Showing posts with label vaccination. Show all posts
Showing posts with label vaccination. Show all posts

Sunday, November 28, 2010

pharmacology: anti-virals

the pharm lecture on the conventional meds used to treat viral conditions. these drugs are designed to specifically target an aspect of the viral reproduction mechanism-- whether it be interfering with viral binding with the host cell, replication within the host cell, or budding off of the host cell. the drugs used to treat influenza, for example, are neuramidase inhibitors, which is an enzyme that allows the virus to bud off the host cell. oseltamivir / tamiflu is an oral neuramidiase inhibitor and zanamivir / relenza is the inhaled form. both have to be taken within 48 hours of the onset of symptoms in order to be effective. amandatine / symmetrel is a drug that is no longer used for treatment of influenza A, but has found some use as treatment for mild to moderate parkinson's disease symptoms.

the herpes family of viruses, which includes HSV-1 and 2, and herpes zoster (the cause of chicken pox and shingles) is treated by drugs such as acyclovir / zofirax, which acts as a guanine analog that is incorporated into viral DNA and halts replication. this particular drug crosses the blood brain barrier and thus is effective against herpes encephalitis and herpes meningitis, although resistance is becoming more widespread. it is administered in oral, IV, and topical form, each with its own side effects. higher IV doses can cause transient renal insufficiency.

drugs used to treat HIV fall into several categories: fusion inhibitors, integrase inhibitors, reverse transcriptase inhibitors, and protease inhibitors. zidovadine / retrovir is an example of a reverse transcriptase inhibitor, and is a pyrimidine analog that halts RT's action when incorporated into viral DNA. saquinivir is a protease inhibitor (protease is the enzyme that HIV uses to break viral proteins into component parts to be assembled into new viral particles) which is used for both HIV and hep C patients. interferon alpha is a naturally occurring cytokine that stimulates anti-microbial activity in phagocytic cells. it is used to treat HIV as well as hep C, where it is combined synergistically with ribavarin, a nucleoside antiviral.

a few notes on vaccinations (some background here) there are in general at least 3 different types of vaccinations in terms of what is injected into the patient to mount an immune response: live attenuated (inactivated), killed, and protein fragment. the live vaccines have the strongest immune response but have a small potential for reactivation, whereas killed vaccines have no chance for reactivation but less of an immune response. influenza vaccines are either live attenuated or "trivalent inactivated". laiv / flumist is the attenuated influenza vaccine which is delivered nasally. HPV vaccines such as gardasil and cervarix are available to guard against HPV 16 and 18, the strains most likely to cause cervical cancer. gardasil also is effective as a vaccine against HPV 6 and 11, the strains likely to cause genital warts.

questions
oseltamivir / tamiflu...
1. type A influenza is referred to as...
2. two most common strains of type A influenza?
3. when must tamiflu be given in order to be effective?
4. tamiflu shown to be effective against which strains of influenza?
5. mechanism of action for tamiflu?
6. method of administration?
7. usual adult dosage?
8. common side effects?

zanamivir / relenza...
9. mechanism of action?
10. strains of influenza that zanamivir is effective against?
11. when must relenza be given in order to be effective?
12. method of administration?
13. not recommended when patient is in...
14. contraindicated in patients with history of...
15. side effects?

amandatine / symmetrel...
16. effective against which forms of influenza?
17. used for what other condition?

acyclovir / zofirax...
18. how many families of the herpes virus are there that infect humans?
19. acyclovir is only effective against...
20. mechanism of action?
21. method of administration?
22. can or cannot cross BBB?
23. higher IV doses can cause what side effect?

HIV: reverse transcriptase inhibitors...
24. four categories of HIV drugs?
25. current treatment combination for HIV?
26. what are the forms of reverse transcriptase inhibitors?
27. what category does zidovadine (AZT) / retrovir fall under?
28. mechanism of action of zidovadine?
29. another example of a nucleoside RTI?
30. advantages of nucleotide RTI's over nucleoside RTI's?
31. difference in mechanism for non-nucleoside RTI's?

HIV: protease inhibitors...
32. what function does viral protease have?
33. which two viruses are protease inhibitors used to treat?
34. example of protease inhibitor?
35. side effect of [34]?

HIV: interferons...
36. what are interferons?
37. interferons stimulate which immune cells to do what?
38. what are the types of interferons and what are they used for?
39. indications for interferon alpha?
40. mechanism of action?
41. what is pegylated interferon alpha?

ribavirin...
42. structurally similar to...
43. which family?
44. used synergistically with what other drug for what condition?
45. effectiveness against HIV / AIDS?

vaccinations...
46. 3 types of vaccinations?
47. advantages / disadvantages to the first type?
48. ...second?
49. disadvantage to third?
50. examples of third?
51. two types of influenza vaccines?
52. laiv / flumist is what type of vaccine? method of delivery?
53. two HPV vaccines?
54. both protect against which strains?
55. gardasil also protects against...

ånswers
1. seasonal flu.
2. H1N1 and H3N2.
3. before 48 hours after onset of symptoms.
4. H5N1-- avian flu.
5. neuramidase inhibition.
6. oral.
7. 75mg bid for 5 days.
8. headache
nausea / vomiting / abdominal effects
neurologic effects

9. neuramidase inhibitor.
10. influenza A and B, and avian flu.
11. before 48 hours after onset of symptoms.
12. inhaler.
13. nursing homes.
14. COPD / asthma.
15. nausea / vomiting.

16. no longer recommended for prophylaxis of influenza A.
17. mild to moderate symptoms of parkinson's disease.

18. eight.
19. actively replicating viruses, not latent viruses.
20. guanosine analog that is incorporated into viral DNA and stops viral synthesis.
21. PO, IV, topical ointment.
22. can; is used to treat herpes meningitis and encephalitis.
23. transient renal insufficiency.

24. reverse transcriptase inhibitors
protease inhibitors
fusion inhibitors
integrase inhibitors.
25. HAART (highly active antiretroviral therapy): at least 3 drugs in at least 2 of the categories:
2 non-nucleoside reverse transcriptase inhibitors plus
[1 nucleoside reverse transcriptase inhibitor OR protease inhibitor]
26. nucleoside, nucleotide, and non-nucleoside RTI's.
27. nucleoside reverse transcriptase inhibitor.
28. pyrimidine analog that is incorporated by reverse transcriptase into viral DNA, thus halting further replication.
29. acyclovir / zovirax.
30. fewer side effects.
31. instead of inhibiting reverse transcriptase at its active site, it binds at the "NNRTI pocket" site.

32. breaks the viral protein chains apart to be assembled into new viral particles.
33. HIV and hep C.
34. saquinavir / invirase.
35. mostly GI upset.

36. cytokines produced by immune cells in response to foreign agents.
37. macrophages and NK cells to elicit anti-microbial and anti-tumor responses.
38. interferon alpha-- hep C
interferon beta-- MS
interferon gamma-- chronic granulomatous diseases.
39. chronic hep B, C
HPV induced genital warts
kaposi's sarcoma
hairy cell leukemia
40. interferes with virus's ability to infect cells, inhibits viral RNA translation.
41. interferon alpha plus polyethylene glycol to make the medication last longer in the body

42. D-ribose sugar.
43. nucleoside anti-viral family.
44. with interferon alpha against hep C.
45. little to none.

46. live/attenuated, killed, protein fragment.
47. stronger immune response that lasts longer, but has a small potential for being reactivated.
48. weaker immune response but cannot be reverted to virulence.
49. weakest immune response of all vaccination types.
50. hep B and HPV.
51. live attenuated and trivalent inactivated.
52. live attenuated, delivered as nasal spray.
53. gardasil and cervarix.
54. HPV 16 and 18.
55. HPV 6 and 11, the strains that cause genital warts.

Wednesday, June 17, 2009

guest post: vaccines

from the mind of Erin Friedman Sharman, fellow ND1:

This blog post is not to be taken as criticizing or condemning vaccines, as vaccines have helped to eradicate debilitating and horrifying diseases. Rather, it serves to educate on the less advertised negative effects associated with vaccines.

Before my education at NCNM I had never thought to question the safety, reason or timing of vaccines. Although I had questioned many other government mandated occurrences, vaccines had always been presented by my community and physician as safe and as an unquestionable milestone in a child’s life. Here are a few basic facts regarding vaccines:

Vaccines are not simply a killed or altered p
athogen, most vaccines have various additives to enhance the immune performance or sterilize, kill and preserve the vaccine. These additives are often ill understood and under-studied resulting in negative side effects. Perhaps the most “famous” of the additives has been thimerosal (contains Mercury) which was taken out of all childhood vaccines from 1999-2004.

The Center for Disease Control and Prevention (CDC) vaccine schedule is created for the most vulnerable of all children, and thus subjects the children with the most protective immunity (and even complete immunity in some cases) to the dangers found in vaccines. For example, passive immunity to Haemphilus influenze B can be conferred through a mother’s breast milk.

The CDC schedule is based on childhood wellness visits, the
majority in the first year of life, as this is the most guaranteed and frequented period of healthcare visits in a child’s life. In doing so, the schedule does not correlate to the development of the child’s immune system, largely incompatible to an appropriate immune response until AFTER the first year of life.

In light of the above, I have come to believe that the CDC vaccine schedule does not parallel the advances in scientific understanding of human development nor does it take into consideration the risks, health and socioeconom
ic standing of each child. I encourage all interested parties, especially those undertaking the enormity of parenting in the near future to consult the advice of a Naturopathic physician well versed in the art of vaccination, as each vaccine has its own complex matrix encompassing patient family history, environmental factors and a multitude of other risk factors. One should also become familiar with the CDC’s website (http://www.cdc.gov/vaccines/) on vaccines, your state’s laws concerning vaccines and their exemption, and the Adverse Reporting System for Vaccines (http://vaers.hhs.gov/)

The following chart summarize
s the major differences between the CDC based vaccine schedule and the Naturopathic Vaccine Schedule:








A neutral and reliable source for more information can be found at John Hopkins Bloomberg School of Public Health: http://www.vaccinessafety.edu

Tuesday, March 3, 2009

immunology: class notes 2/23,2/24- vaccines

this unit dealt with vaccination in all its glory; all the immunological, biochemical, ethical, developmental issues that sprout forth from it. vaccination is basically the act of injecting a small amount of inactive or inactivated antigen into the body in order to purposely create an immune response and develop immunological memory so as to be better prepared for the next encounter with that antigen. in a population, vaccination is effective because of the principle of "herd immunity"- the unvaccinated individual still has good chances of not being infected because everyone else is vaccinated. vaccines can be designed to invoke responses against different types of antigens; a b cell response would be desired for extracellular pathogen or toxins, while a t cell response would be desired for intracellular pathogen.

some developmental considerations: up until 1 year, infants can't invoke a Th1 response due to the inability of the antigen presenting cells to make IL-12, and the inability of their t cells to make IFN-gamma (they receive their IFN-gamma from breastmilk up until this point). thus, infants younger than 1 year will only invoke a Th2 (antibody) response when vaccinated. even though this is the case, it is routine to vaccinate infants within 12 hours of birth for hepatitis B, mainly due to logistical factors (cheaper, more convenient, next checkup might not be for a while).

vaccine design has to take many factors into account, such as safety, timing of administration, cost, mechanism of action, type of antigen involved, etc. there are several different ways to kill or inactivate antigen-- note that "inactivated" antigen means that the antigen can never again be pathogenic, whereas "inactive" or attenuated refers to antigen that is at the moment not pathogenic, but has the potential to be. the old method for producing inactive antigen was to simply boil the antigen- the downside to this being that immune response to these denatured proteins might be different than to the original antigen. now the conventional method is "formalyn inactivation"- a chemical inactivation.

there are other ways to prepare vaccines besides the killing / inactivation route, each with their own advantages and disadvantages. the "protein subunit" method uses just a piece of the toxin as the antigen- while this guarantees that the antigen will not be pathogenic, it also requires multiple doses to get an adequate immune response. some vaccines use just the DNA of the antigenic protein instead of the protein itself-- while this method is cheap, it doesn't work too well with humans. another method tries to make antigenic peptides that fit directly into MHC (as opposed to antigen being processed into peptides in the cell and presented in MHC)-- unfortunately, because of the lack of expression of co-stimulatory molecules, this method produces tolerance rather than immunity. finally, DC vaccines are currently in development- dendritic cells are isolated outside of the host, exposed to the antigen, then put back into the host, where they can go to the lymph nodes and initiate an immune response.


questions
definitions...
1. what is contained in a vaccine?
2. what is the difference between inactive and inactivated pathogens?
3. what is the purpose of a vaccine?
4. what is meant by "herd immunity"?
5. what are some considerations required for the design of vaccines?
6. what sort of immune response would be appropriate for an extracellular pathogen?
7. what sort of immune response would be appropriate for intracellular pathogens?
8. what sort of immune response would be appropriate against toxins?
9. what is thimersol and why was thimersol used in vaccines up until recently?
10. why is aluminum added to vaccines?

developmental issues...
11. why can't infants younger than 1 year old invoke a Th1 response?
12. what is the response to vaccination of an 6 month old infant?
13. where do infants get their IFN-gamma?
14. when is the hepatitis B vaccine generally administered and why?

vaccine preparation...
15. what is a conjugate vaccine?
16. what is an attenuated vaccine?
17. what is the CDC recommendation for the timing of the measles mumps ruebella vaccine?
18. what was the old way for killing viruses for vaccine preparation and what was its downfall?
19. what is the new way for killing viruses for vaccine preparation?
20. how is the flu vaccine formulated?

what are these types of vaccines and what are their advantages and disadvantages:
21. protein subunit
22. DNA
23. peptide
24. DC vaccines

answers
1. an inactive or inactivated form of antigen.
2. inactive can potentially still be activated (also called attenuated), whereas inactivated pathogens will never be harmful again.
3. to increase numbers of T, B cells specific for the injected antigen so as to provide immunological memory to protect against future infection.
4. the idea that the effectiveness of vaccination is proportional to how much of the population is vaccinated- or that the unvaccinated individual has less of a chance of infection because everyone else has been vaccinated.
5. type of antigen / pathway of infection, safety / toxicity, timing of administration, cost.
6. a b cell response.
7. a t cell response
8. an antibody (b cell) response.
9. it is a mercury containing component of vaccines that was used to protect against contamination of the vaccine itself- due to repeated usage of the same bottle for multiple vaccinations by doctors.
10. it enhances the antibody response.

11. their APC's can't make IL-12, and their t cells can't make IFN-gamma; CD8 t cells won't be activated.
12. this infant will produce a Th2 response.
13. breastmilk.
14. within 12 hours, mainly due to convenience, and the fact that before 2 years old the infants have a much higher susceptibility for infection by the Hep B virus.

15. conjugate vaccine is an non-protein antigen (hapten) that is combined with a protein ("carrier") in order to ellicit an immune response.
16. an inactive form of antigen which has been passed through several different animals, usually including a bird, in order to make it non-tropic for humans.
17. 18 months.
18. boil a protein to denature it- but the new protein has might produce a different immune response than the original.
19. "formalyn inactivation"
20. 3 strains of the flu are combined into one vaccine based on what strains are expected to be virulent for the upcoming season.

21. using only a piece of toxin to initiate the immune response; don't get a big immune response, so need multiple doses.
22. injecting the DNA instead of the antigenic protein; cheap but doesn't work well in humans.
23. make the peptide that fits directly into the MHC molecules; instead of creating immunity creates tolerance because doesn't cause co-stimulatory molecule expression.
24. isolating dendritic cells, exposing them to antibody outside of the body, putting them back into the body, where they can travel back to lymph nodes and initiate immune response; is still in development and very expensive.