Exam 4- Histamine and Histamine Blockers

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histamine

Low molecular weight endogenous amine that is found in low concentrations in most tissue except for the brain:

mast cells

What cells are found in the skin, GOT and lungs and have high amounts of histamine?

basophiles

Besides mast cells, what other circulating cells have high amounts of histamine?

activated

In order for cells to release histamine, what state does the cell have to be in?

g-protein

Histamine acts through which transmembrane receptors?

2

How many mechanisms can break down histamine?

histamine N- methyltransferase

What metabolizes histamine first?

monoamine oxidase

What enxyme plays a role in histamine degradation that, if inhibited, will cause an increase in histamine response?

MAOIs

What drugs can inhibit monoamine oxidase resulting in increased histamine response?

diamine oxidase

What is the second way that histamine can be metabolized?

heparin

Histamine is stored in vesicles associated with what?

4

How any types of histamine receptors are there?

g protein receptors

When histamine binds to a receptor, what causes the physiologic and pathologic responses?

stimulates gastric acid secretion

Physiologic response to histamine receptor activation?

allergic reactions

Pathologic response to histamine receptor activation?

anaphylaxis

What is a pathological total body event?

H1

Which histamine receptor is found on all smooth muscle, endothelium, and CNS tissue?

all of it

Which smooth muscle are h1 receptors found on?

- vasodilation
- bronchoconstriction
- bronchial smooth muscle contraction
- separation of endothelial cells
- pain and itching due to insect stings

Five things that h1 activation causes:

because it causes bronchoconstriction

How can h1 receptor activation cause pulmonary HTN?

separation of endothelial cells

How does h1 cause hives?

- allergic rhinitis
- motion sickness

H1 receptors are primarily involved in what two things?

motion sickness

Which one of the 2 symptoms that h1 causes do we care about?

h1 antagonists

What types of drugs will reverse the effects of h1 activation?

parietal cells

Where are h2 receptors located?

stimulate gastric acid secretion

What is the primary action of h2 receptors?

alpha 2

H3 histamine receptor is like which adrenergic receptor?

CNS and peripheral nervous tissue

What 2 places are h3 receptors found?

histamine
acetylcholine
norepinehprine
serotonin

What 4 neurotransmitters are released by h3?

h4

Which receptor is found in basophils, bone marrow, intestines, thymus, and spleen?

chemotaxis

H4 plays a role in what?

h2

Which histamine receptor increases cAMP by stimulating adenylate cyclase?

h1

Which histamine receptor stimulates phophoinositide turnover and influx of calcium?

h3

Which histamine receptor has presynaptic regulation of neurotransmitter release (dopamine, GABA, glutamate, ACH, NE, and 5ht)?

h1

The effects of these receptors on smooth muscles is rapid and transient, they are sensitive to lower histamine concentrations, they cause constriction and increased GI motility:

h3

These receptors on neurons inhibits the release and synthesis of histamine:

h2

Response of these receptors on smooth muscle is slow and sustained and they cause dilation:

- hypotension from vasodilation
- reflex tachycardia
- increased capillary permeability
- decreased peripheral resistance

What are the 4 combined receptor responses of h1 and h2 on smooth muscle?

no

If a pt is on a beta blocker and they experience hypotension, will there be any reflex tachycardia?

- fluid
- increased capillary permeability causes total body edema and depleted intravascular volume

What is one of the major treatments of anaphylaxis and why?

contraction

What is h1's predominant action on the bronchi tissue?

relaxation

What is h2's action on the bronchi tissue?

opposite

The actions produced by h1 and h2 are the same or opposite?

- slows av conduction
- decreases HR
- coronary vasoconstriction

3 actions of h1 on the heart:

promotes ca influx

How does h2 act an a positive inotrope (increases myocardial activity)?

increases

What does the cardiac h2 response do to automaticity, chronotropy, and HR?

increases

What does h2 do to the frequency of arrhythmias?

dilates

What does h2 do to the coronary arteries?

parietal cells

Which cells do h2 receptors cause increased secretion of hydrogen ions?

allergic reaction

What is an immune mediated reaction due to prior sensitization?

no- they're one of several

Are histamines the only signals in allergic reactions?

variable

Are the signal responses by allergens the same or variable?

proteins

Anaphylaxis is an immune mediated response due to prior sensitization of what?

protamine

Which drug is protein from fish sperm and is the reversal agent for heparin?

if they've ever had a vascetomy becuase they will be sensitive to the protamine that is given

What do we have to ask male pts before having cabg and why?

medications

Which substance causes a predominant histamine response but is more responsive to histamine receptor antagonism?

bronchoconstrictors

Leukotrienes are predominant ____.

edema and pruritis

The variable effect of histamines in human is seen when they are blocked by a h antagonist with:

hypotension and bradycardia

The variable effect of histamines in human is seen when they are not completely blocked by a h antagonist with:

surface of the mast cell and inhibits histamine release

Where does cromolyn work and what does it do?

prophylactically

When does cromolyn have to be given to be effective?

anaphylaxis

You're in the OR, the pts PAP and PIP both increase rapidly and the PAOP falls, what is occuring?

fluid is leaving the vasculature and into the interstitium

Why does the PAOP fall in anaphylaxis?

- hypotension
- circulatory collapse
- bronchial artery vasoconstriction
- bronchospasm
- angioedema
- urticaria

6 clinical manifestations of anaphylaxis:

RV failure

What is a risk of acute bronchial artery vasoconstriction?

increased PIP
wheezing
altered ETCO2 curve

3 things that can mean bronchospasm:

B

Which ETCO2 waveform shows bronchospasm?

angioedema can still persist that you cannot see

Why should you let the cuff down a few minutes before pulling the ETT?

severe hypotension

When the IgE antigen stimulates histamine, tryptase, prostaglandins, leukotrienes, kinins, and nitric oxide, what occurs?

IgE
mast cells
basophils

Which antigen's mechanism is via cellular signaling via phospholipase C and what are the inflammatory cells?

IgG
neutrophils
thromboxane

Which antigen's mechanism is via complement activation and anaphylatoxin generation and what are the inflammatory cells?

anaphylactoid

Anaphylaxis or anaphylactiod:
No sensitization required and may occur at first drug exposure.

split dosing

What technique does Dr. Nolan suggest when trying to get around an anaphylactoid reaction?

NMBs

Which drug class has the highest incidence of anaphylactic reactions?

rocuronium, atracurium, succinylcholine

What are the alleged 3 most common NMBs associated with anaphylaxis?

latex

What is the agent that is the second highest in causing anaphylaxis?

antibiotics

What is the third highest in causing anaphylaxis?

PCN
cephalosporins
vanco

What 3 abx are the most associated with anaphylaxis?

PCN and cephalosporins

What two abx are cross reactive?

- bananas
- avocados
- kiwis
- mangos
- stone fruits

5 fruits that are associated with latex allergy:

multiple operations and other incidences of frequent contact with latex

What other situations place people at risk for developing latex allergy?

test dose

What can clinicians administer to see if a reaction is going to occur?

yes

Can nonreactive test doses be followed by analphylaxis?

speed of administration

What is important in drugs that are known histamine releasers, but not for anaphylaxis, since small doses may trigger reactions?

because they are histamine releasing events

Why doesn't pretreating work with dyes?

yes

Can pretreated patients for anaphylaxis with antihistamines or steroids still have anaphylaxis?

no

Are radiocontrast media reactions immunologically related?

hives
angioedema
hypotension

A true drug allergy or allergic reaction has what 3 signs?

5%

What percent chance can pts with penicillin allergies have a reaction with cephalosporins?

10 minutes

How many minutes before the initial loading dose of a drug should the test dose be administered?

1) Discontinuation of drug that caused it
2) 100% o2
3) IVF
4) IV epinephrine
5) diphenhydramine
6) rantidine or cimetidine
7) albuterol
8) cortocosteroids

What are the steps in managing anaphylaxis?

profound vasodilation causes hypovolemia

Why do we need to give volume with anaphylaxis?

norepi or vasopressin

If hypotension is refractory in anaphylaxis then what can we give?

refractory hypotension or vasodilitary shock

Why give vasopressin in anaphylaxis (2)?

5-10 mcg

Initial epinephrine bolus in anaphylaxis?

100-500 mcg

Epinephrine for vascular collapse:

after the epi

Give diphenhydramine when?

alpha 1 and beta 2 agonist

What kind of drug is epinephrine?

H1

Diphenhydramine blocks which receptor?

h2

Randitine or cimetidine blocks which receptor?

relax the bronchial smooth muscle

Why do we give albuterol and ipratropium in anaphylactic reaction?

- to prevent late or delayed symptoms
- early hours of the resuscitation period

Why do we give corticosteroids in anaphylaxis? When do we give them?

7.5

2 mg in 250 mL can run at what rate for 1 mcg/min?

Beta 2 agonists (terbutaline or albuterol)

What do we treat bronchospasm with?

make it longer

What do you need to do to the e time in bronchospasm?

milrinone, inhaled NO, inhaled prostacyclin

What are 4 pulmonary vasodilating drugs that can treat pulmonary HTN if blood pressure is stable?

no

Do histamine receptor antagonists inhibit histamine?

they prevent binding of the histamine to the receptor thus preventing the response

How do h blockers work?

2

How many generations of h blockers are there for the h1 receptor?

classical histamines

1st generation antihistamines are considered what?

nonsedating

Second generation antihistamines are what?

marked
moderate
3-6 hours

Diphenhydramine
- Sedative and anticholinergic effects:
- Antiemetic effects:
- DOA:

moderate
marked
4 to 24 hours

Promethazine
- Sedative effects:
- Anticholinergic and antiemetic effects:
DOA:

first generation H1 antagonists

Diphenhydramine and promethazine are what class?

fexofenadine
loratadine
cetirizine

Which second generation h1 antagonists have no sedative effects, anticholinergic activity, or antiemetic effects?

cimetidine

Which h2 blocker is the only one with mild sedative effects while the rest have none?

first generation h1 blockers

These h blockers are lipid soluble and can cross the BBB, they are well absorbed, and metabolized:

no

Are first generation h1 blockers able to be ionized?

sedation
headache
N&V
cough
constipation or diarrhea
dry mouth
blurred vision
urinary retention

Adverse reactions of 1st gen h1 blockers (8):

no

Are h1 blockers the best choice for inhibition of allergic rhinitis?

conjunctivitis
urticaria

H1 receptor blockers are useful in what symptoms?

PONV
motion sickness
Allergic reaction
sleep aid

H1 receptor blockers are prescribed for (4) in addition to conjunctivitis and urticaria:

H1 antihistamine overdose

Fever, excitement, pupil dilation, hallucinations, and convulsions are all signs of what?

intubate
activated charcoal
gastric lavage
IVF

Treatment for H1 antihistamine overdose (4):

hot as a stove
red as a beet
dry as a bone
mad as a hatter

Way to remember the S&Ss of H1 antihistamine overdose:

2nd gen h1 antihistamines

Lipid soluble with highly ionized functional group resulting in less CNS penetration, well absorbed, metabolized in the liver, and the half life is 5-6 hours:

peripheral receptors

The 2nd gen h1 antagonists are selective for which h1 receptors?

- sedative
- antipruritic
- antiemetic
- anticholinergic

Diphenhydramine actions (4) as a h1 antagonist (1st gen):

- allergenic and allergic reactions
- EPS
- sedation
- prevention of motion sickness

Indications of duphenhydramine (4):

10-50mg IV q4hours
400mg per day max

Adult dose of diphenhydramine:

primarily hepatic metabolism and renal excretion

Clearance of diphenhydramine and promethazine:

adverse effects of diphenhydramine

Hypotension, tachycardia, dizziness, urinary retention, seizures, sedation, delirium are all adverse effects of what drug?

hypotension

What adverse effect of diphenhydramine is the reason that we give epi first?

h1
d2
muscarinic

Promethazine antagonizes what 3 receptors?

antiemetic and sedation

What are the muscarinic receptors responsible for?

mild

The hypotensive and anticholinergic adverse effects of promethazine are mild or marked?

EPS

The action of the D2 receptor causes what adverse effects?

promethazine

What can occur with intraarterial or extravasated injections of promethazine?

yes

Can promethazine cross the placenta?

if the etiology is known

When should be the only time you use promethazine for vomiting?

A- 1st gen h1 antagonists
B- 2nd gen h1 antagonists

2nd gen h1 blockers

Astemizole
fexofenadine
cetirizine
loratidine
All of these are what?

they are considered non-drowsy

2nd gen h1 blockers have what main difference from 1st gen h1 blockers?

allergic rhinitis

2nd gen h1 blockers are recommended as the first line of treatment of what?

chronic urticaria

2nd gen h1 blockers are also used for what problem?

no

Are injected corticosteroids without major reactions?

fexofenadine

This 2nd gen h1 blocker shouldn't be given with fruit juice as it decreases the efficacy and is used to treat seasonal allergies like hay fever and chronic urticaria:

peripheral h1 receptors

Which receptor do histamine blockers work on to relieve chronic urticaria?

loratadine

Which 2nd gen h1 blocker has an active metabolite?

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