Pharm 5 Exam _Histamine & Serotonin

Front 1

Cromolyn sodium MOA and therapeutic uses?

Back 1

Inhibits Mast cell degradation

Used only as prophylaxis for asthma & allergy symptoms

Front 2

Cromolyn breakdown

& side effects

Back 2

excreted unchanged in urine & feces

Minor irritation at site of administration

Front 3

Diphenhydramin MOA & therapeutic uses?

Back 3

Blocks H-1 receptors (1st generation)
Utility for hay fever & allergy symptoms as well as motion sickness reflects anti-muscarinic action

Front 4

Diphenhydramin Side effects & metabolism

Back 4

SEDATION (enters CNS b/c lipid soluble)
urinary retention, blurred vision are from its antimuscarinic effects

Extensively hepatic metabolism!

Front 5

fexofenadine MOA & uses

Back 5

MOA: Blocks H1 receptor (2nd generation, less "dirty"

Uses: allergies & hive

Front 6

Fexofenadine side effects & metabolism

Back 6

drug allergy & headaches

High % is excreted unchanged in feces

Front 7

Cimetidine MOA & uses

Back 7

Blocks H-2 receptors: decrease gastric acid secretion, decrease pepsin concentration in gastric compartment

Ulcers, Gerd, Gastric hypersecretory (zollinger ellison), heart burn

Front 8

Cimetidine Side effects?

Back 8

very dirty drug!!!

GI: diarrhea, constipation, vomiting, cholestasis, decrease hepatic blood flow
CNS: dizziness, somnolence, headache
Endocrine: gynecomastia (men), galactorrhea (women)
GU:decrease sperm count, reversible impotency -->
Blood: granulocytopenia, thrombocytopenia, neutropenia, aplastic anemia
Other: rash, arthralgia
Interacts w/ drugs metabolized by some Cytochrome P-450 enzymes - LIVER TOXICITY!

Front 9

Rantidine MOA & uses

Back 9

Blocks H-2 receptors: decrease gastric acid secretion, decrease pepsin concentration in gastric compartment

(less dirty than cimetidine)

Uses: ulcers, GERD, gastric hypersecretory( Zollinger-Ellison), heartburn

Front 10

Rantidine Side effects & excretion

Back 10

GI: diarrhea, constipation, vomiting, reversible hepatitis
CNS: dizziness, somnolence, headache
Other: rash, arthralgia

Excretion: mostly renal, small amounts of S-oxidate, N oxide & N desmethyl metabolites

Front 11

Omeprazole MOA & uses

Back 11

PPI --> Prodrugs; Block action of hydrogen-potassium ATPase in parietal cells

uses:
GERD
Peptic ulcer disease
Gastric hyper-secretory conditions (e.g., Zollinger-Ellison Syndrome)
Prevent ulcers in patients taking NSAIDs

Front 12

Omeprazole side effects & excretion

Back 12

Minor: diarrhea, headache, abdominal pain
Sub-normal plasma vit B12 levels (due to decrease acid)

Enteric infections (e.g., salmonella, shigella) (due to decrease acid)

Excretion: extensively hepatic; first pass effect!

Front 13

Esomeprazole MOA & uses

Back 13

MOA: PPI (S isomer of omeprazole)

Uses: same, GERD, ulcers, etc

Front 14

Esomoprazole side effects & excretion

Back 14

Diarrhea, headache, abd pain, low B12

Enteric Infections due to decrease acid

Extensive first pass metabolism (HEPATIC)

Front 15

Serotonin metabolism (what's it start as and go to?)

Back 15

tryptophan → 5HT → melatonin

Front 16

Serotonin receptors: how many and what type?

Back 16

7 families of serotonin receptors (6 GPCR; 1 ligand-gated Na/K channel: 5-HT-3)

Front 17

Serotonin effects on:

1) Nervous system
2) Pulm
3) CV
4: GI

Back 17

Nervous System: vomiting due to chemical triggers, stimulates pain/itch in sensory nerve endings
Pulm: broncho-constriction
CV: vasoconstriction (except in muscle & heart: vasodilator), platelet aggregation
GI: increase smooth muscle tone & peristalsis

Front 18

Serotonin metabolism

Back 18

MAO &
5-HT N-acetylase (w/ melatonin as 1 downstream product)

Front 19

Sumatriptan MOA & uses

Back 19

SEROTONIN (5HT 1D/1B) AGONIST

Causes vasoconstriction of cerebral & meningeal vessels via 5-HT 1D/1B receptors

Uses: migraine headaches

Front 20

Sumatriptan Side effects & metabolism

Back 20

Altered sensations, dizziness, muscle weakness, neck pain, coronary vasospasm

Hepatic excretion

Front 21

Ondansetron MOA & uses

Back 21

5-HT 3 ANTAGONIST

Antiemetic (NOT effective for motion sickness)

Front 22

Ondanestron side effects & metabolism

Back 22

Headache, maliase, constipation, diarrhea

Hepatic metabolism

Front 23

Alosetron MOA & uses

Back 23

5HT3 antagonists

Uses: IBS in women

Front 24

Alosetron side effects & metabolism

Back 24

Ischemic colitis

Extensively hepatic metabolism

Front 25

Cyproheptadine MOA & uses

Back 25

MOA: 5-HT 2 Antagonist; Blocks 5-HT 2, also blocks H1 (antihistamine action)

Uses:
Hay fever/allergy symptoms
Urticaria
Off-label: post-gastrectomy dumping syndrome

Front 26

Cyproheptadine side effect & metabolism

Back 26

drowsiness & thickened bronchial secretions

Hepatic metabolism

Front 27

metoclopramide MOA & uses

Back 27

5-HT 4 Agonists

5-HT 4 agonism → release Ach → increase GI motility
D2 antagonism → anti-nausea, anti-emetic actions

Uses: STIMULATE GI MOTILITY

Front 28

Metoclopramide side effects & metabolism

Back 28

Tardive Dyskinesia (irreverisble!!!) <-- parkinson like symptoms!

Metabolism: renal

Front 29

Cisapride MOA & uses?

Back 29

5-HT 4 Agonists→ release Ach →increase GI motility

Uses: Nighttime heartburn in patients unresponsive to other txs

Front 30

Cisapride side effects & metabolism

Back 30

LIFE THREATENING HEART RHYTHM ABNORMALITIES!!!!!!!!
(removed from general market)

Metabolism: hepatic

Front 31

Tegaserod MOA & uses

Back 31

5HT4 partial agonist

IBS in women w/ constipation

Front 32

Tegaserod side effects & metabolism

Back 32

Cardiac Events (MI, stroke, unstable nagina) --> only for hospitalized patients

metabolism: heaptic

Front 33

How is Histamine synthesized?

Back 33

The essential amino acid (histadine) is decarboxylated to make histamine

Front 34

How is Histamine Metabolized?

Back 34

two different mechanisms:

1) N methyltransferase --> N methylimidazole Acetic Acid

2) Diamine Oxidase --> Imidazoleacetic acid Riboside

Front 35

Where is histamine stored?

Back 35

In granules in mast cells and basophils

Front 36

Where are the H1 receptors found?

Back 36

Smooth muscle, endothelium, brain

Front 37

What is post receptor mechanism at H1 receptors?

Back 37

Gq -->activates Phospholipase C --> forms IP3 & DAG

Front 38

Where are the H2 receptors found?

Back 38

Gastric Mucosa, cardiac muscle, mast cells, blood vessels, smooth muscle, brain

Front 39

What is post H2 Receptor mechanism?

Back 39

Gs --> activates Adenyl Cyclase --> activates cAMP - dependent protein Kinase

Front 40

Where are H3 receptors found?

Back 40

Pre-synaptic autoreceptors in histaminergic neurons; presynaptic inhibition of release of neurotransmitters including ACh,DA, NE, and 5HT

Front 41

What is the mechanism of the H3 receptors?

Back 41

Gi --> decrease in cAMP & decrease in intracellular Ca++

Front 42

Where are H4 receptors found & what is there mechanism?

Back 42

Eosinophils, Neutrophils, CD4T cells

Gi --> decrease in cAMP & decrease in Ca++

Front 43

What is histamine's effect on the heart?

Back 43

Directly increases contractility and pacemaker rate – mediated by H-2 receptors, in human atria can decrease contractility through H-1 receptors.

Front 44

What is histamine's effect on the vasculature?

Back 44

Histamine’s action on both H-1 and H-2 receptors in the vasculature causes vasodilation. H-1 receptor causes a vasodilation more rapidly and of shorter duration. H-2 receptor vasodilation occurs more slowly than H-1 but is of longer duration than H-1.

Front 45

Does histamine impact systolic or diastolic BP more?

Back 45

Diastolic has a greater drop w/ histamine

Front 46

What is histamine's impact on the:

Bronchiolar smoothe muscle?
Uterus?
Secretory tissue?

Back 46

Bronchiolar smoothe muscle: H1 mediates bronchoconstriction

Uterus: Induces contractions

Secretory tissue: H2 mediated gastric secretions through increased cAMP; also secretions in large & small intestine