Pediatric Pharm Review

Chris Perry and I made flashcards to answer the questions in the review for Dr. Meibohm’s material. Click the link above to download them.

Zachary Zanfes made flashcards for the pediatric pharm lecture including the review. Also posted above.

Meibohm review updated at 5:02 due to typo. Should be lipophilic drugs that absorb into the fat of an obese individual

Dr. Foster’s Immunization lecture

Dr. Foster said to focus on general concepts, not detailed information.

What are the differences between attenuated live vs inactivated vaccines?  Live vaccine: Replication mimics natural infection.  Inactivated vaccine: non-replicating and non-infectious, produce reactions at the local site.

Do these differences affect timing of vaccinations?  live vaccinations or intranasal infuenza vaccines: can be given at together at the same visit, or should be spaced out by a 4 week interval. reason: the vaccine that is given second will NOT have a very strong immune response…so it will have to be repeated. (Thanks Jess)

Which is likely to cause a mild form of illness?  Live virus causes a mild form of the illness after the incubation period.

What are absolute contraindications to vaccination?  Severe Allergy, likely to hurt pt.

What are temporary contraindications? Pregnancy, Substantial illness, immunosuppression or recent blood transfusion

What about vaccinations in pregnant women? Theoretical risks but never been tested.  Precaution of waiting to 2^nd trimester, use inactive if possible, influenza recommended throughout pregnancy, some may be necessary for int’l travel

What are current target groups for flu vaccine?  People at risk for serious complications from contracting the flu.  That is pt’s 6 months to 18 years, and pt’s older than 50, pregnant women, people with chronic organ problems, immunosuppressed pt’s, anyone with respiratory problems, nursing home pt’s, health care workers.  Basically anyone who doesn’t want or doesn’t want to transmit the virus.

How does DTaP differ from Tdap from Td? The capitalized letters are more potent forms of the vaccine.  DTaP is for children <7 y/o.  Tdap is the booster shot that was recently introduced, routine for 11-12 y/o, or if never received for 11-64 y/o, 1 time use.  Td is for adults and a booster needed about every 10 years, usually also administered after injury where tetanus is a possible bacteria.

What if your patient misses part of Hep B series? If the pt misses a series of the hep B you can just administer it when they come in. there is no need to restart the series (Thanks Glen)

What is the value of a hepatitis titer?  Only valuable 1-2 months after seroconversion.  After this time, circulating antibodies will decline but immunological memory will still be there.  Titers can only check circulating antibodies, thus proving useless for HepB if tested years after seroconversion.

 Download here:

 fosterreview

Passive immunization – passage of antibodies from mother to child (IgG through placenta, IgA through breast milk) or use of serum antibodies from a horse (or other animal) in a human.

Active immunization – introducing the antigen and allowing the immune response to create antibodies and immunological memory against it.  Subsequent vaccinations will produce a stronger immune response.

Herd Immunity – immunity is acquired once a certain amount of people within a community are vaccinated.  This effectively reduces transmission of the disease.

Vaccines have effectively eliminated smallpox, and polio and significantly reduced several others.  To be effective a vaccine must be safe, inexpensive and easily distributable, and establish long term protective immunity against a pathogen or toxin.

Subcutaneous vaccination is most effective followed by ID and IM.  IV is usually a bad route.  Oral vaccines include rotavirus and inhalation or intranasal vaccines include influenza.

Children are immunized most since they see the doctor the most.  Very young childern and eldery people are not good targets since they are not immunologically intact and may have reduced efficacy of the vaccine.

Vaccine types:

1.       Live attenuated

a.       Viral vaccine

b.      Grow virus so that it becomes unable to be viable in humans

c.       Can also be genetically engineered by splicing out the virulence genes.

d.      Examples: MMR, Varicella, Rotavirus, Polio

2.       Live from another species

a.       Viral vaccine

b.      Infect a human virus into monkey

c.       Within the monkey cells, the virus will mutate and become viable in monkeys but not viable in humans. 

3.       Killed or inactivated

a.       Viral vaccine

b.      Killed by radiation heat etc

c.       Safer but stimulate weaker immune responses

d.      Bad for people with poor healthcare (hard to transport and need boosters)

e.      Examples: Influenza, Hep A, Polio

4.       Subunit

a.       Bacterial Vaccine

b.      Only use immunogenic antigens              

c.       Examples: Hep B, Pertussis, S. pneumoniae

5.       Conjugate

a.       Bacterial Vaccine

b.      Link antigen with polysaccharide coats.

c.       Examples: H. influenza type B, S. pneumoniae

6.       Toxoid

a.       Bacterial Vaccine

b.      Neutralize the toxin with formalin then inject it.

c.       Examples: Diphtheria, Tetanus

Review Adjuvants.

DNA and recombinant vaccines are in testing but not currently available for humans.

Review T cell tolerance.

T Regulatory Cells:

They are generated in the thymus.

They have foxp3

They are CD25+

They produce large amounts of TGF-Beta and IL-10 (inhibitory for Th2 cells)

Possible mode of action is through cell to cell contact (unknown exact mechanism)

They have CTLA-4 which binds up B7 on APCs that are most likely presenting self antigen (therefore not allowing other T cells to be costimulated and activated by self antigen).

They are produced through “intermediate” signals (process largely unknown).

IPEX Syndrome is due to dysfunction of foxp3, in turn affecting T regulatory cells.  Triad of symptoms is diarrhea, eczema, endocrinopathy (usually diabetes).

T regs can also be important in preventing autoimmunity, especially during pregnancy (miscarriages often reveal low amounts of T regs). 

There are also Tr1 and Th3 cells.  These are CD4+ cells, but NOT CD25+.  They are generated in the periphery.

Tr1’s secrete high levels of IL-10 and no IL-4 or IFN-gamma (possible low levels of IFN-gamma).

Th3’s secrete high levels of TGF-Beta.

A special subset of CD8+ cells can become CD8+ regulatory T cells that secrete IL-10.

These three have variable Foxp3 expression.

Good animation of T regs:  http://www.ab-direct.com/animation/t-cell/

You should also review the effects of stress, corticosteroids, and diet on immunoregulation

16) Describe the primary drug elimination processes in the kidney.

Free drug, not bound in plasma is filtered through glomerulus into the proximal tubule.  Remaining drug is ACTIVELY secreted into the proximal tubule after leaving the glomerulus.  These transporters are non-specific for either the cation or anion and can lead to competitions between drugs to be secreted.  Most of drug is secreted, not filtered.  In the distal tubule, the drug concentration inside will exceed the concentration outside, leading to diffusion of UNCHARGED (uncharged only) drug back into the lumen and back to the systemic circulation.  Change the pH of the urine to keep the ionic forms of certain drugs.  The drugs must be water soluble compounds so they will not be reabsorbed by the kidneys and will be excreted through urine.  If they are lipophillic they will easily cross the lipid membrane of the tubules.  You can also increase urine flow, to excrete more drug faster.

17) Describe mechanisms of hepatic elimination

Orally absorbed drugs enter the liver via the hepatic portal vein from the GI tract (first pass metabolism).  Drugs, bound or unbound will be either metabolized (inactivated or activated) or excreted.  Drugs are actively secreted into the bile where they are excreted into the feces.  These secreted drugs can be metabolized or unchanged. 

Restrictive clearance means that the liver can only clear unbound drug in the plasma.  This leads to a LOW extraction of the drug.  These drugs are sensitive to changes in protein binding.

Non-restrictive clearance means the liver can clear both bound and unbound drug. 

18) Explain the determinants of intrinsic clearance and the impact of enzyme inducers and inhibitors on each of the factors.

This is the ability of hepatocytes to clear drug, with no blood flow or protein binding limitations.  This can also be described as the capacity and affinity of the drug metabolizing enzymes (DME’s) for the specific drug. 

Enzyme inducers effectively increase the capacity of the liver, by increasing the actual number of enzymes present.  Increasing the capacity increases the intrinsic clearance.  Note that this process takes TIME.

Enzyme inhibitors are usually competitive inhibitors.  This will lead to increase in Km for the drug, essentially lowering the affinity of the enzyme for the drug.  This effect is IMMEDIATE.

1)  Define genetic polymorphism

An altered sequence of a particular gene.  More than one genetically distinct allele.  Might be a main reason for such diversity in the human population.  To be considered an allele it must be present in >1% of the population.

2)  Compare and contrast extensive and poor metabolizer phenotype

An individual with two defective alleles (for a drug metabolizing enzyme) for an enzyme are considered to be poor metabolizers.  An individual with either one normal allele OR two normal alleles (for a drug metabolizing enzyme) is considered to be an extensive metabolizer.

3)  Understand relationship between CYP2D6 polymorphism and codeine analgesic response

CYP2D6 PM (poor metabolizers) have two defective CYP2D6 alleles.  This enzyme is known to convert codeine to morphine.  PM therefore do not get as large an analgesic response to codeine as EM do.

4)  Understand relationship between CYP2C9 polymorphism and glipizide-induced hypoglycemia

CYP2C9 PM have an increased oral bioavailability with decreased clearance. The effect of glipizide is hypoglycemia, which will be prolonged due to CYP2C9 faulty metabolism (PMs).

5)  How does CYP2C19 polymorphism affect omeprazole’s h pylori eradication rates?

Eradication rates for h. pylori are higher in PM, since less omeprazole is metabolized.  Patients with EM for CYP2C19 metabolize more omeprazole, therefore leading to less h pylori eradication. 

6)  Enhanced effects from caffeine are experienced by individuals deficient in which enzyme?

N-acetyl transferase 2

Download it here:

Yates Review 2

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/T/Treg.html

Hope this helps!!!