Cancer Chemotherapy + Muscle Relaxants (16.1-16.3, 17.1-17.2)

cancer chemotherapy goal

selective toxicity to neoplastic cells

primary methods of chemotherapy

1. disrupt DNA/RNA function

2. inhibit mitosis and initiate cell death

chemotherapy drug groups

1. direct effect on DNA

2. hormones

3. targeted therapies

4. immunotherapies

5. miscellaneous

chemotherapy direct effect tx

1. alkylating agents

2. antitumor antibiotics

3. platinum drugs

4. antimetabolites

5. topoisomerase inhibitors

what direct chemotherapy tx binds to DNA bases and forms cross-links between strands preventing replication/translation and ultimately causing breaks in DNA chains?

alkylating agent

what direct chemotherapy tx is an antibacterial reserved for cancer because of its toxicity and inserted into a DNA strand to inhibit transcription and break DNA chains?

antitumor antibiotics

what direct chemotherapy tx contains platinum and forms strong cross-links in DNA to inhibit replication?

platinum coordination complexes

what direct chemotherapy tx inhibits topoisomerase - a key enzyme needed for DNA replication resulting in DNA chain breakage?

topoisomerase inhibitrs

etoposide, teniposide are ________ drugs

topoisomerase type I inhibitor

irinotecan, topotecan are ___________ drugs

topoisomerase type II inhibitor

what direct chemotherapy tx acts on pathways for DNA synthesis and impairs DNA synthesis and inhibits enzymes by acting as “fake” ingredients?

antimetabolites

drugs that indirectly inhibit mitosis

antimicrotubule agents

antimicrotubule agents

Vinka alkaloids, Taxanes

Vinka alkaloids

inhibit the formation of microtubules

Taxanes

inhibit breakdown of microtubes

anticancer hormones

act on hormone-sensitive cancers and generally used to

1. inhibit production of a hormone

2. block or reduce function of hormone

3. inhibit cell growth or induce death in certain cells

targeted therapies

focus on a specific trait on cancer cell that is not present in human cells

primary targeted therapies

1. monoclonal antibodies

2. tyrosine kinase inhibitors

monoclonal antibodies

derived from cell-cloning techniques used to manufacture antibodies that bind to a specific antigen on tumor cells - have a targeting effect

MAB effects on cancer cells

block signaling pathways that cause mitosis

initiate apoptosis

inhibit angiogenesis

tyrosine kinase

receptor enzyme system on cell surface that tells cell to divide

malfunctioning or too many can result in cell dividing excessively

tyrosine kinase inhibitors

targets cancers like HER2 and ErB-1

drug binds to tyrosine kinase site and inhibits receptor activation

prevents receptor for initiating signals that cause cell division

tyrosine kinase drugs

“-ihib” drugs

Immunotherapies

encourage immune system to deal with cancer cells

examples of immunotherapy drugs

cytokines, MAB, other techniques

cytokines

small proteins that play role in immune response, directly activate pathways inhibiting cell division, promote cell death and encourage cytotoxic immune cells to attack cancer cells

2 primary strategies of cytokines

interferons (INF alpha 2B)

interleukin (IL-2)

monoclonal antibodies

some MAB can sensitize the cancer cell to attack from the T-lymphocytes

others act as checkpoint inhibitors - inhibit proteins that suppress cancer attacking immune cells

*different from using MAB as targeted therapies

____ and _____ vaccines are examples of anticancer vaccines

HPV, Hep B

adoptive cell transfer

from patient’s T-cells in lab and reinsert in patient

Miscellaneous Agents

generally disrupt DNA structure or cancer cell metabolism

_____ deprives tumor cells of asparagine

asparaginase

______ affect proteins that package DNA in cells

histone deacetylase inhibitors

enhance cell differentiation

retinoids

chemotherapy combos

ABVD, CMF, FOLFOX

ABVD

Adriamycin, Bleomycin, Vinblastine, Dacarbazine

CMF

cyclophophamide, methotrexate, 5-flurouracil

FOLFOX

folnic acid, fluorourucil, oxiplatin

chemo side effects are normally caused due to inhibiting _______.

cell replication

primary goal of muscle relaxants

selective decrease in the skeletal muscle excitability

primary uses of muscle relaxants are ________ and ________.

muscle spasms and spasticity

muscle spasm

injury in muscle or peripheral nerve, strong tonic contraction, common orthopedic issues

spasticity

CNS lesions, exaggerated stretch reflex

agents used to treat muscle spasms

1. centrally-acting anti-spasm drugs

2. Diazepam (Valium)

centrally-acting anti-spasm drugs

use in CNS, control spasms seen in orthopedic

diverse drug group

used commonly in back and neck spasms

carisoprodol

an anti-spasm drug that enhances GABA inhibition in the brain - less peripheral activation of muscle

cyclobenzaprine

an anti-spasm might increase serotonin in brainstem

centrally-acting anti-spasm drugs

are all strong sedatives

_____ is an anti-spasm drug that works in the CNS and increases inhibitory effects of GABA which is an _______ NT with receptors in the brain and spinal cord.

diazepam, inhibitory

Diazepam mechanism of action

works in the CNS by increasing inhibitory effects of GABA

GABA (increases/decreases) excitability in the spinal cord

decreases

valium effects

binds to different site causing GABA to bind stronger and more chloride to enter cell resulting in relaxation due to less excitation

________ was developed initially as an antianxiety drug.

benzodiazepene

anti-spasm drugs should be combined with ______ _______.

aggressive physical therapy

Diazepam length of use

should be discontinued as soon as possible, meant for short term use

Diazepam as an antispasticity drug

acts in the CNS, increases GABA-mediated inhibition

antispasticity doses also cause ______.

sedation

antispasticity may be helpful it patient has ______ and ________.

spasticity, anxiety

baclofen

a synthetic GABA that stimulates GABA receptors in spinal cord (GABA-B agonist), decreases excitation of a-motor neuron

baclofen adminstration

intrathecally (spinal injection) via catheter and pump into subarachnoid space. less drug with fewer side effects

when is intrathecal baclofen used?

severe spasticity

signs of baclofen overdose

decreased respiratory function, cardiac function, stupor, coma

signs of baclofen withdrawal

fever, confusion, hallucinations, seizures

alpha-2 agonists

stimulates alpha-2 (inhibitory) receptors in the CNS

primary alpha-2 agonist drug

Tizanidine (Zanaflex)

Tizanidine function

stimulates alpha-2 receptors in spinal interneurons, causes inhibitions of interneurons and decreases excitatory input onto alpha-motor neuron. efficacy is similar to oral baclofen but less generalized muscle weakness

Gabapentin (Neurontin)

developed originally as an anti-seizure drug, used to read nerve pain, inhibits calcium entry into presynaptic terminals and decreases release of glutamate

GABA

most abundant excitatory neurotransmitter in the brain and CNS

Gabapentin is used primarily to treat ____ and ___________.

multiple sclerosis, spinal cord injury

Dantrolene Sodium (Dantrium)

only direct-acting muscle relaxant, inhibits the release of calcium from skeletal muscle in the sarcoplasmic reticulum on calcium channels

Dantrolene use has risk of ________.

liver toxicity

botulinum toxin

paralytic (not relaxant) injected into specific muscle

excessive use of botulinum toxin results in _______.

spasticity

Botulinum toxin mechanism of action

attaches to receptors on pre-terminal and destroys channels that release NT (Ach)

when does neuron recovery after botox injection?

8-12 weeks

botulinum toxin paralysis occurs ______ and lasts _____.

3-7 days, 2-3 months

Type A botox serotype

Botox, Dysport, Xeomin

Type B botox serotype

Myobloc

botulinum toxin reduces spastic dominance; may allow, increased _______, improved _____, bracing, etc.

residual function, ADL

(T/F) Botox has a possible carry-over & long-term effects on reflex activity in cord & brain

T

botulinum toxin injection problems

local irritation, potential for antibody production, must limit total dose for each treatment

dose for Type A (botox) and type B (myobloc)

botox: adults: 400 units or less, children: 6 units/kg or 300 units

myobloc: 2500-5000 units

other problems with botulinum toxin injection

drooping eyes, difficulty swallowing/speaking, respiratory distress, generalized muscle weakness