Sertonin Agaonists And Antagonist

Front 1

what is important to understand about serotonin agonists?

Back 1

a. Serotonin agonists activate serotonin receptors and mimic the effect of endogenous serotonin. Since there are so many different types of serotonin receptors, the agonists target different receptors for different diseases.

Front 2

what are the serotonin receptors;name only?

Back 2

c. Serotonin receptors:
i. 5HT-1A: role in anxiety/depression
ii. 5HT-1D: role in migraine
iii. 5HT-2: role in CNS various behaviors, and in cardiovascular system
1. 5HT-2 on platelets  aggregation and vasoconstriction
iv. 5HT-3: role in nausea and vomiting, especially due to chemotherapy (present in the CTZ)

Front 3

what is the role of 5HT-1a?

Back 3

i. 5HT-1A: role in anxiety/depression

Front 4

what is the role of 5HT-1d

Back 4

ii. 5HT-1D: role in migraine

Front 5

what is the role of 5HT-2

Back 5

iii. 5HT-2: role in CNS various behaviors, and in cardiovascular system
1. 5HT-2 on platelets  aggregation and vasoconstriction

Front 6

what is the role of 5HT-3

Back 6

iv. 5HT-3: role in nausea and vomiting, especially due to chemotherapy (present in the CTZ)

Front 7

what is serotonin effect on respiratory?

Back 7

i. Respiratory system
1. Bronchoconstriction if asthmatic
2. Stimulation of aortic and carotid chemoreceptors  increased respiratory rates

Front 8

what is serotonin effect on GI

Back 8

ii. GI tract
1. The small intestine is very sensitive to serotonin  intense rhythmic contractions due to direct and indirect effects (diarrhea)
2. Also stimulates vomiting (5HT-3 receptors on vagal afferents and centrally)

Front 9

what is serotonin effect on cardiovascular

Back 9

iii. Cardiovascular system
1. Direct vasoconstriction (large arteries) and indirect vasodilation (NO and PGI2 mediated). The effect is initial contraction with later dilation.
2. Heart: direct inotropic and chronotropic effects
3. Reflex mechanisms due to change in BP
4. Stimulation of sensory nerve endings in baroreceptors and in vagal afferents in the coronary circulation  bradycardia and hypotension (esp if dose is too high)

Front 10

what is serotonin effect on CNS

Back 10

iv. CNS
1. Pain perception
2. Sleep/wakefulness
3. Various normal and abnormal behaviors: depression, schizophrenia, obsessive compulsive behavior, etc.
4. Neuroendocrine regulation: controls hypothalamic cells involved in the release of several anterior pituitary hormones.

Front 11

what is the function of histamine antagonists?

Back 11

blocks teh effect of histamine that mediate allergy

Front 12

where is H1 found?

Back 12

1. Found on smooth muscle, endothelium, CNS

Front 13

where is H2 found?

Back 13

1. Found on parietal cells

Front 14

where is H3 found?

Back 14

1. Found in CNS

Front 15

what is the function of H1

Back 15

2. Activation results in vasodilation, bronchoconstriction, smooth muscle activation, and separation of endothelial cells.

Front 16

what is the function of H2

Back 16

2. Regulates gastric acid secretion

Front 17

what is the function of H3

Back 17

2. Regulates release of other NTs

Front 18

what is the function of H4

Back 18

1. Recently discovered, function not really known.

Front 19

what are the serotonin agonists? name only

Back 19

i. Sumatriptan: 5HT-1D agonist; contraindicated in pts with angina
ii. Fluoxetine: selective serotonin uptake inhibitors for depression and other indications
iii. Buspirone: 5HT-1A agonist for anxiety
iv. Cisapride: 5HT-4 agonist to increase GI motility and decrease gastro-esophageal reflux
1. Removed from the US market due to fatal arrhythmias
v. LSD: 5HT-1A agonist – hallucinogen
vi. Ergot alkaloids: 5HT-a and 2, used for migraine

Front 20

what is the target receptor for sumatriptan?

Back 20

5HT-1D agonist

Front 21

what is sumatriptan contraindicated in?

Back 21

contraindicated in pts with angina

Front 22

what is sumatriptan used for?

Back 22

migraine

Front 23

what is fluoxetine indicated for?

Back 23

selective serotonin uptake inhibitors for depression and other indications

Front 24

what is the receptor target for cisapride?

Back 24

5HT-4 agonist

Front 25

what is the target of buspirone?

Back 25

5HT-1a agonist

Front 26

what is the use of buspirone?

Back 26

anxiety

Front 27

what is the use of Cisapride?

Back 27

: 5HT-4 agonist to increase GI motility and decrease gastro-esophageal reflux

Front 28

what is the receptor target of LSD?

Back 28

5HT-1A agonist

Front 29

what is the activity of LSD?

Back 29

1A agonist – hallucinogen

Front 30

what is the target of the ergot alkaloids?

Back 30

5HT 1a and 2

Front 31

what are the ergot alkaloids used for?

Back 31

migrains

Front 32

what are the serotonin antagonists, names only?

Back 32

b. Serotonin antagonists:
i. Methysergide and Cyproheptadine: 5HT-2 antagonists, used in carcinoid syndrome and migraine
ii. Ketanserin: 5HT-2 and alpha antagonist, used as an antihypertensive
iii. Ondansetron: 5HT-3 antagonist for chemotherapy induced nausea and vomiting
iv. Clozapine: 5HT-2A/2C antagonist for schizophrenia

Front 33

i. Methysergide and Cyproheptadine target what receptor?

Back 33

5HT-2 antagonists

Front 34

what is Methysergide and Cyproheptadine used for?

Back 34

5HT-2 antagonists, used in carcinoid syndrome and migraine

Front 35

what is ketanserin receptor target?

Back 35

5HT-2 and alpha antagonist

Front 36

what is ketanserin used for?

Back 36

antihypertensive

Front 37

what is ondansetron receptor target?

Back 37

-3 antagonist

Front 38

what is ondansetron used for?

Back 38

chemotherapy induced nausea and vomiting

Front 39

what is clozapine target

Back 39

5HT-2a/2c antagonist

Front 40

what is clozapine used to treat?

Back 40

schizophrenia

Front 41

what are qualities of the 1st gen antihistamines?

Back 41

i. Small lipophilic molecules that could cross the BBB
ii. Not specific to the H1 receptor
iii. Cause severe sedation, anticholinergic effects, gastrointestinal reactions, other CNS effects

Front 42

what was the benifit of th second gen antihistamines?

Back 42

more selective for peripheral H1 recpetors

Front 43

what are the second gen antihistamines?

Back 43

ii. Terfenadine
iii. Loratadine
iv. Cetirizine
v. Mizolastine
vi. Astemizole

Front 44

what are the 3rd gen antihistimines made from?

Back 44

i. Metabolite derivatives or active enantiomers of second generation drugs. (It was found that it was actually the active metabolite of the antihistamines that produced its pharmacologic action, and that many side effects were attributed to the parent drug or another, non-active metabolite. Solution  make active metabolite into its own drug).

Front 45

what is the benifit of the 3rd gen antihistimines?

Back 45

ii. Safer, faster acting, and/or more potent than second generation antihistamines

Front 46

what are the 3rd gen antihistimes?

Back 46

iii. Fexofenadine
iv. Desloratadine
v. Levocetirizine

Front 47

what is the action of endothelin-1?

Back 47

a. Endothelin -1 is a potent vasoconstrictor. Its plasma levels are increased in pulmonary hypertension.

Front 48

what are the endothelin-1 antagonists? name only

Back 48

a. Bosentan
i. Sulphonamide-based ETA and ETB receptor blocker
ii. Contraindicated in pregnancy because of its teratogenicity (causes NT defects, cleft lip/palate).
iii. Inducer of CYP2C9, CYP3A4
b. Sitaxentan
i. Sulphonamide-based selective ETA antagonist
ii. Metabolized by CYP2C9  interaction with warfarin
c. Ambrisentan
i. Non-sulphonamide ETA moderately selective antagonist.
ii. No significant interaction with coumarin based anticoagulants.

Front 49

what are the sulphonamide based endothelin receptor antagonists?

Back 49

bosetan
sitaxentan

Front 50

which endothelin antagonist is a non-sulphanamide

Back 50

ambrisentan

Front 51

when is bosentan contraindicated?

Back 51

ii. Contraindicated in pregnancy because of its teratogenicity (causes NT defects, cleft lip/palate).

Front 52

what is bosentan an inducer of?

Back 52

iii. Inducer of CYP2C9, CYP3A4

just remember its a CYP inducer

Front 53

which endothelin antagonists are selective for ETa and which one works on both ETa and ETb

Back 53

selective- sitaxentan, ambrisentan

targets both-bosentan

Front 54

what is sitaxentan metabolized by and what does it interact with as a result?

Back 54

ii. Metabolized by CYP2C9  interaction with warfarin

Front 55

what is an advantage of ambrisentan?

Back 55

ii. No significant interaction with coumarin based anticoagulants.

Front 56

what is the chemical name of serotonin?

Back 56

5-hydroxytyptamine

Front 57

what is the required amino acid for serotonin?

Back 57

tryptophan

Front 58

what drug treatment can lead to increased serotonin

Back 58

MAOI

Front 59

what drug inhibits serotonine synthesis?

Back 59

p-chlorophenylalanine(irreversible)

Front 60

what inhibits neuronal reuptake of serotonine?

Back 60

cocaine, SSRA(fluoxetine), TCA(imipramine)

Front 61

what depletes or inhibits storage of serotonin?

Back 61

reserpine

Front 62

what inhibits metabolism of serotonin?

Back 62

MAOIs

Front 63

what promotes release of serotonin?

Back 63

p-chloroamphetamine

Front 64

what is seretonin a precursor to?

Back 64

melatonin-which is important in sleep

Front 65

where is constriction more prominent in serotonin?

Back 65

large arteries and coronary arteries

Front 66

what is the difference between acute vascular effects and chronic ones?

Back 66

acute-vasoconstriction

chronic-vasodialation due to release of NO

Front 67

what serotonin is used most often in OCD?

Back 67

fluoxetine

Front 68

which drug for serotonins was removed from US market, why?

Back 68

cisapride due to fatal arrythmias

Front 69

what releases histamine?

Back 69

mast cells

Front 70

where are H4 histamine receptors found?

Back 70

throught body, brain, lung, bone marrow, etc..

Front 71

main downside to 1rst gen antihistamine?

Back 71

cross BBB and cause sedation

Front 72

at high enough dose what occurs in ALL antihistamines?

Back 72

ALL will cross the BBB if you take a large enough dose.

Front 73

what is needed to know about Cetirizine in kids?

Back 73

they metabolize it much faster than adults.normal for the other drugs in this class

Front 74

what is the main adverse reactions of antihistamines?

Back 74

sedation/dizzyness/dry mouth

Front 75

what is the origin of all eicosanoids?

Back 75

arachidonic acid

Front 76

what are the eicosanoid examples?

Back 76

protaglandins, leukotrienes, thromboxanes, prostacyclins,

Front 77

what are special about the eicosanoids?

Back 77

local mediators

Front 78

what are the effects of prostaglandins?

Back 78

lower bp
inhibit blood platelet aggregation
control inflammation
lower gastric secretions

relax smooth muscles of the uterous

Front 79

what are the effects of thromboxanes

Back 79

constrict blood vessels
trigger blood platelet aggregration

Front 80

what are the effects of prostacyclins?

Back 80

dilate blood vessels
inhibit blood platelet aggregation

Front 81

what is the effects of leukotrienes?

Back 81

constrict smooth muscle espeacially in the lungs.

Front 82

what is generic name of dinoprostone?

Back 82

PGE2

Front 83

what is dinoprostone used for?

Back 83

prevent preterm labor

Front 84

what is the half life of the natural ecosanoids

Back 84

very short only minutes

Front 85

what is a classic example of a synthetic prostglandin that was developed that has a longer half life?

Back 85

misoprostol an analogue of PGE1. to prevent gastric ulcers

Front 86

what are the mediators of pulmonary hypertension?

Back 86

endothelin-1
serotonin
prostacycline
thromboxane A2
adrenomedullin
VIP
VEGF

mainly just remember that serotonin,some of the eicosanoids, and endothelin-1 all can result in pulmonary hypertension when stimed

Front 87

so any antagonist of serotonin can be used to treat what?

Back 87

pulmonary hypertension

Front 88

what are some adverse effects of sitaxentan?

Back 88

liver issue
headache -everyone usually short term
edema
constipations-common
nasal condgstion
upper respiratory tract innfection
dizziness
insomnia
flushing

Front 89

what is a factor that significantly increase risk of side affect in sitaxentan?

Back 89

smoking or use of any tobacco product