Antihistamines (Lichtman) Flashcards
What are 2 things histamines can be used to diagnose?
- Gastric acid secretion
2. Asthma
What receptors do antihistamines target in the stomach to control GERD?
H2
The antihistamine cromolyn sodium targets what and is it used acutely or prophylactically?
- Targets mast cells inhibiting their degranulation. 2. Only used prophylactically due to increased uptake time
What 2 reactions are histamines involved in?
- Inflammatory
2. Anaphylactic
What is the triple effect of histamine?
- Swelling
- Redness
- Edema
How is histamine synthesized?
Decarboxylation of amino acid L-histidine
I histamine is a bronchodilator or bronchoconstrictor?
A bronchoconstrictor
Histamine in nasal mucosa causes what?
Runny Nose
What are 3 conditions causing histamine release?
- Tissue injury
- Allergic reaction
- Drugs/foreign compounds
What is the term for exposure of an antigen to a previously sensitized (exposed) subject, associated with IgE antibodies?
Allergic reactions
Do antihistamines block all autocoids or just histamines at their receptor?
Only block at the receptor
What are 4 systems that histamine affects?
- Cardiovascular
- Smooth muscle of bronchiole
- Exocrine glands
- Peripheral nervous system
Is the histamine effect on the cardiovascular system, given subcutaneously or intramuscularly?
- Redden at injection site (vasodilation)
- Wheal/disk of edema w/in 1-2 min
- Large bright crimson flare or halo around wheal
Describe cardiovascular effects seen when Histamine is given intravenously.
- Fall in BP
- Cutaneous flush of face and trunk
- Increased skin temperature Intense headache
What does histamine do to nonvascular smooth muscle?
Contracts (bronchoconstriction)
What does histamine do to exocrine glands?
- increase gastric secretion (HCl and Pepsin)
- Increase salivary and lacrimal secretions (large dose)
- Increase catecholamine (epinephrine, norepinephrine) secretion from chromaffin cells of adrenal medulla
What are the peripheral nervous system symptoms associated with histamine?
Itching and pain
What are 6 glands whose secretions are increased by histamine?
- Gastric
- Salivary
- Sweat
- Pancreas
- Bronchial
- Lacrimal
What are 3 effects of histamine on arterioles, capillaries, and venules (triple effect associated)?
- Vasodilation
- Increase permeability (edema)
- Systemic hypotension
Where are 3 places where histamine increases vascular smooth muscle contraction?
- Bronchial tree
- Gastrointestinal tree
- Uterus
1 mg Histamine given subcutaneously serves what purpose?
Stimulates gastric secretion, which can be sampled and acid content determined
Does the 1mg histamine administration to determine gastric secretion have a major effect on blood vessels (vasodilation, increased permeability, systemic hypotension)?
No
Dry powder inhaler of histamine serves what purpose?
Assess pulmonary function
What are 6 toxic reactions and side effects of histamine?
- Cutaneous flushing
- Hypotension
- Headache
- Visual disturbances
- Dyspnea
- GI disturbances
What are 4 types of histamine receptors?
H1, H2, H3, H4
All histamine receptors are what type?
G-coupled protein receptors
Which histamine receptor mediates effects on smooth muscle leading to vasodilation, increased vascular permeability, and contraction of nonvascular smooth muscle?
H1 receptors
Which histamine receptor mediates histamine stimulation of gastric acid secretion?
H2 receptors
Which histamine receptor is a feedback inhibitor in CNS, gastrointestinal tract, lung, heart?
H3 receptors
Which histamine receptor mediates immune and inflammatory responses?
H4
Which 2 histamine receptors currently have no therapeutic agents against?
H3 and H4
What type of receptor antagonists are antihistamines?
Elective receptor antagonists
What are 3 general mechanisms of action for antihistamines?
- Block action of histamine at receptor
- Competes with histamine for binding
- Displaces histamine from receptor
When are antihistamines most beneficial?
when given early
What are 2 things antihistamines do cardiovascularly?
- Prevent dilation
2. Prevent increased permeability
Does HISTAMINE increase or decrease blood pressure?
Decreases blood pressure (vasodilation)
All H1 and H2 antagonists (antihistamines) are competitive or non-competitive antagonists?
Competitive (means they can be overcome by more agonist)
What does antihistamine do to exocrine secretions?
Decrease salivary, gastric, lacrimal and bronchial secretions (think xerostomia)
What does antihistamine do to immune response, e.g. an allergic reaction triggered by IgE?
Binds to receptors to prevent histamine from eliciting response
What is the mechanism of Action of HISTAMINE at H1 receptor?
Attaches to H1, G-coupled protein response leads to IP3 creation, causing a relases of stored Ca++
Antihistamine at the H1 receptor results in the a decrease of what AND where by inhibiting the production of IP3?
Decrease in Ca++ INSIDE of cell
What is the difference between an antihistamine and a decongestant with respect to side effects?
There are no rebound effects with antihistamine use
What do H1 blockers do for allergic rhinitis?
Relieve rhinorrhea, sneezing, itching of eyes and nose
What do H1 blockers do for the common cold and what other drugs are they paired with?
Dry out nasal mucosa. Paired with a nasal decongestant and analgesic.
What do H1 blockers do for allergic dermatoses?
Control itching associated with insect bite
What is an H1 blocker that can be used for preanesthetic sedation, prevention of nausea and vomiting, and also inhibits salivary and bronchial secretions, also can be used as a local anesthetic?
Phenergan/Promethazine
Promethazine/Phenergan, Bendectin, doxylamine with pyridoxine are H1 blockers that are used as antiemitics (prevent or treat nausea and vomiting) how?
Effects on muscarinic receptors
Why is an H1 blocker used for parkinson’s disease?
It helps reduce tremors and muscle rigidity
An H1 blocker can be used for what type of headaches?
Migraines
What are 8 therapeutic uses of H1 blockers?
- Allergic rhinitis
- Common cold
- Allergic dermatoses
- Preanesthetic sedation
- Nausea and vomiting
- Hypnotics
- Parkinson’s disease symptoms
- Migraines
What are the non-selective effects of H1 blockers (non-selective effects are associated with Gen-1 H1 blockers)?
- Antinausea and antiemetic effects
- Anti-parkinsonism effects
- Local anesthesia via Na+ channel blockers
The antinausea, antiemetic, and antiparkinsonism non-selective effects of H1 blockers are due to their effects on what receptors?
Muscarinic
Which gen 1 H1 blockers have non-selective effects that cause local anesthesia via sodium channel block?
Diphenhydramine
Promethazine/phenergan
What is the characteristic of 2nd Gens H1 blockers that make them more selective than 1st Gen H1 blockers?
Do not cross blood brain barrier easily
What are 3 second-generation H1 blockers that are more selective than first-generation H1 blockers?
Fexofenadine (Allegra)
Loratadine (Claritin)
Cetirizine (Zyrtec)
Of the 3 second-generation H1 blockers, which is listed as long acting?
Loratadine (Claritin)
What are the general characteristics of First Generation Antihistamine?
- Sedating side effects
- Anticholinergic side effects
- Many OTC (56% allergy pts use OTC antihistamine)
- Many inexpensive
What are the general characteristics of First Generation Antihistamines?
- Sedating side effects
- Anticholinergic side effects
- Many OTC (56% allergy pts use OTC antihistamine)
- Many inexpensive
What are the general characteristics of second-generation antihistamine?
- Not as sedating and drying as Gen 1 H1 blockers
- Do not cross BBB as easily as Gen 1
- Lipophobic
- Large Molecular size
- Electrostatic charge
Which antihistamine seems to be the standard first-generation H1 blocker, that along with the normal anti-inflammatory, anti-itch, anti-rhinitis, vasodilation/permeability/itch blocking, also is
anti-muscarinic, gives pronounced sedation making it
useful as a hypnotic, and as a topical in Caladryl?
Diphenhyrdramine (benedryl)
What are two first-generation blockers that have the standard
antihistamine characteristics, but are not as sedating as Diphenhydramine(Benedryl)?
- Chlorpheniramine (Chlor-trimeton)
2. Brompheniramine (Dimatane)
Would a second-generation H1 blocker’s characteristic be sedation? Why or why not?
No, because they do not cross the blood-brain barrier readily
Which second-generation H1 blocker has P-450 metabolism, and what other drug will affects its levels?
Loratidine (Claritin). Levels affected by anti-fungal agents.
What is a first-generation H1 blocker that is anti-emetic via
antimuscarinic effects, blocks vasodilation/permeability,gives marked sedation, and can give local anesthesia via sodium channel blockade?
Promethazine (Phergan)
Which first-generation H1 blocker is solely an antiemetic via
antimuscarinic effects, which also has the sedation and sodium channel blockade but does not block vasodilation and/or permeability?
Dimenhydrinate (Dramamine)
Fexofenadine (allegra) a second-generation H1 blocker is a safe metabolite of what previous H1 blocker that caused
fatal heartbeat irregularities?
Safe metabolite of Terfenadine (Seldane)
What first-generation H1 blocker is a metabolite of Hydroxyzine and has a potential for sedation?
Cetirizine (Zyrtec)
What are 7 toxic reactions and side effects of H1 blockers?
- CNS depression (1st gen)
- Allergic rxn on topical application
- GI/appetite loss, nausea, vomiting
- Irritable, tachycardia, xerostomia, constipation
- Hallucinations, tremors
- Cross placenta
- Secreted in breast milk
What is a concern if you take an H1 blocker and a barbiturate, opiate, general anesthetic or alcohol?
Potentiates CNS depression
What is a risk associated with prescribing an H1
blocker that has antimuscarinic effects
(diphenhydramine[benedryl], promethazine[phergan], dimenhydrinate [Dramamine]) to a patient already on an
antimuscarinic drug?
Excessive blockade, e.g. dry mouth, constipation, blurred vision
If Terfenadine (Seldane), no longer available, was taken with grapefruit juice, erythromycin, or other drugs that inhibit CYP3A4, what is the danger?
Cardiotoxicity
Where are H2 receptors located?
Stomach
What causes the release of histamine in the stomach and from what cells is it released?
Gastrin causes histamine release by enterochromaffin cells in the gastric mucosa
Histamine released by entrochromaffin cells of the gastric mucosa in response to Gastrin, act on what cells to cause what?
Binds H2 receptors on parietal cells to cause HCl secretion
What are 4 H2 blockers?
- Cimetidine (Tagmet)
- Ranitidine (Zantac)
- Famotidine (Pepcid)
- Nizatidine (Axid)
Which H2 antagonist is associated with most side effects?
Cimetidine (Tagment)
Are H2 antagonists competitive or non-competitive antagonists?
Competitive
Do H2 antagonists have many affects beyond those on the gastric mucosa?
No
What is a concern when taking H2 antagonists?
Increase stomach pH so it could affect the absorption of other drugs
What are the 8 most common adverse effects associated with H2 antagonists?
- Diarrhea
- Dizziness
- Somnolence (drowsiness)
- Headache
- Rash
- Constipation
- Vomiting
- Arthralgia (joint pain)
Are H2 antagonists ant-acids?
No, they do not buffer acid already released, they decrease output of subsequent HCl
What are 7 H2 antagonist therapeutic uses?
- Duodenal ulcer
- Gastric ulcer
- Zolling-Ellison syndrome
- Gastroesophageal reflux disease (GERDs)
- GI obstruction pre-surgery
- Reflux esophagitis
- Antacid
Why would an H2 antagonist not be used for Gastric ulcer much anymore?
Gastric ulcers are caused by H. pylori, so they are better treated by antibiotics
What is a rare disorder that causes ulcers in the stomach and duodenum from excessive gastric pepsin and HCl,
treated with an H2 antagonist?
Zollinger-Ellison syndrome
Why give a patient an H2 antagonist prior to surgery for gastric obstruction?
To elevate gastric pH by decreasing HCl secretion
When an H2 antagonist is being used as an antacid,is it really acting as an antacid?
No, it is a pre-emptive way of decreasing acid release and increase stomach pH
How do H2 antagonists work?
Displace Histamine from H2 receptor, turning of g-coupled protein increase of cAMP, which results in a decrease of Ca++
What is the difference in H1 and H2 antagonist blocking of G-coupled protein when both result in a final decrease in Ca ++?
H1 cause a decrease in Ca++ by decreasing IP3
H2 cause a decrease in Ca++ by decreasing cAMP
What are some CNS effects seen with the H2 antagonist Cimetedine(Tagment), and what population are they most common in?
Slurred speech, delirium, confusion in older patients or those with liver or kidney impairment
The H2 antagonist Cimetedine (Tagmet) has minor and reversible effects on what endocrine function?
Antiandrogen effect: loss of libido, impotence, reduced sperm count
The H2 antagonist Cimetedine (Tagment) can have what adverse effect on the liver?
Reversible cholestasis (impaired bile flow)
How do H2 antagonists increase bioavailability of ethanol?
They block gastric alcohol dehydrogenase enzyme
What is the only H2 antagonist that does not increase the bioavailability of ethanol?
Famotidine (Pepcid)
Which H2 antagonist has the most drug interactions because it affects the cytochrome P450 pathway and reduces blood flow through the liver?
Cimetidine (Tagmet)
Agents that inhibit gastric secretion can be expected to have what type of drug interaction?
Alter bioavailabilty and rate of absorption of many other drugs
What substance serves as an inhibitor of Histamine release, other granular contents and leukotriene production?
Cromolyn sodium
Does Cromolyn sodium (Intal, Nasalcrom) have bronchodilating capability?
No
What is the method of action of Cromolyn sodium (Intal, Nasalcrom)?
It inhibits pulmonary mast cell degranulation in response to stimuli (e.g. cell bound IgE and antigen interation)
Does Cromolyn sodium (Intal, Nasalcrom) relax bronchial or other smooth muscle?
No
What is the benefit of long term administration of Cromolyn sodium (Intal, Nasalcrom)?
Diminishes bronchial hyperactivity
Is Cromolyn sodium (Intal, Nasalcrom) effective for acute asthma attack?
No
Cromolyn sodium (Intal, Nasalcrom) reduces the need for what other mild to moderate asthma treatment?
Reduce the need for steroid or bronchodilators
What are other therapeutic uses for Cromolyn sodium (Intal, Nasalcrom) beyond mild to moderate asthma prophylaxis?
- Allergic rhinitis
- Atopic diseases of the eye
- Giant papillary conjunctivitis
How long does it take for Cromolyn sodium (Intal, Nasalcrom) to become effective?
2-3 weeks
Cromolyn sodium (Nasalcrom) is used to treat what?
Allergic rhinitis as a nasal spray
Cromolyn sodium (Intal) is used to treat what?
Asthma as an aerosol powder and solution
Cromolyn sodium (Opticrom) is used to treat what?
Allergic conjunctivitis
What are some side effects of Cromolyn sodium?
Irritation from powder inhaler, stinging, burning, bad taste, cough, sneeze, allergic reaction
How do antihistamines produce their effect?
Competition at the receptor
Is sedation a side effect of histamine?
No
What are 3 antihistamines that are approved for use by heavy-machine operators because they do not have a sedative effect?
- Fexofenadine (Allegra)
- Certirazine (Zyrtec)
- Loratadine (Claritin)
Are antihistamines ever given to someone to reverse anaphylaxis?
No. Anaphylaxis is acute. Its reversal agent is epinephrine.
What is the most common sign of histamine?
Triple effect
A low does of what substance can be used to diagnose asthma when inhaled?
Histamine
H2 Blockers do what?
Decrease HCl
