7.2 - THERAPEUTIC DRUGS

Cardioactive

Antibiotics

Antiepileptics

Psychoactives

Immunosuppressive

Antineoplastics

Bronchodilators

Therapeutic Drugs (7)

Digoxin (Lanoxin)

Quinidine

Procainamide & N-acetylprocainamide (NAPA)

Disopyramide (Norpace)

Therapeutic Drugs

Cardioactives (4)

Digoxin (Lanoxin)

Therapeutic Drugs

Cardioactives

Type: Cardiac glycoside, an inotropic agent

Digoxin (Lanoxin)

Therapeutic Drugs

Cardioactives

Treats arrhythmias and congestive heart failure

Lanoxin

Therapeutic Drugs

Cardioactives

Generic name of Digoxin

increases intracellular calcium

Therapeutic Drugs

Cardioactives

Digoxin (Lanoxin)

Mechanism: Inhibits Na⁺/K⁺-ATPase = ? = improved contractility

~38

Therapeutic Drugs

Cardioactives

Digoxin (Lanoxin)

Half-life: _ hours (slow tissue release)

kidneys

Therapeutic Drugs

Cardioactives

Digoxin (Lanoxin)

Eliminated via _ (mainly unbound form); some hepatic metabolism

0.8-2.0 ng/mL

Therapeutic Drugs

Cardioactives

Digoxin (Lanoxin)

Therapeutic range: ?

8-10

Therapeutic Drugs

Cardioactives

Digoxin (Lanoxin) Consideration

Collect blood _-_ hrs post-dose

toxicity risk

Therapeutic Drugs

Cardioactives

Digoxin (Lanoxin) Consideration

Low K⁺/Mg²⁺ = ↑ _ _

hyperthyroid

hypothyroid

Therapeutic Drugs

Cardioactives

Digoxin (Lanoxin) Consideration

Resistant to _ patients; sensitive to _ patients

Quinidine

Therapeutic Drugs

Cardioactives

Use: Treat arrhythmias

Quinidine

Therapeutic Drugs

Cardioactives

Use: Treat arrhythmias

Natural cinchona bark

Therapeutic Drugs

Cardioactives

Quinidine

Source

Sulfate, gluconate

Therapeutic Drugs

Cardioactives

Quinidine

Formulations: (2)

70-80

Therapeutic Drugs

Cardioactives

Quinidine

_-_% protein-bound

6-8

Therapeutic Drugs

Cardioactives

Quinidine

Half-life: _-_ hrs

hepatically

Therapeutic Drugs

Cardioactives

Quinidine

Metabolized _ (with increased clearance with barbiturates)

thrombocytopenia

Therapeutic Drugs

Cardioactives

Quinidine

Toxicity may result to _

N-acetylprocainamide

procainamide

Therapeutic Drugs

Cardioactives

_: Active hepatic metabolite of _

Disopyramide (Norpace)

Therapeutic Drugs

Cardioactives

Use: Antiarrhythmic; substitute for quinidine

Norpace

Therapeutic Drugs

Cardioactives

Disopyramide

Generic name

nephrotoxicity and ototoxicity

Therapeutic Drugs

TDM necessary due to narrow therapeutic ranges and risk of _ and _

Gentamicin, Tobramycin, Amikacin, Kanamycin

Therapeutic Drugs

Antibiotics (4)

IV/IM

Therapeutic Drugs

Antibiotics

Administration: Mostly _/_ due to poor GI absorption

Aminoglycosides

Therapeutic Drugs

Antibiotics

Mechanism: Inhibit bacterial protein synthesis

Ototoxicity

Nephrotoxicity

Therapeutic Drugs

Antibiotics

Aminoglycosides

Risks:

_ (irreversible)

_ (often reversible)

Renal

Therapeutic Drugs

Antibiotics

Aminoglycosides

Elimination: _ filtration

1-2

Therapeutic Drugs

Antibiotics

Aminoglycosides

Peak levels: _-_ hrs post-dose

2-3

Therapeutic Drugs

Antibiotics

Aminoglycosides

Half-life: _-_ hrs

Trough

Therapeutic Drugs

Antibiotics

Aminoglycosides

_ levels critical for minimizing toxicity

Gentamicin

Therapeutic Drugs

Antibiotics

Aminoglycosides

Severe gram-negative infections; sometimes with S. aureus

Tobramycin

Therapeutic Drugs

Antibiotics

Aminoglycosides

Similar to gentamicin; includes P. aeruginosa

Amikacin

Therapeutic Drugs

Antibiotics

Aminoglycosides

Severe gram-negative infections

Vancomycin

Therapeutic Drugs

Antibiotics

Aminoglycosides

Glycopeptide antibiotic; for gram-positive infections

Vancomycin

Therapeutic Drugs

Antibiotics

Aminoglycosides

Toxicity may result to Red-man syndrome (flushing)

Measurement only via trough levels (due to long distribution phase)

Therapeutic Drugs

Antibiotics

Aminoglycosides

Toxicity may result to Red-man syndrome (flushing)

Measurement only via trough levels (due to long distribution phase)

Primidone

Phenobarbital

Phenytoin/Free Phenytoin (Dilantin)

Valproic Acid/Valproate (Depakote)

Carbamazepine (Tegretol)

Ethosuximide (Zarontin)

Felbamate (Felbatol)

Gabapentin (Neurontin)

Lamotrigine (Lamictal)

Levetiracetam (Keppra)

Oxcarbazepine (Trileptal)

Tiagabine (Gabitril)

Topiramate (Topamax)

Zonisamide (Zonegran)

Therapeutic Drugs

Antiepileptics (14)

Primidone

Therapeutic Drugs

Antiepileptics

Used for grand mal seizures unresponsive to other AEDs

phenobarbital, phenylethylmalonamide

Therapeutic Drugs

Antiepileptics

Primidone

Converted to _ and PEMA (_, an active metabolites)

phenobarbital

Therapeutic Drugs

Antiepileptics

Primidone

Toxicity mainly due to _ accumulation

Phenobarbital

Therapeutic Drugs

Antiepileptics

Long-acting barbiturate for various seizures

Phenobarbital

Therapeutic Drugs

Antiepileptics

Potent inducer of the MFO system

Phenobarbital

Therapeutic Drugs

Antiepileptics

Induces hepatic MFO enzymes

Phenytoin/Free Phenytoin (Dilantin)

Therapeutic Drugs

Antiepileptics

Used for seizure disorders and post-brain injury prophylaxis

Dilantin

Therapeutic Drugs

Antiepileptics

Phenytoin/Free Phenytoin (_)

Phenytoin/Free Phenytoin (Dilantin)

Therapeutic Drugs

Antiepileptics

Also, an inducer of the MFO system

protein binding

Therapeutic Drugs

Antiepileptics

Phenytoin/Free Phenytoin (Dilantin)

Toxicity can still occur at normal total levels if _ _ is reduced

Valproic Acid/Valproate (Depakote)

Therapeutic Drugs

Antiepileptics

For petit mal and absence seizures

Depakote

Therapeutic Drugs

Antiepileptics

Valproic Acid/Valproate (_)

hallucinations, hyperammonemia, and pancreatitis

Therapeutic Drugs

Antiepileptics

Valproic Acid/Valproate (Depakote)

Toxicity of >200 μg/mL may cause (3)

Carbamazepine (Tegretol)

Therapeutic Drugs

Antiepileptics

Effective for various disorders but reserved due to serious adverse effects (agranulocytosis & aplastic anemia); thus only used when patients do not respond well to other AEDs

Tegretol

Therapeutic Drugs

Antiepileptics

Carbamazepine (_)

Leukopenia

Therapeutic Drugs

Antiepileptics

Carbamazepine (Tegretol)

Most serious effect: _

Ethosuximide (Zarontin)

Therapeutic Drugs

Antiepileptics

For petit mal seizures

Toxicities are self-limiting

Zarontin

Therapeutic Drugs

Antiepileptics

Ethosuximide (_)

Felbamate (Felbatol)

Therapeutic Drugs

Antiepileptics

For Lennox-Gastaut syndrome and refractory epilepsy

Felbatol

Therapeutic Drugs

Antiepileptics

Felbamate (_)

orally

enzyme inducers

phenobarbital, primidone, phenytoin, and carbamazepine

Therapeutic Drugs

Antiepileptics

Felbamate (Felbatol)

Most commonly administered _

Metabolism enhanced by _ _ (4)

Gabapentin (Neurontin)

Therapeutic Drugs

Antiepileptics

Most frequently used AED in patients with liver disease, and partial-onset seizures in patients with acute intermittent porphyria

Neurontin

Therapeutic Drugs

Antiepileptics

Gabapentin (_)

60, antacids

Children

Therapeutic Drugs

Antiepileptics

Gabapentin (Neurontin)

Maximum bioavailability of _%, which is reduced when _ are administered concurrently

_ require a higher dose than adults

Lamotrigine (Lamictal)

Therapeutic Drugs

Antiepileptics

For partial and generalized seizures

Lamictal

Therapeutic Drugs

Antiepileptics

Lamotrigine (_)

pregnancy

32

Therapeutic Drugs

Antiepileptics

Lamotrigine (Lamictal)

Marked increases in clearance during _, peaking at _ weeks of gestation

Valproic acid

Therapeutic Drugs

Antiepileptics

Lamotrigine (Lamictal)

Lamotrigine metabolism inhibitor: _ _

Levetiracetam (Keppra)

Therapeutic Drugs

Antiepileptics

For partial and generalized seizures

TDM not as pronounced as for other AEDs due to its lack of pharmacokinetic variability

Keppra

Therapeutic Drugs

Antiepileptics

Levetiracetam (_)

Oxcarbazepine (Trileptal)

Therapeutic Drugs

Antiepileptics

Metabolized further by glucuronide conjugation

Sensitive to enzyme inducers

Trileptal

Therapeutic Drugs

Antiepileptics

Oxcarbazepine (_)

(R)-licarbazepine

(S)-licarbazepine

Therapeutic Drugs

Antiepileptics

Oxcarbazepine (Trileptal)

Metabolized by the liver into two active enantiomeric forms: _-_ and _-_

Tiagabine (Gabitril)

Therapeutic Drugs

Antiepileptics

For partial seizures

Free:bound drug ratio affected by other protein-binding drugs (valproic acid, naproxen, salicylates) and by pregnancy

Gabitril

Therapeutic Drugs

Antiepileptics

Tiagabine (_)

Topiramate (Topamax)

Therapeutic Drugs

Antiepileptics

For partial and generalized seizures

Increased secondary to renal insufficiency but may be decreased when used with other enzyme-inducing AEDs

Topamax

Therapeutic Drugs

Antiepileptics

Topiramate (_)

Topiramate (Topamax)

Therapeutic Drugs

Antiepileptics

Adverse CNS side effects include change of taste with particular foods (e.g., diet soda and beer) and a sensation of “pins and needles” in the extremities

Zonisamide (Zonegran)

Therapeutic Drugs

Antiepileptics

An anticonvulsant; adjunctive therapy for partial and generalized seizures

Zonegran

Therapeutic Drugs

Antiepileptics

Zonisamide (_)

acetylation, oxidation

glucuronide conjugation

Therapeutic Drugs

Antiepileptics

Zonisamide (Zonegran)

Metabolized by the liver via _ and _, then _ _

Lithium

Tricyclic Antidepressants (TCAs)

Clozapine

Olanzapine (Zyprexa)

Therapeutic Drugs

Psychoactives (4)

Lithium

Therapeutic Drugs

Psychoactives

Cationic metal that does not bind to proteins

Mood-altering drug

Lithium

Therapeutic Drugs

Psychoactives

For bipolar disorder, recurrent depression, and aggressive or self-mutilating behavior

migraines

cluster headaches

Therapeutic Drugs

Psychoactives

Lithium

May also be used as a preventative treatment for _ and _ _

2

hypothyroidism

Therapeutic Drugs

Psychoactives

Lithium

>_ mmol/L: Renal impairment, _, and CNS disturbances

colorimetric

lithium

Therapeutic Drugs

Psychoactives

Lithium

Measured by _ methods

Tubes with _ anticoagulants must be avoided

Tricyclic Antidepressants

Therapeutic Drugs

Psychoactives

For depression, insomnia, extreme apathy, and loss of libido

Imipramine, Amitriptyline, Doxepin

Therapeutic Drugs

Psychoactives

Tricyclic Antidepressants (3)

Desipramine

Therapeutic Drugs

Psychoactives

Tricyclic Antidepressants

Active metabolite of imipramine

Nortriptyline

Therapeutic Drugs

Psychoactives

Tricyclic Antidepressants

Active metabolite of amitriptyline

Immunoassays

total tricyclics

Therapeutic Drugs

Psychoactives

Tricyclic Antidepressants

_ are used for TCA screening rather than TDM; results are reported out as “_ _”

Clozapine

Therapeutic Drugs

Psychoactives

For otherwise treatment-refractory schizophrenia

Clozaril, FazaClo

Therapeutic Drugs

Psychoactives

Clozapine (2)

Olanzapine

Therapeutic Drugs

Psychoactives

A thienobenzodiazepine derivative

For schizophrenia, acute manic episodes, and the recurrence of bipolar disorders

Women and nonsmokers tend to have lower clearance

Zyprexa

Therapeutic Drugs

Psychoactives

Olanzapine (_)

Cyclosporine

Tacrolimus

Sirolimus (Rapamune)

Everolimus

Mycophenolate Mofetil

Therapeutic Drugs

Immunosuppressives (5)

Cyclosporine

Therapeutic Drugs

Immunosuppressives

Cyclic polypeptide

For suppression of host-versus-graft rejection of heterotopic transplanted organs

Appears to sequester in cells, including RBCs

Gengraf, Neoral, Sandimmune

Therapeutic Drugs

Immunosuppressives

Cyclosporine (3)

temperature

whole blood

Therapeutic Drugs

Immunosuppressives

Cyclosporine (Gengraf, Neoral, Sandimmune)

RBC content is highly _ dependent; therefore, _ _ specimens are used

Renal tubular

glomerular dysfunction

hypertension

Therapeutic Drugs

Immunosuppressives

Cyclosporine (Gengraf, Neoral, Sandimmune)

Primary adverse effects: _ _ and _ _, which may result in _