EXAM 3- Khan (IBD and Pancreatitis)

based on sg

Sulfasalazine contains ____ bonds, which is broken down by __________________ in the colon.

Sulfasalazine contains azo bonds, which is broken down by bacterial azo-reductase in the colon.

What is the main therapeutic moiety of sulfasalazine? What is the structure of sulfasalazine?

main moiety is 5-ASA (5-amino salicylic acid)

What percentage of an orally administered dose of sulfasalazine reaches the colon?

25%

How is 5-ASA metabolized when absorbed systemically? (Be able to also identify on the structure where it is metabolized.)

5-ASA metabolized to N-acetyl-5-ASA through ACETYLATION

What are the ADRs of sulfasalazine caused by the sulfapyridine?

• GI (abdominal pain, n/v, anorexia)

• rash, HA, oligospermia

• INHIBITS folate absorption

• hemolytic anemia in G6PDH deficiency

What does the sulfapyridine from sulfasalazine do to glutathione to cause hemolytic anemia?

Sulfapyridine OXIDIZES glutathione. this is not good because the reduced (non-oxidized) form is necessary for fxn as a cellular antioxidant.

What is the name of the 5-ASA drug used for IBS?

Mesalamine

What are the contraindications of 5-ASA or Mesalamine?

salicylate or aminosalicylate allergy

What is the MOA of glucocorticoids?

inhibits production of cytokines and other inflammatory mediators (ex: TNF-a, IL-1)

What are the long-term ADRs of glucocorticoids?

• impaired wound healing

• IMMUNOSUPPRESION

• decrease bone density

What is the advantage of the acetyl group in budesonide?

DECREASES MINERALCORTICOID ACTIVITY

What is the MOA of methotrexate? (Include the specific enzyme) What is the effect?

Inhibits DHF (Dihydrofolate reductase), which depletes folate cofactors needed for DNA synthesis

What is the MOA of infliximab and adalimumab? What is the difference between the 2 drugs?

MOA- inhibit TNF-a

Difference: Infliximab is a mouse-human chimeric antibody, Adalimumab is FULLY humanized

What are the BBW of infliximab and adalimumab?

INFECTIONS (TB reactivation, RTIs, fungal, sepsis)

What is the MOA of natalizumab? What is the BBW?

MOA- humanized antibody alpha-4 integrin

BBW- increases the risk of progressive multifocal leukoencephalopathy (an opportunistic viral infection of the brain)

Natalizumab blocks the adherance of ___ integrin to ________.

alpha-4 integrin to VCAM

What is the MOA of vedolizumab?

humanized antibody a4/b7 integrin

Vedolizumab blocks the adherence of _____ integrins to ___________.

a4/b7 integrins to MAdCAM1

How is vedolizumab different from natalizumab?

• vedolizumab is more specific

• Vedolizumab is used for UC and CD, while natalizumab can only be used in CD

What are the composition of pancreatic enzymes?

amylase, lipase, protease

How are pancreatic enzymes prescribed?

based on lipase content

What is the indication of pancreatic enzymes?

1. malnutrition

2. steatorrhea

3. pain reduction

How do pancreatic enzymes reduce pain?

basically: we give proteases that degrade CCK, and that stops the pain

• CCK is the secretagogue of pancreatic enzymes, when not broken down by trypsin in pancreatitis, it causes pain

What are the ADRs of pancreatic enzymes?

• nausea/ abdominal pain, flatulence

• mucosal irritation

• fibrosing colonopathy

• hyperuricemia

• hypersensitivity

What is the BBW of NSAIDs?

• risk of CV thrombotic event

  • C/I in CABG surgery

• GI bleeding, ulcers, perforation

What is the BBW of Acetaminophen?

• risk of errors

• hepatoxicity

What is the max daily dose of APAP a day?

≤4 grams/day

What is the difference between opioids and opiates?

o   Opioid- any drug, natural or synthetic, with morphine-like actions

o   Opiate- natural compound present in opium (morphine, codeine)

What are the effects mediated by mu and kappa receptors?

BOTH RECEPTORS ARE ASSOCIATED WITH ANALGESIA

mu- respiratory depression, sedation, euphoria, physical dependence, decrease GI motility

kappa- sedation, dysphoria, psychotomimetic effects, decrease GI motility

Discuss the mechanism of cellular actions from mu receptor activation PRESYNAPTIC

• Inhibit voltage-gated Ca++ channels

  • Inhibit NT release

Discuss the mechanism of cellular actions from mu receptor activation POSTSYNAPTIC

• Causes hyperpolarization

  • Action potential is inhibited

What neurotransmitters deal with pain transmission?

• glutamate

• neuropeptide NK

How is pregabalin different from GABA in its effect?

• Although they look similar----

• Pregabalin binds to alpha2delta-1 subunit of Ca channel

• Causes presynaptic effect that was previously discussed (inhibit NT release)

• GABA binds to GABA receptors and inhibits nerve transmission

What is the MOA and ADRs of beta-lactam antibiotics?

MOA: bacterial cell wall synthesis inhibitors

ADRs: GI, hypersensitivity, seizures

What is the MOA of fluoroquinolones?

MOA: DNA synthesis inhibitor (Inhibit DNA gyrase and Top IV)

What is the BBW of fluoroquinolones?

BBW: serious ADRs (Tendon rupture, CNS effects, exacerbate myasthenia gravis)

Explain the R6 and R7 positions in the structure of fluoroquinolones:

R6- F Cell Wall Penetration (Fluorine group)

R7- heterocyclic substitution increases spectrum

What are the ADRs of insulin?

• HYPOGLYCEMIA!!!!

• Insulin allergy

• Lipodystrophy atrophy of SQ fat

• Weight gain

What is the BBW of antidepressants?

suicidal ideation