THERAPEUTIC DRUG MONITORING Flashcards
- Involves the analysis and evaluation of circulating concentrations of drugs in blood
THERAPEUTIC DRUG MONITORING (TDM)
- To ensure that a given drug dosage produces maximal therapeutic benefit and minimal toxic adverse effects
THERAPEUTIC DRUG MONITORING (TDM)
INDICATIONS OF TDM
- Consequences of [?] are serious
- Narrow [?]
- Good correlation between circulating concentrations and [?]
- Change in [?] that may affect circulating drug concentrations
- Occurrence of [?]
- Monitoring [?]
over- and under-dosing
margin of safety
therapeutic or toxic effects
patient’s condition
drug interactions
patient compliance
- The rate at which the drug is absorbed is dependent upon the route of administration
ABSORPTION
require dissolution
- Tablets & capsules
are rapidly absorbed
liquids
- Transport mechanism:
passive diffusion
- Weak acids are absorbed in the [?] ; weak bases in the [?]
stomach
intestine
Crucial step in obtaining accurate and meaningful results
Single most important factor :
timing
Peak concentrations:
1 hour after an orally administered dose (1-hr post-dose)
Type of sample/sample matrix:
• Serum or plasma – typically used
• Heparin – commoly used anticoagulant
Avoid any degree of [?]– affects conc of elements;
proper phlebotomy techniques, gentle mixing
hemolysis
[?] of sample is important
Prompt processing
may be collected overtime to asses blood level at different points in the dosing interval
Multiple samples
(provides more comprehensive picture in the drug exposure and aids in dosage adjustment)
Multiple samples
Maintain [?], including choice of anticoagulant and collection techniques
consistency in collection
• Used to treat congestive heart failure and cardiac arrhythmias
CARDIOTROPICS
• Act on the conduction system of cardiac muscle
CARDIOTROPICS
• Net effect: slow down electrical conduction
CARDIOTROPICS
- for supraventricular and ventricular arrhythmias
Quinidine
Procainamide
Cinchonism
Quinidine
Quinidine Common formulation:
Quinidine sulfate & Quinidine gluconate
- for supraventricular or ventricular arrhythmias
Quinidine
Procainamide
Procainamide Metabolite :
n-acetylprocainamide
Reversible lupus-like syndrome w/ elevated ANA titers, urticaria, rash, agranulocytosis and nephrotic syndrome
Procainamide
- local anaesthetic
Lidocaine
- acute control & prevention of ventricular arrhythmias after MI
Lidocaine
- convulsions, coma, respiratory depression, bradycardia, hypotension
Lidocaine
- a short-term prophylactic agent in brain injury
Phenytoin (Dilantin)
- Toxicity is seen at the level of the therapeutic range
Phenytoin (Dilantin)
Major toxicity: initiation of seizures
Phenytoin (Dilantin)
Other toxic effects: hirsutism, gingival hyperplasia, Vit. D & folate deficiency
Phenytoin (Dilantin)
- Antagonizes effects of epinephrine on the heart, arteries and arterioles of skeletal muscles and on the bronchus
Propranolol
- causes vasodilation
Propranolol
- used for treatment of hypertension and angina pectoris
Propranolol
Verapamil
- for life-threatening ventricular arrhythmias
Amiodarone
- angina, hypertension, supraventricular arrhythmias
Verapamil
Treatment of gram (-) bacterial infections
AMINOGLYCOSIDES
Toxic effects: nephrotoxicity and ototoxicity
AMINOGLYCOSIDES
VANCOMYCIN
Administered IM or IV
AMINOGLYCOSIDES
PHENYTOIN
Effective against gram (+) cocci & bacilli
VANCOMYCIN
Administered by IV infusion and orally
VANCOMYCIN
Toxic side effects occur in the therapeutic range (5 - 10 ug/mL)
VANCOMYCIN
Trough levels are monitored
VANCOMYCIN
Toxic effects: “red-man syndrome” nephrotoxicity and ototoxicity
VANCOMYCIN
Characterized by erythematous flushing of the extremities
RED MAN SYNDROME
TYPES OF SEIZURE
1. Focal/Partial Seizure
a. Simple Partial
b. Complex partial
TYPES OF SEIZURE
2. Generalized
a. Tonic-Clonic (Grand Mal Seizure)
b. Absence Seizure (Petit Mal Seizure)
c. Myoclonic Seizure
d. Atonic Seizure
• originates in one specific area of the brain and will not cause loss of consciousness
Simple Partial
• symptoms may vary, but may include altered emotions, sensory changes, or motor symptoms
Simple Partial
• originates in one specific area of the brain and will lead to loss of awareness/consciousness
Complex partial
changes in behaviour, automatic movements, and confusion
Complex partial
• Muscle stiffening
(Tonic)
• Rhythmic jerking of the limbs
(Clonic)
• Most common seizure
Tonic-Clonic (Grand Mal Seizure)
• sudden loss of consciousness
Tonic-Clonic (Grand Mal Seizure)
• Brief episode of starring/absence/blanking
Absence Seizure (Petit Mal Seizure)
• Often mistaken for daydreaming
Absence Seizure (Petit Mal Seizure)
• Typically seen in children
Absence Seizure (Petit Mal Seizure)
• Involuntary jerking/twitching of muscles
Myoclonic Seizure
• Affects specific muscle groups or the entire body
Myoclonic Seizure
• Sudden loss of muscle tone leading to a person collapsing
Atonic Seizure
Generalized tonic-clonic seizures and simple partial seizures
PHENOBARBITAL
Toxicity :
• Nystagmus
• Ataxia
• Stupor
• Respiratory depression
• Hypotension
• Coma
PHENOBARBITAL
• short-term prophylactic agent in brain injury
PHENYTOIN
• Major toxicity: initiation of seizures
PHENYTOIN
Other toxic effects:
• Hirsutism
• Gingival hyperplasia
• Vit. D & folate deficiency
PHENYTOIN
PHENYTOIN Injectable proform:
Fosphenytoin
• Used for treatment of petit mal & absence seizure
VALPROIC ACID
ETHOSUXIMIDE
• Enhance the activity of Gamma Amino Butyric Acid-mediated inhibitory system
VALPROIC ACID
• Hepatic dysfunction: hyperammonemia
VALPROIC ACID
• Teratogenic effects
VALPROIC ACID
• Toxicity: sedation, gastric disturbances, ataxia
VALPROIC ACID
• Generalized tonic clonic, simple partial and complex partial seizures
CARBAMAZEPINE
PRIMIDONE
• Tic douloureux (trigeminal neuralgia)
CARBAMAZEPINE
• Reduction of excitatory synaptic transmission in the spinal trigeminal nucleus
CARBAMAZEPINE
CARBAMAZEPINE Metabolites
• 10,11-epoxide form
• 10,11-dihydroxy form
• Toxicity: drowsiness, ataxia, dizziness, nausea and vomiting
CARBAMAZEPINE
Rare:
- aplastic anemia,
- thrombocytopenia
- agranulocytosis
CARBAMAZEPINE
• Generalized tonic clonic, simple partial and complex partial seizures
CARBAMAZEPINE
PRIMIDONE
PRIMIDONE Metabolites
• Phenobarbital
• Phenylethy|malonamide
• Petit mal (absence) seizures
ETHOSUXIMIDE
• Chemically related to imipramine (TCA)
ETHOSUXIMIDE
• Toxicity: GI : nausea, vomiting, gastric distress
ETHOSUXIMIDE
COPD : chronic obstructive pulmonary disease
ASTHMA
ASTHMA
First phase :
Second phase:
bronchoconstriction (bronchodilators)
inflammation (steroids)
• For moderate or severe asthma attacks
THEOPHYLLINE
• Bronchodilator, vasodilator
THEOPHYLLINE
• Stimulates respiration and strengthens the action of cardiac muscles
THEOPHYLLINE
• known CNS stimulant
THEOPHYLLINE
• Oral or IV form
THEOPHYLLINE
THEOPHYLLINE Metabolite:
3-methyl-xanthine
THEOPHYLLINE Drug interactions (decreased metabolism):
• Phenytoin, carbamazepine
• Erythromycin
THEOPHYLLINE
• Adult therapeutic range:
10-20ug/mL
THEOPHYLLINE
• Newborns :
5-10ug/mL
THEOPHYLLINE
• Toxicity : Nausea, vomiting, headache and anxiety
• 15-20 ug/mL
THEOPHYLLINE
• Toxicity : Tachycardia, arrhythmias
20-40 ug/mL
THEOPHYLLINE
• Toxicity : Seizures, cardiac arrest
> 40 ug/mL
• Tissue damage —arachidonic acid
INFLAMMATION
2 pathways producing inflammatory mediators:
- lipo-oxygenase pathway
- cyclo-oxygenase pathway
leukotrienes
- lipo-oxygenase pathway
• thromboxanes
- cyclo-oxygenase pathway
• prostaglandins
- cyclo-oxygenase pathway
Anti-inflammatory
CORTICOSTEROIDS
Block the cyclo-oxygenase pathway
CORTICOSTEROIDS
Fluid retention, weight gain, osteoporosis, gastrointestinal bleeding and mental changes
CORTICOSTEROIDS
• Anti-inflammatory w/o undesirable side effects
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)
• Acetaminophen/Paracetamol
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)
• Acetylsalicylic acid/ Aspirin
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)
• Naproxen, Ibuprofen, Piroxicam
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)
• Analgesic, antipyretic and anti-inflammatory
ASPIRIN
• Lower doses: anti-thrombotic (cutting problems)
ASPIRIN
• Chronic toxicity: tinnitus, muffled hearing
ASPIRIN
• Acute toxicity : acidosis
ASPIRIN
• Reye’s syndrome: hepatotoxicity
ASPIRIN
• Analgesic and anti-pyretic
ACETAMINOPHEN
• ACETAMINOPHEN Metabolites :
glucoronide and sulfate conjugates
• Acute toxicity: nausea, vomiting and abdominal pain
ACETAMINOPHEN
• Chronic toxicity: anemia, renal damage, GI disturbances
ACETAMINOPHEN
• Autoimmune diseases
IMMUNOSUPPRESSIVES
• Tissue transplant recipient
IMMUNOSUPPRESSIVES
• Drug of choice for maintenance of kidney, liver, heart and heart- lung allografts
CICLOSPORIN
• Adverse effect : nephrotoxicity
CICLOSPORIN
• Other effects: neurologic, dermatologic, hepatotoxic
CICLOSPORIN
• Currently used in transplant surgery to prevent organ rejection
TACROLIMUS
• Similar toxicity profile to ciclosporin
TACROLIMUS
• Available as citrate and CO3 salts
LITHIUM
• Anti-manic agents
LITHIUM
• Prophylaxis and treatment of bipolar disorder
LITHIUM
• Toxicity: from single toxic dose or prolonged use
LITHIUM
• Renal toxicity and hypothyroidism
LITHIUM
• Block reuptake of adrenergic and dopaminergic neurotransmitters
TRICYCLIC ANTIDEPRESSANTS
• Amitriptyline, imipramine, nortriptyline, despramine, doxepin
TRICYCLIC ANTIDEPRESSANTS
• Toxicity: excess CNS stimulation
TRICYCLIC ANTIDEPRESSANTS
• Inhibits dihydrofolate reductase
3.METHOTREXATE
(enzyme cofactor important for DNA synthesis)
dihydrofolate reductase
Uses :
- Psoriasis
- Refractory rheumatoid arthritis
- Malignant neoplastic diseases
METHOTREXATE
• Toxicity: hematologic effects, GI effects
METHOTREXATE
• Treat leukemias and lymphomas prior to BM transplantation
BUSULFAN
• Toxicity: hepatic veno-occlusive disease
BUSULFAN
Block Na channels during depolarization
Rapid sodium channel blockers
Used to treat atrial and ventricular arrhythmias
Rapid sodium channel blockers
• Mechanism: Antagonize the effect of catecholamine (epinephrine and norepinephrine) on beta receptors
Beta adrenergic blockers
• Net effect: Decreases the HR and reduce myocardial contractility
Beta adrenergic blockers
• Used in management of various arrhythmias (atrial fibrillation and atrial flatter)
Beta adrenergic blockers
• Given to patients with heart failure and hypertension
Beta adrenergic blockers
• Leads to delayed depolarization
Potassium channel blockers
• Used to treat atrial and ventricular arrhythmias
Sodium channel blockers
Potassium channel blockers
• Inhibits Ca influx during depolarization
Calcium channel blockers
• Used to treat supraventricular arrhythmias (atrial fibrillation
and atrial flatter)
Calcium channel blockers
• Given to patients with angina and hypertension
Calcium channel blockers
• Escherichia coli, Klebsiella pneumoniae, Pseudomonas spp
AMINOGLYCOSIDES
• Commonly used w/ other antibiotics for synergistic effects
AMINOGLYCOSIDES
• Oral is not common due to poor absorption in the IT
AMINOGLYCOSIDES
• Can cause kidney damage esp if high conc persists in the renal tubules
AMINOGLYCOSIDES
• Ototoxicity: damage to the inner ear leading to hearing
loss or balance issues
AMINOGLYCOSIDES
• Methicillin Resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Enterococcus spp
VANCOMYCIN
• Not effective against gram (-) bacteria
VANCOMYCIN
– available but mainly used to treat GI infection caused by Clostridium difficile
• Oral vancomycin
• Blood sample is collected just before the next dose
VANCOMYCIN
• Common adverse reaction to rapid IV infusion of
vancomycin
RED MAN SYNDROME
• Characterized by flushing, red rash, hypotension
RED MAN SYNDROME
• Prevention: slow down infusion process
RED MAN SYNDROME
• Anti-convulsant
PHENOBARBITAL
: involuntary rhythmic eye movement
• Nystagmus
: lack of coordination of muscle movements
• Ataxia
: state of mere consciousness or insensibility
• Stupor
: low blood pressure
• Hypotension
: state of deep unconsciousness
• Coma
• Anti-epileptic medication to treat various seizure disorders
PHENYTOIN
• Pro-convulsant effect
PHENYTOIN
: abnormal growth of hair in females
• Hirsutism
: overgrowth of gum tissues (remedy: good oral hygiene)
• Gingival hyperplasia
: long-term use; can interfere w/ absorption metabolism
• Vit. D & folate deficiency
(water-soluble; IV or IM administration; converted to phenytoin in the body; often used when more controlled and rapid movement of phenytoin is needed)
Fosphenytoin
: known neurotransmitter that sends chemical signals to CNS; involved in the regulation of communication of the brain cells
Gamma Amino Butyric Acid
• Works to decrease nerve impulses that can cause nerve seizure and pain
CARBAMAZEPINE
: severe stabbing pain to one side of the face
Tic douloureux (trigeminal neuralgia)
Syndrome of variable airflow obstruction
COPD : chronic obstructive pulmonary disease
Characterized by bronchial inflammation with prominent eosinophil infiltration and bronchial hyper responsiveness
ANTIASTHMATICS
Common clinical symptoms: cough chest tightness, wheezing
ASTHMA
one of the most well-known antiasthmatics
THEOPHYLLINE
: involved in asthmatic and allergic reactions; acts to sustain inflammatory reactions
leukotrienes
- made at sites of tissue damage/infection involved w/ healing injury
Thromboxanes
Prostaglandins
used to provide relief for inflamed areas
CORTICOSTEROIDS
lessens swelling, redness, itching, and allergic reactions
CORTICOSTEROIDS
given to patients w/ severe allergies, skin problems, asthma, arthritis
CORTICOSTEROIDS
popular pain reliever
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)
bipolar disorder, mood swings, depression, mania
MANIC DEPRESSION DRUGS
most well-known MANIC DEPRESSION DRUGS
LITHIUM
controls processes such as inflammation, blood flow, or formation of blood clots
Thromboxanes
Prostaglandins
seizures, coma, hypotension, respiratory depression
TRICYCLIC ANTIDEPRESSANTS
vertigo, tinnitus, headache, visual disturbances and disorientation
Quinidine
