Tx of Asthma And COPD, antihistamines Flashcards

1
Q

Asthma

A

narrowing of the airways, esp small airways

involves reversible airway obstruction, inflammation & increased airway responsiveness to a variety of stimuli

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2
Q

Inflammation in asthma contributors (4)

A

INFLAMMATORY CELLS: leukocytes, mast cells, EOSINOPHILS, neutrophils, alveolar mactophages & lymphocytes are seen in the airways

PROSTAGLANDINS: prostaglandin D2 is a potent bronchoconstricor

INTERLEUKINS-4,5 & 13: attract & activate eosinophils & stimulate IgE production by B lymphocytes
LEUKOTRIENES: liberated during inflammation in the lunch, cause bronkoconstriction & edema

PLATELET-ACTIVATING FACTOR: causes immediate bronchoconstriction & sustained airway hyperreactivity, edema & chemotaxis of eosinophils. selective antagonists are being developed
-also increased mucus production

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3
Q

often used to diagnose and characterize asthma

A

increased responsiveness to challenge with METHACHOLINE, HISTAMINE & EXERCISE are often used to dx and characterize asthma

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4
Q

B2-Adrenergic Agonists

A

MOST EFFECTIVE bronchodilators

B2 receptor stimulation ACTIVATES ADENLYATE CYCLASE & INCREASES cAMP, which causes RELAXATION OF SMOOTH MUSCLES IN THE BRONCHIOLES & STABILIZATION OF MAST CELLS

generally given by INHALATION, which restricts action to the lung & increases the speed of action, important in relieving bronchospasm

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5
Q

selective B2 agonists

A

are more effective at stimulating B2 receptors (of the lungs) than B1 (of the heart)

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6
Q

First line tx for asthma

A

selective B2 agonists

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7
Q

name the 3 fast-acting (immediate effect) beta 2 agonists

what is their duration of action

A

Albuterol (Ventolin)
Levalbuterol (Xopenex)
Pirbuterol (Maxair)

duration of action: 4-8 hours

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8
Q

Salmeterol (Servent)

A
  • lasts for 12 hours
  • very BRONCHOSELECTIVE & designed to have a long duration of action
  • decrease likelihood of bronchospasms & for nocturnal asthma
  • given PROPHYLACTICALLY on a CHRONIC BASES
  • a CORTICOSTEROID SHOULD ALWAYS BE GIVEN IN CONJUNCTION

effects take abt 20 mins to occur
so NOT EFFECTIVE FOR THE RELEIF OF ASTHMA ATTACK IN PROGRESS
pts need a fast acting bronchodilator (rescue inhaler)

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9
Q

Formoterol

A

long acting bronchodilator, like salmuterol

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10
Q

Advair (salmeterol/fluticasone)

A

intermediate acting bronchodilator & corticosteroid

salmeterol should always be given with a corticosteroid

pts will need a fast acting rescue inhaler too

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11
Q

Dulera (formoterol/mometasone)

A

long acting bronchodilator + a corticosteroid

-pts should be given a fast acting rescue inhaler (-buterol) in addition to this

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12
Q

Inhaled selective B2 agonists SEs

A

the have very few

tachycardia
nervousness & dizziness
tremor

generally ppl become tolerant to these effects & they are often short-lived

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13
Q

B2 agonist controversies

A

TOLERACE TO B2 agonists could occur w/long-term tx, but this is more of a prob in places other than the lungs

CONCOMITANT use of CORTICOSTEROIDS can prevent & in fact reverse, the phenomenon of tolerance & prevent loss of B receptors

so, unless B agonists are used only on an as-needed basis, standard practice is to combine them with an inhaled steroid

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14
Q

Ipratropium (Atrovent)
class

absorption

activity

USE

A
  • Muscarinic antagonist
  • QUATENARY compounds, not absorbed systemically but STAY IN THE LUNG

bronchodilation develops more SLOWLY than with the B2 agonists

USE:

  1. widely for COPD or emphysema
  2. used in conjunction with a B2 agonists when B2 alone is not sufficient to tx sxs or if pt cannot tolerate B-agonists
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15
Q

Combivent

A

Iptratroprium (muscarinic antagonist) combined w/ Albuterol in one spray

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16
Q

Tiotropium (Spiriva): what is it?

A

similar to ipratropium (muscarinic antagonist)
has a longer duration of action & only needs once a day administration
-may work in some patients who do not respond as well to ipratroprium

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17
Q

Theophylline (Theo-Dur)

class

2 main actions (contributing to therapeutic effect)

therapeutic effect

therapeutic index

A

CNS stimulant acts like caffeine-decreases fatigue, elevates mood

  1. BLOCKS ADENOSINE RECEPTORS, which normally cause bronchoconstriction & inflammation
  2. inhibits PHOSPHODIESTERASE, increases amt of cAMP, similar to beta2 stimulation

very effective bronchodilator, RELAXES SMOOTH MUSCLE< ESP BRONCHIOLES, stimulates cardiac muscle & acts as a diuretic in the kidney
-used in pts who don’t respond sufficiently to B2 agonists alone in COPD

VERY LOW THERPEUTIC INDEX

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18
Q

Theophiline (The-Dur) pharmokinetics: administration, elimination, affected by

A

given ORALLY in sustained release prep
rate of absorption varies, so ONCE A DOSE IS ESTABLISED, IT IS BETTER NOT TO SWITCH BETWEEN BRANDS (prob. w/ generic prescribing)

eliminated by liver

  • clearance increased 2x by phenytoin
  • smoking, rifampin, & oral contraceptives also increase clearance of theophylline

cimetidine DECREASES clearance

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19
Q

Theophylline: side effects & toxicity

A

CNS: NERVOUSNESS, INSOMNIA, similar to caffeine, anxiety & tremors can occur

Cardiac: increases rate & force of contraction; in higher doses, can cause tachycardia & may predispose to ARRHYTHMIAS

MUSCLE: increases contractility of diaphragm & decreases fatigue

weak diuretic effect

Toxicity: overdose can be fatal (U) due to arrhythmias & seizures

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20
Q

Corticosteroids: use in asthma

A

-used to DECREASE INFLAMMATION in airways

should ALWAYS be included with long acting B2 agonists

IMPROVE SYMPTOMS & DECREASE THE REQUIREMENTS FOR BETA-AGONISTS

beneficial effects begin in 1 wk, improvement can continue for months

oral steroids used in severe cases of asthma, when other things are not enough;

oral steroids often used for SHORT PERIODS of EXACERBATION to BRING SYMPTOMS INTO CONTROL, may be used prophylactically (U) do not cause serious SEs when used short term

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21
Q

5 inhaled steroids

A
Beclomethasone
Flunisolide
Triamcinolone
Fluticasone
Budesonide
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22
Q

Inhaled steroids: side effects

A

oropharyngeal candidiasis (THRUSH)
HOARSENESS is common
modest decrease in BONE DENSITY in women

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23
Q

Oral Steroids (2)

A

Methylprednisone

Prednisone

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24
Q

Oral steroids: side effects
long term?
short term?

A

Long term: SEs can be significant
osteoporosis
thinning of skin, hyperglycemia
truncal obesity

short term: hyperactivity, insomnia, restlessness, possibly psychotic txns, increase appetite, GI disturbances
-these all decrease as dose is decreased, drug is stopped

25
Q

Leukotriene Inhibitors:

what do they do?

what are their benefits in asthma (3)

what can’t they do? (1)

SEs (3)

A

leukotrienes are involved in the inflammation of asthma

interfere w/the synthesis or receptor binding of leukotrienes

benefits:
-decrease the asthmatic response to exercise or cold air

  • decrease the need for inhaled oral steroids
  • may decrease need for inhaled steroids

cannot stop and asthma attack in progress, inhaled B-agonists still needed

SEs: slight increase in URIs, SORE THROAT, SLEEPINESS

26
Q

3 drugs which block the leukotriene receptor

A

“-leukast”s
Zafirlukast (Accolate)
Montelukast (Singulair)
Pranlukast (Ultaire)

27
Q

Zileuton (Zyflo):

what does it do

how is it used

what may it do

A

blocks 5-lipoxygenase & decreases synthesis of leukotrienes

effective orally, must be taken CHRONICALLY

may decrease asthmatic rxn to ASA & NSAIDS

28
Q
Cromolyn sodium (Intal)
Nedcromil (Tilade)
A

NOT a bronchodilator; INHIBITS RELEASE OF HISTAMINE FROM THE MAST CELLS

used to tx asthma, esp in KIDS, but may work in some adults

(U) inhaled, use SEVERAL TIMES A DAY CHRONICALLY to be effective PROPHYLAXIS
-takes 2-3 months for effects to be seen

can prevent development of asthma in response to allergens & induced by exercise

few SEs: BAD TASTE is most common complaint

29
Q

Omalizumab (Xolair):

what is it

use

admin

SEs

A
  • monoclonal antibody targeted to IgE, prevents it from binding to mast cells & basophils
  • used to prevent allergic rxns in patients with moderate to severe asthma
  • may decrease need for steroids & reduce exacerbations

subQ injection q 2-4 weeks

may cause SERIOUS ALLERGIC & skin rxns

30
Q

Histamine:

involved in?

stomach?

highest concentration?

central role in what?

A

neurotransmitter in brain, involved in arousal, neuroendocrine control & weight & temp regulation

ENTOCHROMAFFIN-LIKE CELLS in stomach fundus release H->inc. gastric acid production

highest cnctrtn in tissues that contain MAST CELLS, as well as in BASIPHILS in the blood
-mast cells: prominent in nose, mouth feed, near pressure pts & bifurcations of blood vessels

central role in IMMEDIATE HYPERSENSTIVITY & ALLERGIC RXNS

31
Q

Histamine release from mast cells can be triggered by: (5)

A
  1. intrxn of IgE & antigen- antibodies bind to mast cells & basophils via high affinity Fc receptors specific for IgE=the classic ALLERGIC RESPONSE
  2. DRUGS, esp organic bases given IV: MORPHINE & CODEINE, RADIOCONTRAST DYES
  3. VENOMS
  4. scratching, cold, sun damage
  5. certain cancers may increase mast cells resulting in increased histamine release
32
Q

H1 receptor:

what kind of receptor is it?

what dose it do in 3 places?

what drugs block it?

A

coupled to Gq
stimulation inc. production of IP3 & DAG

in CNS: produce wakefulness & inhibit appetitie

in endothelium & blood vessels releases NO & causes vasodilation

in other smooth muscles cause inc. calcium, leading to contraction

classical “antihistamines” block the H1 receptor

33
Q

H2 receptor

A

Gs, increases cAMP

significant in secretion of gastric acid, heart, brain & on smooth muscles

in blood vessels: leads to vasodilation

34
Q

H3 receptor

A

Gi-linked, decreases cAMP

found in brain, mostly presynaptically

35
Q

H4 receptor

A

on leukocytes inbone marrow & circulating blood

36
Q

histamine: cardiovascular effects

A

H1 stim causes vasodilation of small blood vessels (via NO): rapid short effects

higher amts of histamine cause H2 receptor med. vasodlation: slower onset, longer duration

dilation of blood vessels-> DECREASE BP w/ REFLEX TACHYCARDIA, FLUSHING of skin, feeling of WARMTH, & HA

capillary permeability increased & endothelial cells separate in response to H1 stimulation-> HIVES & EDEMA

LARGE DOSES of HISTAMINE->SHOCK due to decreased BP

37
Q

histamine in respiratory system

A

BRONCHOSPASM (H1) due to inc. Ca2+, histamine stimulates secretory activity in the lung & inc. prostaglandin formation, small H2 bronchodilator effect too, bronchospasm is (U) mild in most ppl

ASTHMATICS ARE VERY SENSITIVE TO THE EFFECTS OF HISTAMINE & likely to experience bronchospasm, may also involve irritation of vagal nerve endings

38
Q

histamine effect on glandular tissue

A

INCREASED SECRETION OF GASTRIC ACID & pepsin from gastric mucosa (H2)

39
Q

histamine: intradermal effects

A

LEWIS TRIPLE RESPONSE (wheal & flare) occurs after intradermal injection of histamine
FLUSH: seconds, max w/in 1 min, due to dilation of capillaries
FLARE: dilation of arterioles causing redness over a wider area, (response develops more slowly, due to stim of axon reflexes)
WHEAL: swelling in the area of capillary dilation; appreas after 1-2mins & the result of edema due to increase capillary permeability

pain & itching due to stimulation of nerve endings, transmitted to CNS

40
Q

Manifestations of histamine release

tx?

A

hay fever/allergic rhinitis
hives & skin rashes
ANAPHYLAXIS: life threatening
-drop in BP, shock, respiratory difficulty, abdominal cramps, edema, hives, throat swells
TX w/: EPINEPHRINE, STEROIDS, INJECTED ANTIHISTAMINES (BOTH H1 & H2 blockers used together (diphenhydramine & cimetidine)

41
Q

H1 receptor antagonists

A

ALL ANTIHISTAMINES BLOCK H1 RECEPTORS

  • compete w/histamine so effects dependent on amt of histamine present
  • in severe rxns, may not be sufficient to block effect

1st gen drugs have CNS effects & often block muscarinic receptors

2nd gen drugs are very selective for H1 receptor & have little or no CNS effect

most are OTC

42
Q

First Generation H1 antagonists

A

enter the brain & many of them are quite SEDATING

43
Q

Diphenhydramine & dimenhydrainate (Dramamine)

characteristics

A

H1 antagonists
HIGHLY SEDATING
SIGNIFICANT ANTICHOLINERGIC ACTIVITY

44
Q

Doxylmaine (Unisom) use

A

H1 antagonist

sleep aid

45
Q

Brompheniramine (Dimetane) & chlorpheniramine (Chlor-Trimeton)

A

1st gen H1 antagonists w/little sedative effect

46
Q

Promethazine (Phenergan)

A

1st gen H1 antagonist

a phenothiazine derivative w/significant ANTI-EMETIC effect & is VERY SEDATING

47
Q

drugs used for motion sickness (3)

A

first gen H1 antagonists w/SIGNIFICANT ANTICHOLINERGIC ACTIVITY
eg. diphenhydramine (Bendryl)
dimenhydrate (Dramamine)
promethazine (Phenergram)

48
Q

2nd gen H1 antagonists

features (4)

A
  1. do not enter the brain well
  2. primarily block peripheral receptors
  3. NOT anticholinergic, so
    NON-SEDATING & have few SEs
  4. may be better at preventing allergic rxns than tx the once they occur
49
Q

2nd gen antihistamines: pharmokinetcs

A

given orally
well absorbed in GI tract
onset of activity 15-30 mins
duration of actin: some 4-6 hrs, some 12-24 hrs

also topical and injectable preps

most are metabolized by the liver
some metabolized by CYP3A4 & cncntrations can increase when tx w/drugs that inhibit metabolism

50
Q

which 2nd gen antihistamines are eliminated only be the kidney (3)

advantage

A

CETIRIZINE (Zyrtex)
levocetirizine (Zyxal)
& activastine (Semprex)

in pts w/liver dz or where drug intrxns are a concern

51
Q

Antihistamines: clinical applications (5)

A

allergic RHINITIS, seasonal rhinitis & conjunctivitis: response is best if used prophylactically (esp. tru for 2nd gen drugs)

ITCHING & HIVES: inhibits inc. in capillary permeability that causes edema & wheal

MOTION SICKNESS: diphenhydramine, dimenhydrinate & promethazine (b/c of anticholinergic effects)

SEDATION: 1st gen H1 antagonists-diphenhydramine, doxylamine

SECRETIONS: 1st get drugs w/anticholinergic effects decrease salivary & lacrimal secretions & frequently in cold preps for this

not effective inasthma

52
Q

1st gen antihistamines: side effects

A

SEDATION: potentiated by alcohol, CNS depressants; may impair motor skills, esp pronounced in ELDERLY

CONTRAINDICATION IN KIDS

ANTICHOLINERGIC: dry mouth & resp passages, dry, hot skin, urinary retention ro frequency, urinary retention, constipation, blurred vision

other CNS EFFECTS: dizziness, tinnitus, lassitude, poor coordination, fatigue, blurred vision, diplopia, paradoxical excitement, nervousness, restlessness & insomnia

ALLERGIC RXS: can occur w/topical preps

may lower seizure threshold

53
Q

Side effects of ALL ANTIHISTAMINES

A

GI: anorexia, N/V, epigastric distress, constipation, diarrhea, effect reduced if given w/food
-some ppl have inc. appetite & weight gain
TERATOGENIC EFFECTS are POSSIBLE, so avoid using in pregnant

OTC preps combined w/cold meds a/w death in young kids so NOT recommended in kids under the age of 4

54
Q

Antihistamines: drug intrxns

A

don’t take w/other CNS depressants incl. alcohol, phenzothiazines, benzodiazepines, & barbiturates

ERYTHROMYCIN & KETOCONAZOLE may inhibit metabolist of 2nd gen antihistamines, CIMETIDINE also decreases metabolism
GRAPEFRUIT JUICE INHIBITS CYP3A4 and INCREASES CONCENTRATIONS OF MANY DRUGS

55
Q

Antihistamines: acute poisoning
1st gen effects
2nd gen effects

A

fairly nontoxic, but kids are likely to take overdoses

sxs of 1st gen antihistamine poisoning-sim to those of atropine: excitement, convulsions, ataxia, hallucinations, tremors, fixed dilated pupils, flushed, hot skin, coma, cardiorespiratory collapse
others: SEDATION, & DRY OF SALIVARY & BRONCHIAL SECRETIONS

2nd gen OD-may cause CARDIAC ARRHYTHMIAS

56
Q

Cromolyn sodium & nedcromil

what do they do

use?

administration?

A

inhibit release of histamine from mast cells

used to tx asthma

INHALED, need to be taken chronically in order to be effective

57
Q

Azelastine:

admin?

what is it?

what is it good for?

A

applied NASALLY

NON-COMPETATIVE H1 BLOCKER that also decrease release of histamine from mast cells

used for allergic rhinitis

58
Q

Ceterizine (Zyrtec)

A

may also inhibit release of histamine from mast cells