Antihistamines

Question 1

What do these two drugs do?
Cromolyn Sodium
Nedocromolin

Answer 1

Prevent histamine release.

Question 2

What effect does ACh have on histamine?

Answer 2

Induces histamine release from mast cells

Question 3

What effect do B-adrenergic agonists have on histamine?

Answer 3

Inhibit histamine release

Question 4

What type of receptor class do Histamine receptors belong?

Answer 4

All 4 are G-coupled receptors

Question 5

H1 Receptors are found…..?

Answer 5

CV, Resp. Sys., GI smooth mm.

Question 6

What effect does histamine have on the IP3 pathway?

Answer 6

When linked to the phosphoinositol pathway, activation causes contraction of smooth muscle.

Question 7

Outline the cellular signal pathway starting with H1 that causes smooth muscle contraction.

Answer 7

Histamine+H1==>Gq==> PLC==>IP3+DAG==>Increaseed Ca2+==> Increased Ca2+-Calmodulin==> Phosphorylation of Myocyte Light chains (MLC)

Question 8

The H1 receptor causes__________Via_______release from the vascular smooth muscle===> Increase cGMP==> Decreased Ca++.

Answer 8

1. Vasodilation

2. NO

Question 9

What other reflexes does the H1 receptor enable?

Answer 9

Sneezing and itching (pruritis). (Sensation from sesory nerve endings

Question 10

What role does the H2 receptor play?

Answer 10

Linked to relaxation of vascular smooth muscle and gastric secretions. also reduces histamine release from mast cells as a negative feedback loop.

Question 11

Where is the H2 receptor distribited?

Answer 11

CV, GI smooth muscle, Stomach

Question 12

Colocalization of H1 and H2 receptors causes?

Answer 12

H1 in vasc. endothelium==> Increased NO release and contraction of the endothelial cells.
H2 in vascular muscle===> causes relaxation (vasodilation)

Question 13

Where are H3 receptors found?

Answer 13

In the CNS

Question 14

What role does the H3 receptor play in the brain?

Answer 14

Linked to inhibition of NT release.

(Hist===>H3====> Decreased Ca++) Gi coupled!

Question 15

Where the hell are H4 receptors located?

what’s their role?

Answer 15

1. On mast cells, basophils and eosinophils.

2. Linked to hista,mine-induced chemotaxis

Question 16

What do the H1 and H2 receptors do in the CV system?

Answer 16

H2: Moderate increase in rate and force of contraction.

Vasodilation (H1 in endothelium and H2 in smooth muscle.

Question 17

What histamine receptor is in the resp. sys and how does it work?

Answer 17

H1 mediated bronchial constriction of smooth muscle.

Question 18

What histamine receptor is in the stomach and how does it function?

Answer 18

H2 mediated acid release from parietal cells of stomach

Question 19

What effect does histamine have on the heart?

Answer 19

Positive chronotropy and ionotropy.

Question 20

Cardio crap: Define Chronotropy and Ionotropy.

Answer 20

Chronotropy affects the heart rate.

Ionotropy affects force of heart contraction.

Question 21

Outline pathway of how H2 receptor modulates chronotropy?

Answer 21

Hist+H2R==>G-couple»» AC…..Increase cAMP which binds to and opens HCN channel allowing Na+ influx. cAMP+PKA bind L-type Ca++ channel allowing Ca++influx into cell.
In inotropy, Histamine binds….G-coupled signaling….L-type Ca++ channels open=Contraction (No HCN)

Question 22

What does histamine do do veins?

Answer 22

Constricts them

Question 23

What effect does histamine have on capillaries?

Answer 23

Increases permeability. H1=Endothelial contraction, H2=Vascular smooth muscle relaxation.

Question 24

List pathologies caused by histamine

Answer 24

Urticara-Hives, rash, edematous welts
Dermatographia- Redness on mechanical stimulation.
Flushing- Due to vasodilation or seeing bae.

Question 25

Histamine causes_______ in the respiratory system via_______. This receptor uses________as second messengers.

Answer 25

1. Broncocontriction 2. H1 3. Gq, IP3, DAG.

Question 26

Anaphylaxis is treated with?

Answer 26

Epinephrin (Epi-Pen)

Question 27

Differentiate H1 and H2 receptor antagonists

Answer 27

H1 antagonists are reffered to as antihistamines (Don't bind H2) H2 antagonists are referred to as acid blockers (don't bind H1 receptors)

Question 28

What is an inverse agonist?

Answer 28

This is basically a clown agent that binds a selected receptor like an agonist would but instead of causing an agonist effect, it does the exact opposite. (SO structurally these guys have to retain a structure very close to histamine)

Question 29

Name the 1st gen antihistamine classes.

Answer 29

``` Alkymines Ethanolamines Ethylenediamines Phenothiazides Piperadines Piperazines ```

Question 30

Give examples of 1st gen antihistamines

Answer 30

``` Bromopheniramine Cyproheptadine Diphenhydramine Promethazine Hydroxyzine Pyrilamine ```

Question 31

What effct do H1 antagonists have in the CNS?

Answer 31

They have sedative effects as the block H1/H2 receptors in the brian which are important in wakefulness.

Question 32

Which H1 class of drugs are the most sedative?

Answer 32

Ethanolamines and phenothiazines (ie diphenhydramine, promethazine)-Older H1 antagonists are sedating (someday we won't have to give a shit about old drugs)

Question 33

What other effect do H1 antagonists have?

Answer 33

Anticholinergic effects (atropine-like effects) only in 1st gen drugs. Anti-motion sickness and antiemetic effects likely derived from anti cholinergic effect (Promethazine is potent ; Scopalamine-like) Also cause typical anticholinergic effects: Dry mouth, decreased urination

Question 34

Which 1st gen drugs are used as local anesthetics?

Answer 34

Pyrilamine, Promethazine

Question 35

Which H1 antagonists have anti-serotonin activity? Used for?

Answer 35

Cyproheptadine, azatidine | Antipruritic

Question 36

Which drugs H1 antagonists have Alpha adrinergic antagonism? Used for?

Answer 36

Phenothiazines, Used for hypertension

Question 37

Which H1 antagonists have extrapyramidal activity? used for?

Answer 37

The Phenothiazine; promethazine | Dystonia, akathisia

Question 38

Name the 2nd generation H1 antagonists!

Answer 38

``` Loratadine (Claitin) Desloratadine(Clarinex) Fexofenadine(Allegra) Cetirizine(Zyrtec) Terfidine (Seldane) ```

Question 39

Difference between the 1st gen and second gen H1 antagonists

Answer 39

1st Gen H1 antagonists=Lipid soluble, CNS effects, not very selective 2nd gen= Low lipid solubility, little/no sedation, no antimuscarinic activity, no anti-emetic activity, no anti-motion sickness activity. Efflux from CNS via P-glycoprotein transporter

Question 40

What other effects does Cetrizine (zyrtec) have?

Answer 40

Blocks: LTC4, Neutrophil migration, Eosinophil infiltration (H4 block maybe?)

Question 41

What is Olopatadine? Whst is it used for?

Answer 41

2nd gen H1 antagonist eye drops

Question 42

What are azelastine and Ketotifen?

Answer 42

Azelastine and Ketotifen are H1 antihistamines used as eye drops in the US to relieve eye irritation.

Question 43

Name the 3 antihistamine drugs to treat motion sickness.

Answer 43

Dimenhydinate (Diphenydramine+Chlorotheophylline), Meclizine | Promethazine

Question 44

Which antihistamines cause sadation?

Answer 44

Ethanolamines Phenothiazines These may interact with other sedatives (alcohol, anxilytics, antipsychotics

Question 45

What are 1st gen antihistamines contraindicated in?

Answer 45

Urinary retension, narrow angle glaucoma