Drugs: Infection, Immunopharmacology, Cancer Chemotherapy

what type of drug injures/kills a microorganism without harming the host (patient) cells?

antimicrobial drug

what is the most common used antimicrobial drug?

antibacterial

what do antibacterial drugs treat?

bacterial infections like tuberculosis, c.diff, MRSA, pneumonia, and UTIs

antibacterial drugs are also called what?

antibiotics

what is the mechanism of action for antibacterial drugs?

- injure or kill bacteria by...

1. inhibiting bacterial cell wall

2. inhibit bacterial protein synthesis

3. inhibit bacterial DNA/RNA function

what are the adverse effects of antibacterial drugs?

- allergic reactions

- GI problems

how do we pick an antibiotic?

- identify the selecting organism by culturing it

- choose a drug that the organism is susceptible to

- use a drug that reaches the infected site

- note any contraindications to the drug

- think about safety, cost, route of administration, and dosing

what are some factors that go into choosing a drug that the organism is susceptible to?

- bacterias shape (rod or Cocci) and histological standing

- bactericidal vs bacteriostatic drugs (kill bacterial vs limit their growth/proliferation)

- broad vs narrow spectrum

what are some examples of bacterial cell wall inhibitors?

- penicillin

- cephalosporin

- bacitracin

what is the mainstay drug for many infections?

Penicillin

what is used if penicillin cant be used, or as a first line for some UTIs?

Cephalosporins

what is an over the counter topical antibacterial used for prevention and treatment of skin infections?

bacitracin

what antibacterial drug is a broad spectrum for tissue and wound infections that inhibits bacterial protein synthesis?

aminoglycosides

what antibacterial drug is a broad spectrum that is used if there is a penicillin allergy or for respiratory tract infections/inflammation?

Erythromycin

what antibacterial drug is a broad spectrum that cant be used much now due to an increased resistance?

Tetracycline

what antibacterial drug is used to treat UTIs?

Fluoroquinolones (Ciproflaxin/Cipro)

what antibacterial drug is used as a broad spectrum (but not used frequently due to its resistance) with the specific use of topical application with silver nitrate to control burn bacterial infections?

**wound care

Sulfonamides

what is natural or acquired defense of bacteria against specific antibiotics?

Resistance

what is the main cause of resistance to antibacterial drugs?

overuse or inappropriate use of antibiotics

what are some examples of overuse/inappropriate use of antibiotics?

- animals in the food chain (growth enhancer)

- overuse or inappropriate use of antibiotic soaps/cleaners

- prescription before identification of bacteria

- prescription for viral infections

what is a PT implication of resistance to antibacterial drug?

- focus on good hygiene so there is less spread of infection and less need to treat

what is a small microorganism that has a nucleic acid core and a protein shell?

Virus

what does a virus need to replicate?

the host cells machinery

what are some examples of viruses?

- influenza (Flu)

- HIV

- Hepatitis

what are the 2 types of antiviral agents?

- vaccines

- antiviral drugs

what type of antiviral agent is just a prophylaxis of viral infection?

vaccines

what type of antiviral agent is Both a prophylaxis and treatment for viral infections?

antiviral drug

what is a viral preparation that does not hurt the person but stimulates the immune system to be ready to fight an infection by that virus later?

Vaccine

what is an important note when it comes to vaccines and allergic reactions?

a lot of vaccines are grown in egg medium, so they should not be given to someone with an egg sensitivity

what is the mechanism of action for antiviral drugs?

- focus is destroying the virus without damaging the host cell

inhibits replication at various points in the process

what are proteins that have non-specific antiviral activity?

they allow healthy cells to resist infection from viruses as well as modifies certain immune processes.

Interferons

how many classes of interferons are there?

3 based on structure and effects on cell receptors

what are interferons used for?

Initially used as antivirals, now they are often treatments for MS, Hepatitis, Leukemias, Lymphomas, and some other cancers

what is the mechanism of action for HIV/AIDs treatment?

- there arent any drugs (yet) that selectively kill HIV in humans, so use drugs to inhibit HIVs replication

- using combination therapy through highly active antiretroviral therapy

what are the details of combination therapy for HIV?

- usually 3+ drugs

- often successful in prevention progression of HIV infection

- Can be difficult to adhere to due to side effect and complicated regimens

- can be ineffective in some patients

what is a disease that infects the immune system?

HIV

what happens if HIV goes untreated?

progressive immune suppression

what is advanced HIV?

acquired immune deficiency syndrome (AIDS)

what is the result of having HIV?

susceptibility to opportunistic infections (certain cancers, tuberculosis, autoimmune conditions)

what is mycoses?

a fungal infection

what are some examples of superficial/local fungal infections?

- tinea (ringworm)

- athletes foot

- yeast infections

how can we treat superficial/local fungal infections?

topical treatment

what are the PT implications of superficial/local fungal infections?

- PTs can indentify tinea (ringworm) and help stop spread among team members

** dont share towels or combs

a systemic fungal infection is more likely in what patient population?

those with immune suppression wether it be from HIV/AIDS or Immunosupressants

How long is the treatment for systemic fungal infection?

6 months or more

what is an adverse effect of antifungals?

can cause liver damage

what are the two types of immunopharmacology?

- specific drugs to suppress immune response

- immunosuppressant antibodies and fusion proteins

- immunomodulators

what are the steps for immune response?

- ingestion

- recognition

- proliferation

** drugs will inhibit the process at one of these steps

what are some reasons for pharmacological immune response suppression?

- post-transplant rejection

- Auto-immune diseases to limit damage to bodys tissues (RA, myasthenia gravis, Lupus, Scleroderma, IBS)

what are two immunosuppressive drugs that limit lymphocyte proliferation?

- Azathioprine (Imuran)

- Mycophenolate Mofetil (CellCept)

what does Azathioprine treat?

transplant rejection and autoimmune disorders

what does Mycophenolate Mofetil (CellCept) treat?

transplant rejection, often used in combination

what are the adverse effects of Azathioprine (Imuran) and Mycophenolate Mofetil (CellCept)?

- decreased bone marrow function (Leukopenia)

- GI distress

what are the immunosuppressive drugs that suppress T cell activation?

- Cyclosporine (Neoral, Gengraf)

- Tacrolimus (Prograf)

what does cyclosporine (Neoral, Gengraf) treat?

its a main anti-rejection medication after organ transplant, also used to treat autoimmune disorders

what are the adverse effects of Cyclosporine (Neoral, Gengraf)?

- neurotoxicity

- Hypertension

what does Tacrolimus (prograf) treat?

its an anti-rejection medication for organ transplant

what are the adverse effects of Tacrolimus (prograf)?

- GI Disturbance

- Weakness

- Itching/Rash

RARE: Renal and CNS Toxicity (headache, anxiety, seizures)

what are glucocorticoids used to treat?

uses systemically to prevent transplant rejection and treat autoimmune disorders (often in combination)

what is the mechanism of action of a glucocorticoid?

nonspecific immune suppressant and anti-inflammatory drug

what are the key side effects of glucocorticoids?

- breakdown of muscle, bone, and skin

can also have growth retardation, hypertension, and increased chance of infection

what is an example of an mTOR inhibitor?

Sirolimus/Rapamycin

what does Sirolimus/Rapamycin treat?

prevention of organ transplant rejection

what is the mechanism of action for Sirolimus/Rapamycin?

inhibit mTOR - a key enzyme in pathways allowing T and B cells to undergo cell division

what are the adverse effects of mTOR inhibitors Sirolimus/Rapamycin?

- blood lipid disorders

- impaired wound healing

- possible blood disorders (Leukopenia, thrombocytopenia)

- muscle/joint pain

what are the traditional disease modifying antirheumatic drugs?

- Methotrexate (Flolex, Rheumatrex)

what are the side effects of traditional disease modifying anti rheumatic drugs?

toxicity

what are the biological disease modifying anti rheumatic drugs?

tumor necrosis alpha (TNF) inhibitors

what are the mechanisms for antibodies and fusion proteins as immunosuppressive agents?

they suppress immune responses by binding to proteins that are important in the response

like IL 1 or 2 receptors

what is the use of antibodies/fusion proteins?

some are biological DMARDs and other are used to treat autoimmune disorders or prevent transplant rejection

what are the key side effects of antibodies and fusion proteins?

- varied but often an increased risk of infection and may cause rash/skin irritation

what are some examples of cytokines?

these are you interferons or interleukin-2

what is the mechanism for a cytokine?

act as an immunoregulatory chemical

what is the use for cytokines?

varied!

includes interferons to treat MS, Hepatitis B&C, leukemias, lymphomas, and other cancers

what has non-specific antiviral activity as well as modifies certain immune processes?

Interferons

what are some rehab concerns for immunosuppressive agents and immunostimulants?

- post-transplant rehabilitation (patients will be on immunosuppressive agents)

- immunosuppressive drugs may stop/slow disease progression for patients with musculoskeletal and autoimmune disorders

- side effects may interfere with rehab

what are the goals of chemotherapy treatment?

- cure, control, or palliation

when do we want to have the goal to cure using chemotherapy?

when the patient has local or local-advanced cancer

when do we want to have control as the goal when using chemotherapy?

when the cancer is somewhere in the middle of localized and metastatic

when do we have palliation as a goal for chemotherapy?

when you have severe metastatic cancer for alleviation of symptoms and avoidance of life-threatening toxicity

**may not be reaching end of life asap

what are some indications of cancer chemotherapy treatment?

- if neoplasm (tumor) cannot be surgically treated

- as a supplement with surgery/radiation

- maintenance to prolong remission

what is a chemotherapy regimen?

usually a combination of drugs scheduled intermittently to allow recovery of the immune system

what does tumor susceptibility and cell growth cycle depend on for chemotherapy drugs?

it usually depends on the fraction of tumor cells that are in the growth phase

what is a growth fraction for cancer?

fraction of tumor cells that are in the proliferating phase

what is the cytotoxic strategy of chemotherapy?

- limit cell proliferation by killing or slowing cell growth

- also harms healthy cells

what is the total kill cell in chemotherapy?

this is your goal! essential you want to kill all cells because all cells that can replicate must be killed to eliminate the cancer completely

**not always possible to achieve

what are some Adverse Effects of Cancer Chemotherapy?

- hair loss

- fatigue

- nausea, vomiting, Loss of appetite

- Anemia

what are some tissues with cells that divide rapidly?

- hair follicles

- immune system cells

- bone marrow

- epithelial cells in skin and GI tract

what can be given to minimize the adverse effects of chemotherapy?

- antiemetic and anti nausea drugs

- other drugs to minimize pain, anemia, cough, weight loss, and constipation

do chemotherapy drugs have a low or high TI?

low

what are the PT implications of cancer chemotherapy?

- adverse effects often impact PT

- PT can assist in improving quality of life of patients with cancer

Pain reduction via physical agents, pain and anxiety reduction via massage, encouraging and supportive role