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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