5070 Deck 4?: Meds for Inflammation

what is receptor for Histamine called?

H1 receptor

histamine is associated with what?

allergic reactions

what does a mild allergic reaction result in?

rhinitis, itching, local edema

what does a more severe allergic reaction with massive release of histamine cause?

bronchoconstriction

hypotension

anaphylaxis

what type of receptor is a H1 receptor?

G protein coupled receptor

what is the mechanism of action of an antihistamine?

selectively antagonize H1 receptors/ H1 blockers

what is the difference between first and second gen antihistamines?

what causes this?

first gen are more sedating than second gen

they are easier to move across BBB

what is the generic name for benadryl?

diphenhydramine

what class of drug is diphenhydramine?

antihistamine, H1 blocker

what is the indication for diphenhydramine? x 4

allergic reactions

rhinitis associated with allergies and common cold

motion sickness

occasional insomnia

what is the normal dose of diphenhydramine?

25 to 50 mg PO q 4-8 h

what is the form diphenhydramine is normally found in? what could it also be found in?

tablets or oral solution

IV/IM/topical

what is the peak/duration of diphenhydramine?

peak is about 2 hrs

duration is 10-12 hours

what is the half-life of diphenhydramine in children? in adults? in older adults?

children 5 hrs

adults 9 hrs

older adults 13. 5 hours

how is diphenhydramine eliminated?

hepatic metabolism

renal excretion

what are some adverse effects of diphenhydramine?

what is a special ADR that happens more frequently in children?

sedation, anticholinergic effects

paradoxical CNS excitation

during pregnancy and lactation, what happens with diphenhydramine? Is it contraindicated in any population?

drug crosses the placenta

contraindicated in neonates and premature infants and breastfeeding

what are some interactions that can occur with diphenhydramine?

what characteristics do these have with other medications that affect the same thing?

CNS depressant, anticholinergics

additive effect

what populations should we avoid/minimize diphenhydramine use ?

older adults

what are some ‘anticholinergic effects’

dizzy, drowsy

dry mouth and mucus membrane

decreased bronchial secretions

hypotension, palpitations, urinary retention

constipation, blurry VA, confusion

what does and overdose indicate?

an emergency situation

what is the first line treatment of anaphylaxis?

what does this do?

epinephrine IM

vasoconstrictor and bronchodilator

what medication will not relieve bronchospasm, hypotension and/or shock in the case of anaphylaxis?

antihistamines like diphenhydramine

depending on respiratory status during anaphylaxis, what medication could be given to improve patient’s breathing?

what does this medication do?

albuterol

bronchodilator

if epinephrine is injected into your finger, what should you do?

what can this cause?

go to the ER

ischemia

what was approved as of 08/2024 that treats anaphylaxis?

epinephrine nasal spray

NSAIDS stands for what?

nonsteroidal anti-inflamatory drugs

what are some examples of NSAIDS?

salicylic acids (aspirin)

acetic acids

fenamic acids

propionic acid (ibuprofen)

what is an example of a glucocorticoid?

prednisone

what type of drugs have a broad effect on the immune system?

immunosuppressant drugs

what do immunosuppressants have higher risk of causing medically when compared to immunomodulators?

infection and cancer

what is the function of immunomodulators generally?

targeting a specific cytokine or signaling pathway

do immunomodulators have zero risk of infection and cancer?

no

what is the abbreviation for cyclooxygenase?

COX

in local injury, what does cyclooxygenase do?

what does this do?

catalyzes production of PGE2 and PGD2

promotes inflammation, sensitize to pain

in the stomach, what role does COX play?

promotes PGE2 and PGI2 which have a protective role and keep gastric mucosa healthy

in platelets, what is the function of COX?

what does this do?

promoting synthesis of TXA2

stimulates platelet aggregation

in healthy blood vessels, what is the role of COX?

what does this do?

promotes the synthesis of PGI2 (prostacyclin)

vasodilation AND prevents platelet aggregations

in healthy kidneys, what does COX do?

what does this cause?

promotes PGE2 and PGI2

promote vasodilation and renal blood flow

in the brain, what does COX do?

mediates fever and perception of pain

in uterus, what does COX do?

promotes contractions

what are the isoform names of COX?`

COX-1 AND COX-2

where is COX-1 found?

practically all tissues

where is COX-2 primarily found?

what is this produced in response to?

sites of tissue injury

cytokines

what does COX-2 mediate and sensitize?

inflammation

sensitizes receptors to painful stimuli

what are the HARMFUL effects of COX-1 inhibition? x3

gastric ulceration

bleeding

renal impairment

what is the major beneficial effect of inhibition of COX-1?

protection against MI/stroke 2/2 reduced platelet aggregation

what is the major benefit of inhibiting COX-2? There are 4

suppression of inflammation

alleviation of pain

reduction of fever

protection against colorectal cancer

what harmful effects result from inhibition of COX-2?

renal impairment

promotion of MI and stroke

why would inhibition of COX-2 promote MI and stroke?

2/2 suppressing vasodilation and production of prostacyclin (PGI2)

NOT suppressing platelet aggregation

what is a commonly known salicylate?

aspirin

what is a commonly known propionic acid?

ibuprofen

what do NSAIDS do to COX-1 and COX-2 with regard to their functions?

block either/or to varying degrees

can NSAIDS selectively target either COX-1 or COX-2? which do they normally target?

COX-2

COX-2

what can all NSAIDS cause primarily, with what other two concomitants following?

renal impariment

HTN, edema

if COX-1 is inhibited (and sometimes even COX-2), generally NSAIDS can cause this to occur?

general bleeding

all NSAIDS except what medication increase risk of MI and stroke?

aspirin

all NSAIDS except what can cause fetal abnormalities?

low-dose aspirin

what gen of NSAID is aspirin?

1st generation

what class is aspirin?

NSAID

what is an indication for aspirin

inflammation, pain, fever

promotion of decreased platelet aggregation

what is the mechanism of action for aspirin?

which COX is affected most by aspirin?

irreversibly inhibits COX

COX-1

how long does the mechanism of action for aspirin last?

until new molecules of COX-1 and COX-2 can be synthesized by specific tissues

what is the dose of aspirin given for platelet inhibition?

8-325 mg ONCE daily

what is onset and duration of aspirin?

30-60 min onset

4-6 hr duration

how is aspirin eliminated?

hepatic then renal

what are some adverse effects of aspirin consumption?

bleeding, GI bleeding

renal dysfunction, tinnitus, reyes syndrome,

ANAPHYLAXIS

What does the mechanism of aspirin irreversibly binding to COX and inhibiting it?

inhibits platelet aggregation BY

preventing TXA2 production and release

what is the metabolite of aspirin called?

salicylate

are aspirin and metabolite both active?

yes

what is the metabolite salicylate responsible for ?

analgesic, antipyretic and general anti-inflammatory effects

during pregnancy, what do we do regarding aspirin consumption?

what time period of pregnancy do we focus on

AVOID IT

especially at 20+ weeks

when during pregnancy is aspirin contraindicated?

30+ weeks

what are contraindications of aspirin at 30+ weeks

anemia, PP hemmorrhage, suppression of uterine contractions

what is an exception to contraindication of aspirin during pregnancy?

low-dose aspirin to prevent preeclampsia and in certain clotting disorders

how many days prior to a surgery would we reccommend someone to discontinue taking their aspirin?

7-10 days prior to surgery

why do we advise patients to stop aspirin prior to surgery?

the average lifespan of a platelet is 7-10 days, and new COX will be there with new platelets

what are some drug interactions of aspirin?

anticoagulants, glucocorticoids, EtOH, NSAIDS

what is the drug interaction that happens with aspirin and anticoagulants?

increased risk of bleeding

what is the drug interaction that occurs with aspirin and glucocorticoids?

increased risk of gastric ulceration

what is the drug interaction with EtOH and aspirin?

increased risk of gastric ulceration

what is the drug interaction between NSAIDs and aspirin?

can block access to COX-1 on platelets

what is the indication for routine low-dose aspirin?

prevention of secondary MI and/or stroke prevention

ibuprofen is also know by what other names?

motrin, advil

what generation NSAID is ibuprofen?

1st

what drug class is ibuprofen?

NSAID

what are indications for ibuprofen?

inflammation, pain, fever

what is the mechanism of action for ibuprofen?

inhibits both COX about the same

what is the dose of ibuprofen that we normally give? both PO and IV

400-600 mg PO q 4 h

5-10 mg/kg IV

what is the onset/duration for ibuprofen?

onset: w/i 60 min

duration: 4-6 h

elimination of ibuprofen is what?

hepatic then renal

what are ADRs for ibuprofen?

bleeding, GI bleeding, tinnitus, renal dysfunction

increased risk of MI/stroke

during pregnancy, what can happen when taking ibuprofen past 20 wks gestation?

oligohydramnios

30+ weeks of pregnancy, ibuprofen is contraindicated for what reason?

risk of premature closure of ductus arteriosus

is ibuprofen excreted in breast milk?

are serious events common with this?

yes

no

how early should ibuprofen be d/c prior to surgery?

3 days

what are drugs that can interact with ibuprofen? there are 2

aspirin, glucocorticoids

celecoxib goes by what brand name?

celebrex

what gen NSAID is celecoxib?

NSAID

what are some indications for celecoxib

osteoarthritis, RA, ankylosing, spondylitis