Autocoids Flashcards
Activation of H1 receptor
Vasodilation (NO induced)
Increases vascular permeability
Bronchoconstriction
Activation of H2 receptor
Increases gastric acid secretion
Diphenhydramine
1st generation H1 receptor inhibitor
Muscarinic blocker - strong
Sedation - strong
Blocks motion sickness - strong
Promethazine
1st generation H1 receptor inhibitor Muscarinic blocker - strong Sedation - strong Blocks motion sickness - moderate Some alpha blocker and local anesthetic action
Chlorpheniramine
1st generation H1 receptor inhibitor Muscarinic blocker - mild Sedation - moderate Blocks motion sickness - moderate May cause CNS stimulation
Meclizine, cyclizine, hydroxyzine
1st generation H1 receptor inhibitor Muscarinic blocker - mild Sedation - moderate Blocks motion sickness - strongest For motion sickness
Doxylamine
Includes vitamin B6
Used for morning sickness during pregnancy
Which are the 2nd generation H1 receptor inhibitors?
Cetirizine (mild sedation)
Loratadine (Claritin, most used)
Fexofenadine
No CNS entry
What are H1 receptor inhibitors used for?
Allergic or anaphylactic reaction Pruritis Allergic rhinitis, conjunctivitis Motion sickness (imbalance signal of motion from ear and eye ---histaminergic neurons in hypothalamus----H1 and M receptor in vomiting center in medulla----nausea, vomiting) Vertigo - meclizine
Side effects of H1 receptor inhibitors (1st generation)
Enter CNS, causing sedation; anti-muscarinic effect causing dry mouth and urine retention
What is the marker of carcinoid syndrome?
5HIAA > 25mg
Symptoms of carcinoid syndrome
Flushing ( caused by kallikrein, the precursor of bradykinin) Intermittent abdominal pain Diarrhea BP decrease Palpitation Wheezing
5-HT1 receptor
Gi –> decreases cAMP
Causes arterial contraction in carotid and cranial circulation
5-HT2 receptor
Gq –> increases IP3
Causes vasoconstriction, platelet aggregation, increases GI peristalsis, increases gastric acid secretion, increases vascular permeability
In the CNS it causes excitation and hallucination
5-HT3 receptor
Couples to Na+/K+ channel in the nervous system of the GIT and vomiting centre of the medulla
Causes vomiting
5-HT4 receptor
Gs –> increases cAMP
In enteric nervous system, it increases Act release –> GI motility increases
Sumatriptan
5-HT1D agonist
Used for acute migraine attacks
Buspirone
Partial 5-HT1A agonist
Used for manage anxiety
Clozapine, olanzapine, risperdone
Atypical anti-schizophrenic agents
5-HT2A antagonists
Cyproheptadine
5-HT2 and H1 antagonist
Used in carcinoid syndrome, seratonin syndrome and allergy
Ondansetron (and granisetron, dolasetron and alosetron)
5-HT3 antagonist
Central antiemetic
Used to control vomiting associated with chemotherapy
Alosetron used in IBS
Octreotide
Somatostatin analog
Suppresses GI 5-HT secretion
Reduces GI motility
Supresses gastrin, cholecystokinin, glucagon, growth hormone, insulin, secretin, pancreatic polypeptide, TSH, and vasoactive intestinal peptide secretion
Reduces secretion of fluids by the intestine and pancreas
Vasoconstriction
Decreases portal vessel pressure, treats variceal hemorrhage
Ergots (in general)
Partial agonist to alpha and 5-HT2 receptor
LSD
Ergots
Lysergic acid diethylamide
5-HT2A partial agonist in CNS
Causes hallucination
Bromocriptine, cabergoline, pergolide
Ergots
Agonists to dopamine D2 receptor
Used for hyperprolactinemia
Pergolide can cause valvular heart disease
Bromocriptine used for Parkinson’s disease
Ergonovine
Ergots
Contract uterus
Used for obstetric bleeding, post part hemorrhage
Ergotamine
Ergots Vasocontrictor Contract uterus Used for obstetric bleeding, post part hemorrhage Can also be used for migraine attacks
Methysergide
Ergots
Vasoconstrictor
Used for diarrhea but can cause retroperitoneal fibrosis, subendocardial fibrosis, valvular disease
Side effects of ergots
GI distress –> nausea, vomiting, diarrhea
When are ergots contraindicated?
Coronary ischemic disease
Pregnancy
Drugs for acute migraines
Ergotamine
Sumatriptan
Drugs for prophylaxis of migraines
B blocker: Propranolol
Calcium channel blocker: Verapamil
Anti-histamine: Cyproheptadine
Ergot: ergonovine, methysergide
Uses of NO
Pulmonary artery hypertension and acute respiratory distress syndrome in neonates - Given by inhalation
Dietary supplements with arginine: slows process of atherosclerosis
Sildenafil MOA
Increases cGMP by inhibiting its breakdown by phosphodiesterase isoform 5 (PDE5)
Potentiates the actions of NO –> vasodilation
What can happen if sildenafil is taken with nitrates?
Can result in severe hypotension an MI
Patients who are maintained with nitrate for ischemic heart disease should never have viagra!!!
Patients who are not on nitrate can have viagra but within 24 h should not use nitrate!!!
Side effects of sildenafil
Can affect colour vision, causing difficulty in blue-green discrimination
Which are the PDE-5 inhibitors?
Sildenafil, tadalafil, vardenafil
High dose PGE2 causes:
Uterus relaxation
Low dose PGE2 causes:
Uterus contraction
PGE/PGI2
Dilation
TXA2/PGF2a
Constriction
Alprostadil
PGE1
Maintains a patent ductus arteriosus
Penile injection treats impotence (side effect: priapism)
Treats pulmonary hypertension (half life is 5-10min)
Misoprostol
PGE1
Protects patients from NSAID-induced peptic ulcers
COX-1 enzyme expressed in stomach synthesizes PGE1 stomach mucus secretion
Mucus has cytoprotective action (protects mucosa from damage by gastric acid
Chronic use of NSAIDs or corticosteroids (CS) COX-1 activity local PGE mucosal damage by acid leads to peptic ulcer
Can also be used with mifepristone to induce abortions
Dinoprostone
PGE2
Induces labor and abortion (“cervical ripening”)
Epoprostenol
PGI2
Treats pulmonary hypertension
Half life is 3-5 mins
Latanoprost
PGF2a
Treats glaucoma
Side effect: dark pigment in iris
Which drug is used to close a PDA
Indomethacin
Carbaprost
PGF2a
Contraction of uterine muscle
Abortifacient
Postpartum bleeding
Bosnian, ambrisentan, macitentan
Endothelin receptor antagonists
Treat idiopathic pulmonary arterial hypertension
ADR: flushing, headache, hypotension
Contraindication: pregnancy
Drugs that treat idiopathic pulmonary arterial hypertension
Endothelin receptor antagonist (Bosentan, Ambrisentan, Macitentan)
Prostacyclin (PGI2): Epoprostenol, Iloprost, Treprostinil PDE5 inhibitor-increases cGMP: Sildenafil, Tadalafil
PGE1: Alprostadil
Nitric oxide inhalation
Guanylyl cyclase stimulator: Riociguat
