Autocoids Flashcards
What two greek words are in Autacoids?
“Autos” - self
“Akos” - Medicinal Agent or Remedy
What are Hormones?
Act beyond their site of production carried by way of bloodstream for selective action elsewhere in the body.
What are Autacoids?
Local Hormones - Have a brief lifetime and act near their site of synthesis.
What are 4 examples of Autocoids?
- Histamine
- Prostaglandins
- Leukotrienes
- Serotonin
Where is Histamine stored?
Mast Cells and Basophils
What receptors does histamine act on and what is their effect?
H1Receptor: Mediated Allergic Reactions; Can Act as a NT in the Nervous System
H2 Receptor: Promortes Gastric Acid Secretion
What is histamine bound to when stored?
Heparin Sulfate
OR
Chondroitin sulfate E
How and why is histamine released?
Released by exocytosis in response to allergens.
What drugs promote histamine release?
- Opioids (Morphine)
- NMJ Competitive Blocks (tubocuranine)
These typically causes itch to develop. Commonly used in anesthesia.
These displace histamine from the heparin0protien complex in mast cells.
What are some drugs that prevent histamine release?
- Cromolyn (Sodium Cromoglycate)
- Theophylline/Aminophylline
- Beta-2 Agonists - Ventolin - Salbutamol (Also cause Bronchodilation)
Cromolyn = Mast Cell Stabilizer - Prevents Degranulation
Does not affect IgE or Allergen Binding
What allergic indications is Sodium Cromoglycated used for?
Allergic Rhinitis - Nose Spray
Allergic Conjunctivitis - Eye Drops
Asthma - Inhaler
What does the action of histamine at H1 receptors cause at various differnt organs?
Respiratory - Bronchoconstrictions
Skin - Pain, Itching
Reductions in Vascular Resistance - Decreased Blood Pressure; Increased Heart Rate (Dilates Blood Vessels)
Gastointestinal Smooth Muscle - Relaxing/Contraction
Gall Bladder - Smooth Muscle Contraction
Dilation of Blood Vessels can cause closure of upper airways.
What is the mechanism of antihistamines and what is it used for?
Mechanism: H1 receptor Antagonists
Used to mediate itch - Histamine not only mediator of itch so effect depends on what is causing itch
In the CNS causes Sedation - Particularly with 1st generation agents, which cross the BBB.
How are antihistamine drugs most effective?
Taking on a regular basis proactively for managing seasonal allergies.
Not as good for acute anaphylactic attacks.
Why do Antihistamines not work in Anaphylaxis?
It works to slow and too late.
At the time of Anaphylaxis, histamine has already been released and bound to receptors - the downstream effects of histamine are the ones that need to be addressed.
What are the routes of administration of antihistamines?
Oral
Topical - Dermal; Opthalmic
What are the 2 types of of Oral antihistamines?
1st Generation: Benadryl and Topical Diphenhydramine - Crosses BBB and causes sedation.
2nd Generation: Loratadine (Claritin) - Non Sedating - Does not cross BBB.
Advantage to sedating is that itch can cause trouble sleeping.
Sedation at night can persist to the next morning.
What type of side effect do many antihistamines have?
Anticholinergic Effects - Dry Mouth
Especially First Generation.
What are the 2 isoforms of COX and what are their unique properties?
New NSAIDS focus on COX 2 to prevent stomach ulcers.
What is the Arachidonic Acid Cascade?
Describe the COX pathway.
COX - Cycloxygenase.
COX converts arachiodonic acid to PGH2 which is then acted upon by various enzymes to form:
PGE2 - Mediated Fever, Pain, Inflammation, Vasodilation, Mucous Production (Protective).
TxA2 - Platelet Aggregation; Vasoconsriction
PGI2 - Platelet Inhibition; Vasodilation
How did they make the selective blockers of COX only work on COX 2?
Made them bulkier so they could only reach the binding site of COX 2 and did not fit in COX 1.
What was an unexpected problem of selective COX-2 inhibitors?
Cardiovascular Complication.
Heart Attacks
What what the pharmacological reasoning why selective COX-2 inhibitors caused heart attacks?
What are the most noteworthy drugs that target prostaglandins?
NSAIDS
What are the targets other than COX in the COX pathway?
PGI2 - Prostacyclin
TxA2 (Thromboxane A2)
PGF2a
What drug is used to treat pulmonary hypertension and is a prostacyclin analogue?
In PH, vessels in the lungs become constricted, causes strain on the heart and right heart failure.
Epoprostenol
Must be given intravenously through catheter/infusion pump.
What is the side effect of Prostacyclin and Epoprostenol?
Bleeding - Has Anti-Platelet Effects.
What drugs target Thromboxane A2 and used to treat peripheral artery disease(PAD)?
TRASI - Thromboxane Receptor Antagonist or/and Synthase Inhibitor
Picotamide - Used in Europe
What effects does PGF2a have?
Promotes uterine Contractions
Promotes outflow of aqueous humour from the eye.
What drugs are used to promote secretion of GI mucous, abortions, and Management of Glaucoma?
PGF2a Analogues
Misoprostol - Abortion
Latanaprost - Glaucoma
What are some examples of Leukotrienes?
LTC4, LTD4, LTE4
Cysteinyl Leukotrienes
They. mediate inflammation, allergy, bhronchoconstricition.
Describe the Lipoxygenase Pathway.
What are some examples of Leukotriene targeting drugs and where do they target in the Lipoxygenase pathway?
What are the benefits of LTRA (Leukotrine Receptor Antagonists)?
- Well Tolerated
- Can be used orally
- Interest in investigating leukotriene inhibitors for other inflammatory conditions.
Used in Canada
What type are most serotonin receptors?
G-Protein coupled
And Various subtypes
5HT-1 - 5HT-7
What is another name for serotonin?
5-Hydroxytryptamine (5HT)
What are the main sites of action of serotonin and what is their role?
GI Tract (Enterochromaffin Cells) - Major source of Serotonin
Platelets - Results in platelet aggregation.
Brain - Key role in anxiety and depression.
What do we do to improve symptoms of depression?
Promote Serotonin
Almosot all antidepressants work by promoting 5HT in the CNS
What mechanism do antidepressants use?
Reuptake Inhibition
Leaves more NT in the synapse.
What is an example of a selective reuptake inhibitor for serotonin used to treat depression?
Fluoxetine
What are the properties of the different serotonin receptors?
