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Prelims Notes
CANCER CHEMOTHERAPY
Carcinogenesis
Types of Cancer
1. Benign tumor – are generally slow growing, resemble normal cells, localized, and are not
harmful.
2. Malignant tumor – often proliferate more rapidly, have an atypical appearance, invade and
destroy surrounding tissues, and are harmful if left untreated.
CATEGORY (according to location of tumor growth)
a. Solid tumors:
Carcinomas are tumors of epithelial cells. (breast, lungs, kidney,
liver, colon, brain, prostate)
Sarcomas include tumors of connective tissues (blood, bone, fats,
muscles, ligaments)
b. Hematological malignancies:
Lymphomas are tumors of the lymphatic system and include
Hodgkin and non-Hodgkin lymphomas.
Leukemia are tumors of blood- forming elements and is classified as
acute or chronic; myeloid or lymphoid
1. M phase, or mitosis, is the phase in which the cell divides into two daughter cells.
multiplication and cell division
Vinca Alkaloids - synthesized in Periwinkle or chichirica– Catharanthus roseus
Taxanes or taxol– synthesized in Pacific Yew Tree – Taxus brevifolia or Taxus
baccata (bark)
2. G1 phase, or postmitotic gap, is when RNA and the proteins required for the specialized
functions of the cell are synthesized in preparation for DNA synthesis.
Synthesis of important proteins responsible for DNA replication
Asparaginase and Prednisone
3. S phase is the phase in which DNA synthesis and replication occurs.
DNA replication
antimetaboliteS
4. G2 phase, or the premitotic or postsynthetic gap, is the phase in which RNA and the
enzymes topoisomerase I and II are produced to prepare for duplication of the cell.
formation of Topoisomerase I and II (aka DNA gyrase) – responsible for DNA
splicing
Bleomycin and Etoposide
5. G0 phase, or resting phase, is the phase in which the cell is not committed to division. Cells
in this phase are generally not sensitive to chemotherapy. Some of these cells may re-enter
the actively dividing cell cycle. In a process called recruitment, some chemotherapy
regimens are designed to enhance this reentry by killing a large number of actively dividing
cells.
not sensitive to CT agents
resting phase
determinant whether the cells become cancerous
Tumor Markers – are natural cells inside the body the increases their concentration when you
have a specific type of cancer
1. Genetic
Primitive Neuro Ectodermal Tumors; expected LE is 25yo
2. Lifestyle – smoking and drinking alcohol, fatty foods
3. Environment and Occupational
Benzopyrene and aromatic substances
4. Medications
Immunosuppresants (Cyclosporine and GCs)
5. Viruses
EBV (Epstein Barr Virus)
HPV (Human Papilloma Virus) – cervical and ovarian cancer
HBV (Hepatitis B Virus) – liver CA
Treatment
Objectives of Chemotherapy
Chemotherapy dosing:
DRUGS
A poisoning case can present to a doctor or hospital in any one of a number of ways:
1. Fulminant
Produced by a massive dose
Death occurs very rapidly
Ex. Ingestion of muriatic acid, ingestion of
2. Acute
Produced by a single dose or several small doses taken in a short period.
Onset of symptoms is abrupt
Ex. One large dose of APAP
3. Chronic
Produced by small doses taken over a long period
Onset is insidious
Ex. Arsenic poisoning
4. Subacute
Characterized by a mixture of features of acute and chronic poisoning
For unconscious patients, these are the following non-specific features: (General
Symptoms)
a. Impairment of consciousness
b. Respiratory/Cardiovascular depression
either tachycardia or bradycardia
c. Dehydration due to vomiting/diarrhea
esp. those with drug addiction
d. Hypothermia
e. Convulsions
f. Cardiac arrhythmias
Some valuable clues to narrow down the differential diagnosis (PURPOSE: narrowing down
of diagnosis):
a. Ocular clues – several drugs/poison affect the pupils of the eyes (miosis or
mydriasis)
b. Olfactory clues – some poisons have distinctive odors which may be perceived in the
vicinity of a poisoned patient, esp. in the breath.
c. Dermal clues – some poisons have characteristic dermal manifestations in acute
toxicity.
d. Oral clues – careful examination of the mouth
Different Toxic Syndromes
1. Anticholinergic Syndrome
CAUSES:
a. Antihistamines h. Antispasmodics
b. Antiparkinsonian i. Skeletal muscle relaxants
drugs j. Plants [Datura – stramonium
c. Atropine (Jimson or Jamestown weed,
d. Scopolamine devils snare) & metel (devils
e. Amantadine trumpet)]
f. Antipsychotic drugs k. Fungi (Amanita muscaria -
g. Antidepressants muscarine)
SYMPTOMATOLOGY:
1) Delirium with mumbling speech
2) Tachycardia
3) Dry hot skin
4) Mydriasis
5) Myoclonus
6) Urine retention
7) Decreased bowel sounds
8) Convulsions and arrhythmias (severe cases)
2. Cholinergic Syndrome
CAUSES:
a. Organophosphate
b. Carbamates
c. Parasympathomimetic drugs (AChE Inhibitors)
d. Some mushrooms
SYMPTOMATOLOGY:
1) Confusion 7) Sweating
2) CNS depression 8) Fasciculations
3) Salivation 9) Seizures
4) Lacrimation 10) Miosis
5) Urinary and fecal 11) Pulmonary edema
incontinence 12) Tachy/Bradycardia
6) Vomiting
3. Sympathomimetic Syndrome
CAUSES:
a. Cocaine
b. Amphetamines
c. Upper respiratory decongestants (PPA, Ephedrine, and Pseudoephedrine)
SYMPTOMATOLOGY:
1) Paranoia 6) Sweating
2) Delusions 7) Mydriasis
3) Tachycardia 8) Seiures
4) HTN 9) Arrhythmias
5) Hyperpyrexia
4. Sedative Syndrome
CAUSES:
a. Opiates (morphine, f. Meprobamate
fentanyl, codeine, g. Ethchlorvynol
heroin) h. Gluthethimide
b. Barbiturates i. Clonidine (off-label use: ADHD
c. BZDs due to sedation – has
d. Ethanol Peripheral: anti-HTN and
e. Methaqualone Central: anxiolytic)
SYMPTOMATOLOGY:
1) Miosis
2) Hypotension (respiratory depression in use of Opiates and BZDs)
3) Bradycardia
4) Hypothermia
5) CNS depression
6) Hyporeflexia
7) Coma
8) Convulsions (rare)
Sympathetic Syndrome
1. Stabilizations
The initial survey should always be directed at the assessment and correction of life-
threatening problems, if present. Attention must be paid to the airway, breathing,
circulation, and depression of the CNS.
2. Evaluation
As far as treatment is concerned, the emphasis should be on basic supportive
measures
3. Decontamination
This is with reference to skin/eye decontamination, gut evacuation and
administration of activated charcoal
4. Poison Elimination
Depending on the situation, this can be accomplished by different methods
5. Antidote Administration
Unfortunately, antidotes are available for less than 5% of poisonings
6. Nursing and Psychiatric Care
General nursing care is especially important in comatose patients and those who
have been incapacitated by the poison. Psychiatric intervention is frequently
essential in suicidal overdose.
Depression
This is generally defined as an unarousable lack of awareness with a rating of <8 on the
Glasgow Coma Scale
Before proceeding to an elaborate exercise in diagnosis however, it may be desirable to first
ascertain for sure that the patient is really comatose and not just pretending (psychogenic
or hysterical coma). This is often encountered in suicide gesture in contrast to attempted
suicide.
1. Eye Opening
a. Spontaneous E4
b. To speech 3
c. To pain 2
d. Nil 1
2. Best Motor Response
a. Obeys M6
b. Localises 5
c. Flexes (withdrawal) 4
d. Flexes abnormally (decorticate rigidity) 3
e. Extends (decerebrate rigidity) 2
f. Nil 1
3. Best Verbal Response
a. Oriented V5
b. Confused conversation 4
c. Inappropriate words 3
d. Incomprehensible sounds 2
e. Nil 1
Generally, brain injury is classified as:
Severe – GCS ≤8
Moderate – GCS 9-12
Minor – GCS ≥13
Respiratory Insufficiency
Cardiac Arrhythmia
CNS Depression
Hypothermia
Rewarming: water bath (115 deg F) until temp is 92 deg F
Rectal and esophageal thermometers
There is a need to correct underlying problems: Hypotension (failed circulation) and
Hypoventilation (↓O2)
Drugs that produces hypothermia:
1. Alcohols 6. Hypoglycemics
2. Antidepressants 7. Opiates
3. Barbiturates 8. Phenothiazine
4. BZDs 9. Sedative-hypnotics
5. CO
Hyperthermia
Oral temperature above 102 deg F is referred to as hyperthermia. If it exceeds 106 deg F
(which is very rare), there is imminent danger of encephalopathy.
In a few individuals there is a genetic susceptibility to hyperthermia, especially on exposure
to skeletal muscle relaxants, inhalation anaesthetics, and even local anaesthetics—
malignant hyperthermia. (Genetically determined; lahat ng tao pwede magkaron ng MH)
This should be distinguished from neuroleptic malignant syndrome (not genetically
determined), which is also characterized by high fever apart from other neurological signs,
but is the result of adverse reaction to phenothiazines and antipsychotic or neuroleptic
drugs, and has no genetic basis.
Treatment:
Remove all clothes, and pack the neck and groin with ice.
Immersion in cold water bath (77oF) is very effective but dangerous in the elderly and in
heart patients.
Stop cooling measures when core temperature falls below 102 deg F, and nurse the patient
in bed in a cool room.
Administration of Dantrolene may be benefcial in some cases.
Do not use antipyretic drugs like paracetamol. They are ineffective
Convulsions (Seizures)
Treatment:
Administer O2 by nasal cannula or mask.
BZDs (Diazepam or Lorazepam) → Phenytoin → Phenobarbitone
Movement Disorders
DECONTAMINATION
Eye
Skin
Gut
1. Emesis
Syrup of Ipecac (Cephalis ipecacuanha/acuminata) during 60s and 70s
MOA: stimulation of Chemoreceptor Trigger Zone (CTZ)
INDICATION: Conscious and alert poisoned patient who has ingested a
poison not more than 4 to 6 hours earlier.
Has three main substances:
Cephaline
Emetine - responsible for emesis
Psychotrine – responsible for psychosis
DOSE: 30mL (adult) and 15mL (child)
CI:
Pregnant
Infants <1yo
Heart disease
Patients intoxicated with Digitalis
Convulsion
Patient with mental problems
AE:
aspiration pneumonia
cardiotoxicity
Mallory Weiss tears (resembles stomach ulceration); due to
protracted vomiting
Not used today due to no assurance of effectivity and has many
contraindication
Other Emetics
Apomorphine [SQ]
MOA: targets CTZ
DOSE: 6mg (adults) and 1-2mg (child)
CI: respiratory depression (TCA, BZDs, Barbiturates)
2. Gastric Lavage
1-2hrs after ingestion
CI: acid ingestion, coma, sharp substances
3. Catharsis
CATEGORIES:
a. Saline – MOA: osmotic retention→defacation (ex. D-sorbitol – agent of choice
for catharsis)
MgSO4
Mg citrate
NaSO4
b. Saccharide
CI: recent bowel surgery, corrosives and electrolyte imbalance
4. Activated charcoal
MOA: adsorption
DOSE: 1g/1000m2 of SA or 1g/kg
AE: pulmonary aspiration, unpleasant taste, & vomiting
5. Whole bowel irrigation
Using NGT in the stomach that contains solutions like PEG-Electrolyte Lavage
Solution (ELS), specifically PEG-3500
USES: Cocaine ingestion
1. Hemodialysis
2. Hemoperfusion
3. Peritoneal Dialysis
4. Hemofiltration
5. Plasmapheresis
6. Plasma perfusion
7. Cardiopulmonary Bypass