Gentamicin, Tobramicin, Kanamycin, and Amikacin)
12
Q
Antibiotics
What bacteria do aminoglycosides target?
A
Gram Negative (-) Bacteria
13
Q
Antibiotics
How are aminoglycosides eliminated?
A
Via kidney filtration
Note: If one has kidney problems, this is not recommended
14
Q
Antibiotics
What 2 methods can be used to measure aminoglycosides?
A
- Chromatography
- Immunoassay
15
Q
Toxic Effects of Aminoglycosides
- There is an impairment of proximal tubule function
- Electrolytes are imbalanced
- There is proteinuria
- High levels of exposure lead to kidney necrosis and failure
A
Nephrotoxocity
16
Q
Toxic Effects of Aminoglycosides
Disruption of the inner cochlea and vestibular membranes causing impairments in both hearing and balance
A
Ototoxicity
17
Q
Antibiotics
- Treats infections caused by Gram(+) bacteria
- Administered via IV but not orally because GIT absorption is poor
- Measured using Chromatography and Immunoassays
- Associated with nephrotoxicity, ototoxicity, and the red-man syndrome
A
Vancomycin
18
Q
Antibiotics
What bacteria does vancomycin target?
A
Gram Positive (+) Bacteria
19
Q
Antibiotics
What 2 methods can be used to measure vancomycin?
A
- Chromatography
- Immunoassay
20
Q
Antibiotics
Refers to the erythemic flushing of the extremities caused by a Vancomycin overdose
A
Red-Man Syndrome
21
Q
- Alters the transmission of nerve impulses to minimize seizures
- Treats and controls cases of epilepsy, convulsions, and seizures
- Are mainly used as prophylactics with therapeutic ranges considered as guidelines
- Measured using Chromatography or Immunoassays
- Measures the free or bound fractions in either serum or plasma
- Is collected at the end of the dosing interval
A
Anti-Epileptic Drugs
22
Q
Anti-Epileptic Drugs
- What fractions are measured in these types of drugs?
- What specimens can be used?
A
- Both free and bound
- Both serum and plasma
23
Q
Anti-Epileptic Drugs
When is serum/plasma collected when measuring these types of drugs?
A
At the end of the dosing interval
24
Q
Classifications of Seizures
May be simple, complex, or generalized
A
Partial Seizure
25
# Classifications of Generalized Seizures
- There are no manifestations/physical signs of seizing
- Presents with a blank stare with or without subtle body movements such as lip smacking or eye blinking
Absence Seizures (Petit Mal)
26
# Classifications of Generalized Seizures
- The person's muscles initially stiffen and will eventually lose consciousness
- The eyes will roll back into their head as the muscles contract (chest, arms, and legs) and the back arches
Tonic Seizures
27
# Classifications of Generalized Seizures
- Aka drop seizures, drop attacks, and akinetic seizures
- There is a brief lapse in muscle tone caused by temporary alterations in brain function
- Usually lasts less than 15 seconds
Atonic Seizures
28
# Classifications of Generalized Seizures
The individual's muscles begin to have rhythmic jerking movements
Clonic Seizures
29
# Classifications of Generalized Seizures
There are brief contractions or relaxations of a muscle or muscle group resulting in sudden jumpy movements
Myoclonic Seizures
30
# Classifications of Generalized Seizures
- Formerly known as Grand-Mal Seizures
- Both types are experienced at the same time
- It is rare to experience one without the other
Tonic-Clonic Seizures
31
# Anti-Epileptic Drugs
What 2 major classifications were discussed in Anti-Epileptic Drugs?
1st and 2nd Generation Drugs
| Note: 2nd Gen. are supplemental to 1st Gen.
32
# Anti-Epileptic Drugs
Familiarize yourself with the first and second generation drugs
First Generation
1. Phenobarbital
2. Phenytoin (Dilantin)
3. Valproic Acid (Depakene)
4. Carbamazepine (Tegretol)
5. Ethosuximide (Zarontin)
Second Generation
1. Gabapentin (Neurontin)
2. Felbamate
3. Levetiracetam
4. Oxcarbazpine
5. Lamotrigine
6. Zonisamide
7. Tiagabine
8. Topiramate
33
# Anti-Epileptic Drugs
TOF: The optimal concentrations of 1st generation drugs are not established while for 2nd generation drugs, it is established
False (reverse)
34
# Anti-Epileptic Drugs
- In the blood stream, it is 50% protein-bound
- Overdosage leads to excess storage in the brain
- A hydantoin-derivative anticonvulsant
- A long-acting barbiturate that controls Grand-Mal seizures and focal epileptic episodes
- Is not used for Petit Mal seizures
Phenobarbitals
35
# Anti-Epileptic Drugs
- Used for treating withdrawal symptoms in infants or mothers addicted to opiates
- Also treats congenital hyperbilirubinemia to enhance bilirubin metabolism
- Absorption is slow but complete
- Elimination is via Hepatic Metabolism
Phenobarbitals
| Note: In cases of renal impairment, elimination is slowed down
36
# Anti-Epileptic Drugs
1. What is the inactive proform of Phenobarbitals?
2. What is its half life?
3. When is the peak level reached after an oral dose?
1. Primidone (Mysoline)
2. 70 to 100 hours
3. 10 hours after
37
# Anti-Epileptic Drugs
What are the therapeutic levels for:
1. Phenobarbital
2. Primidone
1. 20-40 µg/mL
2. 5-12 µg/mL
38
# Anti-Epileptic Drugs
Familiarize yourself with the toxic effects of Phenobarbitals
1. Nystagmus
2. Stupor
3. Ataxia
4. Respiratory depression
39
# Anti-Epileptic Drugs
- In the system, around 87-97% are protein-bound
- It controls tonic-clonic seizures and simple partial seizures
- Cannot be used for petit mal and atonic seizures
- A short-term prophylactic agent in cases of brain injury
Phenytoin
40
# Anti-Epileptic Drugs
What is the injectable proform of Phenytoin called?
Fosphenytoin
41
# Anti-Epileptic Drugs
What is the therapeutic range for both the protein-bound and free forms of Phenytoin?
1. Protein-bound: 10-20µg/mL
2. Free: 1-2µg/mL
42
# Anti-Epileptic Drugs
What is the toxic level for Phenytoin?
> 20 µg/mL
43
# Anti-Epileptic Drugs
Familiarize yourself with the toxic side effects of Phenytoin
1. Initiation of seizures
2. Teratogenic action (cleft lip or palate)
3. Nystagmus
44
# Anti-Epileptic Drugs
- Is 93% protein-bound and used to treat Petit Mal seizures, atonic seizures, and Grand Mal seizures
- Is orally administered as absorption is rapid and complete
- Eliminated via Hepatic Metabolism but hepatic dysfunction is often seen hence monitoring after 6 months is recommended
Valproic Acid
45
# Anti-Epileptic Drugs
What is the therapeutic level of Valproic Acid?
50-100µg/mL
46
# Anti-Epileptic Drugs
Familiarize yourself with the toxic side effects of Valproic Acid
1. Nausea
2. Lethargy
3. Pancreatitis
47
# Anti-Epileptic Drugs
- Is 70-80% protein-bound
- A tricyclic compound related to imipramine (TCA)
- Is highly effective for Grand Mal seizures and can treat them when also accompanied by pain
- Is orally administered
- Has serious side effects and is not frequently used
Carbamazepine (Tegretol)
48
# Anti-Epileptic Drugs
What is the therapeutic range of Carbamazepine (Tegretol)?
4-16µg/mL
49
# Anti-Epileptic Drugs
Familiarize yourself with the toxic effects of Carbamazepine (Tegretol)
1. Hematologic dyscarias
2. Irregular pulse
3. Aplastic anemia
4. Ataxia
50
# Anti-Epileptic Drugs
- Exists as the free-form in the serum
- The drug of choice for treating and controlling Petit Mal seizures
- Is orally administered
- Toxic effects include: GI disturbance, ataxia, aplastic anemia, pancytopenia, and SLE
Ethosuximide (Zarontin)
51
# Anti-Epileptic Drugs
What are the therapeutic and toxic ranges of Ethosuximide (Zarontin)?
1. Therapeutic: 40-100µg/mL
2. Toxic: >100µg/mL
52
- Used to treat psychotic patients (may be moderate or severe)
- For patients with abnormal thinking or perception and those who are losing touch with reality
- Treats hallucinations, delusions, and other mental disorders
Psychoactive Drugs
53
# Psychoactive Drugs
- A known mood-stabilizer but with unknown mechanism
- Treats manic-depressive illnesses
- Administered orally as lithium carbonate
- Does not bind to plasma proteins in the circulation
Lithium
54
# Psychoactive Drugs
- Peak levels are at 2-4 hours after oral ingestion
- It is filtered by the renal glomerulus and eliminated as the unchanged drug
- The therapeutic range is 0.8 to 1.2 mmol/L
Lithium
55
# Psychoactive Drugs
What are the toxic ranges for lithium:
1. Range that causes apathy, lethargy, and speech difficulties
2. Range the causes muscle rigidity, seizures, and possibly a coma
1. 1.2 to 2 mmol/L
2. > 2 mmol/L
56
# Psychoactive Drugs
- Used to treat depression that has no apparent organic or social cause
- Is metabolized by the liver to form its active metabolite (Desipramine)
- Are measured by chromatography and immunoassays
Tricyclic Anti-Depressants
| Examples are Imipramine, Nortiptyline, Amitriptyline, and Desipramine
57
# Psychoactive Drugs
- The steady state is after 2-4 weeks of initiation of therapy
- Toxic effects are drowsiness, constipation, blurred vision, memory loss, and seizures, and cardiac arrythmia in much higher doses
Tricyclic Anti-Depressants
58
# Psychoactive Drugs
This Tricyclic Anti-Depressant treats depression, insomnia, extreme apathy, and loss of libido
Doxepin
59
# Psychoactive Drugs
- Treats those with refractory schizophrenia (patient is failing to respond to continuous therapy)
- Negative symptoms include: suicidal tendencies and various types of cognitive deficiencies
- There is no well-established clinical serum concentration
Clozepine
60
# Psychoactive Drugs
- The therapeutic range is 350-420 ng/mL
- Used to check for compliance and in patients with altered pharmacokinetics
- A symptom of toxicity is seizures
Clozepine
61
# Psychoactive Drugs
- A thienobenzodiazapine derivative
- Treats schizophrenia, acute manic episodes, and the recurrence of bipolar disorders
- Administered by IM at 2.5 to 10 mg per injection
Olazepine
62
# Psychoactive Drugs
- When administered orally, 85% is absorbed and approximately 40% are inactivated by the first-pass metabolism
- The therapeutic range is 20-50 ng/mL
- Women and non-smokers tend to have a lower clearance leading to higher serum concentrations
Olazepine
63
- These act to relax the bronchial smooth muscles for the relief or prevention of asthma
- Used to treat asthma and COPDs
Bronchodilator Drugs
64
# Bronchodilator Drugs
- Used for the treatment of asthma and COPD
- Is administered orally and metabolized by the liver to produce several metabolites like caffeine
- Is filtered by the kidney
Theophylline
65
# Bronchodilator Drugs
- The therapeutic range is 10 to 20 µg/mL
- The toxicity level varies along with its effects
- The toxic ranges include > 20 µg/mL which causes nausea, vomiting, and diarrhea and > 30 µg/mL causes cardiac arrythmia and seizures
Theophylline
66
- These prevent rejections associated with transfusions and transplantations
- Most require the establishment of individual dosage regimens to optimize therapeutic outcomes and minimize toxicity
Immunosuppressive Drugs
67
# Immunosuppressive Drugs
- Functions by blocking the production of IL-2
- Used to suppress transplant rejections and GVHDs
- Is administered orally and peak levels are observed after 4-6 hours
- The specimen of choice is whole blood
- Is detected using HPLC
Cyclosporine
68
# Immunosuppressive Drugs
What are the therapeutic ranges for Cyclosporine for the transplants:
1. Liver, pancreas, and heart
2. Kidney
1. 200-350 ng/mL
2. 100-300 ng/mL
69
# Immunosuppressive Drugs
- Elimination is dependent on liver function
- Is toxic at 350-400 ng/mL
- Side effects include renal tubular dysfunction and glomerular dysfunction which leads to hypertension
Cyclosporine
70
# Immunosuppressive Drugs
- Aka Rapamycin
- An antifungal agent with immunosuppressive activity
- Approved for patients who underwent kidney transplants
- Absorbed after once-daily oral administration
- Levels peak at about 1 hour
- The oral bioavailability is 15% when taken in conjunction with cyclosporine
Sirolimus
71
# Immunosuppressive Drugs
- Has a half life of 62 hours
- The specimen of choice is whole blood
- Can be detected via HPLC
Sirolimus
72
# Immunosuppressive Drugs
What are the therapeutic ranges of Sirolimus:
1. With cyclosporine
2. Without cyclosporine
1. 4 to 12 ng/L
2. 12 to 20 ng/L
73
# Immunosuppressive Drugs
- 95% of it is protein-bound
- It inhibits the proliferation of lymphocytes
- Commonly used as a supplemental drug with cyclosporine and tacrolimus for renal transplant patients
Mycophenolic Acid
74
# Immunosuppressive Drugs
What is the prodrug and active form of Mycophenolic Acid?
1. Prodrug: Mycophenolate Mofetil (MMF)
2. Active: Mycophenolic Acid (MPA)
75
# Immunosuppressive Drugs
- Low levels of this result in increased risk for acute rejection while high levels result in toxicity
- Is orally administered and absorbed under neutral pH conditions in the intestine
- The therapeutic range is 1 to 3.5 g/mL
- The specimen of choice is plasma when using chromatography
Mycophenolic Acid
76
# Immunosuppressive Drugs
- Can be detected via immunoassays because it is commonly done but is less specific compared to HPLC
- Cross reactivity between this and its active metabolite, Acyl-mycophenolic acid glucuronide (AcMPAG) is possible
Mycophenolic Acid
77
# Immunosuppressive Drugs
- Has the same function as cyclosporine but its potency is much higher (100x higher)
- Toxic effects include: nephrotoxicity and thrombus formation
- The specimen of choice is whole blood
- Measured using HPLC
Tacrolimus
78
- Used in the management of tumors found in the breast, testicles, pharynx, and sometimes lungs
- Works by inhibiting DNA synthesis
- Most are administered via IV as a single bolus
- Is rapidly metabolized or incorporated into cellular macromolecular structures within seconds to minutes
Anti-Neoplastic Drugs
79
# Anti-Neoplastic Drugs
- This is used to destroy neoplastic cells
- It inhibits the synthesis of DNA in all cells (because neoplastic cells contain greater amounts of DNA because of their rapid division rates)
- Is administered by IV
Methotrexate
80
# Anti-Neoplastic Drugs
- Is filtered by the kidneys for elimination
- Its toxic effect is that cytotoxicity affects most cell types
Methotrexate
81
# Anti-Neoplastic Drugs
To control the period of cytotoxicity, this is administered after dosing the patients with Methotrexate as this ensures that the cytotoxicity is not deleterious by inhibiting the action of Methotrexate
Leucovorin Rescue
82
TOF: Whole Blood in Citrate is commonly used as the specimen of choice for Immunosuppresive Drugs
False (Whole Blood EDTA)
83
The most important step in TDM is the ____ of specimen collection
Timing
84
The importance of timing the specimen collection is that you want to get the specimen when the drug concentration is at its ____
Peak
