Immunopharm - Antihistamines and Migraines Flashcards Preview

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Flashcards in Immunopharm - Antihistamines and Migraines Deck (58):

A migraine is a ___ headache. The inflammatory response spreads along the ___ system and arrives in the ___ ___ ___ and other areas to convey pain.

A migraine is a neurovascular headache. The inflammatory response spreads along the trigeminovascular system and arrives in the trigeminal nucleus caudalis and other areas to convey pain



Derived from ___ of ___, catalyzed by L-___ ____. Once formed it is stored or inactivated by ___-N-____ (in the CNS) or diamine oxidase (resulting in ____)


Derived from decarboxylation of histidine catalyzed by L-histidine decarboxylase. Once formed, it is stored or inactivated by histamine-N-methyltransferase (in the CNS) or diamine oxidase (resulting in deamination)



1. Where is it stored? Speed of turnover?

2. Where does it have rapid turnover?


1. Stored in mast cells and basophils with slow turnover

2. Rapid turnover in neurons and enterochromaffin-like cells in the gastric mucosa



The allergen stimulates __ cells to produce ___ antibodies that then bind to ___ receptors on mast cells and basophils. This causes _____ and further allergen binding causes ___ of __/___ receptors producing degranulation (____ release)


The allergen stimulates B cells to produce IgE antibodies that then bind to Fc receptors on mast cells and basophils. This causes sensitization and further allergen binding causes crosslinking of IgE/Fc receptors producing degranulation (histamine release)


Function of Histamine:

1. ____ responses: rhinitis and ___ (hives)

2. 4 cardiovascular effects?

3. What does it do to the airways?

Function of Histamine:

1. Allergic response: rhinitis and urticaria

2. CV: vasodilation, increased vascular permeability, injection produces a triple response (red spot/flare/wheal), and increase force of contraction of the heart

3. Causes bronchoconstriction


Function of Histamine:

1. Increases ___ ___ secretion

2. Causes itch and potential ____ (severe hypotension, bronchoconstriction, and ____ swelling)

Function of Histamine:

1. Increases gastric acid secretion

2. Causes itch and potential anaphylaxis (severe hypotension, bronchoconstriction, and epiglottal swelling)


Histamine receptors:


1. Distribution?

2. Function?

Function of Histamine:


1. In smooth muscle, vascular endothelium, and brain

2. Bronchoconstriction, separation of endothelial cells (hives), pain, and itching


Histamine Receptors:


1. Distribution?

2. Function?

Histamine Receptors:


1. Gastric mucosa, cardiac muscle, and brain

2. vasodilation and stimulation of gastric acid secretion


Histamine Receptors:


1. Distribution?

2. Function?

Histamine Receptors:


1. CNS and some PNS (autoreceptor in the PNS)

2. Decreases NT release: histamine, ACh, NE, 5-HT


Histamine Receptors:

1. All receptor subtyptes are ___ ____ ___.

2. H1 receptors activate __ ___ that convert ____ to IP3 and ___ and are primarily involved in ___ and ___.


Histamine Receptors:

1. All receptor subtypes are G protein couples

2. H1 receptors activate G proteins that convert phosphatidylinositol to IP3 and DAG and are primarily involved in inflammation and allergy


Histamine Receptors:

1. H2 receptors linked through G proteins to increase ___ with its primary function to regulate ___ ___ ___.

2. H3 receptors function as ____ ____ in the CNS and PNS

Histamine Receptors:

1. H2 increase cAMP and regulate gastric acid secretion

2. Function as feedback inhibitors


3 strategies to inhibit histamine's actions?

a. Administer drugs to counter pathology (Ep for aniphylaxis)

b. Prevent mast cell degeneration - cromolyn

c. Use Histamine receptor antagonists 


H1 receptor antagonists:

1. All agents are ___, ___, inhibitors.

2. They all ___ the effects at H1 receptors and thus are useful in treating?

3. What are the NOT effective in treating?

H1 receptor antagonists:

1. All agents are reversible, competitive, inhibitors

2. They all attenuate the effects at H1 and are good for allergic reactions, rhinitis, urticaria, itch, and flare



H1 receptor antagonists:

First vs. Second generation Antagonists:

1. First generation are highly ___ soluble and distribute to the ___ whereas second do not.

2. First generation drugs produce ___ and ___ and exhibit some anti-_____ activity. Second generation in comparison?

H1 receptor antagonists:

First vs. Second generation Antagonists:

1. First generation are highly lipid soluble and distribute to the CNS whereas second do not

2. First generation drugs produce drowsiness and sedation and exhibit some anti-muscarinic activity. Second generation has no anti-muscarinic activity and much less drowsiness/sedation


H1 receptor antagonists:

First vs. Second generation Antagonists:

1. Why dont second generation drugs readily penetrate the CNS?

2. Example of a girst generation drug with anti-muscarinic activity? Uses?

H1 receptor antagonists:

First vs. Second generation Antagonists:

1. Dont penetrate because they are ionized at pH=7.4 and they are highly bound to albumin

2. 1st generation: meclozine --> antiemetic or some antiparkinsons


First generation H1 receptor Antagonists:

1. 5 drugs?

2. Absorption? Distribution? Metabolization?

First generation H1 receptor Antagonists:

1. Diphenhydramine, chorphenamine, dimenhydrinate, hydroxyzine, and promethazine

2. Well absorbed, widely distributed (even to CNS), and extensively metabolized


First generation H1 receptor Antagonists:

1. The major side effect? Which drug thus is best and why?

2. What are the anticholinergic SE?

3. Other SE?

First generation H1 receptor Antagonists:

1. Major SE: sedation - chlorphenamin is best because its the least sedating

2. Anticholinergic SE: dry mouth, cough, urinary retention, and blurred vision

3. Other SE: loss of appetitie, N/V, dizziness, fatigue, tremor, hypersensitivity reactions


First generation H1 receptor Antagonists:

Dimenhydrinate and diphenhydramine have a ___ therapeutic index and often are used ____ as OTC ____.

First generation H1 receptor Antagonists:

Dimenhydrinate and diphenhydramine have a low therapeutic index and are often used recreationally as OTC hallucinogens


Second Generation H1 Receptor Antagonists:

1. Drugs?

2. Absorption? Distribution? Metabolism?

3. SE?

Second Generation H1 Receptor Antagonists:

1. Cetirizine, loratedine, desloratadine, and fexofenadine

2. Well absorbed; no distribution to CNS; CYP450

3. Minimal SE: sedation/drowsiness --> no anticholinergic effects


Therapeutic Actions of Antihistamines:

1. Acute ____ reactions

2. Reduce ___

3. Diminish symptoms of ___ and ___

4. What first generation drugs are used for prophylaxis and treatment of motion sickness?

Therapeutic Actions of Antihistamines:

1. Acute allergic reactions

2. Reduce itching

3. Diminish symptoms of cold and flu

4. Motion sickness: diphenhydramine and promethazine


Therapeutic Actions of Antihistamines:

1. What can diphenhydramine reduce?

2. What can promethazine treat?

3. First generation drugs are used for ___ and occassionally for ___ but routine use is not recommended.

Therapeutic Actions of Antihistamines:

1. Diphenhydramine can reduce Parkinson's symptoms

2. Promethazine can treat nausea and vomitting

3. 1st generation: somnolence and occasionally insomnia but shouldnt be used long term


H2 receptor antagonists:

1. Drugs?

2. Function?


H2 receptor antagonists:

1. Cimetidine, famotidine, ranitidine, and nizatidine

2. Inhibits stomach acid production


H2 receptor antagonists:

1. Indicatons?

2. Why is cimetidine no longer recommended?

Therapeutic Actions of Antihistamines:

1. Indications: GERD, peptic ulcer disease, and heartburn

2. Cimetidine: no longer recommended because it is used as a suicide substrate for CYP 3A4 and potential toxicity of concurrently ingested drugs that are metabolized by this CYP isoform


5-Hydroxytryptamine (serotonin):

1. Mainly found where?

2. 80% is in what cells?

3. Mainly metabolized to ____ by the ___. This is used to determine 5HT levels in the body via urine analysis.

5-Hydroxytryptamine (serotonin):

1. Found in gut, platelets, and CNS

2. 80% in enterochromaffin cells in the gut

3. Mainly metabolized to 5-HIAA by the liver


5-Hydroxytryptamine (serotonin):

Has three fates after synthesis, what are these?

5-Hydroxytryptamine (serotonin):

a. Storage (gut)

b. Rapid inactivation by MAO

c. Precursor for melatonin in pineal gland


5-Hydroxytryptamine (serotonin) receptors:

1. 5HT1A/1B: thought to be ____ receptors in the ___ nuclei and _____.

2. 5HT2A: contributes to ____ aggregation in the ___, ___, blood vessels, GI, and ____ muscle

3. 5HT1D: produces ___ in the ___

5-Hydroxytryptamine (serotonin) receptors:

1. 5HT1A/1B: thought to be auto-receptors in the raphe nuclei and hippocampus

2. 5HT2A: contributes to platelet aggregation in the CNS, PNS, blood vessels, GI, and smooth muscle

3. 5HT1D: produces vasoconstriction in the brain


5-Hydroxytryptamine (serotonin) receptors:

1. 5HT2A/3/4: is involved in ___ excitation in the ___, ___, and ___

2. 5HT2A/2B: ____ smooth muscle in the ___, PNS, ___ ___, and GI

5-Hydroxytryptamine (serotonin) receptors:

1. 5HT2A/3/4: is involved in neuronal excitation in the CNSPNS, and GI

2. 5HT2A/2B: contracts smooth muscle in the CNS, PNS, blood vessels, and GI


5-Hydroxytryptamine (serotonin) receptors:

1. All of the roles of 5HT2A?

2. Which receptor produces vasoconstriction in the brain?

3. Which receptors are auto-receptors?

5-Hydroxytryptamine (serotonin) receptors:

1. 5HT2A: platelet aggregation, neuronal excitation, and contraction of the smooth muscle

2. 5HT1D - vasoconstriction in brain

3. 5HT1A/1B - autoreceptors (raphe nuclei and hippocampus)


5-Hydroxytryptamine (serotonin) receptors:

1. Which receptors produce neuronal excitation?

2. Which receptors contracts smooth muscle?

5-Hydroxytryptamine (serotonin) receptors:

1. 5HT2A/3/4 - neuronal excitation

2. 5HT2A/2B - contracts smooth muscle


Actions of Serotonin:

1. ___ aggregation

2. Contraction of vascular smooth muscle where?

3. Function on the heart?

Actions of Serotonin:

1. Platelet aggregation

2. Contraction of vascular smooth muscle in splanchnic, renal, pulmonary, and cerebral vasculatures

3. Acts as a positive inotrope (increases strength) and positive chronotrope (increases HR) on the heart


Actions of Serotonin:

1. Stimulaes what part of the GI? Inhibits what part?

2. Sensitizes small diameter ___ neruons

3. What "cerebral" functions does it effect?

Actions of Serotonin:

1. Stimulates SI motility, inhibits stomach smooth muscle

2. Sensitizes sensory neurons

3. Affects sleep, cognition, temperature regulation, and motor activity


Actions of Serotonin:

1. Drugs that block 5HT2C are associated with?

2. Migraine = complex _____ disorder. Key features are ___ (often ____ and throbbing) and associated with ___, as well as sensitivity to __, ___, and exacerbation with head movements

Actions of Serotonin:

1. Block 5HT2C: wt gain because generally serotonin inhibits stomach smooth muscle and decreases appetite. By blocking this inhibition - stimulating appetite

2. Migraine = complex neurobiological disorder. Key features are HA (often unilateral and throbbing) and associated with nausea as well as sensitivity to lightsound, and exacerbations of heat movements


Overview of migraines:

1. In about 20-30% of subjects, headache is preceeded by ___ ( visual, ___, or ___ deficits). There is often a strong ___ component.

2. The key pathway for the pain is the __-_____ input from the ___ vessels. These nerves pass through the ___ ganglion and synapses, and project though the _____ tract and form synapses in the ___.

Overview of migraines:

1. Preceeded by aura (visual, motor, or speech deficits). There is often a strong genetic component

2. The key pathway for the pain is the tri-geminovascular input from the meningeal vessels. These nerves pass through the trigeminal ganglion and synapses, and project through the quintothalamic tract and form synapses in the thalamus


Phases of a migraine attack:

What are the 5 phases?

Many dont have which?


a. Prodrome

b. Aura phase

c. Migraine headache

d. Resolution phase

e. Migraine hangover

-- Many dont have prodrome or postdromes


Phases of a migraine attack:

1. Prodrome: vague ___ or ___ symptoms as much as ___ (time) prior

2. Aura - what does this involve? Length of time?

Phases of a migraine attack:

1. Prodrome: vague vegetative or affective symptoms as much as 24 hours prior

2. Aura: focal neurological symptoms - up to one hour long preceeding the migraine headache


Phases of a migraine attack:

1. Migraine headache: within _ __ (time) of resolution of the aura, typical migraine (often with ___) occurs for up to ___ hours

2. Resolution phase is characterized by ___ ___

3. Migraine hangover: duration? What does it involve?

Phases of a migraine attack:

1. Migraine headache: within 1 hour of resolution the aura, typical migraine (often with throbbing) occurs for up to 72 hours

2. Resolution phase is characterized by deep sleep

3. Migraine hangover: up to 24 hours after with fatigue, maliase, and transient return of pain following cough/sudden head movement



1. What does CSD stand for?

2. What is it the cause of?


1. Cortical Spreading Depression

2. The cause of migraine aura


Cortical Spreading Depression:

1. Wave of ___ - lasting electrophysiological ____ followed by a wave of ___ ___ of neuronal activity usually in the cerebral ____.

2. CSD upregulates a variety of genes coding for?

3. Increased metalloproteinases leads to ___ of BBB allowing ___, ___, and ___ to reach the dural perivascular ___ afferents. 

Cortical Spreading Depression:

1. Wave of short lasting electrophysiological hyperactivity followed by a wave of prolonged inhibition of activity in the cortex

2. Upregulates genes for: COX-2, TNF, IL-1, galanin, or metalloproteinases

3. Leads to leakage of BBB allowing K+, NO, and adenosine to reach perivascular trigeminal afferents



1. The aura phase is a primarily ____ phenomenon as it may activate the ____ fibers through the ___.

2. Nonspecific treatment of acute attack migraine?

3. Specific treatment of acute attack migraine?

4. What is the first choice combination as analgesic and antipyretic?


1. The aura phase is a primarily cortical phenomenon as it may activate the trigeminal fibers through the dura.

2. Nonspecific: NSAIDs, anti-emetics, opioids, corticosteroids, and dopamine antagonists

3. Specific: ergotamine, DHE, and triptans

4. Aspirin, acetaminophen, and caffiene



1. Act at what receptor? Subtypes?

2. Drug examples?


1. Act at 5HT1 --> 5HT1B and 5HT1D

2. Sumatripan and zolmitriptan



Two proposed MOA:

a. Direct ____ action on ______ blood vessels by binding ___.

b. _____ inhibition on ___ neurons by blocking ____ gene regulated peptide. This is a _____ NT


Two MOA:

a. Direct vasoconstrictive action on intracrania blood vessels by binding 5HT1

b. Presynaptic inhibition on sensory neurons by blocking calcitonin gene regulated peptide. This is a proinflammatory NT



1. Indications? Not useful for?

2. Administration?

3. SE?


1. DRUG OF CHOICE for acute treatment of migraine; not for long term or prophylaxis

2. Subcutaneous injection, orally, or nasal spray

3. SE: nausea, malaise, dizziness, weakness, dry mouth, paresthesia, pain at injection site 



1. Rare SE?

2. Who should be screened prior to administration of sumatriptan/zolmitriptan?


1. Rare: coronary artery spasm, ischemia, and arrhythmias

2. Screened: those at risk for coronary heart disease, diabetes, obesity, severe uncontrolled hypertension, or hypercholesterolemia




1. History of?

2. Those with what vascular diseases?

3. Uncontrolled ____

4. Taking ____.

5. Naratriptan is not for patients with severe ___ or ___ disease



1. History of coronary artery disease

2. Those with cerebrovascular or peripheral vascular disease

3. Uncontrolled hypertension

4. Taking MAOIs

5. Naratriptan: not for hepatic or renal disease


Ergot Alkaloids:

1. Drug examples?

2. Mechanism is attributed to ___ action at ___.

Ergot Alkaloids:

1. Ergotamine and dihydroergotamine

2. Mechanism is attributed to agonist action at 5HT1


Ergot Alkaloids:

1. What are these for? Not for?

2. Administration of ergotamine?

3. Administration of DHE?

Ergot Alkaloids:

1. For moderate to severe migraine; not for prophylaxis

2. Ergotamine: oral, IV, or IM

3. DHE: IV


Ergot Alkaloids:

1. What increases rate/extension of absorption?

2. This is best when given in ___ phase.

3. Major SE?

Ergot Alkaloids:

1. Caffiene increases rate of absorption

2. Best in prodromal phase

3. Major SE: nausea, vasoconstriction with ischemia/leg weakness/muscle pain


Ergot Alkaloids:

Contraindications? (7)

Ergot Alkaloids:


a. Pregnancy: stimulate uterus and restric uterine BF

b. Coronary/peripheral artery disease

c. Liver/renal disease

d. stroke

e. Severe hypertension


Prophylactic Agents:

Name some categories.

Prophylactic agents:

a. Beta blockers

b. Antidepressants

c. Ca++ antagonists

d. Anticonvulstants


f. Methysergide

g. 5HT antagonists



1. Class of drug?

2. MOA?

3. SE?


1. TCA

2. 5HT/NE reuptake inhibitor and antagonist at some 5HT/histamine receptors

3. SE: sleepy, dry mouth, and can induce hepatotoxicity



1. Class?

2. Used for treatment of ___, anxiety, panic, ___ ___, and cluster HA prophylaxis

3. MOA: blocks action of ___ and ___ on what receptors?


1. Non-selective beta blocker

2. Used for treatment of hypertension, anxiety, panic, migraine prophylaxis, and cluster HA prophylaxis

3. MOA: blocks action of epinepherine and NE on both beta1 and beta2 receptors



1. Class of drug?

2. Used for wt loss in combination with ___, treatment of ____ in kids/adults, and most frequently prescribed for ___ ___.

3. SE?


1. Anticonvulsant

2. Wt loss in combo with phentermine, treatment of epilepsy in kids/adults, but most frequently for migraine prophylaxis

3. SE: parasthesia, upper RTI, diarrhea, and nausea



1. Class?

2. Antagonist at ____ receptor. Prevents or decreases __ and ___. Inhibits release of ___ from ___ cells. Antagonist at ___ alters patients feeling of satiety.

3. Metabolism?


1. Ergot Alkaloid

2. Antagonist at 5HT2B receptor. Prevents or decreases pain and frequency. Inhibits release of histamine from mast cells. Antagonist at 5HT2C alters feelings of satiety

3. Metabolised by CYP450 3A4



1. Short term SE?

2. Long term SE:


1. Short: nausea, vasoconstriction with ischemia/leg weakness/muscle pain

2. Long: retroperitoneal, heart, or lung fibrosis





Pregnancy, coronary artery disease (may cause MI), peripheral vascular disease, hypertension, hepatic or renal impairment



1. Acts at what receptors?

2. For ___ reactions, nightmares, ____ syndrome, management of ______ from ___ producting carcinoid tumor.


1. Acts at H1, 5HT2A/2B/2C

2. For allergic reactions, nightmares, serotonin syndrome, management of hyperseritonemia from serotonin producing carcinoid tumor



1. Acts at what receptor?

2. Indication?


1. Acts at 5HT3 receptor (antagonist)

2. For nausea following chemotherapy/post operative as well as vomitting: acts as antiemetic



1. MOA: decreases activity of the ___ which deactivates ___ center in medulla oblongotta and ___ receptor in ___ receptor trigger zone

2. SE?

3. Metabolism?


1. MOA: decreases activity of the vagus which deactivates vomitting center in the medulla oblongotta and serotonin receptor in the chemo-receptor trigger zone

2. SE: HA, dizziness, constipation

3. Metabolism: CYP450