Gatrointestinal Infection Case Drugs

Question 1

Prednisolone

Answer 1

Binds to glucocorticoid receptors, inhibits NFkB (pro inflammatory) and induces IL10 (anti inflammatory)

●Effects:
○Anti-inflammatory.
○Immunosuppression.
○Anti-neoplastic.
○Vasoconstriction.

●Mechanism:
○Metabolite of prednisone, converted in liver.
○Lipophilic, passes through cell membrane and binds to glucocorticoid receptors in cytoplasm.
○GR’s bound to chaperone proteins before arrival of glucocorticoid, dissociate when complex formed.
○Prednisolone and glucocorticoid receptor complex enters the nucleus, undergo dimerisation, interacts with DNA Steroid-receptor complex enters nucleus, binds and activates nuclear receptors, alters gene expression and inhibits proinflammatory cytokine production (AP-1, NF-κB).
○At higher doses, stimulates expression of anti-inflammatory cytokines. (IL-1, IL-10 etc.)

Side effects
These common side effects of prednisolone happen in more than 1 in 100 people.
Weight gain
Indigestion
Problems sleeping
Restlessness
Sweating
Mood changes
Long term side effects - thinner bones (osteoporosis), poorly controlled diabetes, eyesight problems, high blood pressure (hypertension)

Question 2

Adalimumab

Answer 2

Inhibits TNfα reduces recruitment of white blood cells, lowers the releases IL 6 (pro inflammatory) so reducing swelling

MOA
○Monoclonal anti-TNFα antibody.
○Binds with specificity to TNFα and inhibits its binding to p55 and p75 cell surface TNF receptors.
○Adalimumab also lyses surface tumour necrosis factor expressing cells in vitro when in the presence of complement.
○Inhibition of TNFα reduces recruitment of white blood cells such as NK cells and MΦ (macrophage), leads to lower accumulation of these cells = reduced swelling, temp etc. (Hallmarks), the release of serum cytokines (IL-6), acute phase reactants of inflammation, and the expression of adhesion molecules responsible for leukocyte migration

●Effects:
○Anti-inflammatory.

Side effects
Pain, swelling, redness, itching where injection given
Mild nose, throat, sinus infection
Headache
Stomach pains and nausea
Muscle or bone pain

Question 3

Metronidazole

Answer 3

Oxidises bacterial DNA

● Mechanism:
oProdrug​: requires an anaerobic environment to form active metabolites, so aerobes (most human cells) are relatively unaffected​.
oCan target C. diff. (Spore forming, v. hard to kill). ​
oActive metabolites bind to DNA and cause DNA damage, some deplete anti-oxidants and induce oxidative stress.
oResults in bacterial cell death.​

● Effects:
○Slows spread of bacterial infection.
○Allows IS to ‘catch up.’

●Side Effects:
○Nausea
○D&V
○Intense alcohol sensitivity

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