Pharmacology of Histamine and Serotonin

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What role does histamine play in the body?

Inhibits gastric acid secretion

Functions as a circulating hormone

Mediates allergic and inflammatory responses (correct)

Decreases neurotransmission in the brain

Which of the following statements about autocoids is true?

They are produced in specific endocrine glands.

They function as local hormones produced by many tissues. (correct)

They have no pharmacologic activities.

They are homogenous substances with consistent structures.

Where is histamine primarily synthesized in the body?

In the liver

In the thyroid gland

In the brain exclusively

In mast cells (correct)

What is the main enzyme involved in the synthesis of histamine?

Histidine decarboxylase Signup and view all the answers

Which of the following is NOT a characteristic of histamine?

It has clinical applications as a drug. Signup and view all the answers

What distinguishes first-generation antihistamines from second-generation antihistamines?

First-generation antihistamines penetrate the central nervous system and can cause sedation. Signup and view all the answers

Which of the following drugs is classified as a partially sedating second-generation antihistamine?

Cetirizine Signup and view all the answers

What is a common adverse effect associated with first-generation antihistamines?

CNS depression leading to sedation Signup and view all the answers

What are second-generation antihistamines specifically characterized by regarding their pharmacokinetics?

They do not penetrate the blood-brain barrier effectively. Signup and view all the answers

Which of the following correctly describes the actions of H1-receptor blockers?

They are utilized for allergic and inflammatory conditions. Signup and view all the answers

What is the primary mechanism of action for triptans?

Activation of 5-HT<del>1B/1D</del> receptors Signup and view all the answers

Which of the following is true about the pharmacokinetics of sumatriptan?

Sumatriptan is administered subcutaneously, intranasally, or orally. Signup and view all the answers

What is the most common adverse effect associated with triptan use?

Elevation of blood pressure Signup and view all the answers

How effective is the first dose of triptans in aborting a migraine?

Approximately 70% effective in about 70% of patients Signup and view all the answers

What should be done before administering triptans to certain patients?

Perform a cardiac evaluation Signup and view all the answers

What is a common pattern of headache occurrence after taking triptans?

Headaches commonly recur within 24 to 48 hours. Signup and view all the answers

What distinguishes Zolmitriptan from other triptans in terms of administration?

Can be administered by nasal spray Signup and view all the answers

Which of the following statements about the variability of triptan response is true?

Individual response to triptans may vary. Signup and view all the answers

Why are beta blockers not recommended as initial therapy for migraine prevention in certain patients?

They may be associated with a higher rate of cardiovascular events. Signup and view all the answers

What is the primary drug class recommended for migraine prophylaxis?

β-Blockers Signup and view all the answers

Which medication is suggested for patients with depression as an option for migraine prevention?

Venlafaxine Signup and view all the answers

Which of the following is NOT an alternative medication for migraine prophylaxis?

Acetaminophen Signup and view all the answers

What are reasonable options for migraine prevention in patients with epilepsy?

Topiramate or valproate Signup and view all the answers

For patients suffering from insomnia, which medication is considered a reasonable option for migraine prevention?

Amitriptyline Signup and view all the answers

In cluster headache treatment, which method is used as a first-line abortive strategy?

Inhalation of 100% oxygen Signup and view all the answers

For a patient with hypertension who is 30 years old and a non-smoker, which medication would be a reasonable option for migraine prophylaxis?

Metoprolol Signup and view all the answers

Which drug is recommended for obesity in the context of migraine prevention?

Topiramate Signup and view all the answers

Which of the following is a common initial treatment suggested for patients with episodic migraine?

Venlafaxine Signup and view all the answers

What is recommended for patients with Raynaud phenomenon in terms of migraine prevention?

Verapamil or flunarizine Signup and view all the answers

Which CGRP antagonist is injected and has shown effectiveness in migraine treatment?

Erenumab Signup and view all the answers

Which patient group requires discussion about potential risks of pharmacotherapy due to their reproductive status?

Females of childbearing potential Signup and view all the answers

Which of the following is NOT considered a reasonable option for migraine prevention?

Beta blockers for anxiety Signup and view all the answers

What is the preferred therapy for symptom relief of tension headaches?

NSAIDs Signup and view all the answers

Which combination of medications would NOT be appropriate for a patient who is a smoker and over 60 years old with hypertension?

Propranolol Signup and view all the answers

Which class of drugs is often used for migraine prophylaxis but is NOT a β-blocker?

All of the above Signup and view all the answers

Which of the following medications is specifically categorized as an anticonvulsant used for migraine prophylaxis?

Divalproex Signup and view all the answers

What is a primary mechanism of action for Ergotamine?

Actions at 5-HT<del>1</del> receptors Signup and view all the answers

What significant risk is associated with using ergotamine within 24 hours of triptans?

Risk of coronary ischemia Signup and view all the answers

Which of the following is a contraindication for the use of Lasmiditan?

Driving after consumption Signup and view all the answers

Which of the following statements accurately describes Dihydroergotamine?

Has similar efficacy to sumatriptan Signup and view all the answers

What class of medication does Rimegepant belong to?

CGRP receptor antagonists Signup and view all the answers

What is the common side effect associated with CGRP receptor antagonists?

Nausea Signup and view all the answers

In what situation is prophylaxis for migraine headaches indicated?

If attacks occur two or more times a month Signup and view all the answers

Which of the following drugs should Ubrogepant not be used with due to interactions?

Strong CYP3A4 inhibitors Signup and view all the answers

What role does dopamine receptor action play in Dihydroergotamine's mechanism?

It has no role in its mechanism. Signup and view all the answers

Which drug is indicated for acute treatment of migraines?

Dihydroergotamine Signup and view all the answers

What condition could arise from dependence on Dihydroergotamine?

Rebound headaches Signup and view all the answers

What type of treatment does Rimegepant provide for patients?

Rescue medication for acute migraine Signup and view all the answers

What is a major downside of using potent CYP3A4 inhibitors in conjunction with Dihydroergotamine?

Inhibition of drug metabolism leading to increased side effects Signup and view all the answers

Study Notes

Drugs with Important Actions on Smooth Muscles - Histamine and Serotonin

Overview: Histamine, serotonin, and prostaglandins are autocoids, local hormones produced by tissues rather than endocrine glands. This chapter covers these autocoids and antagonists.

Histamine

Chemical Messenger: Primarily generated in mast cells, mediating cellular responses like allergic and inflammatory reactions, gastric acid secretion, and neurotransmission.
Clinical Application: No clinical drug applications for histamine exists, but agents inhibiting its activity are therapeutically important.
Location: Found in high concentrations in tissues like lungs, skin, blood vessels, and the gastrointestinal tract, especially in mast cells and basophils. It also functions as a neurotransmitter in the brain.
Synthesis: Formed by decarboxylation of the amino acid histidine by the enzyme histidine decarboxylase.
Release: Released from tissues in response to various stimuli; including cell destruction (cold, toxins), insect/spider venoms, and trauma. Allergies/anaphylaxis can also trigger histamine release.
Mechanism of Action: Acts via histamine receptors (H1, H2, H3, H4). H1 and H2 receptors are clinically relevant drug targets. Histamine affects smooth muscle contraction, vascular dilation, and capillary permeability.
Role in Allergy/Anaphylaxis: Symptoms result from the release of several mediators including histamine, serotonin, leukotrienes, and eosinophil chemotactic factor of anaphylaxis; these can cause localized allergic reactions or full-blown anaphylaxis.

H1 Receptors

Exocrine Excretion: Increased mucus production, especially nasal and bronchial, causing respiratory symptoms.
Bronchial Smooth Muscle: Bronchiole constriction, leading to asthma symptoms and reduced lung capacity.
Intestinal Smooth Muscle: Constriction causing cramps and diarrhea.
Sensory Nerve Endings: Causes itching and pain.

H1 and H2 Receptors

Cardiovascular System: Lowering of systemic blood pressure; positive chronotropism (H2) and positive inotropism (H1 and H2).
Skin: Dilation and increased capillary permeability resulting in fluid and protein leakage; "triple response" (wheal formation, redness, flare).
Stomach: Stimulation of gastric hydrochloric acid secretion.

H1 Antihistamines

Overview: Referred to as antihistamines, primarily as H1-receptor blockers. Divided into first and second generation.
First Generation: Older, inexpensive, but effective in their action. Penetrate the central nervous system (CNS), causing sedation, interacting with other receptors.
Second Generation: More specific to peripheral, H1 receptors. Do not enter the CNS and cause less sedation than first-generation, but some of these can be sedating.
Actions: These compounds work by blocking the receptor-mediated response of a tissue. They are more effective in preventing symptoms than in reversing established ones.
Therapeutic Uses: Allergic and inflammatory conditions, including allergic rhinitis, urticaria, and allergic conjunctivitis. Also useful for motion sickness,
Pharmacokinetics: Well absorbed after ingestion, with maximum serum levels within 1-2 hours; varying average plasma half-lives.
Adverse Effects: Drowsiness, fatigue, dizziness, lack of coordination, tremors, blurred vision, and urinary retention. Other drug interactions are also possible.

Serotonin

Neurotransmitter: Plays a role in vasoconstriction, inhibition of gastric secretion, and smooth muscle contraction in the enteric nervous system and CNS.
Location/Synthesis: Found in enterochromaffin cells of the gastrointestinal tract, platelets, and raphe nuclei of the brainstem. Synthesized from tryptophan.
Mechanism of Action: Several types of serotonin receptors, mostly G protein-coupled, controlling numerous physiological responses.
Therapeutic Use: Agonists and antagonists used for disorders like depression and migraine headache.

Migraine

Types: Two main types: migraine with aura (preceded by neurologic symptoms like visual disturbance) and without aura.
Triggers and Symptoms: Symptoms include severe, unilateral, pulsating headaches, lasting 2-72 hours; aggravated by physical activity; and associated with nausea, vomiting, sensitivity to light/sound.
Treatment and Prophylaxis: Abortive treatments (serotonin agonists, ergot alkaloids) and prophylactic therapies.

Additional Notes

Key terms like selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) are discussed in context with clinical depression, but not separately.
Specific details about some medications (such as dosage, exact mechanisms, and drug interactions) are not present here.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

This quiz explores the important actions of histamine and serotonin on smooth muscles as autocoids. You will learn about their synthesis, release mechanisms, and clinical implications, including the therapeutic significance of histamine antagonists. Test your knowledge on these crucial chemical messengers and their roles in various physiological responses.