Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
100 Cards in this Set
- Front
- Back
|
Hormones
|
referred to as general hormones or telecrine hormones
secreted directly into the circulation by endocrine organs target distant organs/tissues/cells slow acting |
|
|
Neurotransmitters
|
released by neurons
target adjacent cells rapid acting |
|
|
Autocoids
|
referred to as local hormones or paracrine hormones
act short range on adjacent target cells rapid acting for brief periods of tiem |
|
|
Histamine
|
mediator of immediate allergic and inflammatory reactions
plays only a modest role in anaphylaxis plays an important role in gastric acid secretion functions as a neurotransmitter and neuromodulator chemotactic agent for WBCs |
|
|
Histamine - Pharmacokinetics and chemistry
|
synthesized by the decarboxylation of L-histidine by the enzyme histidine decarboxylase
upon synthsis, must be stored or rapidly inactivated most tissue histamine is sequestered and bound in the granules of mast cells or basophils found in the nervous tissue of the brain, functioning as a neurotransmitter stored in ECL cells of the stomach fundus |
|
|
Histamine - immunological release
|
IgE sensitized mast cells/ basophils will explosively degranulate when exposed to the proper antigen
this released histamine is a mediator of immediate type 1 allergic rxns via negative-feedback mechanisms, histamine modulates its own release from sensitzed mast cells int eh skin and basophils endogenous histamine exhibits a modulation role in several inflammatory and immune responses tissue-injury released histamine causes local vasodilation and leakage of chemical mediators chemotactic agent for neutrophils, eosinophils, basophils, monocytes, lymphocytes inhibits release of lysosomal contents inhibits several t and b cell functions regulates nerve mediated release of peptides in respones to inflammation |
|
|
histamine - chemical and mechanical release
|
tissue injury by trauma, radiation and chemical agents (strong acids/bases, animal venoms) can cause mast cell release of histamine
|
|
|
histamine - pharmacological release
|
high mw drugs, curare-like drugs, opiodes, vancomycin, radio-contrast media, can induce mast cell degranulation or direct histamine release
|
|
|
H1-receptor MOA
|
located in smooth muscle, endothelium, and brain
in brain are located on postsynaptic membranes activates IP3/DAG signaling cascade which increases intracellular Ca2+ |
|
|
H2-receptor MOA
|
located in gastric mucosa, cardiac muscle, mast cells and brain
in brain are located on postsynaptic membranes stimulates production of cAMP may also stimulate IP3/DAG signaling cascade |
|
|
H3-receptor MOA
|
located on presynaptic membranes in the brain, myenteric plexus, and other neurons
inhibits cAMP production and Ca2+ influx via N-type calcium channels causes a decrease in histamine, NE, serotonin, Ach, and other neurotransmitters release from histaminergic and other neurons |
|
|
H4-receptor MOA
|
located on leukocytes in bone marrow and circulating blood
exerts chemotatic effects on eosinophils and mast cells, causing modulation of inflammation and allergy response modulates production of these cells and of cytokines |
|
|
Histamine - clinical uses
|
histamine aerosol has been used as a provacative test for bronchial hyperreactivity
|
|
|
Histamine - toxicity
|
adverse effects are dose-related
include flushing, hypotension, tachycardia, headache, wheals, bronchoconstriction and GI upset major causative agen of scombroid fish poisoning should not be administered to patients w/ asthma active ulcer disease, or GI bleeding |
|
|
Physiological antagonist
|
have effects on smooth muscle that are opposite of histamine
epinephrine - injection can be lifesaving in systemic anaphylaxis other adrenergic drugs |
|
|
Histamine release inhibitors
|
reduce the degranulation of mast cells
cromolyn, nedocromil, theophylline (used to treat asthma) Beta 2 adrenoreceptor agonists glucocorticoids |
|
|
H1 -receptor antagonist chemistry
|
stable amines w/ a 3'amino group linked by a alkyl chain to 2 aromatic subsituents
|
|
|
1st generation H1- receptor antagonists
|
strong sedative effects
likely to block autonomic receptors |
|
|
2nd generation H1- receptor antagonists
|
much less sedating
less complete distribution in CNS |
|
|
pharmacokinetics of H1-receptor antagonists
|
rapidly absorbed after oral administration
widely distributed in all body tissues and organs 1st generation enter cns readily and are substrates for P-glycoprotein transporter in BBB many are extensively metabolized especially by the microsomal systems of the liver several 2nd generations are metabolized by the CYP3A4 system |
|
|
H1-receptor antagonists - MOA
|
reversible competitive inhibition of H1-receptors
negligible effects on H2 and H3 receptors 1st gen also exert competitve inhibition at muscarinic cholinoceptro alpha adrentoceptor, serotonin and local anesthetic receptors some 2nd gen agents inhibit histamine release from mast cells/ basophils |
|
|
Phamacological effects mediated by H1-receptor blockade
|
strong inhibition of edema formation and itching
partial inhibiton of histamine induced hypotension strong antinausea and antiemetic actions strong inhibition of bronchiolar and GI smooth muscle contraction |
|
|
Effects mediated by non H1 receptor blockade
|
sedation - common effect of 1st generation agents, intensity varies among chemical subgroups and patients, effect in some agents is so prominent they are used as sleep aid, opposite effect may occur in children
antiparkinsonism effects - dure to central antimuscarinic actions, suppresses undesirable effects of several antipsychotic drugs anticholinoceptor actions - many 1st generation agents exhibit atropine - like effects on peripheral muscarinic receptors, may be the cause of urinary retention and blurred vision adrenoceptor-blocking actions- many demonstrate alpha receptor blocking effects serotonin-blocking actions- some 1st gen agents block serotonin receptors Local anesthesia- high doses of some 1st gen agents are potent local anesthetics due to blockade of both Na and K channels in excitable membranes |
|
|
Therapeutic uses of H1 receptor antagonists
|
allergic reactions
motion sickness and vestibular disturbances systemic mastocytosis parkinsonism |
|
|
Toxicity of H1-receptor antagonists
|
CNS (1st gen)- sedation, sleepiness, dizziness, fatigue
restlessness insomnia tinnitus, tremors exctitement, ataxia, hallucinations, seizures GI system - negligible 2nd gen, dry mouth, constipation CV system- postural hypotension, sinus tachycardia, arrhythmias other system- blurred vision, cough, urinary retention, dysuria, increased appetite, allergic reacitons |
|
|
Contraindications of H1-receptor antagonists
|
glaucoma
prostatic hypertrophy, urinary tract obstruction GI obstruction, ileus Severe infectious diarrhea Asthma and COPD concomitant treatment w/ CNS depressants tachyarrhythmias severe hepatic disease children,neonates pregnancy |
|
|
H2 receptor antagonist - chemistry
|
histamine congeners w/ a bulky side chain
more hydrophilic than H1 receptor antagonists |
|
|
H2 receptor antagonist - pharmacokinetics
|
rapidly absorbed from the intestine
duration of action depends on dose given distributed in all tissues cleared by combination of hepatic metabolism, glomerular filtration, and renal tubular secretion into urine |
|
|
H2 receptor antagonist - MOA
|
competitive inhibitors of H2 receptors in gut parietal cells
inhibits cAMP production in parietal cells |
|
|
H2 receptor antagonist- pharmacological effects
|
suppress basal and meal stimulated gastric acid secretion
reduces volume of gastric secretion and [pepsin] strongly reduces histamine-stimulated gastric acid secretion reduces gastrin and cholinomimetic agent mediated gastric acid secretion |
|
|
H2 receptor antagonist - pharmacological effects not at H2 receptor
|
cimetidine only inhibits cyt p450 system
cimetidine and rantidine can inhibit the androgen receptor when given at high doses |
|
|
H2 receptor antagonist- therapeutic uses
|
GERD
dyspepsia, pyrosis, sour stomach peptic ulcer disease ( unless caused by H. pylori or NSAIDs) esophagitis hypersecretory conditions hiatal hernia prevention of bleeding from stress related gastritis in critically ill |
|
|
H2 receptor antagonist - toxicity
|
overall incidence is low
CNS- headache, diziness, vertigo, insomia, mental confusion, agitation, hostility, paranoia, depression GI system - elevated liver enzymes, acute pancreatitis endocrine - gynecomastia, galactorrhea, loss of libidio, impotence (cimetidine) hematopoietic system - leukopenia, thrombocytopenia, agranulocytosis, aplastic anemsi allergic rxns drug-drug interactions - absoption reduced by antacids, cimitedine and high doses of ranitidine may decrease drug clearance |
|
|
H2 receptor antagonist - CI
|
renal impairment
renal disease concomitant use of drugs metabolized by cyt. p450 system |
|
|
Serotonin- chemistry and pharmacokinetics
|
synthesized by hydroxylation of the indole ring of L-tryptophan followed by its decarboxylation
upon syn either stored or rapidly inactivated via MAO in pineal gland serves as precursor to melatonin syn |
|
|
Serotonin- GI storage and release
|
90% stored in ECC of GI tract
synthesize and store 5-HT in a complex w/ ATP in granules released in response to mechanical or neuronal simuli |
|
|
Serotonin- Blood storage and release
|
stored in platelets
acquired from the GI secreted 5-ht that has diffused into vasculature able to concentrate by means of a SERT where it is then concentrated into vesicles by a VAT release can be stimulated by thromboxane A2 |
|
|
Serotonin-neuronal storage and release
|
found in raphe nuclei of brain containing cell bodies of serotonergic neurons that syn. store adn release 5-ht as a NT
Brain serotonergic neurons found in ENS of GI tract and around blood vessels mediate mood, sleep, appetite, temperature regulation, pain perception, blood pressure, vomiting 5-ht is released in response to action potential generation involved in clinical conditions such as depression, anxiety and migrane release can be stimulated by Reserpine |
|
|
Serotonin MOA
|
binds numerous cell surface receptors each of which have a specific structure, localization and signal transduction effect
|
|
|
5- HT 1A
|
GPCR
Raphe nuclei, hippocampus decreae cAMP |
|
|
5-HT 1B
|
GPCR
substantia nigra, globus pallidus, basal ganglia decrease cAMP |
|
|
5-HT 1D
|
GPCR
brain decrease cAMP |
|
|
5-HT 1E
|
GPCR
cortex, putamen decrease cAMP |
|
|
5-HT 1F
|
GPCR
cortex, hippocampus decrease cAMP |
|
|
5-HT 1P
|
GPCR enteric nervous system
slow EPSP |
|
|
5-HT 2A
|
GPCR
platelets, smooth muscle, cerebral cortex increases IP3/DAG |
|
|
5-HT 2B
|
GPCR
stomach fundus increases IP3/ DAG |
|
|
5-HT 2C
|
GPCR
choroid, hippocampus, substatia nigra increases IP3/DAG |
|
|
5-HT 3
|
Na-K ion channel
area postrema, sensory and enteric nerves changes cellular Na and K |
|
|
5-HT 4
|
GPCR
CNS and myenteric neurons, smooth muscle increases cAMP |
|
|
5-HT 5A
|
brain
decreae cAMP |
|
|
5-HT 5B
|
brain
decrease cAMP |
|
|
5-HT 6
|
GPCR
Brain increase cAMP |
|
|
5-HT 7
|
GPCR
brain increase caMP |
|
|
Serotonin effects on neurons
|
Poweful stimulant of sensory nerve endings particularu of those mediating pain and itching
H1-mediated, critical in urticarial response Modulates repiratory neurons controlling inspiration and expiration H1-mediate Modulates neurotransmitter release H3-mediated |
|
|
Serotonin effects on reproductive system
|
large doses can induce contraction of uterus (H1-mediated)
spontaneou abortion may occur in pregnant woment sufferring from anaphylactic rxns |
|
|
Serotonin effects on respiratory system
|
causes bronchioconstriciton
h1-mediated contraction of bronchiolar smooth muscle problematic in patients w/ asthma (effects can be blocked using autonomic blocking agents) |
|
|
serotonin effects on stomach
|
powerful stimulant of gastric acid secretion and some degree of induction of gastric-pepsin and intrinsic factor production
H2 mediated stimulation of gastric parietal cells |
|
|
serotonin effects on intestines
|
causes contraction of intestinal smooth muscle
H1 mediated, large doses may induce diarrhea stimulates secretion in both the small and large intestines |
|
|
serotonin effects on heart
|
injection/infusion increases heart rate (H2 Mediate, direct effect of histamine, typically accompanied by induction of reflex tachycardia)
Increase contractility and pacemaker rate (H2 mediated) decrease atrial muscle contractility (H1 mediated) |
|
|
Serotonin Triple Response
|
Intradermal injection causes a characteristic red spot, edema adn flare response
-involves microcirculation vessel smooth muscle cells, capillary/venular epithelium, sensory neuron -at site of injection dilation of small vessels causes reddening of the skin, formation of edemaous wheals and produciton of red irregular flares surrounding the wheals -appears to be mostly H1 mediated though H2 and H3 may also play a role |
|
|
Serotonin Metabolic effects
|
modulates food intake, energy expenditure, fat metabolism [insulin]blood, [leptin]blood
H3 mediated |
|
|
Serotonin cardiovascular system
|
injection/infusion causes decrease in systolic and diastolic blood pressure
causes vasodilation of arterioles and precapillary sphincters (may cause flushing and headache, mediated by H1 activation and NO release form endothelium upon low dose administration, mediated by H2 activation upon high dose administration) usually accompanied by reflex tachycardia induces edema in pervascular tissue via its effects on microcirculation vessels, particularly postcapillary vessels (H1 mediate, causes endothelia cell separation, responsible for urticaria) |
|
|
serotonin CNS
|
plays a role in nociception
|
|
|
serotonin clinical pharmacology
|
bronchial hyperreactivity - the tendency to develop bronchospasm on encountering stimuli that do not affect healthy nonasthmatic airways and is characteristic of asthma
scombroid fish poisoning-ingestion of spoiled fish |
|
|
LSD
|
5-HT 1a/2a/2c agonist
hallucinogen |
|
|
Ergotamine
|
5-Ht 1a/1b/1d agonist
used to treat migranes |
|
|
Triptan drug family
|
5-HT 1d/1b agonist
used to treat migranes |
|
|
Ergonovine
|
50HT 1/2A /2c agonist
used to treat postpartum bleeding |
|
|
Busiprone
|
5HT 1a agonist
used to treat anxiety |
|
|
Metclopramide
|
5-HT 4 and D2 agonist
used to treat GI disorders |
|
|
Triptans- chemistry
|
indole derivatives
|
|
|
Triptans - pharmacokinetics
|
all administered via oral route
-sumatriptan and zolmitriptan may be administered nasally -sumatriptan may also be administered subcutaneously time to onset ranges from 1-3 hours |
|
|
Triptans- MOA
|
selective activation of 5-Ht 1B and 5-HT 1D receptors
found in cerebral and meningeal vessels (mediate vasoconstriction) also found on neurons (function as presyntaptic inhibitory receptors) |
|
|
Triptans - pharmacological effects
|
inhibit release of vasodilating peptides from trigeminal nerve ending
induce vasoconstriction of cerebral vessels of the trigeminovascular system |
|
|
Triptans- therapeutic uses
|
drugs of choice for treatment of severe acute migrane attacks
treatment for cluster headache (sumatriptan) |
|
|
Triptans - toxicity
|
altered sensations
diziness muscle weakness neck pain injection site reactions chest tightness/pain cardiac arrhytmias myocardial infarction |
|
|
triptans - contraindications
|
cerebrovascular disease
peripheral vascular disease heart disease, especially patients at risk for vascular ischemia wolff-parkinson-white syndrome severe hepatic or renal impairment conconmitant use of 5-Ht agonists, SSRIs and mao inhibitors |
|
|
Sumatriptan
|
flagship drug of 5-HT agonists
partial agonist at 5-HT 1b/1d receptors may reduce release of CGRP and perivascular edema in cerebral circulation used for migrane and cluster headaches toxicity - paresthesias, dizziness, coronary vasoconstriction |
|
|
Phenoxybenzamine
|
inhibits 5-HT2 receptors
|
|
|
Cyproheptadine
|
inhibits 5-HT 2 receptors
prevents smooth muscle effects of 5-HT has significant antimuscarininc effects and causes sedation used to treat smooth muscle manifestations of carcinoid tumor and cold induced urticaria |
|
|
Ketasnserin
|
inhibits 5-HT 2 receptors on smooth muscle
inhibits 5-HT 2 receptros on platelets, blocking platelet aggregation |
|
|
Ritanserin
|
inhibits 5-Ht2 receptors
alters bleeding time and reduces thromboxane formation |
|
|
ondasetron
|
inhibits 5-HT3 receptors
used to treat nausea and vomiting assoc. w/ surgery and chemotherapy |
|
|
phenothiazien and butyrophenones
|
non selective 5-Ht receptor inhibitors
used in the treatment of schizophrenia and mania |
|
|
ergot alkaloids - general
|
produced by the fungus Claviceps purpurea (parasitic fungus to grasses and grains)
affect alpha adrenoceptors, dopmine receptors, 5-HT receptors and other receptor types |
|
|
Ergotism
|
ergot poisoning caused by ingestion of contaminated grain
effects include dementia w/ florid hallucinations, prolonged vasospasm, and stimulation of uterine smooth muscle |
|
|
ergot alkaloids - chemistry
|
derivatives of 6-methylergoline
divided into amine alkaloids and peptide alkaloids |
|
|
ergot alkaloids- pharmacokinetics
|
variable absorbed from GI tract after oral administration which is improved w/ coadministration of caffein
absorbed from rectum and buccal cavity, administration via aerosol inhaler and intramuscular injection |
|
|
ergot alkaloids - MOA
|
may act as agonists, partial agonist, antagonists at 5-Ht adrenergic and dopamine receptors depending on the agent, dose and tissue
|
|
|
ergot alkaloids effect on CNS
|
induces mood changes, perceptual disorders and hallucinations ( prejunctional/ postjunctional 5-HT2 receptor agonist)
effects extrapyramidal motor control (bromocriptine) suppresses prolactin release from pituitary gland (bromocriptine, cabergoline, pergolide, dopamine receptor agonist) |
|
|
ergot alkaloid effect on cardiovascular system
|
effects are drug and vessel dependent
constriction of arteries and veins is most pronounced w/ ergotamine -AV anastomoses are expecially sensitive -due to activation of alpha adrenorecptors and 5-HT receptors prolonged vasospasm induced w/ overdosage |
|
|
ergot alkaloid effect on uterine smooth muscle
|
increases the force and frequency of uterine contractions due to activation of alpha adrenoreceptors and 5_HT receptors
low doses cause rhythmic contraction and relaxation of the uterus, high doses induce powerful and prolonged contraction sensitivity of uterus increases and pregnancy progresses |
|
|
ergot alkaloid effect on GI tract
|
quite sensitive
increases intestinal peristalsis and tone (5-HT 3 receptors) stimulates chemoreceptor trigger zone (5-HT 3 receptors and dopamine receptors) in some induce nausea, vomiting and diarrhea |
|
|
ergot alkaloid- toxicity
|
therapeutic index is very narrow
diarrhea, n and v prolonged vasospasm (especially in arms and legs may lead to gangrene, may be reversed w/ high doses of nitroprusside or nitroglycerin) bowel infarction uterine cramping drowsiness CNS stimulation and hallucinations |
|
|
ergot alkaloid - contraindications
|
cerebrovascular disease
obstructive vascular disease coronary heart disease collagen diseases sever hepatic or renal impairment sepsis pregnancy concomitant use of SSRIs or MAO inhibitors |
|
|
Ergotamine
|
vasoselective
ergot alkaloid mixed partial agonist effects at 5-Ht2 and alpha adrenoreceptors causes marked smooth muscle contraction but blocks alpha agonis vasoconstriction used for migraine and cluster headaches taken orally toxicity are prolonged vasospasm causing gangrene, uterine spasm |
|
|
Ergonovine
|
uteroselective
ergot alkaloid mixed partial agonist effects at 5-HT2 and alpha adrenoreceptors same effects as ergotamine, some selectivity for uterine smooth muscle used for postpartome bleeding, migraine headaches toxicity same as ergotamine |
|
|
Lysergic acid diethylamide (LSD)
|
CNS selecive
CNS 5-ht2 and dopamine agonist 5_HT2 agonist in periphery hallucinations, psychotomimetic widely abused toxicity: prolonged psychotic state, flashbacks |
|
|
Ecosanoids
|
add here
|
