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386 Cards in this Set
- Front
- Back
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What type of drug is albuterol
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short-acting beta 2 adrenergic receptor agonist (SABA)
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What type of drug is atropine?
|
muscarinic receptor antagoist; anticholinergic;
parasympatholytic |
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What type of drug is bethanecol?
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direct parasympathomimetic
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What type of drug is diphenhydramine?
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first generation antihistamine
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What type of drug is dobutamine?
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sympathomimetic;
beta 1 agonist |
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What type of drug is dopamine?
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sympathomimetic;
neurotransmitter |
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What type of drug is epinephrine?
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mixed sympathomimetic; adrenergic
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What type of drug is fenoldopam?
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synthetic benzazepine derivative; selective peripheral dopamine D1 receptor weak partial agonist.
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What type of drug is fluticasone?
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inhaled corticosteroid
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What type of drug is amphetamine?
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modulates several key neurotransmitters in the brain (dopamine, serotonin, and norepinephrine); psychostimulant
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What type of drug is isoproterenol?
|
sympathomimetic beta adrenergic agonist medication;
beta 1 and 2 |
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What type of drug is labetalol?
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mixed alpha/beta Adrenergic antagonist
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What type of drug is metoprolol?
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selective β1 receptor blocker
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What type of drug is neostigmine?
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parasympathomimetic; a reversible cholinesterase inhibitor.
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What type of drug is phentolamine?
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reversible nonselective alpha-adrenergic antagonist.
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What type of drug is phenylephrine?
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α1-adrenergic receptor agonist
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What type of drug is pralidoxime?
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Reversibly binds to the enzyme acetylcholinesterase, competing with organophosphate binding
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What type of drug is propranolol?
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non-selective beta blocker
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What type of drug is pseudoephedrine?
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sympathomimetic amine; weak α- and β-adrenergic agonist; causes the release of endogenous norepinephrine
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What type of drug is salmeterol?
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long-acting beta2-adrenergic receptor agonist
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What type of drug is castor oil?
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laxative; cathartic
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What is albuterol used to treat?
|
acute bronchospasm
COPD asthma |
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What can be treated with amphetamine?
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ADD/ ADHD
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What can be treated with atropine?
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bradycardia
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What can be treated with bethanecol?
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urinary retention
GI atony |
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What can be treated with diphenhydramine?
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antihistamine
sedative |
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What can be treated with dobutamine?
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heart failure
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What can be treated with dopamine?
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increases cardiac output
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What can be treated with epinephrine?
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anaphylaxis
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What can be treated with fenoldopam?
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hypertension
vasodilator |
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What can be treated with fluticasone?
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anti-inflammatory
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What can be treated with isoproterenol?
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bradycardia
heart block |
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What can be treated with labetalol?
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hypertension
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What can be treated with metoprolol?
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hypertension
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What can be treated with neostigmine?
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myasthenia gravis
urinary retention |
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What can be treated with phentolamine?
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hypertensive emergency
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What can be treated with phenylephrine?
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decongestant
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What can be treated with pralidoxime?
|
organophosphate poisoning
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What can be treated with propranolol?
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hypertension
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What can be treated with pseudoephedrine?
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decongestant
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What can be treated with salmeterol?
|
Asthma
COPD |
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What is the predominant ANS tone of arterioles?
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sympathetic
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What is the predominant ANS tone of veins?
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sympathetic
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What is the predominant ANS tone of the heart and SA node?
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parasympathetic
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What is the predominant ANS tone of the heart ventricular muscle?
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sympathetic
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What is the predominant ANS tone of the iris?
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parasympathetic
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What is the predominant ANS tone of the ciliary muscle?
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parasympathetic
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What is the predominant ANS tone of the GI tract?
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parasympathetic
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What is the predominant ANS tone of the urinary bladder?
|
parasympathetic
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What is the predominant ANS tone of the salivary glands?
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parasympathetic
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What is the predominant ANS tone of the sweat glands?
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sympathetic
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In the sympathetic nervous system, what is the preganglionic NT/ receptor pair?
|
ACh
nicotinic or muscarinic |
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In the sympathetic nervous system, what are the two NTs of postganglionic fibers and their receptor?
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NE (a1, a2, b1)
EPI (a1, a2, b1, b2) |
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In the parasympathetic nervous system, what is the preganglionic NT/ receptor pair?
|
ACh
nicotinic or muscarinic |
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In the parasympathetic nervous system, what is the postganglionic NT and its receptor?
|
ACh
muscarinic |
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From what is ACh synthesized?
|
acetyl CoA and choline
|
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Where is ACh synthesized?
|
cytoplasm
|
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What enzyme catalyzes the formation of ACh?
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choline acetyltransferase (ChAT)
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How is ACh transported into storage vesicles?
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antiporter exchanges hydrogen ions for ACh
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How is ACh released from storage vesicles and on what is it dependent?
|
exocytosis into nerve terminals
requires calcium |
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What are the subtypes of nicotinic receptors?
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N-G
N-M |
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Where are nicotinic G receptors located?
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ganglionic/ postsynaptic
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Where are nicotinic M receptors located?
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neuromuscular junction/ postsynaptic
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What are the subtypes of muscarinic receptors?
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M1-5
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Where are M1 receptors located?
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ganglionic (post and pre synaptic)
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Where are M2 receptors located?
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cardiac, ganglionic
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Where are M3 receptors located?
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neuroeffector junction (post and presynaptic)
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What does stimulation of M1, M3, and M5 receptors cause?
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stimulates PLC to produce IP3 and DAG
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What does stimulation of M2 and M4 receptors cause?
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inhibit production of cAMP, decrease intracell calcium, stimulate opening of potassium channels
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In general, what are muscarinic receptors?
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G-protein coupled
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What type of receptor are nicotinic receptors?
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ligand-gated ion channels
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From what is dopa formed? By what enzyme?
|
from tyrosine by tyrosine hydroxylase
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From what is dopamine formed? By what enzyme?
|
dopa
L-aromatic amino acid decarboxylase |
|
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From what is norepinephrine formed? By what enzyme?
|
dopamine
dopamine beta-hydroxylase |
|
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From what is epinephrine formed? By what enzyme?
|
norepinephrine
phenylethanolamine N-methyltransferase |
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Give the correct order in going from tyrosine to epinephrine.
|
tyrosine
dopa dopamine norepinephrine epinephrine |
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Name the endogenous catecholamines.
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epinephrine
norepinephrine dopamine |
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What receptors are stimulated by epinephrine?
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alpha1, alpha2, beta 1, and beta2
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What receptors does norepinephrine stimulate?
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alpha1, alpha2, beta1
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What receptors does dopamine stimulate?
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D1, D2, alpha 1, and beta1
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What are the non-endogenous catecholamines?
|
isoproterenol
dobutamine |
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What receptors does isoproterenol stimulate (agonist)?
|
beta1, beta2
|
|
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Name the direct acting adrenergic agonists?
|
NE EPI
isoproterenol dobutamine phenylephrine clonidine albuterol |
|
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Name the indirect adrenergic agonists?
|
tyramine
amphetamine cocaine entacapone |
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What is the mechanism of indirect adrenergic agonists?
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inhibit uptake, deplete storage, or prevent metabolism of catecholamines
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Name the mixed acting adrenergic agonist.
|
ephedrine
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Name the non-selective adrenergic agonists.
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NE
EPI |
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Name the selective alpha1 adrenergic agonist.
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phenylephrine
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Name the selective alpha 2 adrenergic agonist.
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clonidine
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Name the non-selective beta adrenergic agonists.
|
isoproterenol
EPI |
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Name the selective beta-1 adrenergic agonist.
|
dobutamine
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Name the selective beta-2 adrenergic agonist.
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albuterol
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Name the dopamine DA-1 selective adrenergic agonist.
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fenoldopam
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What is ritodrine?
|
aka yutophar
only beta-2 adrenergic agonist approved for use as uterine agonist to delay premature labor |
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In asthma, what type of antibodies are produced?
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IgE
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What mediators are released d/t IgE during an asthma attack?
|
histamine
leukotriene C4 & D4 prostaglandins |
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What are the two categories of drugs for the treatment of asthma?
|
bronchodilators
anti-inflammatories |
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Name the classes of bronchodilators used for the treatment of asthma.
|
sympathomimetics, B2 adrenergic receptor agonists
anticholingergics PDE inhibitors |
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Name the classes of anti-inflammatory drugs used in the treatment of asthma
|
corticosteroids
mast cell degranulation inhibs leukotriene recep antagonists leukotriene synth inhibs anti-IgE |
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What is the mechanism of action of B2 adrenergic receptor agonists?
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increase cAMP levels, activating PKA,
activating K+ channels & Ca+ sequestration; relax bronchiol sm muscle |
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Name the short acting B2 adrenergic receptor agonists
|
albuterol
levalbuterol pirbuterol |
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Describe the pharmacokinetics of SABAs.
|
administered by inhalation
onset 1-5 min duration 2-6 hr |
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What is the therapeutic choice for relief of acute asthma?
|
SABAs
used as needed |
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What are the adverse effects of SABAs?
|
skeletal muscle tremor
hyperglycaemia hypokalaemia hypomagnesaemia inc heart rate cardiac arrhythmias |
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Name the LABAs
|
salmeterol
formoterol |
|
|
Describe the pharmacokinetics of LABAs
|
inhaled
onset 15-30 min duration 12 hrs |
|
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Why do LABAs provided a longer duration of bronchodilation?
|
high lipid solubility
|
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What can long-term use of LABAs cause?
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B2 adrenergic receptor desensitization
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What are LABAs generally combined with for long-term asthma control?
|
inhaled corticosteroids
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Name the phosphodiesterase inhibitors used for the treatment of asthma
|
theophylline, a methylxanthine
|
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What is the MAO of PDE inhibitors
|
inc intracellular cAMP by suppressing PDE
competitively blocks adenosine receptors |
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Describe the pharmacokinetics of PDE inhibitors
|
rapidly absorbed, oral or IV
pleak plasma level w/in 1-2 hr metabolized by liver by chr P450 narrow therapeutic index |
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Why is theophylline not a preferred alternative for asthma treatment?
|
may potentiate anti-inflammatory action of corticosteroids
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What are the adverse effects of theophylline?
|
sinus tachycardia
nausea, tremor, indigestion |
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What antimuscarinic is used in the treatment of asthma?
|
ipratropium
|
|
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What is the mechanism of action of antimuscarinics? (asthma)
|
blocking M3 receptors
decrease intracell IP3 reduced intracell Ca+ bronchodilation/ dec mucus |
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Describe the pharmacokinetics of antimiscarinics. (asthma)
|
inhaled
slower onset that B2 agonists most excreted unchanged |
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What is the clinical use of antimuscarinics for the treatment of asthma?
|
Pts intolerant of inhaled B2 agonists
administered w/ SABA in moderate to severe exacerbations |
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What are the adverse effects of antimuscarinics?
|
anticholingeric reactions (dry mouth, contipation, mydriasis, blurred vision, hypoT, urinary retention)
allergic rxns |
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What is the MOA of glucocorticoids/ corticosteroids?
|
interact w/ transcription factors of growth factor and cytokines resulting in anti-growth, anti-inflammatory, and immunosuppression
|
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What are the anti-inflammatory effects of corticosteroids?
|
1. inhibiting inflammatory cell migration and activation
2. decreased synthesis of inflammatory proteins 3. decreased airway hyperresponsiveness 4. decreased mucus secretions |
|
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What is the indirect result of corticosteroids?
|
relax airway smooth muscle by potentiating action of B2 receptor agonists
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How do corticosteroids potentiate the actions of B2 receptor agonists?
|
increase receptor expression
prevent receptor down-regulation and uncoupling |
|
|
Describe the pharmacokinetics of corticosteroids.
|
inhaled or oral
10-20% of inhaled enter resp. tract onset for ICS is 7-14 days, full is 6-8 wks |
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What are the clinical use of corticosteroids?
|
1. long-term control of asthma
2. short-term relief |
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What is the most effective long-term therapy for asthma?
|
combination therapy of ICS and LABA
|
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When are oral corticosteroids used for the treatment of asthma?
|
severe persistent asthma
control before initiation of long term w/ SABA for acute exacerbations |
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What are the potential adverse effects of ICS?
|
oral candidiasis (rinse mouth after)
dysphonia dec bone density in women generally well tolerated at therapeutic dose |
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What are the potential adverse effects of systemic corticosteroids?
|
mood change, inc appetite & glucose levels
inc chances of infection, peptic ulcer, & osteoporosis |
|
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What are the potential adverse effects of cortico steroids at high doses?
|
pituitary-adrenal axis suppression
osteoporosis/ osteopenia suppressed growth rate in kids |
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Name the ICSs.
|
beclomathasone dipropionate
triamcinolone acetonide flunisolide budesonide fluticasone propionate |
|
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Name the oral corticosteroids for the treatment of asthma.
|
prednisone, prednisolone
|
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What is the other name for mast cell stabilizers and name the two prototypes?
|
chromones
cromolyn, nedocromil |
|
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What is the MOA of mast cell stabilizers on mast cells?
|
activating a natural "turn-ff switch" and blocking a chloride channel, preventing opening of Ca+ channels that cause degran
|
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What is the MOA of mast cell stabilizers on eosinophils?
|
inhibit response to inhaled allergens
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Describe the pharmacokinetics of mast cell stabilizers.
|
inhaled
rapidly excreted unchanged in urine & bile plasma conc peak w/in 15 min half-life cromolyn 1-2 hr, nedocromil 3 hr |
|
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What are the clinical uses of mast cell stabilizers?
|
1. prevention before exercise or exp to known allergen
2. alternative for mild astham |
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What is cromolyn preferred in children of all ages?
|
no toxicity
|
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What is the age range for nedcromil?
|
children over 5
|
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What are the two products of arachidonic acid?
|
prostaglandins
leukotriene (LTC4, LTD4) |
|
|
What is the result of interaction between leukotrienes and receptors?
|
bronchoconstriction
bronchial hyperactivity mucosal edema mucus hypersecretion |
|
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What enzymes convert arachadonic acid to prostaglandin?
|
COX
|
|
|
What drug inhibits COX enzymes?
|
aspirin
|
|
|
What enzyme converts arachadonic acid to leukotrienes?
|
5-lipoxygenase
|
|
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What drug inhibits 5-lipoxygenase?
|
zilueton
|
|
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Name the leukotriene receptor antagonists.
|
zafirlukast
montelukast |
|
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Name the leukotriene synthesis inhibitor.
|
zilueton
|
|
|
Describe the pharmacokinetics of leukotriene pathway inhibitors.
|
oral administration
4x a day dosing |
|
|
What are the clinical uses of zilueton?
|
alternative Tx for mild persistant astham and moderate persistant asthma w/ ICSs
|
|
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Why is zileuton less desirable thatn LTRAs?
|
toxicity
must monitor liver function |
|
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What are the clinical uses of LTRAs?
|
1. less preferred alternative for mild persistant asthma
2. alternative adjunctive therapy w/ ICSs to reduce exacerbation freq |
|
|
What is aspirin-induced asthma?
|
d/t increased leukotriene synthesis; aspirin blocks synthesis of prostaglandins, resulting in shift of arachadonic acid to increasse leukotriene synthesis
|
|
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What are the potential adverse effects of zileuton?
|
monitor liver function, enzyme elevation can occur but rare
|
|
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What are the potential adverse effects of zafirlukast?
|
inc half-life of warfarin by inhibition of CYP2C9 actvity
|
|
|
What is the prototype anti-IgE therapy for the treatment of asthma?
|
omalizumab
|
|
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What is the MOA of anti-IgEs?
|
binds to IgE to prevent interaction w/ receptors on mast cells & basophils
|
|
|
Describe the pharmacokinetics of anti-IgEs.
|
subcu injections every 2-4 wk
cleared from blood w/o deposition in kidneys or joints |
|
|
What are the clinical uses of anti-IgE?
|
in combination w/ ICS and LABA
adjunctive therapy for Pts w/ severe asthma not controlled by ICS/LABA therapy |
|
|
What are the potential adverse affects of omalizumab?
|
rare: uticaria, anaphylaxis
injection-site bruising |
|
|
Name the quick-relief mediations for the treatment of asthma.
|
SABAs
anticholinergics oral corticosteroids |
|
|
Name the long-term control medications for the treatment of asthma.
|
corticosteroids
LABAs immunomodulators leuotriene modifiers PDE inhibitors mast cell degranulation inhibitors |
|
|
From what is histmamine synthesized, and by what enzyme?
|
histidine
H-decarboxylase |
|
|
What happens to histamine once formed?
|
either stored or inactivated
|
|
|
What are the major storage sites of histamine?
|
tissue mast cells
blood basophils |
|
|
What are the other lesser sites of histamine storage?
|
histaminergic CNS neurons
gastric enterochromaffin-like cells (ECL) immune system cells |
|
|
What is sensitization?
|
initial exposure to an allergen stimulates production of IgE antibodies which bind to mast cell receptors
|
|
|
After sensitization, what is the result of subsequent exposure to an allergen?
|
degranulation and histamine release as well as other inflammatory mediators
|
|
|
Name some drugs that can stimulate histamine release.
|
organic bases (morphine, codeine, tubocurarine, succinylcholine)
vancomycin some carb plasma expanders x-ray contrast media |
|
|
Name some basic polypeptides that can stimulate histamine release.
|
bradykinin
substance P anaphylatoxins bee venom |
|
|
Name the inhibitors of histamine release.
|
1. autoregulation by histamine
2. agents that increase cAMP 3. cromones |
|
|
How does histamine autoregulate its release?
|
histamine acts on H2 receptors on some mast cells and basophils to decrease release of mediators
|
|
|
Name the agents that can increase cAMP production and inhibit histamine release.
|
isoproterenol
theophylline epinephrine |
|
|
What is mastocytosis and what is the treatment?
|
abnormal mast cell proliferation & degranulation
oral cromolyn sodium |
|
|
How is cromolyn administered for asthma vs allergic rhinitis?
|
asthma: inhaled aerosole or nebulizer solution
rhinitis: nasal spray |
|
|
What are the adverse effects of cromolyn?
|
local irritant
serious effects are rare d/t poor absorption |
|
|
What is the role of H1 receptors?
|
mediate many manifestations of acute allergic reactions
|
|
|
What does activation of H2 receptors stimulate, major effect?
|
gastric acid secretion
contributes to GERD, PUD, etc |
|
|
What is the lesser effect of H2 stimulation?
|
cardiovascular system
nonvascular smooth muscle |
|
|
What is the result of activation of H3 receptors?
|
prejunctional receptor
inhibits neurotransmission in various organs |
|
|
What is the role of H4 receptors?
|
production and chemotaxis of immune cells such as eosinophils and mast cells
|
|
|
Stimulation of what histamine receptors may have effects on the CV system?
|
H1, H2, H3
|
|
|
What is the effect of histamine release on the small blood vessels? Receptor?
|
vasodilation (H1, H2)
inc permeability (H1) |
|
|
What is the effect of histamine release on the large blood vessels?
|
vasoconstriction (H1)
|
|
|
What is the effect of histamine release on the heart?
|
inc contration force- minor (H2)
SA node inc rate- minor (H2) |
|
|
What is the effect of histamine release on the GI system?
|
sm muscle contraction (H1)
stomach HCl secretion (H2) H3 inhibits acid secretion |
|
|
What is the effect of histamine release on the pulmonary system?
|
bronchoconstriction (H1)
|
|
|
What is the effect of histamine release on the peripheral nerves?
|
stimulation of pain & itching (H1)
|
|
|
What is the effect of histamine release on the CNS?
|
arousal, appetite, memory (H1-stimulates, H3- inhibits)
|
|
|
What is the effect of histamine release on the skin?
|
induces wheal and flare rxn (H1)
|
|
|
What is the effect of histamine release on nonvascular smooth muscle?
|
contraction (H1)- bronchoC, abd cramps & diarrhea, uterine contractions
H2 modulates, causing relaxation |
|
|
What receptors to antihistamines antagonize?
|
H1
|
|
|
What type of drug are antihistamines?
|
either inverse agonists or competitive antagonists
|
|
|
What are the major effects of antihistamines on H1 receptors?
|
1. dec vasoD
2. antagonize sm muscle constrition 3. dec vas perm & edema 4. dec itching & pain |
|
|
Do H1 antagonists inhibit histamine release?
|
NO except at high conc
|
|
|
What are the therapeutic uses of antihistamines?
|
1. allergic conditions
2. nausea/ vomitting, motion sickness, vertigo 3. common cold 4. anaphylactic shock 5. asthma |
|
|
Why are topical corticosteroids more effects for patiets w/ chronic allergies that antihistamines?
|
greater anti-inflammatory effects
|
|
|
How are antihistamines used in anaphylactic shock?
|
as a prophylatic or adjunctive Tx, epinephrine is drug of choice
|
|
|
What are the differences among H1 antagonists?
|
receptor specificity, antihistaminic potency, duration of action
|
|
|
Name some first generation antihistamines.
|
*diphenhydramine (Benadryl)
chlorpheniramine dimehydrinate (dramamine) hydroxyzine meclizine (antivert) prmethazine |
|
|
Name some second generation antihistamines.
|
fexfenadine (allegra)
loratidine (claritin) |
|
|
How do the sedative effects of first vs second generation antihistamines differe?
|
first gen- med to high
second- very low to low |
|
|
How do the antiemetic effects differ between first and second generation antihistamines?
|
first- med to high
second- none |
|
|
How do the anticholinergic effects differ between first and second generation antihistamines?
|
first- med to high
second- very low |
|
|
What are the anticholinergic effects of first generation antihistamines?
|
dry mouth
blurred vision tachycardia dysuria urinary retention |
|
|
What are the potential adverse effects of antihistamines on the GI system?
|
anorexia
appetite stimulation nausea, vomitting epigastric distress constipation diarrhea |
|
|
What are the principle active components of slow-reacting subastance of anaphylaxis (SRS-A)?
|
cysteinyl leukotrienes, LTC4 & LTD4
|
|
|
Give the progression from arachadonic acid to LTC4.
|
AA
5-HPETE LTA4 LTB4 or LTC4 |
|
|
What enzyme converts arachadonic acid to 5-HPETE then LTA4?
|
5-lipoxygenase with FLAP
|
|
|
How is LTA4 converted to LTC4?
|
conjugated w/ glutathione
|
|
|
What cells produce luekotrienes?
|
leukocytes and mast cells
|
|
|
What type of subastance is LTB4?
|
chemotactic for neutrophils, eosinophils macrophages
|
|
|
What leukotrienes cause bronchoconstriction?
|
LTC4 and LTD4
|
|
|
What is montelukast?
|
leukotriene receptor antagonist (LTRA)
|
|
|
From what is platelet activating factor derived? Produced by?
|
membrane phospholipids
platelets, leukocytes MAST CELLS, vascular endothelial cells |
|
|
What are the actions of PAF?
|
incudes bronchoconstriction, platelet aggregation, vasoD, chemotaxis, inc mucus, inc vascP
|
|
|
What can PAF activate?
|
phopholipase A2, stimulating production of eicosanoids
|
|
|
In what conditions is PAF implicated?
|
allergy
inflammation asthma shock |
|
|
What enzymes do corticosteroids prevent activation?
|
cyclooxygenase-2 (COX-2)
nitric oxide synthase (iNOS) |
|
|
What is mometasone?
|
inhaled corticosteroid for allergic rhinitis
|
|
|
In treating allergic rhinits, what druge will have a rapid onset?
|
oral antihistamines
oral leukotriene modulators |
|
|
In treating allergic rhinits, what drugs will have a slow onset?
|
intranasal corticosteroids
intranasal mast cell stabilizers |
|
|
In treating allergic rhinitis, what drugs will be more effective in treating rhnorrhea?
|
oral antihist- moderate
intranasal CS- high LM- low MCS- low |
|
|
What drugs will be more effective at managing sneezing d/t allergic rhinits?
|
oral antihist- high
IN corticoster- high oral LM- low IN MCS- low |
|
|
What drugs will be more effective at managing congestion d/t allergic rhinits?
|
oral antihist- low
IN corticoster- high oral LM- mod IN MCS- low |
|
|
What are the classifications of beta-adrenergic receptor antagonists?
|
non-selective
cardioselective |
|
|
Give two examples of non-selective beta-adrenergic receptor antagonists.
|
propranolol, nadolol
block both B1 and B2 |
|
|
Give two examples of cardioselective beta-adrenergic receptor antagonists.
|
metoprolol, bisoprolol
selectively block B1 but at high doses will block B2 |
|
|
What are the effects of beta-adrenergic receptor antagonists on the CV system?
|
lower BP
negative inotropic (B1) negative chronotropic (B1) bronchoconstriction (B2) |
|
|
What are the two routes by which beta-adrenergic receptor antagonists lower BP?
|
renin angiotensin system
heart & blood vessel effects |
|
|
How do beta-adrenergic antagonists affect the renin-angiotensin system?
|
antagonize B1 mediated release of renin
|
|
|
How do beta-adregergic receptor antagonists affect the heart and blood vessels to lower BP?
|
blockade of B1 receptors in
1. SA & AV nodes slows sinus rate & conduction velocity 2. myocardium inhibits inotropic effect of sympathomimetics reduce O2 requirements |
|
|
For what patients are beta-blockers recommended as a first line treatment?
|
Hx of angina, prior MI, heart failure
|
|
|
What are the clinical uses of beta blockers?
|
CVS- HTN, ischemic heart disease, MI, arrhythmia, CHF
glaucoma hyperthyroidism |
|
|
What beta-blockers may be used to treat glaucoma?
|
nonselective- timolol
selective B1- betaxolol |
|
|
How to beta blockers treat glaucoma?
|
dec intraocular P by reducing production of aqueous humor
|
|
|
How do beta blockers benefit hyperthyroidism?
|
inhibit effects of catecholamines on the heart
|
|
|
For what neurological disease may beta blockers be effective?
|
migraine headaches (dec freq and intensity)
skeletal muscle tumors anxiety |
|
|
What are the adverse effects of bete blockers on the CVS?
|
bradycardia
cold extremeties (unopp alpha1 vasoC) Raynaud's disease precipitation of heart failure |
|
|
What are the adverse effects of beta blockers on the respiratory system?
|
non-selectives will block B2 in airways, causing bronchoconstriction
|
|
|
What are the potential adverse metabolic effects of beta blockers?
|
dec plasma glucose levels
mask tachycardia alter plasma lipid levels |
|
|
How do beta blockers dec plasma glucose levels?
|
inhibit hepatic glycogenolysis, gluconeogenesis, and glucose release
inc uptake of glucose into skeletal muscles |
|
|
Why is the masking of tachycardia by beta blockers potentially dangerous?
|
tachycardia can be an indicator of falling plasma glucose levels
|
|
|
How do nonselective beta blockers alter plasma lipid levels?
|
inc plasma triglycerides (VLDL)
dec levels of HDL-cholesterol |
|
|
What are the potential adverse effects of beta blockers on the GI system?
|
diarrhea, nausea, gastric pain, constipation, flatulence, heartburn
|
|
|
What are the potential adverse effects of beta blockers on the CNS?
|
mental depression
insomnia fatigue dreams |
|
|
What are the contraindications for beta blockers (specify all vs nonselective)?
|
asthma (nonselective)
AV conduction defects (all) |
|
|
Name the alpha and beta adrenergic antagonists and what receptors they block.
|
labetalol, carvedilol
alpha 1, beta 1, beta 2 competitive & reversible |
|
|
What additional properties may carvedilol possess?
|
anti-oxidant, antiproliferative
|
|
|
What are the effects of alpha/beta adrenergic antagonist?
|
CVS- lowers BP, less reflex tachycardia, dec rate and force of contraction
Resp- bronchoconstriction |
|
|
What is the primary mechanism by which alpha/ beta receptor antagonists lower blood pressure? Secondary?
|
p- blockade of alpha 1 in vascular smooth m
2- dec renin, dec CO |
|
|
What is the mechanism by which alpha/ beta adrenergic receptor antagonists decrease reflex tachycardia?
|
1. blockade of beta-1
2. intact presynaptic alpha-2 mediated inhibiton of NE release |
|
|
What is the mechanism by which alpha/ beta adrenergic receptor antagonists effect the heart muscle?
|
blockade of beta-1
block positive chronotropic & inotropic effects of sympathetics inc AV conduction time |
|
|
What are the clinical uses of alpha/ beta adrenergic receptor antagonists?
|
HTN
ischemic heart disease chronic heart failure |
|
|
What is the most important clinical indication of carvedilol? Why?
|
chronic heart failure
block adrenergic receptors, antioxidant, antiproliferative |
|
|
What are the long term effects of carvedilol use on CHF?
|
slow progression of CHF
promote regression dec hospitalization dec mortality may take 3 mo |
|
|
What are the adverse effects of alpha adrenergic receptor blockade?
|
nasal stuffiness, postural hypoT, failure to ejac
dizziness, fatigue nausea, heartburn |
|
|
What are the effects of adrenergic agonists on the hear?
|
binding to B1 receptors increases contractility leading to inc CO
|
|
|
How do adrenergic agonists effect HR?
|
reflex response to increased BP
|
|
|
How do adrenergic agonists increase blood pressure?
|
alpha vasoC of arterial and venous smooth muscle, increase peripheral resistance
|
|
|
How does alpha receptor stimulation decrease HR?
|
increased peripheral resistance increases BP which actives the baroreceptor reflex, increasing vagal tone and decreasing HR
|
|
|
What are the effects of EPI, NE, and ISO on the systolic BP?
|
EPI ++
NE +++ ISO 0+ |
|
|
What are the effects of EPI, NE, and ISO on the diastolic BP?
|
IPE --
NE ++ ISO -- |
|
|
What are the effects of EPI, NE, and ISO on the mean blood pressure?
|
EPI +0-
NE ++ ISO -- |
|
|
What is the effect of EPI, NE, and ISO on the total peripheral resistance?
|
EPI --
NE +++ ISO --- |
|
|
What is the effect of EPI, NE, and ISO on the hear rate?
|
EPI +
NE - ISO ++ |
|
|
What is the effect of EPI, NE, and ISO on the stroke volume?
|
EPI ++
NE + ISO ++ |
|
|
What is the effect of EPI, NE and ISO on the cardiac output?
|
EPI +++
NE -0 ISO +++ |
|
|
What are the therapeutic effects of alpha 1 adrenergic agonists on the CVS? Give two drug names.
|
phenylephrine, methoxamine
control hemorrhage- (a1 vasoC) delay abs of local anesthetics (a1 vasoC) nasal & mucus membrane congestion treat hypoT treat shock c/t sympathetic failure |
|
|
What are the uses of selective alpha2 adrenergic agonists? Give drug names.
|
HTN (clonidine, guanabenz, guanfacine)
|
|
|
What is the primary MOA of clonidine for Tx of HTN?
|
stimulation of alpha2
1. receptors in lower brainstem dec sympathetic output inc paraS output 2. dec peripheral NE release 3. activates alpha1 causing initial inc then prolonged dec in BP |
|
|
Why should clonidine be slowly withdrawn?
|
rebound HTN
|
|
|
What are the uses of beta1 adrenergic agonists? Give drug names.
|
cardiogenic shock (dobutamine, dopamine)
severe CHF (dobutamine, dopamine) septic shock (dopamine) |
|
|
What is the effect of low dose dopamine on the CVS?
|
direct activation of DA1 in renal & mesenteric blood vessels, vasoD, lowers BP
|
|
|
What is the effect of intermediate dose dopamine on the CVS?
|
direct activation of B1
stimulates release of NE inc CO and HR |
|
|
What is the effect of high dose dopamine on the CVS?
|
direct activation of alpha 1
inc BP, total peripheral resistance, and renal artery vasoC |
|
|
What effects does dopamine have that other vasoactive agents do not?
|
at low & intermed doses:
inc renal blood flow, GFR, Na+ excretion, and urine flow |
|
|
How do dobutamine and dopamine benefit CHF?
|
direct activation of B1 increases force of contraction
short term inc mortality w/ chronic use |
|
|
How can dopamine benefit septic shock?
|
vasoC effects increase BP
|
|
|
What is the CVS clinical use of selective DA1 receptor agonist fenoldopam?
|
HTN emergency or urgency
peripheral vasoD or renal & mesenteric vessels inc renal blood flow, diuresis, and naturiuresis |
|
|
What is the CVS clinical use of nonselective beta adrenergic agonist isoproterenol?
|
AV block: speeds His bundle pacemaker, improving CO
Emergency (Stokes-Adams attack: syncope d/t less CO) Bradycardia |
|
|
What is the clinical use of non selective adrenergic agonists on the respiratory system?
|
epinephrine for anaphylatic shock
|
|
|
What are the effects of epinephrine on the respiratory system in anaphylactic shock?
|
B2- relaxation & inhibition of histamine release
a1- reduced mucus secretion |
|
|
What are the uses of phenylephrine on the eye?
|
1. fundus examinaton (a1 mydriasis)
2. minor allergic hyperemia & itching 3. localizing leision in Horner's 4. open-angle glaucoma |
|
|
Why is phenylepherine useful in localizing the leision producing Horner's syndrome?
|
pregang leision: pupil dilates d/t BOTH cocaine & phenylephrine
postgang: pupil only dilates d/t phenylephrine |
|
|
How does phenylephrine treat wide-angle glaucoma?
|
a1 contraction of radial muscle increase outflow of vitreal humor;
can exacerbate narrow-angle |
|
|
What are the uses of selective beta2 adrenergic receptor agonists on visceral smooth muscle?
|
ritodrine relaxes uterus to delay premature labor
|
|
|
What are the effects of adrenergic agonists on the bladder?
|
a1 receptors in trigone and sphinctor contract- can't void
b2 in detrusor causes relaxation- distention |
|
|
What are the effects of adrenergic agonists on the GI smooth muscle
|
all receptors present
relax muscle contract sphinctor |
|
|
What are the effects of arenergic agonists on the metabolic activity?
|
increased plasma free fatty acid
inc plasma glucose levle |
|
|
What is the effect of adrenergic agonists on white blood cells?
|
leukocytosis by promoting margination
|
|
|
What are the benefits of indirect-acting adrenergic agonists on narcolepsy?
|
amphetamine, methylphenidate
accelerates and desynchronizes electroenecphalogram |
|
|
What are the benefits of indirect-acting adrenergic agonists on ADHD?
|
increases alertness & working memory
methyphenidate |
|
|
What are the adverse effects of epinephrine?
|
HTN crisis (vascular alpha vasoC)
tachycardia & arrhythmia (B1) exacerbates narrow-angle glaucoma (a1) |
|
|
What are the roles of storage vesicles and NT?
|
1. acumulate DA or EPI from cytoplasm
2. oxidize DA to NE by DBH 3. bind and store NE & EPI 4. provide release mechanism 5. provide removal mechansim |
|
|
Why vesicle storage of NE and EPI important?
|
prevents degredation by MAO
|
|
|
Upon what is release of CAs from storage vesicles dependent?
|
influx of extracellular calcium
|
|
|
What is primary mechanism by which CA action at the synapse is terminated?
|
active transport back into the adrenergic nerve terminal
aka uptake 1 |
|
|
What is uptake 2?
|
active transport of CAs into non-neuronal dissue where it is metabolized by MAO and/or COMT
|
|
|
What is the other very minor route of CA removal?
|
1. difussion into circulation where it is metabolized by MAO/ COMT in liver/kidney
2. exrected in urine unchanged |
|
|
Name the three major classes of adrenergic receptors.
|
alpha
beta dopamine |
|
|
How many alpha receptor subtypes are there, and where are they located?
|
alpha 1- post synaptic at neuroeffector junction
alpha 2- pre & post synaptic a neuroeffector junction |
|
|
How many beta receptor subtypes are there, and where are they located?
|
beta 1- post synaptic at neuroeffector junction
beta 2- pre & post at NE junction beta 3- post at NE junction |
|
|
How many dopamine receptor subtypes are there and where are they found?
|
D1- postsynaptic at neuro effector junction
D2- presynaptic at NE junction D3, D4, D5 ??? |
|
|
All adrenergic receptors are what type of receptor?
|
G-protein coupled
|
|
|
What are postsynaptic receptors?
|
located on effector end organ/ tissue cells
|
|
|
What are presynaptic adrenergic receptors?
|
located on adrenergic nerve varicosities
|
|
|
When can dopamine inhibit adrenergic transmission?
|
if uptake 1 is inhibited by cocaine or tricyclic antidepressants
|
|
|
What is the cellular result of a1 stimulation?
|
activates PLC to form IP3 (Ca+ release) and DAG (activates PKC)
|
|
|
How can a1 stimulation cause relaxation of intestinal smooth muscle?
|
activates Ca+ dependent K+ channels leading to hyperpolarization
|
|
|
What are the cellular inhibitory effects of a2 stimulation?
|
inhibits adenylate cyclase decrease cAMP
increase K+ conductace, hyperpolarizing cell |
|
|
What are the cellular excitatory effects of a2 stimulation?
|
stimulate PLC increasing intracellular Ca+
|
|
|
How does B1 stimulation produce excitatory effects on cells?
|
increases cAMP
activates voltage-sensitive Ca+ channels in cardiac/ skeletal muscle |
|
|
How does B2 stimulation produce inhibitory effects on cells?
|
relaxes smooth muscle
cAMP dependent phosphorylation reduces cytosolic Ca+ |
|
|
Name two parasympathomimetic drugs.
|
bethanechol (direct)
physostigmine (indirect) |
|
|
Name a parasympatholytic drug and its MAO.
|
atropine
muscarinic receptor antagonist |
|
|
Name an anticholinergic drug that inhibts synthesis of ACh.
|
hemicholinium
|
|
|
Name an anticholinergic drug that inhibits release of ACh.
|
botulinum toxin
|
|
|
Name a cholinergic drug that inhibits breakdown of ACh.
|
physostigmine
|
|
|
Name two drugs that act on ganglia and their MAO.
|
DMPP (stimulant/ nicotinic agonist)
hexamethonium (blocking) |
|
|
Name sympathomimetic drugs and their MAO.
|
phenylephrine (direct)
tyramine (indirect) ephedrine (mixed) |
|
|
Name three sympatholytic drugs and their MAO.
|
phenoxybenzamine (alpha antagonist)
propranolol (beta antagonist) haloperidol (dopaminergic antagonist) |
|
|
Name a drug that inhibits synthesis at adrenergic nerve terminals.
|
alpha methyltyrosine
|
|
|
Name a druge that inhibits storage at adrenergic nerve terminals.
|
reserpine
|
|
|
Name a drug that inhibits release at adrenergic nerve terminals.
|
guanethidine
|
|
|
Name a druge that causes formation of false transmitters at adrenergic nerve terminals.
|
alpha methyl dopa
|
|
|
Name a druge that inhibits breakdown at adrenergic nerve terminals.
|
pargyline
|
|
|
Name a drug that inhibits uptake at adrenergic nerve terminals.
|
desipramine
|
|
|
What is the mechanism of direct parasympathomimetics?
|
cholingeric agonists
|
|
|
What is the mechanism of indirect parasympathomimetics?
|
anticholinesterase agents
|
|
|
Name the direct parasympathomimetics.
|
choline esters (ACh, carbachol, bethanechol)
alkaloids & misc (pilocarpine, metoclopramide) |
|
|
Name the reversible indirect parasympathomimetics.
|
edrophonium
neostigmine physostigmine |
|
|
Name the irreversible parasympathomimetics.
|
echothiophate
parathion malathion |
|
|
What is the effect of skeletal muscle nicotinic receptor stimulation?
|
increase permeability to Na+ and Ca+
localized depolarization, initiation of AP, muscle contration |
|
|
How can ACh affect smooth muscle and cardiac muscle?
|
acts on muscarinic receptors to change the rate of fluctuation in membrane potential and alter wave conduction thru tissue
|
|
|
What is the effect of small doses of ACh on the CVS?
|
generalized vaso D d/t stimulation of M3 which increases NO
|
|
|
What is the effect of large doses of ACh on the CVS?
|
direct action on SA node- bradycardia
muscarinic receptors direct action on SA & AV node- block conduction negative chronotropic & dromotropic |
|
|
What is the effect of ACh/ muscarinic receptor interaction on the SA node?
|
hyperpolarizes & dec rate of spontaneous diastolic depol
|
|
|
What is the effect of ACh/ muscarinic receptor interaction on the atrial muscle?
|
dec strength of contraction
slow conduction rate of AP can exacerbate afib |
|
|
What is the effect of ACh/ muscarinic receptor interaction on the AV node/ Purkinje system?
|
slows conduction
inc refractory period |
|
|
What is the effect of ACh/ muscarinic receptor interaction on the ventricle?
|
minor dec in contractility (inotropic)
|
|
|
What is the effect of large doses of ACh on the CVS in the presense of atropine?
|
stimulate nicotinic receptors in ganglia & adrenal medulla
|
|
|
What is the effect of ACh on the GI system?
|
inc tone, contraction amplitude & perstalisis
inc secretions |
|
|
What is the effect of direct application of ACh in the eye?
|
msucarinic effects:
sphintor muscle contration (miosis, dec IO pressure) near vision accomodation |
|
|
What is the effect of ACh on the respiratory system?
|
bronchoconstriction, inc secretions
stimulation of carotid and aortic body chemoreceptors |
|
|
What is the effect of ACh on the genitourinary tract?
|
dec bladder capacity
micturation inc voiding pressure |
|
|
What is the effect of ACh on glands?
|
stimulates lacrimal, tracheobronchial, salivary, digestive, and sweat glands
|
|
|
What is the effect of ACh on the CNS?
|
muscarinic & nicotinic
N- important to certain responses alertness |
|
|
What is the effect of ACh on the PNS?
|
N & M receptors
Ganglia- N- symp & paraS neuroeffec junction- M neuroM junction- N |
|
|
Name two choline esters totally resistant to AChE and psuedo-ChE
|
bethanechol
carbachol |
|
|
What limits the usefulness of carbachol?
|
nicotinic action, at ganglia
|
|
|
What are the major therauptic uses of cholinostimulants?
|
1. glaucoma
2. paralytic ileus 3. bladder atony 4. myasthenia gravis 5. antagonism of NM blocking drugs 6. intoxication by anticholinergics 7. CNS for certain dementias |
|
|
What are the potential adverse effects of ACh on the eye?
|
miosis, spasm of accomodation (blurred distance)
|
|
|
What are the potential adverse effects of ACh on the GI?
|
pain d/t spasm, nausea, vomiting, diarrhea, invol defecation
|
|
|
What are the potential adverse effects of ACh on the respiratory tract?
|
bronchoconstriction, can cause resp failure & death
|
|
|
What are the potential adverse effects of ACh on the CVS?
|
bradycardia, hypoT
|
|
|
What are the potential adverse effects of ACh on the skeletal NM junction?
|
fasciculations, weakness, paralysis
|
|
|
What are the potential adverse effects of ACh on the secretory glands?
|
sweating, salivation, lacrimation, gastric acid secretion
|
|
|
What are the potential adverse effects of ACh on the autonomic ganglia?
|
excition followed by depol blockade
|
|
|
What are the potential adverse effects of ACh on the CNS?
|
restlessness, insomnia
confusion, convulsions, coma ataxia, resp depression circulatory collapse |
|
|
Describe the absorption of tertiary amines vs quaternary amines.
|
tertiary- well abs in GI
quat- poorly abs in GI |
|
|
Why are organophosphates well absorbed by all routes? What is the exception?
|
high lipid-solubility
echothiphate (charged) |
|
|
Describe the distribution of tertiary amines vs quaternary amines.
|
tert/ organphos- penetrate CNS readily
quat- do not penetrate CNS well |
|
|
Describe the metabolism of most cholinostimulants.
|
to inactive products in liver, plasma, kidneys, lungs
|
|
|
What is the danger of malation and parathion in metabolism?
|
prodrugs
|
|
|
Which can be found in feces in given orally, tertiary or quaternary amine?
|
quaternary, poorly absorbed
|
|
|
How should cholinostimulants be administered?
|
only oral or subcu for systemic or locally to eye
|
|
|
What are the contraindications of cholinostimulants?
|
asthma- bronchC
hyperthyroidism- afib peptic ulcer coronary insuff |
|
|
What is muscarine?
|
alkaloid cholinergic agonist
|
|
|
What is the primary alkaloid cholinergic agonist used clinically?
|
pilocarpine
muscarinic effects esp on sweat glands tertiary amonium |
|
|
What are the clinical uses of pilocarpine?
|
initial Tx for wide-angle glaucoma
xerostomia |
|
|
What is cevimeline?
|
alkaloid cholinergic agonist
Tx of xerostomia |
|
|
How many binding sites are present on AChE?
|
three:
acyl pockt of active center choline subsite of active center peripheral anionic site |
|
|
What makes up the catalytic triad of the AChE active site?
|
serine
histidine glutamate |
|
|
What are the three stages of ACh breakdown?
|
1. complex forms btwn ACh and AChE
2. relase of choline 3. rxn w/ water to give acetic acid and regenerated enzyme |
|
|
What is pseudocholinesterase?
|
butyrylcholinesterase
in plasma, liver, glial cells hydrolyzes ACh and other choline esters |
|
|
How does the site of binding affect the inhibition of AChE?
|
to active site- total
to anionic or esteratic- prevents hydrolysis of ACh? |
|
|
Name the reversible carbamate AChE inhibitors.
|
neostigmine 4amine
physostigmine (3amine) pyrostigmine (4amine) |
|
|
Name the anionic site inhibitor that is a reversibe inhibitor of AChE.
|
edrophonium (4amine)
|
|
|
Name two reversibel AChE inhibitors.
|
donpezil (3 amine)
tacrine (3) |
|
|
Name the irreversible AChE inhibitors.
|
organophosphates
echothiophate parathion malathion |
|
|
What is the duration of action of the carbamate AChE inhibitors?
|
6 hrs
|
|
|
What is the duration of quaternary ammonium inhibitors of AChE?
|
mono-quat (edro)- minutes
bis-quats- hours |
|
|
How long is the duration of action of organophosphates?
|
100s of hours
|
|
|
What is the treatment for acute organophosphate poisoning?
|
atropine + pralidoxime
|
|
|
What is the prototypical antimuscarinic drug?
|
atropine
|
|
|
What are the characteristics fo atropine muscarinic blockade?
|
1. comptetive
2. speccific 3. quaternary analogues do not cross BBB 4. non-quaternaries and atropine cna produce CNS effects 5. differing sensitivity of organs |
