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175 Cards in this Set
- Front
- Back
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tyrosine is converted to ______ with tyrosine hydroxylase
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Dopa
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what converts tyrosine to dopa
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tyrosine hydroxylase
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dopa is converted to Dopamine by
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L-aromatic amine decarboxylase
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dopa is converted to ______
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dihydroxyphenylethylamine (dopamine)
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dopamine enters the synaptic vesicle by the...
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amine transporter system
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dopamine is converted to norepinephrine by
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dopamine beta-hydroxylase
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norepinephrine is converted to epinephrine by
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phenyethanolamine-N-methyl transferase
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what are the three ways norepi is removed
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1. diffusion into general circulation
2. metabolism to inactive metab 3. reuptake into presynaptic neuron |
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what prevents reuptake into presynaptic neuron
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cocaine and TCAs
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what is the method of metabolism for presynaptic neuronal mitochondria
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Monoamine oxydase
MAO |
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what is the metabolism method for the adrenergic synaptic cleft
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carboxymethyl transferase
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what does both MAO and COMT form
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VMA, vanillyimandelic acid
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what distinguishes the 2 classes (alpha and beta) of adernergic receptors
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their affinity for epi norepi and isoproterenol
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alpha receptors affinity for epi norepi and isoproteranol
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epi:high
norepi: intermediate iso: low |
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beta receptors affinity for epi norepi and isoproteranol
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epi: intermediate
norep: low iso: high |
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alpha 1 characteristics
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vasoconstriction
inc Peripheral resistance mydriasis inc BP bladder sphincter contraction |
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alpha 2 characteristics
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feedback inhibition of norepi (pre syn)
plt aggregation, hyperpolarization of CNS (post syn) (beta cells of pancreas) inhibition of insulin release |
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beta 1 receptors
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inc conduction velocity, automaticity(spontaneous heart contraction), inc contractility, release of renin and lipolysis
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beta 2 receptors
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vasodilation
dec periph resistance bronchodilation inc release of glucagon uterine smooth musc relaxation bladder relaxation inc musc and liver glycogenolysis |
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characteristics of adrenergic agonists
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derivatives of beta phenylethylamine
substitutions on benzene ring effect receptor affinity and CNS stimulant effects |
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characteristics of catecholamines
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sympathetic amines containing the 3,4-dihydroxybenzene group
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3 properties of catecholamines
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1. highest potency for alpha and beta receptors
2. poor penetration into CNS 3. rapid inactivation and elimination |
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non catecholamine characteristics
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lack catechol hydroxyl group
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properties of non catecholamines
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long half life
lipid solubility allows passage into CNS |
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characteristics of direct adrenergic agonists
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act directly on the receptor
produce effects similar to endogenous catcholamines natural or synthetic |
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what receptors does epi activate
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all 4
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clinical effects of epi
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inc contractility and HR(b1), bronchodilator(b2)
inc lipolysis(b) inc glycogenolysis, release of glucagon and dec release of insulin |
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why do noncatecholamines have a long half life
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because it is not inactivated by COMT or MAOs
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clinical uses of epi
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added to LA
tx of allergic rxns (bronchodilation) cardiopulmonary resuscitation myocardial contractility glaucoma and asthma tx |
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doses of epi
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ACLS: 1 mg
cardiac contractility: 10mcg/kg allergic rxn: 0.3-1mg infusion:0.05mcg/kg/min |
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receptors activated by norepi
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alpha 1 &2 and beta 1
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what is the doses of norepi
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4-16mcg/kg
infusion: 0.05mcg/kg/min |
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receptors activated by isoproterenol
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beta 1 and 2
2-3x more potent than epi |
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dose of isoproterenol
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1-5 mcg/min
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what receptors does dopamine activate
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D 1 and 2 and beta receptors
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what do dopamine receptors do
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vasodilate mesenteric and renal beds
presynaptic interference with NE release |
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unique catecholamine effects
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inc in: myocardial contractility, renal blood flow, GFR, Na+ excretion, urine output
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dosing of dopamine
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renal (D1): 0.5-3mcg/kg/min
contractility (b1): 3-10 mcg/kg/min vasoconstriction (a1):>10mcg/kg/min |
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receptors activated by dobutamine
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b1, inc hr and co with little vascular effect
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dosing of dobutamine
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2-10mcg/kg/min
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receptors activated by phenylephrine
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a1, inc bp with bradycardia
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doses of phenylephrine
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0.5-1.5mcg/kg
infusion: 0.2-0.5 mcg/kg/min nasal: 0.25-0.5 mg |
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receptors activated by clonidine
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alpha 2, inhibition of sympathetic vasomotor centers
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clinical uses of clonidine
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anti-hypertensive
analgesia tx of opioid or EtOH withdrawl or tourettes |
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receptors activated by albuterol
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selective short acting beta 2 agonist, bronchodilator
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2 other bronchodilators
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terbutaline
salmeterol |
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characteristics of indirect adrenergic agonists
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induce the release of norepi from presynaptic terminals, potentiate NE effects but dont stimulate the receptors
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indirect adrenergic agents
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amphetamines and tyramines
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receptors stimulated by ephedrine
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alpha and beta agonist
stimulate norepi release and receptor binding |
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clinical uses of ephedrine
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intraoperative hTN or after regional anesthesia and parturient
bronchial asthma |
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dosing of ephedrine
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0.1-0.2 mg/kg IV
25-50 mg IM |
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other synthetic non catecholamines
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modafinil and ritrodine
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all drugs that activate alpha 1
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epi, norepi, dopamine, phenylephrine, ephedrine
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all drugs that activate alpha 2
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epinephrine, norepinephrine, clonidine, and ephedrine
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all drugs that activate beta 1
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epi, norepi, isoproterenol, dopamine, dobutamine, ephedrine
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all drugs that activate beta 2
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epi, isoproterenol, ephedrine
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where do adrenergic antagoinsts bind
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bind to adrenoreceptors but do not trigger receptor mediated responses
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how are adrenergic antagonists classified
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by relative affinities for adrenoreceptors
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characteristics of alpha adrenergic antagoinsits
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bind to alpha adrenergc receptors
prevent effects of catecholamines and sympathomimetics on the heart and periph vasculature |
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side effects of alpha adrenergic antagonists
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reduce sympathetic tone (cause hypotension)
reflex tachy impotnence/priapism |
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where does phenoxybenzamine bind (dibenzyline)
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nonselective irreversible alpha adrenergic blockaid
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what is the onset and duration of dibenzyline
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o: 60 min
d: 24 hrs |
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clinical uses of dibenzyline
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pheochromocytoma, autonomic hyperreflexia and reynauds
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where does phentolamine bind (regitine)
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competative reversible and nonselective alpha adrenergic blockaid
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onset and duration of regitine
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o= <2min
d~ 4 hrs |
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results of giving regitine (phenotolamine)
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dec BP inc HR
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dose of phentolamine
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30-70mcg/kg
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dose of phenoxybenzamine
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0.5-1mg/kg
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4 other alpha adrenergic antagoinsts
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prazosin
tamulosin terazosin doxazosin |
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characteristics of beta adrenergic antagonists
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competitive antag at beta
prevent effects of cat and sympathos on the heart and smooth musc of blood vessels and airway derivatives of isoproterenol |
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how are beta antagonists classified
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nonselective b1 and b2
cardio selective antagonists |
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effects of beta antagonists
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slows sinus rate
slows AV node conduction decreased contractility may inc bronchospasm |
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uses for beta antagonists
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tx of HTN (dec BP, HR and CO)
mgmt of angina pectoris (dec CMRO2 due to dec HR and contractility) tx of acute coronary syndrome mgmt of CHF glaucoma hyperthyroidism performance enhancement |
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negative effects of beta antagonists
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dont give to pt w/ heart block
may inc airway resistance fatigue, withdrawal hypersensitivity, alteration of metabolism, sexual impairment arrhtymias |
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where does propranolol work (inderal)
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non selective b1 and b2 antag
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effects of inderal
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dec HR CO and contractility
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dosing of propranolol
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0.05mg/kg
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how is propranolol metabolized
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hepatic metab with active metabolism
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considerations when giving propranolol
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dec LA clearance
dec pulmonary uptake of fentanyl dec glycogenolysis and glucagon secretion |
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where does esmolol (brevibloc) work
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selective B1 antag
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onset and duration of esmolol
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rapid
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metabolism of esmolol
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plasma cholinesterase
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dose of esmolol
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0.5 mg/kg
infusion: 50-300 mcg/kg/min |
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location of metoprolol action (lopressor)
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selective b1 antagoinst
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effects of lopressor
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dec in chronotropy (HR) and ionotropy (contractility)
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dose of metoprolol
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0.05-0.1 mg/kg
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location of atenolol action (tenormin)
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most selective b1 receptor antag
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effects of atenolol
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prolonged anti hypertensive effects
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dose of atenolol
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0.1-0.2 mg/kg
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other beta blockers
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nadolol
carvedilol timolol |
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site of labetolol action (trandate)
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selective alpha 1 and nonselective b1,2 receptor antag
ratio of 7:1 b:a |
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effects of labetalol
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dec BP and HR, unchanged CO
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considerations for using labetolol
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b2 blockaid can cause bronchoconstriction
orthostatic hTN |
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alpha 1 antagonists
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phenoxybenzamine, phentolamine, prazosin, labetaolol
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alpha 2 adrenergic antagonists
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phenoxybenzamine, phentolamine
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beta 1 antagonists
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propranolol, atenolol, esmolol, metoprolol, labetolol
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beta 2 antagonists
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propranolol, labetolol
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what is phenochromocytoma
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catecholamine producing neuro-endocrine tumor arising from chromaffin cells
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where do phenochromocytomas commonly occur
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adrenal medulla 80-85%
extra-adrenal paragangliomas (head and neck) |
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what is the common age to get phenochromocytomas
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30s to 50s
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signs and symptoms of phenochromocytomas
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pressure (HTN)
pain (headaches) perspiration palpitation pallor paroxysms classical triad of headache perspiration and palpitation |
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characteristics of paroxysms spells
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10-60 min duration
daily to monthly in frequency spontaneous |
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what can cause paroxysms spells
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diagnostic procedures
drugs, strenuous exercise |
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what drugs cause Paroxysms spells
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opioids, unopposed beta blockers, anesthesia induction, histamine, ACTH, glucagon, metoclopramide
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anesthesia for removing phenochromocytomas
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avoid benzos, barbiturates or demerol
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characteristics of cocaine
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LA and intense vasoconstrictor
dopamine reuptake inhibitor and Na channel blocker euphoric high and inc energy risk of cardiovascular toxicity doesnt require epi to be added to it |
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structure of LA
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hydrophilic tertiary amine and lipophilic aromatic ring connected by a hydrocarbon chain
has either ester or amide to link the 2 structures |
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characteristics of amides
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more stable in soln
metabolized by mixed fxn oxidases slower metabolism |
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characteristics of esters
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inc risk of allergy
metabolized by pseudocholinesterase Paraminobenzoic acid metabolite shorter duration of action |
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how to tell amide vs ester
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amides have an i in the first half of the name before the -caine
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how do LA exist in the body
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as uncharged base or as a cation
pKa of 8 <50% lipid soluble nonionized form, acidosis inc ionized form |
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factors affecting LA absorption
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vasodilator activity
dosage vasoconstrictors pharmacological characteristic alkalinization (adding bicarb) pregnancy |
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what does adding bicarb do to absorption of LA
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dc latency of onset and inc potency
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what has the greatest LA absorption and what has the least
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g: IV
l: peripheral |
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the more lipid soluble the LA the...
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higher potency
longer onset of anes longer duration inc tendency for cardiovascular toxicity |
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what dictates the redistribution of LA to tissue sites
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lipid solubility and protein binding
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which is more widely distributed amides or esters
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amides
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which drugs undergo the pulmonary first pass effect
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lidocaine, bupivicaine and prilocaine
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characteristics of esters
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half lives of seconds to min
hydrolyzed by nonspecific esterases clearance independent of liver BF and liver fxn and usually renal failure inactive metabolites allergy with procaine or benzocaine |
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characteristics of amides
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half lives of hours
metabolized in the liver by CYP450 cl depends on liver BF and fxn hepatic hydroxylation and N-dealkylation active metabolites |
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effects of renal failure on LA
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inc Vd of both types
metabolic products accumulate |
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effects of hepatic failure on LA
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inc amide but not ester Vd
dec clearance |
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effects of beta adrenergic and histamine H2 antagoinsts on LA
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dec amide but not ester clearance
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effects of heart failure on LA
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dec amide but not ester clearance
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effects of cholinesterace deficiency or inhibition on LA
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dec ester but not amide clearance
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effects of pregnancy on LA
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inc amide but not ester clearance
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mechanism of LA action
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conduction blockade by inhibitng passage of Na ions through ion selective sodium channels in nerve membranes
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what are 3 forms of sympathomimetics
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catecholamines
synthetic catecholamines synthetic noncatecolamines |
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what are the 2 forms of synthetic noncatecholamines
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direct and indirect
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what response do sympathomimetics give
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those similar to the sympathetic NS
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what do sympathos vasoconstrict
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cutaneous and renal circulations
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what do sympathos vasodilate
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skeletal musc vasculature
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what are other effects of sympathos
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bronchodilation, cardiac stim (inc HR, contractility and vulnerability to arrythmias), liberation of fatty acids from fat tissue, hepatic glycogenolysis,CNS stim
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what do sympathos modulate
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insulin, renin and pituitary hormone secretion
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what are sympathos most used for
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positive inotropic agents to inc contractility or vasopressors to inc systemic BP after SNS blockaid or to eliminate VA
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when should a vasopressor be administered
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when systemic BP must be raised fast to prevent ischemia
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what are 3 other uses of sympathos especially epi
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tx of bronchospasm in asthmatics
mgmt of allergic rxns addition to LA to slow systemic absorption |
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what determines receptor selectivity and causes maximal alpha and beta binding
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the chemical structure of the drug
maximal is presence of hydroxyl group on the 3&4 C of benzene ring |
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what are the direct acting catecholamines
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epi, norepi, dopamine
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what are the synthetic catecholamines
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isoproterenol and dobutamine
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waht are the direct acting synthetic noncatecholamines
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phenylephrine and methoxamine
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what are the indirect acting synthetic noncatecholamines
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mephentermine and amphetamines
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what are the indirect AND direct acting synthetic noncatecholamines
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ephedrine and metaraminol
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beta activation causes
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inc CO, HR, dysrhythmias
dec perif VR, RBF, MAP bronchodilation stimulates CNS |
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alpha activation causes
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dec CO, HR, dysrhythmias, RBF
inc perf VR, MAP no CNS stim or change in airway |
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why dont catecholamines stim the CNS
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they have limited lipid solubility so cant cross BBB
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which types of drugs stimulate the CNS
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synthetic noncatecholamines
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what family of receptors are alpha, beta and dopamine receptors
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G protein coupled receptors
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what is the first step of sympathos action
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binding of sympatho on the cell surface by a receptor that recognizes a ligand
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what is the second step of sympathos action
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conformational change where receptor activates a G protein class
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what is the third step of sympathos action
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G protein diffuses to encounter an effector protein, which changes the conc of a 2nd messenger or cell memb potential
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how are beta effects made
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by activating adenylate cyclase to produce cAMP
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what are the effects of each receptor on Ca or cAMP
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b1=inc Ca influx get stronger contractility
b2=dec Ca influx (smooth musc relax) a1=inc Ca influx a2=inhibits adenylate cyclase red cAMP D=inc cAMP |
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what factor determines the pharm. effect
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the density of a &b rec in tissues
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what is the relationship b/w conc of sympatho and # of rec
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inverse
more plasma drug less rec |
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what does stimulation of b2 do
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cause bronchodilation
inhibits activation of T cells and release of cytokines from airway smooth musc |
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what is unique about changing the dose of epi
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low doses produce beta mediated vasodilation and high doses produce alpha mediated vasoconstriction
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what is the diff b/w b1 and b2 with norepi compared to epi
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b1=same effects
b2=norepi causes less response |
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how do indirect acting sympathos work
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instead of working on the rec they activate the release of endogenous norepi from postganglion
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what does repeated doses of sympathos do
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blunt the response by depleating the neurotransmitter stores
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what type of direct acting sympatho has a higher potency
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catecholamines
Over synth noncate |
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what inactivates drugs containing 3,4-dihydroxybenzene
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MAO (monoamine oxidase) or COMT (catechol-o-methyltransferase)
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where are MAOs and what do they do
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in the liver, kidney and GI they catalyze oxidative deamination
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what do COMTs do
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methylate hydroxyl groups resulting in an inactive metabolite in the urine
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effect of pulmonary uptake on norepi, dopamine and dobutamine
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norepi 25%, dopamine=20% and dobut is minimal
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what is the primary mech of terminating action of catechol
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uptake back into postganglionic nerve ending
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what type of sympatho is only metabolized by MAOs and why
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synthetic noncatecholamines lacking a 3-hydroxyl group b/c COMTs have no effect
metab is slower |
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why is oral administration of catecholamines not effective
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because they are metabolized by enzymes in the liver and GI before they reach systemic circulation
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which drugs are administered only IV
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dopamine, dobutamine and norepi
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what are the natural functions of epinephrine
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regulation of contractility, HR, vascular and bronchial smooth musc tone, glandular secretion, and glycogenolysis and lipolysis
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where is epinephrine naturally stored
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adrenal medulla
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how is epinephrine administered
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SubQ or IV.
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why is sub Q administration of epinephrine slow
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because it causes local vasoconstriction
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what are the metabolic effects of epi stimulating b1 and a1
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b1=inc liver glycogenolysis and adipose tissue lipolysis
a1=inhibits insulin release |
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what 3 things does an infusion of epi increase plasma conc of
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cholesterol, phospholipids and low density lipoproteins
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