14. Drug Allergy of Hypersensitivity Flashcards
Drug Allergy or Hypersensitivity
- Requires previous exposure (sensitizing dose)
- Independent of ____
3. Antigen-Antibody Rxn > Mediator release A. \_\_\_\_ B. Complement C. \_\_\_\_ D. Leukotrienes E. \_\_\_\_
4.Skin/Bronchioles/Cardiovascular System
• Allergic rxn doesn't follow dose-response relationship - what you see has nothing to do with pharm effect of drug ○ Aspirin - treat pain, allergic rxn: you don't see carryover from it's therapuetic effect ○ Not too much vasodilation etc • Durg classes that produce allergic rxns - \_\_\_\_ and \_\_\_\_ • Mild allergic (non-anaphylactic) - released mainly form mast cells that can't be handled with an H1 receptor blocker; with just a rash > you can use just anti-histamine • Bronchoconstriction, vasodilation (BP bottoms) and rash/hives • Platelet activating factor, eosinophil chemotactic factor • LT > pain mechanism > pther way arachonic acid can go (via lipoxygenase) > potent \_\_\_\_; \_\_\_\_ (seasonal allergies, blocks LT receptors, used asa. Pull to prveent asthma attacks)
dose
histamine
heparin
PAF, ECF
penicillins
NSAIDs
bronchoconstrictors
cigulair
Pharmacological Interventions for Drug Allergy
Mild: Oral H-1 receptor ____ (antihistamine) ____ (Benadryl®) 25 – 50 mg
Severe: ____ 1:1000 (____ mg/ml)
____ syringe 0.3 – 0.5 ml
____, Subcutaneous, ____
• Keep antihistime on for a couple of days • H1 blockers have some anti-chol effects (musc receptor antags) > why they're good for \_\_\_\_ • Amt of epi in epi pen is 100x more cxn than a local anesthetic carpule ○ Local: 1:100,000 (.01 mg/ml) - not enough for anaphy > 1:1000 (1 mg/ml) § 0.3 * 1 mg/ml > \_\_\_\_ mg of epi ○ Sometimes 2nd dose ○ Route: \_\_\_\_ - catechols not well absorbed orally, and don't have a lot of time to save person's life § No \_\_\_\_ - hard to find veins, so BP has bottomed out • Once stabilized, give antihistamine (via injection or oral); or a corticosteroid (anti-inflam steroid, not corticoid; \_\_\_\_ - muscle wasting)
blocker dephenydramine epinephrine 1 preloaded IM sublingual
motion sickness 0.3 parenchymal IV catabolic
Epi Receptor Actions
A1: ____ skin and ucous membranes
B1: increased ____, increased ____
B2: ____; ____ skeletal muscle and internal organs
• Why epi good for ana? ○ Stimulate A1, B1, B2 ○ Bc BP bottom > major organs are starved of oxy/nutirnets > \_\_\_\_ in BV in liver/kidney is a good thing, at same time as inc \_\_\_\_ § HR/contract in dental setting is side effect - but in anaphylaxis - you want this! ○ Most impt thing epi does: \_\_\_\_ (ability to stim B2) • Can constrict or dilate - depends on whether it's A1 or B1 receptors
vasconstrict heart rate contraction force bronchodilation vasodilation
vasodilation
HR/contraction force
bronchodilation
Anaphylactic Dose = 1:1000 = 1 gram/1000 ml = 1000 mg/1000 ml = ____ mg/ml.
Typical volume = 0.3 ml = ____ mg subcutaneous, intramuscular, into or under ____.
Have available in pre-loaded syringe.
May have to give several doses.
• Calc doses of epi, and doses used in local anesthetic solutions • 1:1000 of anything = 1 g/1000 ml > convert g to mg > 1000 mg /1000 ml > 1mg/1ml; if vol in epi is 0.3 > then you have 0.3mg ○ If administer 2x > \_\_\_\_ mg
1
0.3
tongue
0.6
Concentrations combined with local anesthetics
• 1:50,000=1gram/50,000ml=1000mg/50,000ml= 0.02 mg/ml x 1.7 ml/carpule = ____ mg/carpule
• 1:100,000=1gram/100,000ml=1000mg/100,000ml= 0.01 mg/ml x 1.7 ml/carpule = ____ mg/carp
• 1:200,000=1gram/200,000ml=1000mg/200,000ml= 0.005 mg/ml x 1.7 ml/carpule =____ mg/carp
MRD in 150 lb adult = ____ mg (11 cartridges of 1:100,000)
• Reason why epi in locals > increase \_\_\_\_ of anesthesia, incrreas perfundity and for local chemostasis • Dental cartridge - 1.7ml • 1:100,000 > 1 g /100000 m > 1000 mg /100k ml > 0.1 mg/ml *1.7 > 0.17 mg/cartridge • Using for local A1 effects - not intreasted in bronchodilation or vasodilating other organs (constriciton in local area) • 1:200k, and 1:50K (only one with 50K, lidocaine solution for enahcned hemostasis) ○ Before incision, stick a 1/10 ml of 1:50K combined with lido in each papilla > double cxn so used \_\_\_\_ • How much is in 1:100 in 2 cartridge > 0.034 mg
0.034
0.017
0.0085
0.20
duration
slightly
• H1 receptor blockers
• H2 receptors - due to ____, GI ulcers
• Now we think there are H3, H4 receptors
• All useful drugs are H1/H2 receptor blockers, nothing on agonist side, and nothing on H3/H4 yet
• Histamine activates on four
○ Can modify to make it a prue agonist at each receptor
○ Want prue H1 agonist > put methyl on ____ position (2 methyl histamine)
○ Pure H2 agonist put a mehtyl on ____ posiiton (4 methyl histamine)
§ Might alos have action at H4
○ Stick methtyl on ____ > R alpha methyl histamine > H3
gastritis
2
4
amine
• H1 > BV, brain (excitatory here, so is Ach, why benedryl is drowsiness), smooth muscle (bronchi)
○ 2MH
○ Stim receptor > cascade > won’t test on what 2nd messengers are!
○ Effects in mild to severe alllergic reactions > vasodilation (can lead to hypo), edema (BV become leaky), uritcaria, reflex tachycardia (body compensates for drop in ____), diarrhea (food allergies)
○ Tiple responsie > hisatine subq > at spot inject > ____ zone (1) > around it, you get raised ____ area (2), and outside tha you get the ____ area
§ Rasie pale > due to vascular ____; ____ casues the firery red, and pale pink is from ____ inflamamtion (nerve fibers are stimualted and spitting out mediators of inflam)
• H2 > only place targeting is ____ cells on gastric mucosa > increase HCl from partetal; some are from the heart, all the ones are preventing gastric hyperacidity in ____ disease, GI ulcers, transient heartburn
• H3, H4 > nothing out that hits them
○ H3 > maybe in brain may function like ____ adrenergic receptor s(Decreasing ____ NT reasle)
○ H4 > most recent > when sitmulated it recruits ____ cells to the area of inflammation/allergy
BP red pale pinkish leakiness vasodilation neurogenic pariteal gastroesophageal A2 presynaptic inflam
H1 receptor Blocker General Structure
* Benedryl, and other is parelomaine * Benzene rings - middle chain - tertiary amino group - looks like \_\_\_\_
local anesthetic
Local anesthetics
* A couple of antihistamines blocks \_\_\_\_ channels and has local anesthetic activity * Someone allegric to conventioanl local anesthetics > all we have are amides in syringes; as ester, topical benzocaine > if allergeric to these, you can use some \_\_\_\_ (pull from vial, can't aspirate as well)
Na+
antihistamines
Therapeutic Uses of H-1 Receptor Blockers
- ____ allergic reactions (hay fever, non- anaphylactic drug or bee sting allergy)
- ____ aids, Pediatric sedation
- Motion ____, ____ also drug- induced vomiting
- ____ disease
- Local anesthesia when allergic to amides and esters
- Can be used anaphylasxis as a secondary/teritary drug; once they’re stabilized
- Mtion sickness - ____ blcoking acitivyt in brain
- One antihistamine has dopamine receptor blockinga ctivity > even better than things that block musc chol receptors at treating/preventing drug-induced naiusea/vomitting
- PD > Ach is weighing down DA, blocking the ____ side is oneway to treat PD
mild sleeping sickness promethazine parkinson's
musc chol
cholinergic
- If treating just motion sickness; they take a while to work (pill/patch)
- Innervation from vestibular and stomach - cholinergic - sitmulates vomiting center > gets turned on during motion sickness
- Drugs with ____ are all you need for motion sickness
- When get to drug0inuce vom > predom have input from chemoreceptor ttrigger > ____ > need drugs here to block DA receptors / SE recpeotrs
- Break on vom center > ____
antimuscarininc
SE/DA
NE
Motion Sickness • Want \_\_\_\_ (muscarinic receptor antagonist) – \_\_\_\_ (Benadryl®) – \_\_\_\_ (Dramamine®) – Meclizine (Bonine®) – \_\_\_\_ (Transderm Scop®)
• All antihistamines nad block H1 • Most motion sickenss > ability to block musc chol receptor ○ Can ge \_\_\_\_ mouth ○ Can get \_\_\_\_ (histamine) • Scop - \_\_\_\_ musc chol antagnoist - takes hour to get absorbed
anticholinergic diphenydramine dimenhydrinate scopolamine dry drowsiness pure
Drug-induced nausea/vomiting • Dopamine-2 receptor blockade – \_\_\_\_ (Phenergan®) – Prochlorperazine (Compazine®) – \_\_\_\_(Tigan®)
• Serotonin 5HT3 receptor blockade
– ____ (Zofran®)
– Dolasetron (Anzemet®)
• Serotonin and dopamine-2 receptor blockade
– ____ (Reglan®)
• Either block DA receptor (D2) ○ Prometh - the oldest • Block SE rceptor (5HT3) ○ The two are big for preventing \_\_\_\_ (ondan and dolasteron) • And both > metoclopramide ○ Use in \_\_\_\_ reflux > doesn't explain why it works, the other action is that it's a \_\_\_\_ musc chol receptor agonist > increases \_\_\_\_ > get food out of stomach into SI quicker and less likely to reflux it
promethazine
trimethobenzamide
ondansetron
metoclopramide
cancer chemotherapy
gastroesophageal
peripheral
peristalsis
Percentage of Patients with Vomiting Over First 24 Hours
• How well prometh can work • CL-108 > norco (acetmoephn 325 + hydrocone 7.5 mg) > added an immediate release layer of \_\_\_\_ (antihistamine that also blocks DA) a tlowest approve dose ○ Nausea/vom > from 1 days use > \_\_\_\_ dose response curve > pure acetominophen > 21% vom at least once ○ Spiked with promeht in Cl-108 > vom reduced by \_\_\_\_% ○ Taking ibuprofen • Moral dilemma > what turns people off from misuing \_\_\_\_ > they get sick; keeps people from taking the drug again • People with \_\_\_\_ allergies > they need acetomen opioid combo ○ Or history \_\_\_\_ ulcers (no advild/aleves)
promethazine quantal 50 opioids NSAID GI
Parkinson’s
Too much ____
stimulation in CNS (ACh)
Too little ____ stimulation in CNS (DOP)
* Why antihistamine good > bc musc chol antagonist effect * PD > AcH is running wild > the neruon's are being destoryed > treat: block the Ach and enhacne DA (give L-Dopa, give DA agonsit, releasers, \_\_\_\_ doesn't go into brain bc it's a catecholamine)
muscarinic
dopaminergic
dopamine
CHEMICAL CLASSIFICATION OF ANTIHISTAMINES
1) ETHANOLAMINES = ____ (Benadryl), ____ (Dramamine)
very sedating, excellent anti-____ drugs, possess local anesthetic activity, first line anti-____ drugs, high likelihood of ____ ADRs
2) ETHYLENEDIAMINES = ____ (PBZ), Pyrilamine (Neo-Antegran)
moderate sedation, major use is as OTC ____ aids, high likelihood of ____ ADRs
3) PIPERAZINES = ____ (Marezine), Meclizine (Bonine) slight sedation, excellent anti-____ activity
4) ALKYLAMINES = ____ (Chlor-Trimeton)
slight sedation, common component of OTC “____” medications
* Bena/dramine are the classics for seasonal allegries * Treating allergies - will have to be on these for anumber of days * All drugs are sedating bc they anti-H1 and anti musc effects * All could tech be used in motion sickness * And anticholinegric ADR > dry-mouth, constipation, don't wanna give with glaucoma, can inc HR (bc vagus is break in heart) * piperazines > swear to not get \_\_\_\_ sick, and do not get as \_\_\_\_
diphenhydramine
dimenhydrinate
motion
parkinson
anticholinergic
tripelennamine
sleeping
anticholinergic
cyclizine
motion sickness
chlorpheniramine
cold
sea
sedated
CHEMICAL CLASSIFICATION OF ANTIHISTAMINES
5) PHENOTHIAZINES = ____ (Phenergan)
very sedating, antiemetic activity (including drug-induced vomiting), local ____ activity, high likelihood of anticholinergic ADRs, ____ effects possible (due to dopamine blockade), alpha ____ blockade
6) 2ND GENERATION = ____ (Seldane), Astemizole (Hismanal), ____ (Allegra), Loratadine (Claritin), Cetirizine (Zyrtec)
non-sedating, major hay fever allergic rhinitis drugs, drug interxs = ____ with macrolides erythromycin, clarithromycin, and ketoconazole lead to removal of terfenadine and astemizole from market. Fexofenadine (Allegra) is the active metabolite of ____. No ____ interactions with macrolides or azoles reported thus far with fexofenadine, loratadine or cetirizine
• Prometh > a drug at crossroads between DA recep acntaggonist and H1 antagonist • Can get into isses > bc DA receptors> extrapyramidal effects > drug-induced parkinson's ○ When stop drug it goes \_\_\_\_ • 2nd gen drugs > what's common > exlcuded from \_\_\_\_ (non-sedating antihistamines) ○ #1 selling drug > a lot of drug interactions > \_\_\_\_ (cytochrome) > common drugs and foods (grapefurit juice) and block 3A4 > seldane and hismanal \_\_\_\_ to toxic levels > including macrolide antiboiotcs, antifungal drugs
promethazine
anesthetic
extrapyramidal
1
terfenadine fexofenadine arrhythmias terfenadine cardiotoxic away
BBB
3A4 substrate
accumulate
- Seldane and Hisamla are ____ substrates
- Agents that inhibit enzyme cause accumulation of ____ > OD on the drug
TABLE!!
3A4
substrate
• Seldane > active metbaolite > ____ (not cardiotoxic)
○ Seldane > can get ventricular arrtyhmia > ____ > resistent to ____ (so heart goes back into rhytym)
§ Bc of agents that block processing (____, clarithromycin, ____): won’t work anymore bc stops from metabolite (acid metabolite bc carboxy)
• P-glycoprotien inhibitor > pump that pumps drugs into ____ for excretion; these agents can block that too > another reason why somehting can accumulate
fexofenadine
torsades de pointes
lidocaine
erythromycin
grape fruit juic
kidney/intestine
Histamine-2 Receptor Blockers
• Look like \_\_\_\_ (H1 don't look like anything like histamine, these do) • OTC > mild \_\_\_\_, mild heartburn, but not for \_\_\_\_ > need to be scoped, cannot self-diagnose ○ Not for \_\_\_\_ or to get people sleepy - used for \_\_\_\_ conditions
histamine dyspesia ulcers allergy gastric hyperacidity
Treatment of GI Ulcers
• Parietal cell (major secreotr of Hcl in stomach) • The + / - is what the RECEPTOR normally does • Can use classic anti cholinergic activity (antagonist) ○ \_\_\_\_ > more selectiviyt ofr GI tract and chol receptors on bronchi, eye, slaivary gladns > FDA won't accept it ○ \_\_\_\_ > therapy for GI ulcers (on for 6-8weeks) > dose of atropine mouth will be very dry > constriptiation, inc intraocular pressure • Major breakthrough > \_\_\_\_ blocks (\_\_\_\_, ranitidine, \_\_\_\_), better tolerated and saem success • PG > they're a break > decrease acid secretion you need an \_\_\_\_ > NSAIDs don't work on PG receptor, they decrease PG > less stimulation of these (PG increase mucous and dec \_\_\_\_) > \_\_\_\_ > PG agonist, combined with progesterone antagonist with misoprestone (induce abortions); have to make sure woman is not pregnant! • First line drugs in GI ulcers > \_\_\_\_ inhibitors > \_\_\_\_ link to pump and heal ulcer in up to \_\_\_\_% of people ○ All end in prazole (\_\_\_\_, lansoprazole, \_\_\_\_) • One thing with ulces > 1/3 of people > put on anitbiotc prevents reoccurence > kill \_\_\_\_ pylori > used in addition to normal drugs (\_\_\_\_, amoxicillin) • Breakthrough pain > antacids (MgOh, AlOh together with milanta) > Mg: \_\_\_\_, Al: \_\_\_\_ > so you have it \_\_\_\_
pirenzepine atropine H2 cimetidine famotidine
agonist
acid
misoprostol
proton pump covalently 90 omeprazole esomeprazole
helicobacter
clarithromycin
diarrhea
constipating
50:50
- Corticosteroids > used in allergic rxns, related to natural oromes from adrenal ____
- Three hormiones: cortisol (glucocorticoids - increase ____ deposition in liver, but it parallels the anti-inflam potency, the most potent ____), mineralocroticoids (ADH, deoxycorticosterone, increase ____ and ____ reabsocrpiton in body; when overactivated > contirbute to high ____)
cortex glycogen anti-inflam H2O Na+ BP
- Cortisol/glucocorticoid
- Hypo/pit control
- Releasing factors form hyp > stim pit > ____ > adrenal cortex > cortisol > ____ mechansm on hypo and pit
- One thing: take a while to work
ACTH
feedback
Steroid MOA: Transcriptional Regulation
Cortisol = ____ steroid hormone
* Takes \_\_\_\_ to make: (2-3 days, hours) * Take coritsol/drug systemically > binds plasma protein > corticosteroid binding globulin > released > penetrates cell it hits into cytoplasm > binds receptors linked with \_\_\_\_ > the HsP spit off > receptor \_\_\_\_ (2 recepotr swith 2 glucocortico) > penetrate nucleus (the complex) > turns on \_\_\_\_ and eventually protein synthesis * Cannot be used in \_\_\_\_ attack
endogenous time Hsp dimerizes DNA/RNA acute
• Primary mineralcorticoid > not under contorl of hypo/pit > ____ > under contorl of ____
• Angiotensinogen floating in blood > synthesized in ____ > from ____ srelase from JG appa > acts on AT > forms angiotensin 1 (10 AA) > no real activity > acted on by ____ in lungs (ACE inhibiotrs block this) > angiotensin II > hits receptors on ____ gland > forms ____ > H2O/Na+ retention
• Becomes an important atrrget in treating BP and cong heart failure
○ Increases ____ retention
○ Also potent ____ and ptoent stimualt of ____ NS in CNS
• Ace inhibtors (ends in -____) > blocks angiotensin I to ____; now also have drugs that block ATII ____ s(end in -____)
○ Two major groups of anti-hypertensive drugs that are used in ____ heart failure
aldosterone
RAAS
liver renin ACE adenal aldosterone
H2O/Na+
vasoconstrictor
sympathetic
pril angiotensin II receptors sartin congestive
