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198 Cards in this Set
- Front
- Back
model indirect-acting sympathomimetic
|
tyramine
|
|
2 fates of tyramine
|
MAO --> deamination metabolite
DBH --> octopamine (biologically inert) |
|
Where does octopamine accumulate
|
synaptic vessels where DBH also catalyzes DA --> NE
|
|
NE _____ BP via ____ receptors and ____ HR by reflex
|
NE increases BP via alpha-1 receptors and decreases HR by reflex
|
|
NE ____ BP by direct beta-1 activation
|
NE increases BP by direct beta-1 activation
|
|
effect of NE on heart rate, combining direct and indirect effects
|
up or down or both
|
|
phenylephrine ____ BP via _____ receptors and _____ HR by reflex
|
phenylephrine increase BP via alpha-1 receptors and decreases HR by reflex
|
|
phenylephrine _____ on HR via direct beta-1 ativation
|
phenylephrine has NO direct effect on beta-1 receptors, and therefore NO direct effect on HR
|
|
overall effect of phenylephrine on heart rate
|
decrease
|
|
isoproterenol ____ BP via _____ receptors and _____ HR by reflex
|
isoproterenol decreases BP via beta-2 receptors and incrases HR by reflex
|
|
Effect of isoproterenol on HR via direct beta-1 activation
|
increase
|
|
Overall effect of isoproterenol on HR
|
BIG INCREASE
|
|
Effect of dopamine on BP
|
none
|
|
Effect of dopamine on HR by _____
|
increase of HR by direct activation of beta-1 receptors
|
|
effect of dobutamine on BP
|
none
|
|
effect of dobutamine on HR by _____
|
increase in HR via beta-1 receptor
|
|
effect of octopamine after repeated injections of tyramine
|
accumulation of octopamine in synaptic vessels dilutes concentration of NE leaving vessel and therefore reduces pressor effect
|
|
effect of MAOI on tyramine effects
|
when MAO inhibited, all tyramine metabolized via DBH --> octopamine
large doses of tyramine --> BIG increase BP --> can lead to brain aneurysm |
|
When compared with epinephrine, ephedrines are:
|
less potent
longer acting (not COMT, MAO substrate) less polar - orally active, passes BBB |
|
which affects the brain more, epi or ephedrine?
|
ephedrine (more lipophilic - passes BBB)
|
|
indirect adrenergic action of ephedrine
|
releases NE
|
|
direct adrenergic action of ephedrine
|
stimulates beta-2
|
|
peripheral actions of ephedrine - 3 medical indications
|
chronic asthma (b2) - replaced by salmeterol
enuresis (a1/CNS) nasal decongestant (a1) |
|
problem with ephedrine
|
CNS stimulation (anorexigenic)
|
|
2 drugs that....
lack direct beta-2 agonist action indirect action as nasal decongestant less CNS stimulation than ephedrine |
pseudoephidrine
phenylpropanolamine |
|
structural significance of amphetamine
|
one asymmetric carbon --> D & L isomers
|
|
pharmacological actions of amphetamines in periphery
|
releases NE
- contraction of smooth muscle in blood vessels and bladder - stimulation of heart |
|
pharmacological actions of amphetamines in CNS
|
D isomer 3-4x more potent than L
releases DA to cause CNS stimulation |
|
pharmacokinetics of amphetamine
|
lipid soluble - orally effective, penetrates BBB
excreted unchanged in urine acidic urine increases excretion |
|
amphetamine toxicity
|
tachycardia
jitteriness, insomnia, anorexia hallucinations, paranoia (high doses) |
|
treatment for amphetamine toxicity
|
acidify urine with NH4Cl
dopamine antagonists (e.g.: haloperidol) |
|
6 therapeutic uses for amphetamine in CNS
|
analeptic
psychic stimulant (e.g.: for narcolepsy) motor stimulant anorexigenic (tolerance; abuse) ADHD ADD |
|
methamphetamine
|
shorter duration of action than amp - longer than coke
chronic high doses --> memory loss, neuro deficits |
|
MDMA
|
"ecstasy"
|
|
cocaine
|
peripheral sympathomimetic and local anesthetic
CNS stimulant |
|
non-fatal adverse effects of cocaine
|
dysphoric agitation
paranoia tachycardia & HTN angina/MI hyperthermia |
|
Signal transduction for alpha-1 receptors
|
activation of PCL
catalyzes release of IP3 & DAG intracellular IP3 stimulates release of Ca2+ from sarcoplasmic reticulum causes smooth muscle contraction |
|
Signal transduction of alpha-2
|
inhibition of AC and reduced levels of cAMP
|
|
signal transduction of beta receptors
|
stimulation of AC and increased levels of cAMP
|
|
The greater the sympathoadrenal tone, the ____ the response of the blocking drug
|
greater
|
|
phenoxybenzamine
|
irreversible, non-selective a1 & a2 antagonist
|
|
phentolamine
|
reversible, non-selective a1 & a2 antagonist
|
|
process by which nonselective alpha antagonists cause orthostatic hypotension
|
reduce sympatheti tone to arteriolar resistance vessels & veins
causes modest reduction in recumbant BP, but marked decrease in compensatory vasoconstriction that occurs upon standing |
|
immediate result of orthastatic hypotension
|
reflex increase in SNS
|
|
relatively selective a1 antagonist
|
prazosin
|
|
4 outcomes of benign prostatic hyperplasia
|
bladder outlet obstruction
obstructive nephropathy acute urinary retention recurrent UTIs |
|
tone of smooth muscle in prostate capsule, bladder neck and urethra is maintained by ____ relased from _____ acting on ______receptors
|
tone of smooth muscle in prostate capsule, bladder neck and urethra is maintained by NE released from sympathetic neurons acting on alpha receptors
|
|
sympatoms of BPH can be relieved by what drug class
|
a1 antagonist
|
|
4 examples of a1 antagonists that alleviate BPH symptoms
|
prazosin
doxazosin terazosin alfuzosin |
|
relatively selective alpha-1A antagonist for treating symptoms of BPH with less postrual hypotension
|
tamsulosin (FLOMAX)
|
|
side effects of alpha antagonists
|
tachycardia
postural hypotension inhibition of ejaculation increased blood volume and Na+ retention nasal stuffiness |
|
5 clinical uses of alpha antagonists
|
pheochromocytoma
HTN hypertensive emergencies peripheral vascular disease BPH |
|
alpha antagonist for treatment of pheochromocytoma
|
phenoxybenzamine
|
|
alpha antagonists for treatment of HTN
|
prazosin
terazosin |
|
nonselective competitive beta antagonist
|
propranolol
|
|
beta adrenergic receptor antagonists reduce the ability of the sympathoadrenal system on CV system to...
|
cause vasodilation
increase rate of conduction in atria & AV node cause positive inotropic and chornotropic effects of heart increase rate of depolarization of ectopic pacemakers |
|
beta adrenergic receptor antagonists _______ of bronchial smooth muscle
|
beta antagonists decrease the relaxation of bronchial smooth muscle (increases airway resistance)
|
|
metabolic effects of beta antagonists
|
reduce release of renin
decreases lipase activation --> increases TGs and decreases FFA in plasma reduces glycogenolysis |
|
effect of propranolol on skeletal muscle
|
reduces tremor
reduces blood flow during exercise |
|
3 conditions for which beta-blockers may be counterindicated
|
heart failure
pulmonary disease insulin-dependent DM |
|
symptoms of sudden withdrawal of beta blocker
|
angina
tachycardia cardiac arrhythmias |
|
effect of beta blockers on plama lipids
|
increase TGs
decrease HDL |
|
first beta blocker to gain widespread clinical acceptance
|
propranolol
|
|
2 non-selective beta blockers that differ from propranolol
|
nadolol (1 qd)
timolol (oral/topical - for glaucoma) |
|
non-selective beta blockers with modest beta-1 agonist properties
|
pindolol:
- less slowing of HR - up-regulation of beta-1 receptors - changes in plasma TGs |
|
non-selective beta blockers with alpha-1 blocking properties
|
labetalol
carvedilol |
|
beta blocker used i.v. for tx of hypertensive emergencies
|
labetalol
|
|
relatively selective beta-1 blockers are less likely than non-selective beta blockers to...
|
increase airway resistance in asthmatics
delay recovery from insulin-induced hypoglycemia cause HTN in response to epi or sympathoadrenal discharge |
|
3 examples of beta-1 blockers
|
metoprolol
atenolol esmolol |
|
use of esmolol
|
ultra short, i.v. emergency tx of A-fib, supraventricular tachycardia
|
|
3 main clinical uses of beta blockers
|
cardiac dysrhythmias
extertional angina HTN |
|
4 lesser clinical uses of beta blockers
|
micgrain
glaucoma essential tremor anxiety and panic |
|
role of beta blockers post-MI
|
counteract harmful effects of sympathoadrenal discharge activated during heart failure
- tachycardia - arrythmias - renin release |
|
effect of long-term tx with beta-1 blockers after an MI
|
reduces incidence of reinfarction and mortality
probably by reducing oxygen demand and arrythmias |
|
pharmacological properties of reserpine
|
blockade of NE storage - long-lasting disruption of aminergic synaptic vesicles
- sedation - reduced SNS activity - reduced responsiveness to indirect-acting sympathomimetics |
|
effects of reserpine toxicity
|
nightmares, depression, suicide
increased GI tone and secretions --> increased appetite and weight gain nasal congestion |
|
2 clinial uses of reserpine
|
calm hyperactive schizophrenics
treat mild to moderate HTN - inexpensive, effective at low doses when combined with a diuretic |
|
drugs that interfere with sympathetic outflow
|
methyldopa
clonidine |
|
methyldopa pharmacological properties and mechanism of action
|
central alpha-2 agonist
stimulation of alpha-2 receptor --> negative feedback to SNS --> decreased SNS tone & outflow --> decrease in total peripheral resistance & cardiac output |
|
4 adverse effects of methyldopa
|
sedation
endocrine dysfunction mild postural hypotension immunological disorders / hepatitis |
|
clinical uses of methyldopa
|
anti-hypertensive, esp. for gestational HTN
|
|
pharmacological porperties of CLONIDINE and mechanism of action
|
reduced BP correlated with reduced [NE] in plasma
reduced cardiac output (reduced HR & stroke volume) relaxation of capacitance vessels baroreceptors only blunted - little postural hypotension |
|
4 adverse effects of clonidine
|
redation / sleep disturbances
dry mouth retention of sodium & water rebound HTN on withdrawal - HA, tremore, tachycardia |
|
3 clinical uses of clonidine
|
moderate HTN
migraine ease opiate/EtOH/nicotine withdrawal symptoms |
|
drug that inhibits tyrosine hydroxylase & clinical indication(s)
|
alpha-methytyrosine inhibits tyrosine hydroxylase
inoperable pheochromocytoma |
|
drug that inhibits DOPA decarboxylase
|
carbidopa
tx of Parkinsonism |
|
drug that inhibits COMT
|
entacapone
reduce drug "wearing off" symptoms in Parkinsonism |
|
drug that inhibits MAO
|
phenelzine
treats severe mental depression |
|
significance of the fact that CARBIDOPA is not a substrate of the amino acid transporter in the brain
|
does not penetrate BBB
|
|
when used in conjunction with L-DOPA, carbidopa...
|
lowers dose of L-DOPA
reduces peripheral side effects resulting from action of DA (N/V, tachycardia, arrhythmias) |
|
2 sets of muscles in iris
|
concentric
radial |
|
class of drugs that produce miosis
|
parasympathomimetic drugs
|
|
2 classes of drugs that produce mydriasis
|
sympathomimetics
muscarinic antagonists |
|
aqueous humor
|
provides nutrients
removes wastes formed by ultrafiltration of plasma by ciliary process |
|
intraocular pressure is proportional to which 2 things?
|
rate of formation of aqueous humor
rate of outflow of aqueous humor |
|
range of normal intraocular pressure
|
10-20 mmHg
|
|
intraocular pressure greater than _____ can cuase irreverible damage to the optic nerve and glaucoma
|
30 mmHg
|
|
primary open angle glaucoma
|
most common type of glaucoma
chronic, progressive results from reduced outflow of aqueous humor due to age-related anormalities of flow-system |
|
drug classes used to treat primary open angle glaucoma
|
beta-adrenergic antagonists
alpha-2 agonists PG analogs topical carbonic anhydrase inhibitors |
|
primary angle-closure glaucoma
|
acute episodes of severe pressure elevation in persons with shallow anterior chambers and narrow angles of filtration
|
|
primary angle-closure glaucoma is often precipitated by ____
|
mydriasis
|
|
reduced outflow of aqueous humor in primary angle-closure glaucoma is reversed by tx w/ ____ & ______
|
pilocarpine (mAChR agonist)
iridectomy |
|
secondary glaucoma
|
associated with ocular ds, drugs or trauma
|
|
activation of mAChR causes ______, resulting in alterations of the _____; thus, reducing resistance to outflow of aqueous humor
|
Activation of mAChR causes contraction of CILIARY MUSCLEe, resulting in alterations of the TRABECULAR MESHWORK; thus, reducing resistance to outflow of aqueous humor.
|
|
direct muscarinic agonist used in pharmacological tx of glaucoma
|
pilocarpine
|
|
AChE inhibitors used in tx of glaucoma
|
physostigmine
echothiophate |
|
PG F2-alpha analog used in tx of glaucoma
|
latanoprost
|
|
3 classes of drugs that reduce resistance to outflow of aqueous humor
|
direct muscarinic agonists
AChE inhibitors PG Fa-alpha analog |
|
3 classes of drugs that reduce aqueous humor production
|
beta blockers
alpha-1/alpha-2 adregnergic receptor agonists carbonic anhydrase inhibitors |
|
dipivefrin
|
epi prodrug
|
|
brimonidine
|
alpha-2 agonist
|
|
dorzolamide
|
carbonic anydrase inhibitor
|
|
3 relatively selective inhibitors of PDE-5
|
sildenafil
vardenafil tadalafil |
|
3 choline esters that are relatively resistant to AChE and are used for systmic administration
|
methacholine
carbachol bethanechol |
|
4 cholinergic drugs from plant sources
|
pilocarpine
muscarine arecholine nicotine |
|
3 muscarinic agonists that treat miosis
|
ACh
carbachol pilocarpine |
|
muscarinic agonist that traets postoperative abdominal distension
|
bethanechol
|
|
muscarinic agonist that treats urinary retention
|
bethanechol
|
|
location of AChE
|
neurons
skeletal muscle RBCs |
|
location of BuChE
|
plasma
neuroglia GI tract |
|
AChE inhibition correlated with ______
|
cholinergic effects
|
|
Is BuChE inhibition correlated with cholinertic effect?
|
No
|
|
AChE hydrolyzes ______& ______
|
ACh
methacholine (both of these inhibit AChE in high doses) |
|
BuCHE has a _____ substrate specificity than AChE
|
broader
|
|
______ in BuChE accounts for variability in the duration of action of some drugs
|
genetic variation
|
|
irreversible inhibitors of choinesterases are what chemical family
|
esters of phosphoric acid (organophosphates)
|
|
3 classes of reversible cholinesteras inhibitors
|
edrophonium
carbamate inhibitors donepezil |
|
edrophonium
|
binds reversibly with anionic and esteratic sites on AChE
short duration - excreted by kidney i.v. administration |
|
donezepil
|
long acting
lipid soluble used to delay progressive loss of cognitive functions in patients with Alzhemier's disease |
|
carbamate inhibitors
|
combines with and carbamoylates AChE
react slowly with water and "tie up" the enzyme |
|
3 examples of carbamate inhibitors
|
physostigmine - orally effective, active in CNS
neostigmine & pryidostigmine carbaryl (SEVIN) - used for head lice |
|
3 examples of irreversible cholinesterase inhibors (organophosphates)
|
parathion, malation
echothiophate |
|
organophosphate toxicity
|
lipid soluble - readily absorbed from gut, skin
death can occur quickly - usually from asphyxia |
|
CNS symptoms of organophosphatge toxicity
|
uneasiness and restlessness, followed by depression, confusion, convulsion, coma
|
|
eye symptoms of organophosphate toxicity
|
miosis and cyclospasm
|
|
respiratory system symptoms of organophosphate toxicity
|
increased glandular secretions and bronchoconstriction
|
|
glandular symptoms of organophosphate toxcitiy
|
sweating, salivation, tearing
|
|
GI system symptoms of organophosphate toxicity
|
abdominal cramping, vomiting, defecation
|
|
urinary bladder symptoms of organophosphate toxicity
|
urinary frequency
|
|
skeletal muscle symptoms of organophosphate toxicity
|
fasciculations followed by muscle weakness and paralysis (including resp. muscles!)
|
|
treatment for organophosphate toxicity
|
quickly remove individual from source of poisoning
atropine: large loses, blocks muscarinic and CNS effects pralidoxime - does not penetrate BBB; most effective at NMJ artificial respiration |
|
2 muscarinic blocking drugs
|
atropine
scopolamine |
|
which has greater action in the CNS, scopolamine or atropine?
|
scopolamine
|
|
Peripheral effects of mAChR blocking drugs in the eye
|
mydriasis
cycloplegia |
|
Peripheral effects of mAChR blocking drugs in the respiratory tract
|
inhibition of glandular secretions
slight relaxation of bronchioles |
|
Peripheral effects of mAChR blocking drugs in the CV system
|
increases HR
dilation of some blood vessels, unrelated to muscarinic receptor blockade |
|
Peripheral effects of mAChR blocking drugs in the GI tract
|
decreased salivation
slight reduction in peristalsis |
|
Peripheral effects of mAChR blocking drugs in the urinary bladder
|
urinary retention
|
|
Peripheral effects of mAChR blocking drugs in the sweat glands
|
reduced sweating and elevation of body temperature
|
|
ipratropium & tiotropium
|
belladonna alkaloids (muscarinic blockers)
administered by aerosol for treatment of chornic bronchitis and bronchospasm associated w/ COPD not absorbed from gut, so muscarinic receptor blockade effects diminished |
|
toxicity of muscarinic antagonists
|
dry as a bone, blind as a bat, red as a beet, mad as a hatter
|
|
conditions that counterindicate muscarinic antagonists
|
childhood
narrow angle glaucoma BPH urinary bladder neck obstruction |
|
3 drug classes not categorized as muscarinic antagonistic that have potent antimuscarinic porperties
|
antihistamines
tricyclic antidepressants antipsychotics |
|
symptoms related to peripheral muscarinic receptor blockade
|
dry mouth
blurred vision dry eyes photophobia constipation urinary retention anhidrosis hyperthermia |
|
class of drugs that alter skeletal muscle function by acting at the spinal cord
|
benzodiazepines
|
|
class of drugs that alter skeletal muscle function by acting at the NMJ
|
curare-like compounds
|
|
class of drugs that alter skeletal muscle function by acting at the skeletal muscle cells
|
dantrolene
|
|
curare was originally used to treat ____
|
tetanus (relaxes violent muscle contractions)
|
|
competitive/ non-deporalizing NMJ blocking drugs - mechanism of action
|
block AChR at the motor end plate
thus depressing amplitude and duration of the end-plate potential below the threshold for initiation |
|
tubocurarine
|
curare w/ 2 quaternary nitrogens
|
|
action of tubocurarine at NMJ
|
paralyzes skeletal muscle in characteristic temporal manner:
extrinsic eye muscles jaw muscles throat muscles peripheral muscles abd & intercostals |
|
action of tubocurarine at autonomic ganglia
|
hypotension
|
|
action of tubcurarine on histamine release
|
bronchoconstriction and hypotension
|
|
absorption and fate of tubocurarine
|
large, charged molecule not absorbed from gut & not penetrate BBB
action terminated by redistirubtion, metabolism & excretion |
|
compared to tubocurarine synthetic blocking drugs, synthetic non-depolarizing skeletal muscle blocking drugs have...
|
more rapid onset
shorter duration fewer side effects |
|
depolarizing NMJ blocker
|
succinylcholine
|
|
effects of succinylcholine
|
initial uncoordinator muscle fasciulations
persistent depolarization of motor end plate short duration skeletal muscle paralysis rapid metabolisms by BuChE in plasma |
|
advantages of succinylcholine as an NMJ blocker
|
rapid onset
short duration |
|
disadvantages of succinylcholine as an NMJ blocker
|
deep muscle pain
prolonged apnea possible phase II block may trigger malignant hyperthermia may cause life-threatening hyperkalemia may increase intraocular pressure no pharmacological antagonist |
|
6 therapeutic uses of NMJ blocking drugs
|
adjuvant in general anesthesia
prevent trauma during electroshock therapy facilitate setting fractures and dislocations facilitate diagnostic therapeutic manipulations ease ventilation in individuals "fighting the respirator" treatment of status epilepticus, tetanus, struchnine poisoning |
|
myasthenia gravis
|
Autoimmune ds: skel mm weakness
symptoms mimic curare action defect in transmission at NMJ b/c high titer of ACh Nm Abs in plasma weakness reversed by AChE inhibitors |
|
drug preferred for tx of myasthenia gravis
|
pyridostigmine (AChE inhibitor)
- long acting - does not penetrate BBB administered with muscarinic antagonist to reduce side effects |
|
edrophonium tests
|
edrophonium reverses muscle weakness in patients with MG, but not in with other neuromuscular ds
test may not be sensitive if patient is not receiveing enought AChE inhibitor or receiving too much |
|
spasticity
|
increased muscle tone resulting from release of LMNs from supraspinal control
as result of ds or injury to UMNs |
|
3 drug classes used to relieve spasticity
|
botulinum toxin
benzodiazepines baclofen |
|
benzodiazepines - mechanism of action
|
facilitate the inhibitory actions of GABA at GABA-alpha receptor by acting on allosteric BDZ receptors to increase the affinity of GABA for its receptor
|
|
major side effects of BDZs
|
sedation
|
|
mechanism of action of baclofen
|
mimcs ations of GABA at GABA-beta receptors in spinal cord
used for spasticity resulting from spinal cord lesion |
|
2 major classes of ganglionic blocking drugs
|
depolarizing blockers
non-depolarizing blockers |
|
ganglionic depolarizing blocker example
|
nicotine
|
|
depolarizing ganglionic blockers - mechanism of action
|
initailly activate the receptor to cuase depolarization of the neuronal membrane
b/c the membrane stays depolarized, it is no longer responsive to ACh released from presynaptic nerve terminal |
|
action of nicotine at ganglion is analogous to the action of what drug, where?
|
succinylcholine at NMJ
|
|
at low doses, nicotine _____ nicotinic nerve receptors
at high doses, it blocks ______ |
at low doses, nicotine acts as an agonist at nicotinic nerve receptors
at high doses, it blocks ganglionic transmission |
|
nicotine acts at which 4 locations
|
peripheral autonomic nervous system
NMJ sensory receptors CNS |
|
action of nicotine in peripheral ANS
|
initial transient stimultion followed by a more persistent depression at all anutonomic ganglia and adrenal medulla
can casue HTN and arrhythmias |
|
action of nicotine at NMJ
|
very breif stimulatory phase followed by a persistent depolarizing blockade --> paralysis
|
|
nicotine action at sensory receptors
|
stimulates sensory nictonic receptors, including chemoreceptors on carotid body, mechanoreceptors, and pain receptors
|
|
nicotine action at CNS at low doses (tobacco smoking)
|
alerting and reinforcing properties, stimulation of respiration
|
|
nicotine action at CNS at moderate doses
|
termor
vomiting diarrhea |
|
nicotine action at CNS at high doses
|
convulsion
coma death due to respiratory depression |
|
treatment of acute nicotine poisoning
|
induce vomiting
provide respiratory assitance |
|
how do nicotine patches work?
|
do not provide pleasure sensation of cigarette smoking
do relieve irritability and diffulty concentrating that occur with smoking withdrawal |
|
non-depolarizing blockers - mechanism of action
|
compete with ACh at the nicotinic receptor and thereby prevent depolarization at post-synaptic membrane
|
|
action of non-depolarizing ganglionic blockers at ganglion is analogous to the action of _____ at the _____
|
curare at the NMJ
|
|
2 examples of non-depolarizing ganglionic blockers
|
trimethaphan camsylate
mecamylamine |
|
side effects of trimethaphan
|
histamine release
direct dilating action on blood vessels |
|
uses of ganglionic blocking drugs
|
controlled hypotension during surgery
emergency management of dissecting aortic aneurysm |
|
purpose of deliberately lowering BP during surgery
|
protect patient from hemorrhage
treat HTN associated with induction of anesthesia |