Chemotherapeutic agents Flashcards by De Vera, Norielle

What are the 5 Chemotherapeutic agents?

– Dapsone
– Amantadine
– Quinine
– Chloroquine and Aminoquinolines
– Isoniazid

How well did you know this?

Not at all

Perfectly

The antibiotic class of drugs has proliferated
immensely since the first clinical use of
__ in 1936 and the mass production of
__ in 1941.

sulfonamide (prontosil), penicillin

How well did you know this?

Not at all

Perfectly

Mechanism of toxicity

Depends on the agent
In some cases, toxicity is an extension of
pharmacologic effects, allergic or idiosyncratic
reactions

How well did you know this?

Not at all

Perfectly

Toxic dose
-Toxic dose is highly variable.
-Life-threatening reactions may occur after
subtherapeutic doses in __

hypersensitive individuals

How well did you know this?

Not at all

Perfectly

Clinical presentation
-After , most agents cause only
nausea, vomiting, and diarrhea.

acute overdose

How well did you know this?

Not at all

Perfectly

Diagnosis is usually based on the history of exposure.

Specific levels. Serum levels are
particularly useful for predicting toxic effects of __(3 drugs)

aminoglycosides, chloramphenicol, and
vancomycin.

How well did you know this?

Not at all

Perfectly

Toxicity of Chloramphenicol

Gray baby syndrome, Aplastic anemia

How well did you know this?

Not at all

Perfectly

Diagnosis

Other useful laboratory studies.
-CBC, electrolytes, glucose, BUN and creatinine, liver function tests, urinalysis, __

methemoglobin level

How well did you know this?

Not at all

Perfectly

Trimethoprim poisoning

Administer __-folinic acid

leucovorin

How well did you know this?

Not at all

Perfectly

LEUCOVORIN

Wellcovorin
Citrovorum factor
Folinic acid
-5- formyltetrahydrofolate
To treat unintentional folic acid antagonist overdose, leucovorin is usually given __ as soon as possible after the
overdose

intravenously

How well did you know this?

Not at all

Perfectly

Dapsone overdose

Administer __ for
symptomatic methemoglobinemia

methylene blue

How well did you know this?

Not at all

Perfectly

Antibiotic used to treat leprosy and rare dermatologic conditions

Dapsone
(Rifampicin, Crofazamine)

How well did you know this?

Not at all

Perfectly

Dapsone

Prophylaxis against __ in patents with AIDS and
other immunodeficiency disorders

Pneumocystis carinii

How well did you know this?

Not at all

Perfectly

Dapsone

Peak plasma levels occur between __ hours after ingestion

4 and 8

How well did you know this?

Not at all

Perfectly

Metabolized by 2 primary routes

Dapsone

How well did you know this?

Not at all

Perfectly

Dapsone

Undergo __

enterohepatic recirculation

How well did you know this?

Not at all

Perfectly

Dapsone

Average elimination half-life is 30 hours after a therapeutic dose and as long as __ hours after an overdose

How well did you know this?

Not at all

Perfectly

Dapsone

Toxic affects are caused by the p-450 metabolites
include

(affects the RBCs)

– Methemoglobinemia
– Sulfhemoglobinemia
– Heinz body hemolytic anemia

How well did you know this?

Not at all

Perfectly

Methemoglobinemia

-high oxidation
antidone __
alternative __

methylene blue, vitamin C

How well did you know this?

Not at all

Perfectly

Mechanism of toxicity

A. metabolites oxidize the ferrous iron hemoglobin
complex to the ferric state, resulting in methemoglobinemia.
B. Sulfhemoglobinemia occurs when dapsone metabolites sulfate
the pyrrole hemoglobin ring; an irreversible reaction, and
there is no antidote.
C. Hemolysis may occur owing to **depletion of intracellular
glutathione by oxidative metabolites. **No antidote available.

Dapsone

How well did you know this?

Not at all

Perfectly

Dapsone Toxic dose

– Therapeutic ranges from 50-300 mg/d.
– Chronic daily dosing of 100 mg has resulted in
methemoglobin levels of 5-8%.
– Persons with glucose-6-phosphate dehydrogenase
(G6PD) deficiency, congenital hemoglobin
abnormalities, and underlying hypoxemia may
experience greater toxicity at lower doses. Death has
occurred with overdose of __

What is the lethal dose?

1.4 g and greater

How well did you know this?

Not at all

Perfectly

Dapsone

Clinical presentation
* Causes cyanosis and dyspnea
* May persist for several days, requiring repeated
antidotal treatment
* Patients appear cyanotic even after receiving antidotal
treatment

Methemoglobinemia

How well did you know this?

Not at all

Perfectly

is a disorder characterized by the presence
of a higher than normal level of
methemoglobin (metHb) in the blood. Methemoglobin is a form of hemoglobin that does not bind oxygen. When its concentration is elevated in red blood cells, tissue hypoxia can occur.

Methemoglobinemia

How well did you know this?

Not at all

Perfectly

Dapsone

Clinical Presentation
– Decreases oxyhemoglobin saturation
– Unresponsive to methylene blue

Sulfhemoglobinemia

How well did you know this?

Not at all

Perfectly

# Dapsone Clinical Presentation – Heinz bodies may be seen – Hemolysis may be delayed in onset 2-3 after the ingestion

Hemolysis

# Dapsone Treatment __ is indicated in the symptomatic patient with a methemoglobin level greater than 15% or with lower levels if even minimal compromise of oxygen-carrying capacity is potentially harmful.

Methylene blue

--Owing to its reducing agent properties, methylene blue is employed as a medication for the treatment of methemoglobinemia --methylene blue acts to reduce the heme group from methemoglobin to hemoglobin

METHYLENE BLUE

# Dapsone Decontamination 1. **Prehospital** Administer __ __ emesis for initial treatment 2. **Hospital ** Administer **activated charcoal and cathartic**

activated charcoal, Ipecac-induced

# Dapsone Enhanced elimination 1. **Repeat-dose activated charcoal** * Interrupts enterohepatic recirculation and is very effective * Reduces half-life from __ * Continue charcoal for at least 48-72 hours

77 to 13.5 hours

# Dapsone Enhanced elimination 2. __ * Reduces the half-life to 1.5 hours, * Effective in a sever intoxication unresponsive to conventional treatment

Charcoal hemoperfusion

- Effective in the treatment of **Parkinson’s disease** * **Prophylaxis **against parkinsonian side effects of neuroleptic agents

Amantadine

- Used in therapy of cocaine addiction - Antiviral agent (uncoating inhibitor, amantadine (__)

Symmetrel

# Amantadine I. Mechanism of toxicity * Enhance the release of __ * Prevent dopamine reuptake in the peripheral and CNS * Has __ properties especially in overdose - high D results to hallucination and affects motor function

Dopamine, anticholinergic

# Amantadine II. Toxic dose * **Has not been determined** * Elimination of amantadine depends entirely on kidney function __ with renal insufficiency may develop toxic intoxication with the therapeutic doses

Elderly patients

# Amantadine III. Clinical presentation A.A Amantadine intoxication causes

* Agitation * Visual hallucinations * Nightmares * Tremor

# Amantadine III. Clinical presentation A.B Amantadine intoxication causes

* Disorientation * Delirium * Slurred speech * Ataxia

# Amantadine III. Clinical presentation A.C Amantadine intoxication causes

* Myoclonus * Seizures - Heart failure

# Amantadine III. Clinical presentation A.D Amantadine intoxication causes * Anticholinergic manifestations include dry mouth, urinary retention and mydriasis * __

Rarely, ventricular arrhythmias

# Amantadine III. Clinical presentation B. Amantadine withdrawal may result in

* Hyperthermia * Rigidity

# Amantadine IV. Diagnosis is based on a **history of acute ingestion** or by noting the above-mentioned constellation of symptoms and signs in a patient taking amantadine. A. Specific levels are not readily available. Serum levels a __ have been associated with toxicity

above 1.5 mg/L

# Amantadine V. Treatment 1. Treat tachyarrhythmias with beta-blockers such as __

propanolol or esmolol

# Amantadine **Neuroleptic malignant syndrome (NMS)** requires urgent cooling measures and may respond to specific pharmacologic therapy with __ | NMS- blockage of dopamine receptor -this drug is a muscle relaxant

Dantrolene

# Amantadine C. Decontamination 1. Prehospital * Administer __ * __ emesis for initial treatment

activated charcoal, Ipecac-induced

# Amantadine ****V. Treatment D. Enhanced elimination. Amantadine is not effectively removed by __, because the volume of distribution is very large (5 L/kg). The serum elimination half-life ranges from 12 hours to 34 days, depending on renal function.

dialysis

other name for G6PD

Favism

 Optical isomer of quinidine  Once used for treatment of malaria and for chloroquine-resistant cases * The bark of the cinchona tree is used to make quinine.

Quinine

* Na blocker * S/E: SLE * Class 1a * anti-arrythmia

Quinidine

Cinchona can cause

cinchonism, tinnitus

* Treatment of nocturnal muscle cramps * Also used as an abortifacient

Quinine

# Quinine I. Mechanism of toxicity * Mechanism of toxicity is believed to be the same with **quinidine** * Quinine is much __ potent cardiotoxin

less

# Quinine I. Mechanism of toxicity * Has toxic effects on the retina resulting to __ * Toxic effects on __ and ganglion cells

blindness, photoreceptor

# Quinine II. Toxic dose  Minimum toxic dose is approx. __ g in adults  __ g is fatal to a child

3-4, 1

# Quinine II. Clinical presentation B. Severe intoxication may cause

* ataxia * obtundation * convulsions

# Quinine III. Clinical presentation B. Severe intoxication may cause: * coma * respiratory arrest * with massive intoxication quinidine-like __

cardiotoxicity

# Quinine III. Clinical presentation C. __  occurs __ hours after ingestion  blurred vision  impaired color perception  constriction of visual fields  blindness  macular edema  disk pallor  pupils are fixed and dilated  retinal artery spasm

Retinal toxicity, 9-10

# Quinine III. Clinical presentation D. Other toxic effects __  hemolysis  congenital malformations when used in pregnancy

* hypokalemia * hypoglycemia

# Quinine A. Specific levels. Plasma quinine levels __ have been associated with visual impairment; 87% of patients with levels __ reported blindness. Levels with __ have been associated with cardiac toxicity

above 10 mg/L, above 16 mg/L,20 mg/L

# Quinine V. Treatment 1.Treat cardiotoxicity with __

hypertonic sodium bicarbonate 1-2 meq/kg rapid IV bolus.

__ has previously been recommended for *quinine-induced blindness.*

Stellate ganglion block

A __ is an injection of local anesthetic in the sympathetic nerve tissue of the neck. These nerves are a part of the sympathetic nervous system. The nerves are located on either side of the voice box, in the neck.

stellate ganglion block

# Quinine V. Treatment D. Enhanced elimination. __ may slightly increase renal excretion but does not significantly alter the overall elimination rate and may aggravate cardiotoxicity | -Vit. C, Ammonium Chloride - alkaloid- High NH (basic)

Acidification of the urine

Used in the prophylaxis or therapy malaria and other parasitic diseases

CHLOROQUINES and other AMINOQUINOLINES

__ are used in the treatment of **rheumatoid arthritis**

Chloroquine and hydroxychloroquine

__ blocks the* synthesis *of *DNA* and *RNA *and also has some *quinidine-like cardiotoxicity.*

Chloroquine

__ and __ are **oxidizing agents** and can cause methemoglobinemia or hemolytic anemia (especially in patients with G6PD deficiency)

Primaquine, quinacrine

# CHLOROQUINES and other AMINOQUINOLINES II. Toxic dose. Therapeutic dose of chloroquine phosphate is **500 mg once a week for malaria prophylaxis**, or * ? * **over 2 days of treatment of malaria.** Deaths have been reported in children after doses as low as 300 mg; the lethal dose of chloroquine for an adult is estimated at 30-50 mg/kg.

2.5 g

# CHLOROQUINES and other AMINOQUINOLINES III. Clinical presentation B. Severe chloroquine overdose may cause: * Quinidine-like ? may be seen including * Sinoatrial arrest  Depressed myocardial contractility

cardiotoxicity

# CHLOROQUINES and other AMINOQUINOLINES III. Clinical presentation B. Severe chloroquine overdose may cause:

* QRS or QT interval prolongation * Heart block * Ventricular arrhythmias * Severe hypokalemia

# CHLOROQUINES and other AMINOQUINOLINES III. Clinical presentation C. ? intoxication cause: * GIT upset * ? * Hemolysis * Ototoxicity * Retinopathy

Primaquine and quinacrine, Sever methemoglobinemia

# CHLOROQUINES and other AMINOQUINOLINES III. Clinical presentation D. ? can cause: * **Fatal neutropenia** | -low neutrophils -attack bacteria and parasites

Amodiaquine

# CHLOROQUINES and other AMINOQUINOLINES E. ? in therapeutic dose or overdose can cause: * Dizziness * Vertigo * Hallucinations * Psychosis * Seizures

Mefloquine

# CHLOROQUINES and other AMINOQUINOLINES IV. Diagnosis A. Specific levels. **Chloroquine levels can be measured in blood** but are not generally available because chloroquine is concentrated ?, whole blood measurements are **5-fold higher than serum or plasma levels.**

intracellularly

# CHLOROQUINES and other AMINOQUINOLINES V. Treatment A. Emergency and supportive measures B. Specific drugs and antidotes 1.**Treat cardiotoxicity** as for **quinidine poisoning** with ?

sodium bicarbonate 1-2 meq/kg IV

# CHLOROQUINES and other AMINOQUINOLINES V. Treatment B. Specific drugs and antidotes 2. ? may be useful in treating hypotension via combined vasoconstrictor and inotropic actions. 3. ? (2 mg/kg IV, given over 30 mins) has been reported to reduce mortality in animals and to **ameliorate cardiotoxicity in human cases.**

Epinephrine infusion, High-dose diazepam

# CHLOROQUINES and other AMINOQUINOLINES V. Treatment D. Enhanced elimination. Enhanced removal procedures are ?.

ineffective

Hydrazide derivative of **isonicotinic acid** Bactericidal drug choice for tuberculosis Known to **cause hepatitis** on chronic use **Drug-induced seizures** and metabolic acidosis on **acute isoniazid** overdose

ISONIAZID (INH)

# ISONIAZID (INH) I. Mechanism of toxicity A. Acute overdose Competes with ? (active form of Vit. B6) for glutamic acid decarboxylase -Lower levels of GABA leads to uninhibited electrical activity **manifested as seizures**

pyridoxal 5-phosphate

Also inhibits hepatic conversion of lactate to pyruvate, resulting in lactic acidosis

ISONIAZID (INH)

# ISONIAZID (INH) B. Chronic toxicity Competes with **pyridoxine** resulting to

peripheral neuritis

# ISONIAZID (INH) * III. Clinical presentation * A. Acute overdose * Slurred speech * Ataxia * Coma ? * Hemolysis

* Seizures

# ISONIAZID (INH) II. Toxic dose Severe toxicity is common after ingestion of ?

80-150 mg/kg

# ISONIAZID (INH) B. Chronic therapeutic INH use may cause: * Peripheral neuritis * Hepatitis * Hypersensitivity reactions like ?

lupus erythematosus and pyridoxine deficiency

# ISONIAZID (INH) * A. Specific levels. A ? dose produces a peak INH concentration of ? at 1hour. * Serum levels higher than ? are associated with acute toxicity.

5 mg/kg, 3 mg/L, 30 mg/L

# ISONIAZID (INH) B. Other useful laboratory studies. Electrolytes glucose BUN creatinine ? arterial blood gases

liver function tests (chronic toxicity)

# ISONIAZID (INH) V. Treatment ? terminates **diazepam-resistant seizures**

Pyridoxine (vitamin B6)

# ISONIAZID (INH) C. Decontamination Prehospital – Administer activated charcoal – ? because of the risk of rapid onset of coma and seizures

Do not induced emesis

# ISONIAZID (INH) Hospital * Administer activated charcoal and cathartic * Gastric lavage for massive ingestions D. Enhanced elimination * Forced ?

diuresis and dialysis