Pharm - S2B2 - 10 Histamine, Serotonin, & Ergot Alkaloids

Front 1

What does "Autacoids" mean?

Back 1

Self-remedy

Front 2

Autacoids are mostly LOCAL HORMONES with these 2 main characteristics

Back 2

1. short duration of action

2. act locally near sites of synthesis or formation

Front 3

Are Autacoids used clinically as drugs or therapeutic agents?

Back 3

No, but Autacoid antagonists are used for treating many diseases
-asthma
-migraine
-HTN
-Peptic ulcer

Front 4

Histamine is found in many plants and animal tissues...how is it formed?

Back 4

Decarboxylation of L-histidine


**then either stored or rapidly inactivated

Front 5

Histamine is mostly bound in granules in what 2 cells?

Back 5

Mast cells

Basophils

Front 6

What are the sites of histamine-containing Mast cells?

Back 6

Nose
Mouth
Feet
Blood vessels
GI

Front 7

List the 2 important non-mast cell sites of Histamine

Back 7

1. Brain where histamine acts as a neurotransmitter

2. Enterochromaffin-like cells in the stomach release histamine to stimulate acid secretion from Parietal cells

Front 8

Bound histamine is inactive but is released by many stimuli to act on surrounding tissues...by what general mechanisms can histamine be released?

Back 8

1. Immunologic

2. Chemical

3. Mechanical

Front 9

Describe the Immunological release of Histamine

Back 9

1. upon exposure to antigens, plasma cells release IgE
2. IgE binds to IgE receptors on Mast cells
3. Mast cell degranulates to release Histamine, ATP, etc

Front 10

The Immunologic release of Histamine mediates __1__ and modulates __2__

Back 10

1. Type 1 allergic rxns

2. acute inflammation

Front 11

What 2 drugs can displace histamine from Mast cell binding sites without injurying the cell?

Back 11

1. Morphine

2. Tubocurarine

Front 12

What are the 3 sites of H1 receptors?

Back 12

1. Smooth muscle
2. Endothelium
3. Brain

Front 13

What are the antagonists to the H1 receptor?

Back 13

1st and 2nd generation H1 blockers

Front 14

Where are H2 receptors found?

Back 14

1. Gastric mucosa
2. Mast cells
3. Cardiac muscle
4. Brain

Front 15

What are the 4 antagonists to the H2 receptors?

Back 15

Cime-tidine
Famo-tidine
Niza-tidine
Rani-tidine

Front 16

What does activation of the H1 receptor cause?

Back 16

Gq = increase in Intracellular Calcium

Front 17

What does activation of the H2 receptor cause?

Back 17

Gs = incrase in intracellular cAMP

Front 18

Histamine effect on Sensory nerve endings due to H1 receptors

Back 18

Pain and itching of urticaria

Front 19

Histamine effect on Arterioles and Precapillary Sphincters due to H1 receptors

Back 19

Vasodilation ➡ lowers BP ➡ reflex tachycardia

Front 20

This may cause flushing, warm sensation, or headache

Back 20

Histamine binding to H1 receptors

Front 21

Histamine effect on Precapillary vessels due to H1 receptors

Back 21

dilation of precapillary vessels ➡ increased permeability ➡ edema

Front 22

Histamine effect on Bronchial smooth muscle due to H1 effects

Back 22

contraction of bronchial smooth muscle ➡ bronchoconstriction

Front 23

Histmine effect on GI smooth muscle due to H1 receptors

Back 23

GI contraction ➡ diarrhea

Front 24

Histamine effect on the gastric mucosa due to H2 receptors

Back 24

Gastric Parietal & Intestinal cells ➡ increased GI secretion

Front 25

Histamine effect on cardiac muscle due to H2 receptors

Back 25

increased heart rate & contractility

Front 26

List the 2 mechanisms in which Histamine influences heart rate

Back 26

Indirectly = via H1 receptors thru REFLEX TACHYCARDIA

Directly = by stimulating cardiac H2 receptors

**direct cardiac stimulation is minimal & H2 antagonists have little or no effect on the heart rate

Front 27

Describe the Histamine "release inhibitors"

Back 27

Prophylactics used to protect against allergic rhinitis or bronchoconstriction related to exercise, antigen inhalation, aspirin, or occupational asthma
-Cromolyn
-Nedocril

Front 28

What are the 2 histamine Release Inhibitors?

Back 28

Cromolyn

Nedocromil

Front 29

Are H1 or H2 antagonists used for allergic reactions such as hay fever, allergic rhinitis, and urticaria?

Back 29

H1 antagonists

Front 30

List 2 H1 antagonists that are used for motion sickness but have marked sedative activity

Back 30

Dimenhydrinate

Diphenhydramine

**many of these end in -amine

Front 31

List 2 H1 antagonists used to prevent MOTION SICKNESS that only have slight sedative effects

Back 31

Cyc-lizine

Mec-lizine

Front 32

List 2 H1 antagonists the have local anesthetic activity

What are they more potent than?

Back 32

Di-phen-hydramine & Pro-meth-azine

Procaine

Front 33

Aside from the H1 antagonistic effects, what other effects do H1 antagonists have? (4)

Back 33

1. Anti-Parkinsonian
2. Anticholinergic
3. Adrenergic-blocking
4. Serotonin-blocking

Front 34

What are the most common side-effects of H1 antagonists? (2)

Back 34

1. Sedation

2. Antimuscarinic activity ➡ urinary retention, blurred vision

Front 35

What are the less common toxic effects of H1 antagonists? (3)

Back 35

1. Postural hypotension = Orthostatic hypotension = due to vasodilation

2. Drug allergy

3. Excitation & convulsions in children

Front 36

List some general properties of 1st generation H1 antagonists

Back 36

1. older
2. have marked sedative activity
3. often available OTC
4. some are used in pediatrics for sedation

Front 37

List some general properties of 2nd generation H1 antagonists

Back 37

1. non-sedating
2. less-lipid soluble = don't cross BBB = less CNS effects
3. less likely to block autonomic receptors
4. little effect on heart, BP, motion sickness, or nausea

Front 38

List the 4 2nd generation H1 antagonists

Back 38

1. Cetiri-zine
2. Fexo-fena-dine
3. Lorata-dine
4. Azelastine

**CALF

Front 39

What are the 2nd generation H1 antagonists mainly used for?

Back 39

Hay fever

Allergic rhinitis

Urticaria

Front 40

2nd generation H1 antagonist used as a nasal spray for seasonal allergic rhinitis and has been shown to be as effective as Fexofenadine

Back 40

Azela-stine

Front 41

What is the sedation incidence of 2nd generation H1 antagonists vs. 1st generation

Back 41

7% vs. 50%

Front 42

What is the main use of the H2 antagonists?

Back 42

block H2 receptors to reduce gastric acid secretion
-peptic ulcers
-GERD
-GI hypersecretory disorders

Front 43

List the 4 H2 antagonists?

Back 43

1. Cime-tidine
2. Rani-tidine
3. Famo-tidine
4. Niza-tidine

***-tidine

Front 44

T or F: Doses of H2 antagonists that suppress gastric secretion have a moderate effect on intestinal secretion, heart, or blood vessels

Back 44

False = they have little or no effect on these

Front 45

T or F: the side effects of H2 antagonists are infrequent and usually minor

Back 45

True

Front 46

What are the most common side effects of H2 antagonists?

Back 46

Diarrhea
Dizziness
Drowsiness
Skin rash

Front 47

High doses of H2 antagonists may cause these adverse effects

Back 47

Men = Gynecomastia or Impotence

Women = Galactorrhea = spontaneous release of milk from breasts

Front 48

Headaches may occur with these 2 H2 antagonists

Back 48

Famo-tidine

Rani-tidine

Front 49

This H2 antagonist has the fewest side effects

Back 49

Niza-tidine

Front 50

Autacoid that is widely distributed in plant and animal tissues, venoms, and stings

Back 50

Serotonin = 5-HT = 5-hydroxytryptamine

Front 51

What is Serotonin formed from?

Back 51

L-tryptophan

**then stored or inactivated

Front 52

Where is 90% of our body 5-HT located?

What other places is it found?

Back 52

GI Enterochromaffin cells

Blood platelets & raphe nuclei of the brain stem

Front 53

What is Serotonin the precursor of in the Pineal Gland?

Back 53

Melatonin

Front 54

T or F: Many 5-HT receptors have no physiologic function

Back 54

True

Front 55

What are the 2 main functions of 5-HT?

Back 55

1. GI motility

2. CNS neurotransmitter

Front 56

What effects does 5-HT have on the Nervous System? (7)

Back 56

CNS neurotransmitter affecting:
1. sleep
2. sensory perception
3. motor activity
4. temp regulation
5. appetite
6. sexual behavior
7. hormone secretion

Front 57

What effect does Serotonin have on the 5-HT3 receptors on the Afferent Vagal Nerve endings?

Back 57

Bezold-Jarisch reflex ➡ bradycardia & hypotension

Front 58

What effect does Serotonin have on 5-HT3 receptors in the GI and medulla?

Back 58

Vomiting reflex triggered by cancer chemotherapy drugs

Front 59

What effect does 5-HT have on Bronchial Smooth muscles?

Back 59

Bronchoconstriction

Front 60

5-HT effects on the Cardiovascular system:

Generally causes __1__ by stimulating vascular 5-HT2 receptors except in the __2__ & __3__ where vessels are DILATED

Back 60

1. Vasoconstriction
2. Heart
3. Skeletal muscles

Front 61

Serotonin effect on:
1. Coronary vessels with endothelial damage
2. Blood pressure
3. Veins
4. Platelets

Back 61

1. constriction
2. Triphasic = decrease, increase, decrease
3. Constricts veins ➡ increased capillary filling ➡ skin flush
4. causes platelet aggregation via platelet 5-HT2 receptors

Front 62

Serotonin effect on GI

Back 62

Contractions from stimulation of 5-HT2 receptors on GI smooth muscles ➡ increased tone & peristaltis

Front 63

How could 5-HT (Serotonin) cause diarrhea?

Back 63

Carcinoid tumor overproducing 5-HT = increases GI motility

Front 64

5-HT(1A) agonist used as an Anxiolytic (anxiety reliever)

Back 64

Buspirone

"One-pirate in a bus" misses exit 1A which causes him anxiety

Front 65

Two 5-HT agonists that were widely used as Appetite Suppressants but later withdrawn when serious side-effects of Pulmonary HTN and Valvular lesions occured in young women using them

Back 65

Fen-fluramine & Dex-fen-fluramine

***when combined with Phenteramine = Fen-Phen

Front 66

5-HT4 agonist used for GERD and GI motility disorders

**acts through serotonin receptors to increase ACh release at the Myenteric Plexus

Back 66

Cisa-pride

**increases esophageal tone, gastric & duodenal contractility
**no longer used due to causing "torsades des pointes"

Front 67

Selective agonists for 5-HT(1D) and 5-HT(1B) receptors

Back 67

-TRIPTAN's

Front 68

What are the -Triptan's used for? What is their mechanism?

Back 68

Acute Migraine Headaches

Constrict Cerebral & Meningeal vessels

**adam TRIPTANS got 1D & 1B on his report card. Mr. TRIPTAN did not get a MIGRAINE due to VASOCONSTRICTION of cerebral vessels

Front 69

What are the adverse effects of the -Triptan's?

Back 69

Tingling or warmth sensations
Dizziness
Muscle weakness
Neck pain
Chest discomfort

"adam TRIPTAN had warm tingling feelings in his fingers, was dizzy, couldn't lift weights, and had neck pain & chest discomfort"

Front 70

What may the -triptan's cause?

Back 70

Coronary vasospasm and angina

Front 71

5-HT antagonist that blocks alpha-adrenergic and 5-HT2 receptors

Back 71

Phenoxy-benz-amine

Front 72

5-HT antagonist that blocks the 5-HT2 and H1 receptors in treatment of Carcinoid tumors, postgastrectomy dumping syndrome, and cold-induced urticaria

Back 72

Cypro-hep-tadine

**Cyprus 7 treats Carcinoid tumors, postgastrectomy dumping, & cold-induced urticaria

Front 73

5-HT antagonist that blocks vascular alpha1-adrenergic and platelet 5-HT2 receptors; used for treatment of HTN and vasospastic conditions

Back 73

Ketan-serin

Front 74

5-HT antagonist that blocks 5-HT2 receptors to alter bleeding time and platelet function; used as an antidepressant and for migraine treatment

Back 74

Ritan-serin

**"Write on Saran" that causes bleeding, no depression, and no migraine due to Anti-Serotonin 2

Front 75

3 5-HT antagonists that block 5-HT3 receptors; used for treatment of nausea and vomiting during cancer chemotherapy

Back 75

Onad-setron
Grani-setron
Dola-setron

**volleyball players SET-RON burgandy up for a spike...he wears 3 "high-tops" (5-HT3) which cause him to fumble around...he has nausea and vomits all over the court due to chemotherapy.

Front 76

List the 6 Ergot Alkaloid preparations

Back 76

1. Dihydro-ERGOT-amine
2. ERGO-novine
3. ERGOT-amine mixtures
4. ERGOT-amine tartrate
5. Methyl-ERGO-novine
6. Methy-sERG-ide

Front 77

What are the Ergot Alkaloids produced by?

Back 77

Claviceps purpurea
-fungus that infects grain (especially rye), under damp storage

Front 78

In ancient times, ingestion of contaminated grain resulted in epidemics of Ergotism characterized by these 3 symptoms

Back 78

1. Hallucination & convulsions
2. Prolonged vasospasm ➡ gangrene and fiery pain
3. Uterine contractions resulting in abortion

Front 79

What were the Ergot Alkaloids called in the medieval ages? Why?

Back 79

St. Anthony's fire

named after the saint who provided relief from the burning pain caused by the vasospasm

Front 80

What are the 2 families of Ergot Alkaloids?

Back 80

1. Amine alkaloids

2. Peptide alkaloids

Front 81

What alkaloids are in the Amine category? (3)

Back 81

1. Ergo-novine
2. Lysergic acid diethy-lamine (LSD)
3. Methy-sERG-ide

Front 82

Why do patient responses vary widely with Ergot Alkaloids?

Back 82

1. GI absorption is erratic
2. Variable central and peripheral effects

Front 83

Ergot Alkaloids can act as partial AGONISTS OR ANTAGONISTS on these receptor types (4)

Back 83

5-HT(1A)

5-HT(1D) = receptor that causes vasoconstriction

CNS Dopamine receptors

Alpha-adrenergic

Front 84

List the 3 peptide ergot alkaloids

Back 84

1. ERGOT-amine
2. ERGO-cryptine
3. Bromo-criptine

Front 85

T or F: Ergot Alkaloids may act on presynaptic or postsynaptic sites

Back 85

True

Front 86

What are the CNS effects of Ergot Alkaloids?

What are the sites of action?

Back 86

Hallucinogens (shown by LSD)

Agonist on pre- or post-jxn 5-HT2 receptors on CNS neurons

Front 87

What are the Ergot Alkaloid effects on Vascular Smooth Muscle?

What is the mechanism?

Back 87

Vasoconstriction

stimulation of alpha-adrenergic and 5-HT receptors

Front 88

Cerebral vessels are very sensitive vasoconstriction by these 4 Ergot Alkaloids

What are they often used for clinically?

Back 88

Ergot-amine
Dihydro-Ergot-amine
Suma-triptan
Methy-sERG-ide

Migraine Therapy

**alkaloid MEDS treat migraine

Front 89

The cerebral vasoconstriction of the Ergot Alkaloids is attributed to the partial agonist effects on these neuronal or vascular receptors (1)

Back 89

5-HT(1D) receptors

Front 90

Ergot Alkaloid effects on the Uterus
1. Small doses
2. High doses

Back 90

1. Rhythmic contraction and relaxation

2. powerful and prolonged contracture due to stimulation of Alpha-adrenergic and 5-HT receptors

Front 91

Ergot Alkaloids:

As pregnancy progresses __1__ receptors becomes more dominant and uterine sensitivity to Ergot Alkaloids increases

In simulating uterine contractions __2__ is much stronger than other ergot alkaloids

Back 91

1. Alpha1-adrenergic receptors

2. Ergo-novine

Front 92

T or F: Bronchial smooth muscles are very sensitive to Ergot Alkaloids, but the GI is unaffected

Back 92

False
-Bronchial smooth muscles = unaffected

- GI = very sensitive

Front 93

What are the most common adverse effects of Ergot Toxicity? What is this due to?

Back 93

GI disturbances = NVD

Increased GI motility resulting from activation of 5-HT receptors in CNS and GI

Front 94

What is the most serious toxic effect of Ergot Alkaloids?

What other effects may occur occasionally?

Back 94

Prolonged vasospasm in arms and legs ➡ gangrene and require amputation

Drowsiness and Hallucinations

Front 95

What are the 4 general clinical uses of Ergot Alkaloids

Back 95

1. Migraine treatment
2. Postpartum hemorrhage
3. Hyperprolactinemia
4. GI disorders

Front 96

The pain onset and relief with Ergot Alkaloids in the treatment of Migraines seem to be related to vasomotor changes that depend on changes in these 2 things

Back 96

1. Platelet

2. 5-HT

Front 97

Ergot Alkaloid that is used to treat migraines that produces vasoconstriction and is long-lasting and cumulative

Back 97

Ergot-amine

**to minimize cumulative toxicity, doses should not exceed 10 mg/wk

Front 98

Ergot Alkaloid and Selective Agonists for 5-HT receptors that are used to constrict Cerebral and Meningeal vessels but are not used in patients with Coronary Artery Disease b/c they may constrict coronary blood vessels

Back 98

Dihydro-ERGOT-amine

-TRIPTAN's = agonists for 5-HT(1D) & 5-HT(1B)

Front 99

What are some "other" drugs used for migrane prophylaxis?

Back 99

Ami-tripty-line
Methy-sERG-ide
Propanolol

Front 100

What are 2 Ca++ channel antagonists that have also been used for migraine treatment?

Back 100

Flu-nari-zine = for acute treatment

Verap-amil = for prophylaxis

Front 101

Ergot Alkaloid that produces a powerful & prolonged uterine spasm useful for control of late uterine bleeding

Back 101

Ergo-novine

Front 102

What may happen if Ergonovine is given before the delivery of the fetus?

Back 102

Maternal and Fetal death incidence may increase

Front 103

Ergot Alkaloids with high affinity for Pituitary Dopamine D2 receptors used to reduce high Prolactin levels produced by Pituitary tumors (3)

Back 103

1. Bromo-criptine

2. Caber-goline

3. Per-golide

**Dopamine is released from the Hypothalamus to decrease the release of Prolactin from the Anterior Pituitary
**High Prolactin levels stimulate the release of Dopamine from the Hypothalamus to decrease the release of Prolactin = negative feedback loop

Front 104

Ergot Alkaloid used as a 5-HT4 receptor agonist used for the treatment of GERD and GI motility disorders

Back 104

Cisa-pride

**kid wearing "4 high-tops" has GERD and GI motility disorders, but still has his "SISSY-PRIDE"

Front 105

Ergot Alkaloid that is a partial 5-HT4 agonist used for treatment of Irritable Bowel Syndrome

Back 105

Tega-serod

Front 106

3 Serotonin inhibitors that are Selcetive 5-HT3 antagonists used as Antiemetics (anti-nausea/vomiting)

Back 106

Dola-setron
Grandi-setron
Ondan-setron

**-Setron's