THERAPEUTIC DRUG MONITORING Flashcards by Arriane Cyrel (MTI)

Involves the analysis and evaluation of circulating concentrations of drugs in blood

THERAPEUTIC DRUG MONITORING (TDM)

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To ensure that a given drug dosage produces maximal therapeutic benefit and minimal toxic adverse effects

THERAPEUTIC DRUG MONITORING (TDM)

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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

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The rate at which the drug is absorbed is dependent upon the route of administration

ABSORPTION

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require dissolution

Tablets & capsules

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are rapidly absorbed

liquids

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Transport mechanism:

passive diffusion

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Weak acids are absorbed in the [?] ; weak bases in the [?]

stomach

intestine

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Crucial step in obtaining accurate and meaningful results

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Single most important factor :

timing

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Peak concentrations:

1 hour after an orally administered dose (1-hr post-dose)

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Type of sample/sample matrix:

• Serum or plasma – typically used
• Heparin – commoly used anticoagulant

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Avoid any degree of [?]– affects conc of elements;
proper phlebotomy techniques, gentle mixing

hemolysis

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[?] of sample is important

Prompt processing

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may be collected overtime to asses blood level at different points in the dosing interval

Multiple samples

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(provides more comprehensive picture in the drug exposure and aids in dosage adjustment)

Multiple samples

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Maintain [?], including choice of anticoagulant and collection techniques

consistency in collection

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• Used to treat congestive heart failure and cardiac arrhythmias

CARDIOTROPICS

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• Act on the conduction system of cardiac muscle

CARDIOTROPICS

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• Net effect: slow down electrical conduction

CARDIOTROPICS

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for supraventricular and ventricular arrhythmias

Quinidine

Procainamide

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Cinchonism

Quinidine

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Quinidine Common formulation:

Quinidine sulfate & Quinidine gluconate

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for supraventricular or ventricular arrhythmias

Quinidine

Procainamide

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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:

1. lipo-oxygenase pathway 2. cyclo-oxygenase pathway

leukotrienes

1. lipo-oxygenase pathway

• thromboxanes

2. cyclo-oxygenase pathway

• prostaglandins

2. 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

THERAPEUTIC DRUG MONITORING Flashcards

(194 cards)