33- Autacoids: Histamine, Serotonin & Bradykinin
This histamine receptor subtype is expressed in hemopoietic related cells. A. H1 B. H2 C. H3 D. H4
*The answer is D.* H4 receptors are coupled to the Gi protein, which inhibits adenylate cyclase, decreasing the concentration of cAMP while also increasing Ca2+. This receptor helps to stimulate chemotaxis and expression of adhesion molecules.
Histamine receptor sites-- H1 (select all that apply) A) endothelium B) smooth muscle C) mast cell D) gastric mucosa
*The answer is A and B.* H1 receptors are found on endothelium (indirect smooth muscle relaxation of vessels) and smooth muscle (direct contraction).
Bradykinin exhibits cardiovascular effects considered similar to those provoked by histamine. A. True B. False
*The answer is A.* Bradykinin exhibits cardiovascular effects considered similar to those provoked by histamine. Both cause increased contractility of the heart.
Antihistaminic most likely to exhibit anticholinergic activity: A. Dimenhydrinate (Dramamine) B. Astemizole (Hismanal) C. Fexofenadine (Allegra) D. Terfenadine (Seldane) E. Loratidine (Claritin)
*The answer is A.* Dimenhydrinate (Dramamine) is the only first-generation H1 blocker listed; all of the other drugs are second generation. First generation antihistamines tend to have adverse effects, such as sedation, antimuscarinic properties, and anti α-adrenergic properties?
A 24-year-old student has been taking over-the-counter (OTC) diphenhydramine for her allergy symptoms most of her life. Lately, however, she has had more frequent symptoms, so she increased the dose of the medication. She now asks her friend, who is a medical student, to explain to her how exactly this agent makes her more sleepy lately. What is the most likely answer regarding diphenhydramine? (A) It blocks H1-receptors in the brain (B) It modulates the release of dopamine and serotonin (C) It acts peripherally, since it does not cross the blood-brain barrier (D) It exerts its effects via muscarinic-cholinergic agonist activity (E) It contains tryptophan, which produces sedation
*The answer is A.* Diphenhydramine blocks H1-receptors in the brain, thereby producing sedation. The release of dopamine and serotonin is modulated via H3-receptors. Diphenhydramine readily crosses the blood-brain barrier. This agent has muscarinic-cholinergic agonist properties. It is not known to contain tryptophan.
Which one of the following drugs could significantly impair the ability to drive an automobile? A. Diphenhydramine. B. Ergotamine. C. Fexofenadine. D. Ranitidine. E. Sumatriptan.
*The answer is A.* Diphenhydramine can impair operation of an automobile by causing drowsiness and by impairing accommodation. The other agents do not have this restriction.
A patient has mild cutaneous and systemic manifestations of a seasonal allergic response. Before you prescribe a short course of diphenhydramine for symptom relief, you should realize that this drug has one mechanism of action resembling, causes many side effects similar to, and shares many contraindications, that apply to an "autonomic" drug which you should be very familiar. Whatis that drug? a. Atropine b. Bethanechol c. Norepinephrine d. Phentolamine e. Physostigmine f. Propranolol
*The answer is A.* Diphenhydramine, an older or antagonist of histamine's effects on H1 receptors, and also strongly blocks muscarinic cholinergic receptors. Other older H1 blockers (but none of the second-generation H1 blockers, such as fexofenadine) possess this atropine-like effect, often to a lesser degree than diphenhydramine. (If you wished to argue that because diphenhydramine was more like scopolamine because it causes not only anticholinergic effects but also a considerable degree of sedation, you would be correct.) Thus, common side effects related to antimuscarinic photophobia, and cycloplegia (paralysis of accommodation). Key contraindications include prostatic hypertrophy, bowel or bladder obstruction or hypomotility, tachycardia, and narrow-angle (angle-closure) glaucoma.
Histamine aerosol: effects on pulmonary function -- A. Bronchoconstriction B. Bronchodilation
*The answer is A.* Histamine causes bronchoconstriction. This is via the H1 receptor, which directly causes smooth muscle contraction.
We look at data that summarize the actions of two prototypic histamine receptor blockers: diphenhydramine as the exemplar of the older antihistamines (competitive histamine receptor antagonists); and fexofenadine as a representative agent of the "second-generation antihistamines. Which statement correctly describes, compares, or contrasts these drugs or the pharmacologic groups to which they belong? a. Diphenhydramine and other drugs in its class (ethanolamines) tend to cause drowsiness more often than fexofenadine and related second-generation antihistamines b. Diphenhydramine is a preferred antihistaminic for patients with prostate hypertrophy or angle-closure glaucoma, whereas fexofenadine and related drugs are contraindicated c. Diphenhydramine overdoses tend to cause bradycardia, whereas fexofenadine overdoses tend to cause significant increases of heart rate d. Fexofenadine and related second-generation histamine antagonists have intrinsic bronchodilator activity, which makes them suitable as primary/sole therapy for people with asthma e. Fexofenadine, and drugs in its class, have better efficacy in terms of suppressing histamine-mediated gastric acid secretion
*The answer is A.* One of the main advantages of the second-generation antihistamines (fexofenadine, loratadine, others) over the older (first-generation) H-1 antagonists such as diphenhydramine is a relative lack of CNS depressant (sedating) effects when administered at usual recommended doses. The implication of this difference is thatthe newer agents are much less likely to cause daytime drowsiness or other problems that might interfere with daytime activities requiring alertness. Sedation is a particular problem with diphenhydramine, doxylamine, and other members of the ethanolamine class of also provides a clinically useful effect based on this action: they are useful as OTC (diphenhydramine, doxylamine) and prescription (diphenhydramine) sleep-aids. Diphenhydramine, and to a large degree all the other first-generation antihistamines, tend to cause appreciable muscarinic receptor-blocking (atropine-like) effects, and so they are unsuitable or potentially dangerous for patients with such atropine-related comorbidities as prostatic hypertrophy, hypomotility disorders of the urinary or Gl tracts antimuscarinic effects, diphenhydramine overdoses are more likely to cause tachycardia (by blocking parasympathetic-ACh-muscarinic influences on the SA node) than bradycardia (c). The second-generation antihistamines do block histamine-related bronchoconstriction, but in the absence of histamine they have no intrinsic bronchodilator activity. More important is the fact that these drugs play no role as primary therapy for asthma. They may be preferred to older antihistamines (largely because they lack the antimuscarinic-related-mucus-thickening effects of such drugs as diphenhydramine), but they should be used only as adjuncts to more appropriate asthma drugs such as inhaled corticosteroids (to suppress airway inflammation) and inhaled β-adrenergic drugs for control or rescue therapy.
Which one of the following statements concerning H1 antihistamines is correct? A. Second-generation H1 antihistamines are relatively free of adverse effects. B. Because of the established long-term safety of first-generation H1 antihistamines, they are the first choice for initial therapy. C. The motor coordination involved in driving an automobile is not affected by the use of first-generation H1 antihistamines. D. H1 antihistamines can be used in the treatment of acute anaphylaxis. E. Both first- and second-generation H1 antihistamines readily penetrate the blood-brain barrier.
*The answer is A.* Second-generation H1 antihistamines are preferred over first-generation agents because they are relatively free of adverse effects. Driving performance is adversely affected by first-generation H1 antihistamines. Epinephrine, not antihistamine, is an acceptable treatment for acute anaphylaxis. Second-generation H1 antihistamines penetrate the blood-brain barrier to a lesser degree than the first-generation drugs.
More likely to be effective in treating an active migraine attack: A) sumatriptan (Imitrex) B) methysergide (Sansert) C) equally effective
*The answer is A.* Sumatriptan (imitrex) is a serotonin 5-HT2R partial agonist, which helps to treat migraine attacks.
The site of action for H2 receptor antagonists with respect to acid production inhibition: A. Parietal cells B. Chromaffin cells C. Mast cells
*The answer is A.* The site of action for H2 receptor antagonists with respect to acid production inhibition is parietal cells.
Alpha-adrenergic receptor blocking characteristics is associated with numerous H1-histamine receptor blockers. A. True B. False
*The answer is A.* This activity is associated particularly with "phenothiazine" H1 blocker class. Promethazine would be an example. This alpha receptor blockade may be manifest in postural (orthostatic) hypotension.
Vagal postganglionic nerve-mediated acetylcholine release and subsequent acetylcholine binding to parietal cell receptors cause an increase in cytosolic calcium thus activating protein kinases which cause increased acid secretion utilizing a proton pump, the H+/K+-ATPase. A. True B. False
*The answer is A.* Vagal postganglionic nerve-mediated acetylcholine release and subsequent acetylcholine binding to parietal cell receptors cause an increase in cytosolic calcium thus activating protein kinases which cause increased acid secretion utilizing a proton pump, the H+/K+-ATPase.
H2 Blocker most likely to inhibit P450 drug metabolizing system: A. Ranitidine (Zantac) B. Cimetidine (Tagamet) C. Famotidine (Pepcid) D. Nizatidine (Axid) E. All inhibit equally
*The answer is B.* Cimetidine is a H2 blocker that inhibits gastric acid formation. It also inhibits the CYP450 drug metabolizing system
Vascular smooth muscle effects --ergotamine: A) vasodilatation B) vasoconstriction
*The answer is B.* Ergotamine is a serotonin 5-HT2R partial agonist, which causes vasoconstriction.
H1 antagonists, comparable to H2 antagonists, decrease gastric secretion albeit to a lesser extent. A. True B. False
*The answer is B.* H1 receptor blockers are not noted to suppress gastric acid secretion.
Competitive blockers at H1 (histamine receptors type 1) effectively reduce gastric acid secretion. A. True B. False
*The answer is B.* H2 (histamine receptors type 2) receptor antagonism is associated with decreasing gastric acid secretion.
A patient with a migraine headache is treated with sumatriptan. This drug is beneficial because it A. blocks 5HT3 receptors B. stimulates 5HT1D receptors C. blocks 5HT4 receptors D. stimulates 5HT2 receptors E. blocks muscarinic receptors
*The answer is B.* It is important to be able to match the serotonin drugs with their respective receptors. The "triptans" used in migraine headaches are agonists at the 5HT1D receptor.
Newer, second-generation "nonsedating" antihistamine H1 receptor blockers are associated with limited sedation despite crossing the blood brain barrier readily. A. True B. False
*The answer is B.* Newer, second-generation "nonsedating" antihistamine H1 receptor blockers are associated with limited sedation because they do not cross the blood brain barrier readily.
Which one(s) of the following agents are classified as H2 histamine receptor antagonists? A. Chlorpheniramine B. Ranitidine C. Both D. Neither
*The answer is B.* Ranitidine is classified as H2 histamine receptor antagonist.
Administration of this agent is less likely to result in cytochrome P450-related drug-drug interaction A. Cimetidine B. Ranitidine
*The answer is B.* Ranitine is much less likely to bind to cytochrome P450 (4-10 times less likely), when compared to cimetidine. Cimetidine reduces the enzymatic activity of several cytochrome P450 isoforms, including CYP1A2, CYP2C9, CYP3A4 and CYP2D6.
Your 37-year-old patient has been diagnosed with a rare metastatic carcinoid tumor. This neoplasm is releasing serotonin, bradykinin, and several unknown peptides. The effects of serotonin in this patient are most likely to include which one of the following? (A) Constipation (B) Episodes of bronchospasm (C) Hypersecretion of gastric acid (D) Hypotension (E) Urinary retention
*The answer is B.* Serotonin causes bronchospasm, but the other effects listed are not observed. Carcinoid is associated with diarrhea and hypertension.
Less sedating: A) diphenhydramine (Benadryl) B) terfenadine (Seldane) C) about equal
*The answer is B.* Terfenadine is a second-generation antihistamine; therefore, it does not penetrate the BBB as much as first-generation antihistamines.
Enzyme responsible for histamine synthesis: A. Histidine transaminase B. Histidine decarboxylase C. Histidine kinase D. Histidine aminotransferase
*The answer is B.* The enzyme responsible for histamine synthesis is histidine decarboxylase.
A 20-year-old woman is taking diphenhydramine for severe hay fever. Which of the following adverse effects is she most likely to report? (A) Muscarinic increase in bladder tone (B) Nausea (C) Nervousness, anxiety (D) Sedation (E) Uterine cramps
*The answer is D.* H1 blockers do not activate muscarinic receptors, mediate vasoconstriction, or cause uterine cramping. They do not cause nervousness or anxiety. Diphenhydramine is a potentsedative.
A 6-year-old is transported to the Emergency Department by a parent, who says the boy took a large amount of an allergy medication. The sole a ctive ingredient in the product the parent mentions is diphenhydramine, and it is clear the child is experiencing toxicity from an overdose. The intern, fresh out of medical school, orders parenteral administration of neostigmine, and the medication order is not questioned. What adverse effect of the diphenhydramine will persist following neostigmine administration? a. Bronchoconstriction and wheezing b. Delirium, hallucinations, and other CNS manifestations of toxicity c. Profuse secretions from lacrimal, mucus, and sweat glands d. Skeletal muscle tremor or fasciculations e. Tachycardia
*The answer is B.* The major signs and symptoms of diphenhydramine toxicity are attributable to its strong antimuscarinic (atropine-like) effects in both the peripheral and CNS. Neostigmine - unlike the preferred antidote, physostigmine - is a quarternary compound and does not enter the CNS. Thus, delirium, hallucinations, and other CNS manifestations of diphenhydramine poisoning will persist.
A 23-year-old woman suffers from recurrent episodes of angioneurotic edema with release of histamine and other mediators. Which of the following drugs is the most effective physiologic antagonist of histamine in smooth muscle? (A) Cetirizine (B) Epinephrine (C) Granisetron (D) Ranitidine (E) Sumatriptan
*The answer is B.* The smooth muscle effects of histamine are mediated mainly by H1 receptors. Cetirizine is a pharmacologic antagonist of histamine. Granisetron is a 5-HT3 antagonist. Sumatriptan is a 5-HT1D agonist. Ranitidine is a histamine antagonist but blocks the H2 receptor in the stomach and the heart, not H1 receptors in smooth muscle. Epinephrine has a physiologic antagonist action that reverses histamine's effects on smooth muscle.
Enterochromaffin-like (ECL) cells stimulate histamine release following activation of this/these receptor(s): A. Acetylcholine B. Gastrin C. Both D. Neither
*The answer is C.* Acetylcholine and gastrin both act on ECL cells to stimulate histamine release.
Atropine-like consequence(s) of those first-generation H1-receptor antagonists with notable antimuscarinic peripheral activity. A. Blurred vision B. Urinary retention C. Both D. Neither
*The answer is C.* Antimuscarinic antagonists cause blurred vision because ciliary muscle stays relaxed, which tenses the zonule fibers and the lens. They also cause urinary retention by relaxing the detrusor of the urinary bladder and contracting the external urethral sphincter.
Which one(s) is/are (an) example(s) of (an) H2 histamine receptor antagonist(s)? A. Cimetidine B. Ranitidine C. Both D. Neither
*The answer is C.* Both cimetidine and ranitine are examples of H2 histamine receptor antagonists.
A patient with annoying hay fever (seasonal allergy) symptoms (mainly rhinorrhea) goes to the store, intent on purchasing an oral medication to make them more comfortable. They see the prices for loratadine and related second-generation antihistamines and are shocked about how high they are. Nearby on the shelf they see store-brand allergy relief pills that are much less expensive, the cheapest ones having diphenhydramine as the sole active ingredient. If they were to take full therapeutic doses of the diphenhydramine, based on label directions, which effects or side effects are they most likely to experience as an additional price to be paid for their allergy relief? a. Bradycardia b. Diarrhea c. Drowsiness, somnolence d. "Heartburn" from increased gastric acid secretion e. Urinary frequency
*The answer is C.* Diphenhydramine, a member of the ethanolamine class of H1 antagonists and arguably the prototype of all the older (first-generation" antihistamines), possesses two main properties in addition to effective competitive blcokade of H1 receptors: sedation(c) in part to the drug's lipophilicity; and muscarinic (cholinergic) receptor blockade that is also competitive. Both effects occur commonly, and can be quite intense. The CNS depressant effects of diphenhydramine are such that this drug is the main (if not only) active ingredient in OTC sleep aids, helping one drift off to sleep even in the absence of allergy signs and symptoms and probably in a way that is unrelated to the drug's peripheral H-1 blocking activity
Ergot alkaloid -- antimigraine specificity mediated by these receptors: A) adrenergic B) cholinergic C) serotonergic D) dopaminergic
*The answer is C.* Ergot alkaloid is a serotonin 5-HT2R partial agonist.
Dihydroergotamine: A. Causes vasodilation. B. Exerts its actions by binding to specific ergotamine receptors. C. Is useful in treating acute migraine headaches. D. Is useful for maintaining uterine muscle tone during pregnancy. E. Has actions similar to those of nitroprusside.
*The answer is C.* Ergotamines act to counteract cerebral vasodilation which plays a role in migraine headaches. Vasoconstriction leading to tissue ischemia is one of the toxic complications associated with an overdose of these drugs. The ergot alkaloids interact with adrenergic, dopaminergic, and serotonin receptors. They are contraindicated in pregnancy because of their ability to cause uterine contraction and abortion. Nitroprusside is a powerful vasodilator used to treat the vasoconstriction that is characteristic of an overdose with ergot alkaloids.
Most likely to be effective and used in current therapy for duodenal ulcer A. Atropine B. Scopolamine C. Famotidine (Pepcid) D. Cyproheptadine (Periactin) E. Diphenhydramine (Benadryl)
*The answer is C.* Famotidine is a H2 blocker, which inhibits stomach acid production, thus helping to treat ulcers. Atropine and scopolamine are both anti-muscarinic drugs. Cyproheptadine and diphenhydramine are first generation H1 blockers, which help with allergies, motion sickness, and acts as a sleep aid.
A long-haul truck driver comes into your asthma clinic complaining that he is sneezing constantly and has burning and watery eyes. He indicates that he seems to have a month or so of these symptoms every spring. Which of the following drugs would be most appropriate to treat this patient? (A) Dimenhydrinate (B) Scopolamine (C) Fexofenadine (D) Cetirizine
*The answer is C.* Fexofenadine is a potent histamine H1-receptor antagonist; its poor central nervous system (CNS) penetration reduces sedative effects. Cetirizine is a second-generation antihistamine, but it still has some sedating effects. Ranitidine is a histamine H2-receptor antagonist.
H1 histamine receptor blockers inhibit which one(s) of the following histamine-induced exocrine secretions? A. Lacrimal secretions B. Gastric secretion C. Salivary secretions D. A & C E. B & C F. A & B G. A, B & C
*The answer is D.* H1 histamine receptor blockers inhibit lacrimal and salivary secretions via antimuscarinic properties. H2 blockers inhibit gastric secretions.
A patient who will be new to your practice makes an appointment for their first visit. Your nurse asks them to bring in all their current prescribed medications and any OTC drugs they take regularly. They comply. One OTC drug is a popular brand-name product that contains doxylamine as its sole active ingredient. Which property or characteristic best describes this drug? a. Likely to lower heart excessively b. May be a cause of diarrhea that the patient says he often gets c. Should not be used by patients with prostatic hypertrophy or angle-closure glaucoma d. Tends to raise blood pressure through a typical catecholamine-like vasoconstrictor (a-adrenergic) mechanism e. Used during the day, helps them keep awake and alert via a weak amphetamine-like action in the CNS
*The answer is C.* First off, I think you should know that the main active ingredient in OTC sleep aids (other than those advertised as "natural" supplements such as melatonin, vitamins, etc) is a sedating antihistamine: doxylamine or, more likely, diphenhydramine. Doxylamine is extremely similar to diphenhydramine, the prototype first-generation (older) "antihistamine"- a competitive H1 receptor antagonist. Chemically, they are in the ethanolamine class and are used not only for allergy relief, but also for sedation and sleep. If one wanted to stay awake and alert (e) these certainly would not be drugs that achieve that goal; more over, they don't have any amphetamine-like catecholamine-releasing activity. These drugs also block muscarinic receptors-and quite effectively to boot. So the answer to this question boils-down to "What best describes the actions or effects of atropine? " As you should know, atropine or drugs with similar antimuscarinic actions should not be used by patients with prostatism or angle-closure (narrow-angle) glaucoma.
Histamine H1 receptor blockers: A. Compete with histamine B. Decrease receptor mediated constitutive activity C. Both D. Neither
*The answer is C.* H1 receptor blockers compete with histamine and decrease receptor mediated constitutive activity.
A laboratory study of new H2 blockers is planned. Which of the following will result from blockade of H2 receptors? (A) Increased cAMP (cyclic adenosine monophosphate) in cardiac muscle (B) Decreased channel opening in enteric nerves (C) Decreased cAMP in gastric mucosa (D) Increased IP3 (inositol trisphosphate) in platelets (E) Increased IP3 in smooth muscle
*The answer is C.* H2 receptors are Gs-protein-coupled receptors, like β adrenoceptors. Blockade of this system will cause a decrease in cAMP.
Kallikreins in terms of their enzyme classification: A. Tyrosine kinases B. Peptidases C. Serine proteases D. Hydroxylase
*The answer is C.* Kallikreins are serine proteases.
Which one of the following is likely to be used in motion sickness, and nausea and vomiting of pregnancy? A. Loratidine B. Ondansetron C. Meclizine D. Fexofenadine E. Cimetidine
*The answer is C.* Meclizine is a first-generation antihistamine that effectively penetrates the CNS. Like all first-generation drugs it also blocks muscarinic receptors. Blocking the H1 and muscarinic receptors are beneficial in motion sickness and nausea and vomiting in pregnancy. Second-generation drugs like loratidine and fexofenadine don't effectively penetrate the CNS and are of no benefit in these conditions.
Many H1 receptor antagonists may reduce secretion in: A. Glands with cholinergic innervation B. The respiratory tree C. Both D. Neither
*The answer is C.* Reduction in secretion is due to the Anti-muscarinic activity of many H1 receptor blockers.
A 24-year old woman has a history of migraine headaches with accompanying aura. During her last attack, ergotamine was much less effective, and you decide to try an alternative to treat her current attack. Agonist activity at which of the following receptors would be the best target for your new treatment? (A) Histamine H1 (B) α-Adrenoreceptors (C) Serotonin 5-HT1B (D) Prostaglandin FP
*The answer is C.* The ''triptans'' as a class are effective against acute migraine attacks and all act as agonists at serotonin 5-HT1B and HT1D receptors. Agonists at a-adrenergic receptors like epinephrine cause vasoconstriction but are not effective for migraine; antihistamines and agents that interfere with the prostaglandin FP receptor would not be effective either.
The most important pathophysiologic mechanism of mast cell and basophil histamine release: A. Chemical (i.e. morphine) B. Mechanical cell injury C. Immunologic
*The answer is C.* The most important pathophysiologic mechanism of mast cell and basophil histamine release is immunologic.
A patient takes a massive overdose of diphenhydramine, suffering not only significant CNS depression but also numerous and serious peripheral autonomic side effects. By what mechanism did diphenhydramine exert its untoward peripheral autonomic actions? a. Activation of both β1 and β2, adrenoceptors b. Blockade of α-adrenergic receptors c. Competitive antagonism of ACh actions on muscarinic receptors d. Massive, direct overactivation of ganglionic nicotinic receptors e. Sudden release of epinephrine from the adrenal medulla (suprarenal medulla)
*The answer is C.* The peripheral autonomic actions of diphenhydramine (an ethanolamine-type "first-generation" histamine H1 antagonist) are very similar to those of atropine, the prototypic competitive muscarinic receptor antagonist. These effects are seen with both therapeutic doses (eg, dry mouth, blurred vision, and occasionally urinary retention or constipation) and with toxicity. In life-threatening cases physostigmine, the "antidote for atropine poisoning, " maybe a valuable adjunct. Diphenhydramine, and other H1 blockers for that matter, have no direct effects either as agonists and no nicotinic receptor-activating activity, whether in autonomic ganglia (d) or at the adrenal medulla (suprarenal gland; e) (a) or antagonist (b) on adrenergic receptors.
Contemporary H1 receptor blockers are best categorized as: A. Pure antagonists B. Partial agonists C. Inverse agonists D. Agonists
*The answer is C.* Upon binding, an inverse agonist produces the opposite effect of the agonist.This action will decrease the level of response in a constitutively active system e.g. the presence of histamine at a basal level.
A patient presents with a history of frequent and severe migraine headaches. When we give one of the more commonly used drugs for abortive therapy, sumatriptan, upon which of the following "local control substances" is it mainly acting? a. Histamine b. PGF c. Prostacyclin d. Serotonin e. Thromboxane A2
*The answer is D.* Acute migraine therapy often involves giving a drug that mimics the effects of endogenous serotonin (5-hydroxytryptamine), thereby reversing the cerebral vasodilation that contributes significantly to migraine signs and symptoms. A good example is sumatriptan (member of a small group of drugs called triptans). These are 5-HT1 B/2 D receptor agonists.
You are asked to consult on a series of cases of drug toxicities. Which of the following is a recognized adverse effect of cimetidine? (A) Blurred vision (B) Diarrhea (C) Orthostatic hypotension (D) P450 hepatic enzyme inhibition (E) Sleepiness
*The answer is D.* The older H1 blockers, not H2 blockers, cause blurred vision, orthostatic hypotension, and sleepiness. Neither group typically causes diarrhea. Cimetidine (unlike other H2 blockers) is a potent CYP3A4 inhibitor.
A patient suffers from troublesome allergic rhinitis due to pollen, and you want to prescribe a drug for her that is least likely to cause sedation. What would your best choice be? A. Betamethasone B. Cimetidine C. Hydroxyzine D. Loratadine E. Metoclopramide
*The answer is D.* The usual choice for pollen-induced allergies would be an H1 antagonist. Of the two listed, loratadine would be the best choice in this case because it does not cross the blood-brain barrier and is nonsedating; hydroxyzine is an effective CNS depressant used for preoperative sedation. Cromolyn (not listed) can also be used in allergic rhinitis and is also nonsedating. Betamethasone, a potent antiinflammatory steroid, is less effective than antihistamines in this situation and would cause more serious side effects. Metoclopramide is a DA-receptor antagonist and prokinetic used as an antiemetic and in GERD. Cimetidine is the prototype H2 antagonist used in gastrointestinal ulcers.
Non-neuronal site(s) of histamine storage and release: A. Basophils B. Enterochromaffin-like cells C. Mast cells D. A & C E. A, B & C
*The answer is E.* Basophils, ECL cells, and mast cells all store and release histamine. Basophils and mast cells release histamine
Gastrointestinal parietal cells express which one(s) of the following receptors, the activation of which results in acid secretion? A. Gastrin B. Acetylcholine C. Histamine (H2) D. A & B E. A, B & C
*The answer is E.* Gastrointestinal parietal cells express receptors for gastrin, acetylcholine, and histamine (H2) to activate acid secretion.
A 40-year-old patient is about to undergo cancer chemotherapy with a highly emetogenic (nausea- and vomiting-causing) drug combination. The antiemetic drug most likely to be included in her regimen is (A) Bromocriptine (B) Cetirizine (C) Cimetidine (D) Ketanserin (E) Ondansetron
*The answer is E.* Ondansetron and other 5-HT3 antagonists have significant antiemetic effects. Diphenhydramine and prednisone are also used for this purpose.
A 43-year-old ship's captain complains of seasonal allergies. Which one of the following would be indicated? A. Cyclizine. B. Doxepin. C. Doxylamine. D. Hydroxyzine. E. Fexofenadine.
*The answer is E.* The use of first-generation H1 antihistamines is contraindicated in the treatment of pilots and others who must remain alert. Because of its lower potential to induce drowsiness, fexofenadine may be recommended for individuals working in jobs in which wakefulness is critical.
A 26-year-old woman has rhinorrhea, excessive lacrimation, and ocular congestion from a bout with the common cold. Diphenhydramine provides symptomatic relief. What is the most likely mechanism by which this drug relieved her symptoms? a. α-adrenergic activation (agonist, vasoconstrictor) b. β-adrenergic blockade c. Calcium channel blockade d. Histamine (H2) receptor blockade e. Muscarinic receptor blockade
*The answer is E.* You may have chosen d (histamine H2 receptor blocker) as your answer to this question. However, H2 receptors are mainly involved in regulating gastric acid secretion, not typical responses to seasonal allergies. What if I had given "Histamine H1 receptor blockade" as an answer choice? Although diphenhydramine blocks H1 receptors quite well, histamine plays a relatively minor role in the symptoms of rhinovirus infections (in contrast with a much more important role in say, seasonal allergies). As a result, blocking the effects of histamine on H1 receptors per se does not account for most of the symptom relief in the common cold. The drying up of nasal secretions afforded by diphenhydramine in this instance is due to the drug's rather intense muscarinic receptor-blocking (atropine-like) actions.
Therapeutic uses of H1 receptor competitive blockers include/includes: A. Motion sickness B. Urticaria C. Insomnia D. A & B E. B & C F. A & C G. A, B & C
*The answer is G.* H1 receptor competitive blockers includes motion sickness, urticaria, and insomnia.
Clinical uses of H2-histamine receptor blockers include/includes: A. Peptic ulcer disease B. Gastroesophageal reflux disease (Gerd) C. Nonulcer dyspepsia D. Prevention of bleeding in gastritis (stress-related) E. A & B F. B & C G. A, B, C & D
*The answer is G.* Histamine receptor blockers are used for all of the conditions mentioned.
A 28-year-old office worker suffers from intense migraine headaches. Which of the following is a serotonin agonist useful for aborting an acute migraine headache? (A) Bromocriptine (B) Cimetidine (C) Ephedrine (D) Ketanserin (E) Loratadine (F) Ondansetron (G) Sumatriptan
*The answer is G.* Sumatriptan, an agonist at 5-HT1D receptors, is indicated for prevention or treatment of migraine and cluster headaches. Ergotamine (not on the list) is also effective for acute migraine but is produced by the fungus Claviceps purpurea.
Which one(s) of the following statements concerning histamine is/are correct? A. Histamine is involved in neurotransmission in some systems. B. Histamine is a major inflammatory mediator.. C. Histamine is involved in gastric acid secretion. D. Histamine plays an important role in anaphylaxis. E. A & B F. B & C G. A & C H. A, B, C & D
*The answer is H.* Histamine is involved in neurotransmission in some systems, a major inflammatory mediator, involved in gastric acid secretion, and plays an important role in anaphylaxis.
