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420 Cards in this Set
- Front
- Back
hypothalamus has internal sensors for
|
Plasma levels of glucose, peptides & hormones
Plasma osmolality Core temperature |
|
peripheral visceral sensory input about
|
Arterial pressure
Skin and spinal cord temperature GI function Biorhythms |
|
hypothalamus integrates information using what kind of control?
|
negative feedback
|
|
hypothalamus coordinates ouputs designed to
|
Correct unwanted changes in internal environment
Protect internal environment from external Adjust internal to meet new demands |
|
A 33 year old male with hypothalamic sarcoidosis* presented with the following:
Panhypopituitarism Hyperphagia Polydipsia Drowsiness Depression Irritability |
sarcoidosis
|
|
sarcoidosis
|
disease of unknown origin in which multiple organs are affected by a type of inflammation involving granulomatus lesions
|
|
panhypopituitarism
|
none of the hormones of pituitary are being secreted
|
|
drowsiness
poikilothermia lack of satiety confusion memory |
large tumor of hypothalamus
|
|
Hypo-osmolality and hyponatremia
Anorexia Memory loss |
compression of hypothalamus by a tumor in pitutary
postoperatively showed: recovery of appetite development of hypothermia |
|
hypothermia
|
cannot produce enough body heat loss of prevent heat loss
|
|
Drowsiness
Hyperphagia Depression Memory loss After resection of the tumor, she developed: Labile blood pressure |
craniopharyngioma above the sella
|
|
symptoms of hypothalamic damage
|
probs with:
food intake fluid intake emotional state sleep state temperature regulation cardiovascular endocrine congenital vascular blunt trauma |
|
congenital probs in hypothalamic dysfunction
|
developmental malformation
-midline brain defects -hydrocephalus developmental failure absence of secretory product |
|
vascular probs in hypothalamic dysfunction
|
hemorrhage
thrombotic event |
|
blunt trauma in hypothalamic dysfunction
|
increased intracranial pressure
direct damage |
|
symptoms of hypothalamic damage
|
probs with:
food intake fluid intake emotional state sleep state temperature regulation cardiovascular endocrine congenital vascular blunt trauma |
|
congenital probs in hypothalamic dysfunction
|
developmental malformation
-midline brain defects -hydrocephalus developmental failure absence of secretory product |
|
vascular probs in hypothalamic dysfunction
|
hemorrhage
thrombotic event |
|
blunt trauma in hypothalamic dysfunction
|
increased intracranial pressure
direct damage |
|
causes of hypothalamic dysfunction
|
presence of tumor
infectious agents inflammatory processes |
|
how does hypothalamic negative feedback control work?
|
Sensor detects level of variable
Level compared with “set point” level Difference is the “error signal” Existing error directs the output response Nature of response depends on: Direction of error Magnitude of error Response eliminates the error Set point can be changed to achieve new level |
|
to localize specific functions of individual nuclei include:
|
induction of small localized lesions
electrical and chemical stimulation |
|
inherent problems with localizing specific functions
|
different cell types within a given nucleus
different agonists and tranmitters fibers of passage connections with other nuclei and input sources |
|
causes of hypothalamic dysfunction
|
presence of tumor
infectious agents inflammatory processes |
|
how does hypothalamic negative feedback control work?
|
Sensor detects level of variable
Level compared with “set point” level Difference is the “error signal” Existing error directs the output response Nature of response depends on: Direction of error Magnitude of error Response eliminates the error Set point can be changed to achieve new level |
|
to localize specific functions of individual nuclei include:
|
induction of small localized lesions
electrical and chemical stimulation |
|
inherent problems with localizing specific functions
|
different cell types within a given nucleus
different agonists and tranmitters fibers of passage connections with other nuclei and input sources |
|
what are the three nuclei anterior to posterior of the hypothalamus?
|
anterior
tuberal posterior |
|
longitudinal regions from 3rd ventricle to lateral
|
periventricular
medial lateral |
|
what is the nucleus that has direct connections with the retina
involved in temporal cycles |
suprachiasmatic
|
|
what are the neural inputs to the hypothalamus?
|
Visceral afferents to Nucleus Tractus Solitarius (NTS)
NTS to other brain centers |
|
what are the humeral inputs to the hypothalamus?
|
blood-born to area postrema and circumventricular organs where BBB is incomplete
regions where chemicals in blood including hormones, drugs, toxins can enter the brain example of area influenced is the chemotaxic center - initiates vomiting |
|
where can chemicals such as hormones, drugs, toxins
|
area postrema
circumventricular organs |
|
hypothalamus is connected to what other brain centers?
|
forebrain
medulla pituitary |
|
structure of the pituitary
|
anterior pituitary
posterior pituitary Hypothalamo-hypophyseal tract to posterior pituitary Hypothalamo-hypophyseal portal system to anterior pituitary |
|
medulla
|
Visceral afferents to NTS to hypothalamus
Hypothalamus to NTS To rostral ventrolateral medulla (SNS) To nucleus ambiguus/dorsal motor nucleus X (PNS) |
|
forebrain
|
connects to limbic system
central nucleus of amygdala hyppocampus |
|
structure of the pituitary
|
anterior pituitary
posterior pituitary Hypothalamo-hypophyseal tract to posterior pituitary Hypothalamo-hypophyseal portal system to anterior pituitary |
|
medulla
|
Visceral afferents to NTS to hypothalamus
Hypothalamus to NTS To rostral ventrolateral medulla (SNS) To nucleus ambiguus/dorsal motor nucleus X (PNS) |
|
forebrain
|
connects to limbic system
central nucleus of amygdala hyppocampus |
|
the efferent systems of visceral motor system are
|
hormonal output
autonomic output |
|
hypothalamus can initiate visceral motor output by influencing what systems?
|
endocrine system
limbic system autonomic output |
|
Hypothalamic Releasing Hormones
|
Small peptides
Secreted from neurons in basal hypothalamus Transported by Portal System to Anterior Pituitary Stimulate/inhibit hormone secretion by Anterior Pituitary |
|
Control of secretion (of hypothalamic releasing hormones) regulated by
|
Innervation from other neural centers
Feedback regulation by hormones (entering brain at area postrema/circumventricular organs?) |
|
ventromedial and arcuate nucleus secrete
|
LHRH (GnRH)
GHRH PIH (dopamine) |
|
paraventricular nucleus secrete
|
somatostatin
CRH TRH |
|
action of oxytocin
|
stimulates milk letdown from breast
|
|
action of ADH
|
decreases free water clearance by kidney
|
|
ADH and oxytocin is manufactured by neurons in
|
SON
PVN |
|
oxytocin neural afferents are activated by
|
suckling
|
|
axonal transport of ADH and oxytocin to what for release?
|
posterior pituitary
|
|
ADH is stimulated by
|
SON PVN osmoreceptors in the SON and PVN and circumventricular organs
central renin-ang system volume receptors (low P receptors in atria) baroreceptor reflex |
|
neurogenic diabetes insipidus
|
failure to secrete ADH
|
|
nephrogenic diabetes insipidus
|
failure to respond to ADH
|
|
syndrome of inappropriate ADH
|
increase ADH with normal or low osmolality
leads to hypoosmolality and hyponatremia |
|
congenital over or undersecretion of releasing hormones
|
1. deficiency in secretory mechanisms
2. malformation |
|
acquired over or undersecretion of releasing hormones
|
1. space-occupying lesion
2. secreting tumor 3. damage to secretory region 4. damage to tract or portal system |
|
Kallman's syndrome
|
LHRH secreting cells fail to migrate from medial olfactory pit resulting in hypogonadotropism and anosma
|
|
Sheehan's syndrome
|
condition affecting women who experience life-threatening blood loss during or after childbirth. Severe blood loss deprives your body of oxygen and can seriously damage vital tissues and organs. In Sheehan's syndrome, the damage occurs to the pituitary gland — a small gland at the base of your brain. The result is the permanent underproduction of essential pituitary hormones (hypopituitarism).
|
|
congenital over or undersecretion of releasing hormones
|
1. deficiency in secretory mechanisms
2. malformation |
|
acquired over or undersecretion of releasing hormones
|
1. space-occupying lesion
2. secreting tumor 3. damage to secretory region 4. damage to tract or portal system |
|
Kallman's syndrome
|
LHRH secreting cells fail to migrate from medial olfactory pit resulting in hypogonadotropism and anosma
|
|
Sheehan's syndrome
|
condition affecting women who experience life-threatening blood loss during or after childbirth. Severe blood loss deprives your body of oxygen and can seriously damage vital tissues and organs. In Sheehan's syndrome, the damage occurs to the pituitary gland — a small gland at the base of your brain. The result is the permanent underproduction of essential pituitary hormones (hypopituitarism).
|
|
angiotensin stimulates what conscious response?
|
thirst
|
|
responses to dehydrations include
|
↓ Water loss in urine by ↑ ADH
↑ Water intake (thirst) with activation of: Osmoreceptors Hypothalamic and peripheral angiotensin II |
|
osmoreceptors and angiotensin II receptors are found in the
|
median preoptic nucleus
circumventricular organs |
|
Cardiovascular functions of hypothalamus
|
Major influences exerted via autonomics
Reciprocal connections with NTS Input from baro- & volume receptors Input from higher centers Output can override baroreflex Cardio-inhibitory area in rostral Cardio-excitatory area in ventromedial (PVN) Sham rage (defense reaction) Input from limbic, can be conditioned Mostly involves PVN ↑ SNS, ↓ PNS |
|
what regions of the hypothalamus regulate temperature
|
preoptic
anterior septal regions |
|
preoptic, anterior, and septal regions receive input from
|
peripheral thermoreceptors
|
|
fever- increase set point involving
|
prostaglandins
|
|
indomethacin
|
blocks increase in set point involving prostaglandins
|
|
what increases metabolism?
|
sympathetics increase lipolysis
glycogenolysis |
|
what mediates responses to increase temperature
|
anterior region
|
|
how do we mediate the increase in temperature
|
vasodilation -> increase heat loss
inhibit heat production |
|
what mediates responses to decrease in temperature
|
posterior region
|
|
intrahypothalamic sensors detect:
|
Plasma glucose (glucostat)
Plasma leptin (lipostat) Plasma ghrelin (secondary glucostat) |
|
extrahypothalamic input
|
Oropharyngeal monitors, GI tract stretch receptors
GI hormones |
|
where is the satiety center?
|
ventromedial nucleus
|
|
where is the feeding center?
|
lateral hypothalamus
|
|
signals of satiety
|
leptin
neuromedin U PYY |
|
signals of feeding
|
ghrelin
|
|
what are the physiological effects of leptin?
|
Regulates body weight by:
Inhibiting feeding center (VMH, arcuate nucleus) Increasing metabolic rate stimualtes GnRH |
|
where does leptin come from?
|
protein hormone expressed by adipocytes containing high level of TGs
|
|
what hormone stimulate secretion of leptin?
|
insulin which also suppresses appetite
|
|
ob gene mutation causes
|
obesity
|
|
how do you treat ob gene?
|
give exogenous leptin --> lose weight
|
|
very skinny people produce how much leptin?
what can this do to girls? |
very little
hypothalamic amenorrhea |
|
excess leptin inhibits
|
steroidogenesis
|
|
where does ghrelin come from?
|
peptide from stomach
|
|
fasting causes increase or decrease in ghrelin?
|
increase
|
|
what acts on hypothalamus to stimualte food appetite?
|
ghrelin
|
|
what hormone stimulates growth hormone?
|
ghrelin
|
|
when are ghrelin levels lowest?
|
right after eating
|
|
ghrelin levels are inversely correlated with what hormone levels?
|
leptin
|
|
what hormone promotes sleep?
|
ghrelin
|
|
fxn of PNS
|
trophotropic
rest and digest: maintains essential body functions and is essential for life |
|
PNS in eye
|
Miosis, Accommodation, Lacrimation
|
|
PNS in heart
|
bradycardia
|
|
PNS in respiratory system
|
bronchoconstriction
bronchosecretion |
|
PNS in digestion
|
salivation
peristalsis bronchosecretion |
|
what system aids urination, defecation, procreation
|
PNS
|
|
sympathoadrenal system fxn
|
ergotropic
fight or flight used to adjust the body to stressful situation but is not needed for life |
|
SNS on eyes
|
dilation of pupils
|
|
SNS on heart/CV
|
increase heart rate and BP
|
|
SNS on blood flow
|
(↓) blood flow to the skin and internal organs
(↑) blood flow to skeletal muscles, brain, and heart |
|
SNS on lungs
|
Dilation of bronchi, (↓) nasal, pulmonary secretions
|
|
Mobilize energy stores
Inhibits Urination, Defecation Aids in Procreation |
SNS
|
|
cholinergic NT
|
Ach
|
|
adrenergic
|
NE
Epi (not a neurotransmitter in the periphery, it is a neurohormone) Dopamine |
|
NANC (nonadrenergic, noncholinergic NTs)
|
ATP
NO dynorphin Neuropeptide Y substance P vasoactive intestinal peptide |
|
sympathomimetic
|
mimicking action of SNS
|
|
sympatholytic
|
inhibition of adrenergic action
|
|
chronotropic
|
altering rate of rhythmic movement
|
|
inotropic
|
altering force of muscular contraction
|
|
direct
|
acts postjunctionally
|
|
indirect
|
acts prejunctionally
release transmitter reuptake transmitter |
|
direct vs reflex
direct |
response of target organ to agent
|
|
reflex
|
autonomic reaction to peripheral acting agent
|
|
integrated response
|
direct + reflex
|
|
desensitization
|
reduction in response
|
|
catecholamines -metabolism
|
metabolized quickly
decreased bioavailability short half life |
|
catecholamines - polarity
|
polar molecules
low oral bioavailability low CNS entry |
|
catecholamines - pharmacodynamics
|
less selectivity
|
|
non-catecholamines - metabolism
|
resistant to metabolism
increased bioavailability longer half life less polar molecules increased oral bioavailability low CNS entry |
|
non-catecholamines - polarity
|
less polar molecules
increased oral bioavailability low CNS entry |
|
chemistry of specificity
|
sub on:
amino group benzene ring alpha-C beta-C |
|
alpha1 agonist
|
phenylephrine
|
|
alpha1 antagonist
|
prazocin
|
|
alpha2 agonist
|
clonidine
|
|
alpha2 antagonist
|
yohimbine
|
|
D1 agonist
|
fenoldopam
|
|
D2 agonist
|
bromocriptine
|
|
what drug interferes with neurotransmitter metabolism?
|
alpha-methyltyrosine
|
|
what drug will block transport at nerve terminal?
|
cocaine
|
|
what drug will block vesicular transport?
|
reserpine
|
|
what drug will promote exocytosis and displacement of transmitter?
|
amphetamine
|
|
what drug will prevent release of transmitter?
|
bretylium
|
|
what drug will inhibit transmitter degradation?
|
tranylcypromine, a MAO inhibitor
|
|
what is the byproduct of fermentation process intermediate in NE metabolism?
has direct sympathomimetic effect via stimulation of NE release similar to NE |
tyramine
patients taking MAOI should avoid food high in tyramine |
|
adrenergic agonists (using epi as a prototypical agent)
ACTIONS |
1-peripheral excitatory action on smooth mm
2-peripheral inhibitory action on smooth mm 3-cardiac excitation --> increase HR, increase contraction force 4-metabolic: increase glycogenolysis, adipose --> FFA 5- endocrine: increase/decrease 6-CNS 7-prejunctional: increase or decrease release of transmitter |
|
therapeutic uses of sympathomimetic agents
|
1. ADHD
2. allergic rxns 3. asthma 4. cardiac arrhythmias 5. congestive heart failure 6. hypertension 7. hypotension 8. narcolepsy 9. nasal decongestion 10. ophthalmic treatments 11. shock 12. weight reduction |
|
what drug interferes with neurotransmitter metabolism?
|
alpha-methyltyrosine
|
|
what drug will block transport at nerve terminal?
|
cocaine
|
|
what drug will block vesicular transport?
|
reserpine
|
|
what drug will promote exocytosis and displacement of transmitter?
|
amphetamine
|
|
what drug will prevent release of transmitter?
|
bretylium
|
|
what drug will inhibit transmitter degradation?
|
tranylcypromine, a MAO inhibitor
|
|
what is the byproduct of fermentation process intermediate in NE metabolism?
has direct sympathomimetic effect via stimulation of NE release similar to NE |
tyramine
patients taking MAOI should avoid food high in tyramine |
|
adrenergic agonists (using epi as a prototypical agent)
ACTIONS |
1-peripheral excitatory action on smooth mm
2-peripheral inhibitory action on smooth mm 3-cardiac excitation --> increase HR, increase contraction force 4-metabolic: increase glycogenolysis, adipose --> FFA 5- endocrine: increase/decrease 6-CNS 7-prejunctional: increase or decrease release of transmitter |
|
therapeutic uses of sympathomimetic agents
|
1. ADHD
2. allergic rxns 3. asthma 4. cardiac arrhythmias 5. congestive heart failure 6. hypertension 7. hypotension 8. narcolepsy 9. nasal decongestion 10. ophthalmic treatments 11. shock 12. weight reduction |
|
ADH is regulated by input from:
|
osmoreceptors in SON, PVN, circumventricular organs
central renin-ang system volume receptors (low pressure receptors in atria) baroreceptors reflex |
|
limbic system connects to hypothalamus, reciprocal with:
|
central nucleus of amygdala
hippocampus |
|
Medulla is connected to hypothalamus via
|
visceral afferents to NTS
rostral ventrolateral medulla (SNS) nucleus ambiguus/dorsal motor nucleus of X (PNS) |
|
pituitary is connected to the hypothalamus (2)
|
hypothalamo-hypophyseal tract to posterior pituitary
hypothalamo-hypophyseal portal system to anterior pituitary |
|
hypothalamus is connected to what other centers in the brain
|
forebrain (limbic system)
medulla pituitary |
|
what are the sensors for water balance by hypothalamic regulation?
|
osmoreceptors
AngII receptors effective blood volume and arterial pressure receptors |
|
what structures contain osmoreceptors and angiotensin II receptors?
|
median preoptic nucleus
circumventricular organs |
|
hypothalamic pathways for water balance
|
afferent in hypothalamus involve the renin-ang system
those for conscious response to thirst is unknown |
|
responses to dehydration
|
decrease water loss in urine by increasing ADH
increase water intake (thirst) with activation of: osmoreceptors/hypothalamic peripheral AngII |
|
what is sham rage?
where input? mostly involve what nucleus? |
defense reaction
limbic PVN increases SNS decreases PNS |
|
regulation of body temperature are found in what regions?
|
preoptic
anterior septal |
|
preoptic/anterior/septal regions sense core temperature by what input?
|
peripheral thermoreceptors
match with set point and coordinate outputs |
|
fever increases set point involving what?
what can it be blocked by? |
prostaglandins
blocked by indomethacin |
|
anterior region of hypothalamus mediates response to
|
increase in temp (HEAT)
VASODILATION to increase heat loss INHIBIT heat production |
|
posterior region of hypothalamus mediates response to
|
decrease in temp (COLD)
vasoconstriction increase heat production (shivering and nonshivering thermogenesis) |
|
cardio-inhibitory is found where?
|
Rostral hypothalamus
|
|
cardio-excitatory is found where?
|
ventromedial (PVN)
|
|
major influences of CV functions exerted by
|
autonomics
|
|
CV functions of hypothalamus receives input from:
|
baro and volume receptors
input from higher centers output can override barorefelx |
|
intrahypothalamic sensorys detect
|
plasma glucose (glucostat)
plasma leptin (lipostat) plasma ghrelin (secondary glucostat) |
|
extrahypothalamic input
|
oropharyngeal monitors
GI tract stretch receptors GI hormones |
|
where is the satiety center?
|
ventromedial nucleus
|
|
where is the feeding center?
|
lateral hypothalamus
|
|
what signals satiety?
|
leptin
neuromedin U PYY |
|
what signals hunger?
|
ghrelin
|
|
what signals satiety?
|
leptin
neuromedin U PYY |
|
leptin is produced by
|
adipocytes containing high levels of TG
|
|
what areas of hypothalamus regulates body weight? prevents weight gain
|
inhibiting the feeding center (VMH, arcuate nucleus)
increasing metabolic rate |
|
in obesity, serum leptin is
|
elevated
suggests that leptin production normal but response NOT present |
|
leptin transport across BBB may be impaired perhaps due to
|
circulating TGs
|
|
what hormone may affect rate of leptin secretion?
|
insulin - stimulates leptin production
|
|
what hormone does leptin stimulate secretion of?
|
GnRH
|
|
leptin acts to suppress
|
food intake
increase metabolic rate |
|
leptin may feedback to inhibit
|
insulin secretion from islet cells
|
|
generally altered mice unable to produce leptin are
|
obese
have reduced oxygen consumption reduced body temperature tx with leptin causes weight loss without leptin receptor, would be ineffective |
|
what gene mutation in humans will prevent leptin synthesis?
|
ob gene
they lose with exogenous leptin tx |
|
obese humans who CAN synthesize leptin: do they respond to leptin tx?
why? |
NO
may reflect decreased sensitivity to leptin in obesity or presence of factors preventing entry into brain |
|
lack of cycling and delayed onset of puberty in very thin individuals may be due to______
girls may exhibit______ |
very low levels of leptin
hypothalamic steroidogenesis |
|
excess leptin inhibits what?
|
steroidogenesis
|
|
in obese males, high levels of leptin may inhibit
|
testosterone production
|
|
ghrelin comes from____
|
stomach
|
|
what will increase plasma level of ghrelin?
|
fasting
|
|
what inhibits insulin secretion from islet cells leading to elevated glucose levels
|
ghrelin
|
|
what hormone stimulates ghrelin
|
GH
|
|
ghrelin levels correlate inversely with _____levels
action on satiety are directly opposite |
leptin
|
|
how does ghrelin correlate with obesity?
|
inversely
|
|
low ghrelin is associated with ____ insulin
|
high
|
|
ghrelin ____ plasma glucose levels
|
increases
|
|
ghrelin ______ glucose induced insulin secretion from islet cells
|
inhibits
|
|
IV ghrelin stimulates what hormone secretion?
|
GH
|
|
a major GH secretory pulse occurs during
|
sleep
|
|
ghrelin_____sleep
|
promotes
|
|
low glucose + high ghrelin stimulate
|
GH secretion
|
|
what hormone?
Decrease appetite and food intake Increase secretion of AVP, ACTH & oxytocin Alter sleep cycles |
neuromedins (U & S)
|
|
Intraluminal nutrients stimulate secretion from mucosa of small intestine
Maximum secretion 1-2 hours post-ingestion Inhibits GI functions such as gastric emptying Inhibits appetite and food intake |
peptide YY (PYY)
|
|
what hormones inhibit appetite?
|
leptin
peptide YY neuromedin |
|
what hormones stimulate appetite?
|
ghrelin
|
|
what brain center activates hypothalamus related to emotions/behavior?
|
limbic system
|
|
output of limbic system in emotion/behavior is modulated by
|
neocortex
|
|
association cortex --> hippocampus to hypothalamus VIA
|
cingulate gyrus
|
|
central nucleus of amygdala
|
activates medial
inhibits lateral |
|
lateral hypothalamus initiates
|
"predatory" aggression
|
|
medial (PVN) hypothalaus initiates
|
"affective" aggression (defense reaction)
|
|
major output of emotions/behavior VIA
|
autonomics
|
|
what pathway for limbic system influences the hypothalamus?
|
papez circuit
|
|
hemicholinium
|
blocks reuptake of choline by blocking CHT (sodium-choline symporter)
|
|
vesamicol
|
blocks storage of ACh by inhibiting VAT
|
|
black widow spider venom
|
stimulates release of Ach
get all PNS responses |
|
cholinomimetic drugs
|
mimic cholinergic agonists
stimulate muscarinic or nicotinic receptors |
|
AChE inhibitors
|
indirect agonists (prejunctional)
|
|
cholinoceptor blocking agents
|
block PNA responses
|
|
Metyrosine
|
blocks the rate limiting step, tyrosine hydroxylase
|
|
reserpine
|
blocks vesicular transport by inhibiting VMAT
|
|
amphetamine
|
promotes exocytosis and displacement of transmitter when taken up by NET
|
|
bretylium
|
prevent release of transmitter by blocking VAMPs
|
|
sympathomimetic drugs
|
direct and indirect
increase sympathetic response |
|
adrenoceptor blocking drugs
|
block sympathetic response
|
|
cocaine
|
blocks reuptake of NE, dopamine
elevate by blocking NET |
|
two types of cholinergic receptors
|
nicotinic
muscarinic |
|
nictonic receptor types
|
ionotropic
Ach opens Na+ channel causing depolarization Nm and Nn |
|
muscarinic receptor types
|
g-protein coupled, primary biochem responses
M1-M5 |
|
types of adrenergic receptors
|
alpha
beta dopaminergic |
|
alpha adrenergic subtypes
|
alpha 1,2
|
|
beta adrenergic subtype
|
beta 1,2
|
|
dopaminergic receptor subtypes
|
D1-D5
|
|
M1 found in
|
nerve cells
|
|
M2 and M3 found in
|
heart and SM
|
|
M4 found in
|
SM and glands
|
|
Nm found in
blocked by what drug? |
neuromuscular
tubocurarine |
|
Nn found in
blocked by |
autonomic ganglia
trimethophan |
|
determine alpha-adrenergic receptors from beta
|
epi>iso
|
|
determina beta from alpha
|
iso>epi
|
|
determine alpha1 from alpha2
|
phenylephrine>clonidine
|
|
determine alpha2 from alpha 1
|
clonidine>phenylephrine
|
|
determine beta1 adrenergic from beta2 or beta 3
|
epi=NE
|
|
beta2 from others
|
epi>ne
|
|
beta3 from other
|
ne>epi
|
|
epinephrine
|
alphabeta agonist
|
|
phenylephrine
|
alpha1 agonist
|
|
clonidine
|
alpha2 agonist
|
|
isoproterenol
|
beta agonist
|
|
dobutamine
|
beta1 dobutamine
|
|
albuterol
|
beta2 agonist
|
|
fenoldopam
|
D1 agonist
|
|
bromocriptine
|
D2 agonist
|
|
clozapine
|
D4 antagonist
|
|
butoxamine
|
beta2 antagonist
|
|
betaxolol
|
beta1 antagonist
|
|
atenolol
|
beta1 antagonist
|
|
propanolol
|
beta antagonist
|
|
yohimbine
|
alpha2 antagonist
|
|
prazocin
|
alpha1 antagonist
|
|
phentolamine
|
alpha
|
|
tyramine
|
byproduct of fermentation process that is an intermediate in NE metabolism
can have an indirect sympathomimetic effect via stimulation of NE release site of action is similar to NE patients take MAOIs should avoid foods high in tyramine |
|
what are the direct-acting selective adrenergic agonists?
|
alpha1 phenylephrine
alphe1 clonidine beta1 dobutamine beta2 terbutaline |
|
what are the direct acting NON-selective adrenergic agonists
|
alpha1,2 oxymetazoline
beta1,2 isoproterenol alpha1,2,beta1,2 epi alphe1,2, beta1 NE |
|
what are the adrenergic mixed acting drugs?
|
alpha1,2 beta 1,2 + releasing agent
response is reduced by prior treatment with reserpine or guanethidine |
|
are direct-acting drugs responses changed by reserpine or guanethidine?
|
no because reserpine or guanethidine are indirect acting which does not interfere with direct acting drugs
|
|
are releasing agents, uptake inhibitor, MAO and COMT inhibitors affected by guanethidine and/or reserpine?
|
yes because they are all indirect acting drugs
|
|
what are some examples of indirect actin releasing agents
|
amphetamine - promote exocytosis and displacement of transmitte
tyramine - indirect sympathomimetic effect via stimulation of NE release |
|
catecholamines and sympathomimetic actions
what is the prototypical agent? |
epinephrine
|
|
catecholamines and sympathomimetic actions FUNCTIONS
|
1. excite SM in periphery
2. inhibit SM in periphery 3. cardiac excitation by increasing HR and contractility 4. increase glycogenolysis and lipolysis 5. increase/decrease endocrine functions 6. CNS 7. prejunctional: increase or decrease release of transmitter tx |
|
tx use of sympathomimetic agents
|
ADHD
Allergic reactions Asthma Cardiac Arrhythmias Congestive Hearth Failure Hypertension Hypotension Narcolepsy Nasal Decongestion Ophthalmic treatments Shock Weight reduction |
|
therapeutic uses of sympatholytic agents
|
Angina
Arrhythmias Benign prostatic hyperplasia (BPH) Congestive heart failure Glaucoma Heart failure Hypertension Hyperthyroidism Ischemic heart disease Pheochromocytoma Priapism Neurologic diseases |
|
BPH
benign prostatic hyperplasia |
nonmalignant enlargement of prostate due to growth of either:
epithelial and glandular mechanical obstruction smooth muscle (dynamic obstruction - urethra) |
|
what are the symptoms of BPH?
|
hesitancy urgency
increased frequency dysuria |
|
incidence of BPH
|
50% of age >60
90% of age >85 |
|
what is the treatment for BHP?
|
watchful waiting (minimal sx)
surgery (severe) pharmacological tx of sx: 5 alpha reductase inhibitors alpha1 adrenergic antagonists: prazocin and tamsulosin |
|
5-alpha reductase (finasteride or proscar) for BHP
|
most effective when VERY LARGE prostate
shrinks prostate size decreases mechanical obstruction |
|
alpha adrenergic antagonists for BHP
|
when relatively small prostate
decrease dynamic obstruction of urethra (relaxes muscle) |
|
pheochromocytoma
|
neuroendocrine tumor of the medulla of adrenal glands
secretes large amounts of catecholamines (Epi NE) treated with prazocin (alpha1 antagonist) 25% genetic contribution |
|
clinical uses for clozapine
|
D4 antagonist
refractory schizophrenia |
|
what are the adverse effects of clozapine?
|
tachycardia, angine
CNS, drowsy, dizzy GI disturbance NM |
|
what are the contraindications of clozapine?
|
drug sensitivity
epilepsy CNS depression myeloproliferative disorders |
|
clinical uses of butoxamine
|
beta2 angtagonist
NONE research use only Dont know adverse effects or contraindications |
|
clinical uses of betaxolol
|
beta1 antagonist
chronic open angle glaucoma hypertension |
|
adverse effects of betaxolol
|
ocular discomfort
bradycardia depression GI disturbance bronchospasm |
|
contraindications for betaxolol
|
drug sensitivity
pregnancy |
|
atenolol
|
beta1 antagonist
hypertension elderly patients with isolated systolic HT angina post MI tx |
|
adverse effects of atenolol
|
bradycardia
CNA GI disturbance impotence |
|
clinical uses of propanolol
|
beta antagonist
hypertension angina arrhrythmias tachycardia pheochromocytoma prophylaxis of migraine tremor, Parkinson, alcohold WD |
|
adverse effects of propanolol
|
angina
CNS GI disturbance |
|
contraindication of propanolol
|
drug sensitivity
congestive heart failure COPD |
|
clinical uses of yohimbine
|
alpha2 antagonist
limited sexual dysfunction diabetic neuropathy postural hypotension |
|
adverse effects of yohimbine
|
increased motor activity
tremors antagonist of most 5HT receptors anxiety insomnia |
|
contraindications of yohimbine
|
drug sensitivity
|
|
function of alpha1 agonists
|
cardiovascular:
direct - vascular contraction indirect - SLOW heart rate MYDRIASIS |
|
clinical uses of alpha1 agonists
|
vasoconstriction:
hypotension paroxysmal supraventricular tachycardia -reflex response to slow heart nasal congestion DILATE EYES |
|
what are the adverse effects of alpha 1 agonists?
|
hypertension
ischemia to organs rebound nasal/sinus hyperemia (desensitization) |
|
what are the contraindications for alpha1 agonists?
|
hypertension
ischemic organ disease prostate enlargement co-administration with agents that also INCREASE NE LEVELS -MAO inhibitors (remember MAO breaks down NE) -indirect acting sympathomimetics (COPY NE actions) |
|
FXN of agonists
|
vasodilation
decrease aq humor production |
|
alpha2 agonists clinical uses
|
ANTI-hypertensive
lower intraocular pressure in open angle glaucoma minimize withdrawal symptoms |
|
alpha2 agonists -adverse effects
|
bradycardia
CNS >50% population: sedation and dry mouth sexual dysfunction |
|
alpha2 contraindications
|
drug HYPERsensitivity
|
|
FXN of beta1 agonists
|
cardiovascular:
increase calcium influx increase rate and force |
|
clinical use of beta1 agonist
|
cardiogenic shock
|
|
adverse effects of beta1 agonist
|
several CV effects
|
|
contraindictaions of beta1
|
drug SENSITIVITY
|
|
FXN beta2 agonists
|
bronchodilation
uterine dilation |
|
drugs for bronchodilation
|
short halflife - albuterol, inhalants
long halflife - admin - inhalant like Salmeterol and formoterol |
|
uterine dilation - what drug?
|
ritodrine
|
|
what are the clinical uses of beta2 agonists?
|
asthma
COPD |
|
tocolytic agents
|
late term gestation
|
|
adverse effects of beta2 agonists
|
peripheral - uncommon if given as an inhalant
sx of beta1 stimulation tachycardia/widening pulse pressure sx of beta2 stimulation widening pulse pressure, drop in serum K+, skeletal muscle tremor |
|
contraindications of beta2 agonists
|
cardiac disease: coronary artery disease, arrhythmias
diabetes hyperthyroidism co-administration: MAO inhibitors, indirect acting sympathomimetics |
|
what is endogenous to sympathetic NS?
|
epi
NE dopamine |
|
what is exogenous to SNS
|
Phenylephrine
Clonidine Isoproterenol Dobutamine Albuterol Fenoldopam Bromocriptine |
|
fxn of epinephrine
|
cardiovascular:
vascular-dose dependent cardiac: direct (response of target organ to agent) + reflex (autonomic reaction to peripheral acting agent) blood pressure -variable Non-CV effects SM respiratory (Direct beta2 bronchodilation) metabolic |
|
clinical uses for Epi
|
hypersensitivity
bronchodilator: asthma, anaphylaxis vasoconstriction: angioedema adjunct to local anesthetics cardiac stimulant lower intraocular pressure in wide angle glaucoma |
|
adverse effects of epi
|
arryhythmias
cerebral hemorrhage anxiety sx (somatic) |
|
contraindications of
|
nonselective beta
|
|
low dose epi causes
|
Vascular effects
redistribution of blood flow (regional responses) regions rich in 1 see vasoconstriction regions rich in 2 see vasodilation no significant change in TPR Cardiac effects: direct responses Blood pressure: Increase systolic, decrease diastolic |
|
high dose epi causes
|
Vascular effects
looks like NE 1 predominates globally, locally there is still 2 stimulation, net effect increased TPR Cardiac effects - NE like direct effects + reflex responses Blood pressure - NE like pulse pressure -narrowing |
|
Norepinephrine
|
alpha1,2, beta2 NOT beta1
endogenous CV effects Vascular (direct: vasoconstriction) Cardiac (direct: 1 [force & HR] + reflex [HR]) Blood Pressure - increased TPR + CO non-CV effects minor |
|
NE clinical uses
|
limited
Vasoconstriction |
|
NE adverse effects
|
arrythmias
cerebral hemorrhage |
|
dopamine functions
|
CV effects: dose dependent
vascular, cardiac, BP Non-CV effects minimal |
|
clinical uses of dopamine
|
increase renal BF
-shock/cardiac failure cardiac stimulant: cardiac failure |
|
dopamine must be given how?
|
IV
limits use in chronic cardiac failure can be advantage in acute cardiac failure |
|
adverse effects of dopamine
|
arrhythmias
|
|
clinical use of oxymethazoline
|
alpha-adrenergic agonist
OTC decongestant |
|
adverse effects of oxymethazoline
|
continued use causes rebound congestion via downregulation of alpha2 receptors
|
|
contraindications of oxymethazoline
|
drug sensitivity
|
|
clinical use of phenylephrine
|
mydriasis
alpha1agonist |
|
adverse effects of phenylaphrine
|
rebound nasal and sinus hyperemia
|
|
contraindications of phenylephrine
|
drug sensitivity
|
|
clincal use of clonidine
|
mild-to-moderate hypertension used alone or in comb.
|
|
adverse effects of clonidine
|
drowsiness
- dry mouth - GI disturbance - muscle weakness - withdrawal symp. |
|
contraindications of clonidine
|
drug sensitivity
|
|
functions of isoproterenol
|
beta1,2 agonist
Vascular Effects (direct vasodilation) Cardiac Effects (direct : force, rate + reflex) Blood Pressure - widening pulse pressure Non-cardiovascular Effects Smooth muscle Bronchial - (direct : bronchodilation) GI/Bladder Uterine - (direct : dilation in late gestation) Metabolic - less than epinephrine |
|
dobutamine
|
beta1 agonist
Cardiac stimulant Cardiogenic shock Cardiac failure |
|
dobutamine must be administered how?
|
IV-limits usefulness for chronic cardiac failure
may be advantageous for acute cardiac failure |
|
clinical use of albuterol
|
bronchodilator
asthma COPD - relaxes bronchial smooth muscle with little effect on heart rate |
|
adverse effects of albuterol
|
CV: angina
- CNS stim.; - GI disturbance - muscle cramps |
|
albuterol contraindications
|
drug sensitivity
- tachyarrhythmias - pregnancy |
|
clinical use of fenoldopam
|
D1 agonist
vasodilation SEVERE Hypertension |
|
adverse effects of fenoldopam
|
hypotension
tachycardia |
|
clinical use of bromocriptine
|
D2 agonist
hyperprolactinemia parkinsons suppress prolactin release from adenomas and shrink tumor, improve motor function |
|
adverse effects of bromocriptine
|
CNS
CV GI |
|
contraindication of bromocriptine
|
hypersensitivity
|
|
why asthma makes it hard to breathe
|
air enters respiratory system from nose and mouth and travels through bronchial tubes
in an asthmatic person, the muscles of the bronchial tubes tighten and thicken and air passages become inflamed and mucus filled --> difficult for air to move in non-asthmatic muscles around the bronchial tubes are relazed and issue thin allowing easy airflow |
|
nonselective alpha antagonists
|
phenoxybenzamine
phentolamine |
|
clinical uses of nonselective alpha antagonists
|
Pheochromocytoma
1-2/100,000 1-5/1000 HT patients Benign prostatic obstruction * Ergot alkaloids Migraine headache |
|
adverse effects of nonselective alpha antagonists
|
Cardiovascular
Tachycardia (reflex) Orthostatic hypotension Nasal congestion Non cardiovascular GI (Phentolamine) Impotence (Phenoxybenzamine) Potential mutagen (Phenoxybenzamine) |
|
nonselective alpha blockers affect on prejunctional alpha receptors
|
alpha2 component causes prejunctional blockade that leads to reflex tachycardia
-used to treat hypertension |
|
labetalol binds what receptors?
|
beta and alpha1 antagonist
Partial beta2 agonist |
|
carvedilol
|
beta and alpha1 antagonist
antioxidant antiiscemic agent improves survival in chronic heart failure |
|
advantage of alpha1 antagonists over nonselective alpha antagonists?
|
lack of alpha2 component --> less reflex tachycardia
|
|
uses of alpha1 antagonists
|
Benign prostatic hyperplasia
Prazosin (BID dosage) Doxazosin & Terazosin (QD dosage) Hypertension – ALLHAT study* Congestive heart failure Pheochromocytoma |
|
adverse effets of alpha1 antagonists
|
orthostatic hypertension - usually becomes tolerated
give first dose at night nasal congestion |
|
“Uroselective” 1A Antagonist
|
Tamsulosin (& alfuzosin)
QD dosage Clinical Use Benign Prostatic Hyperplasia Adverse Effects Retrograde ejaculation (less with alfuzosin) 2O to relaxation of bladder neck (sphincter) smooth muscle? NOTE: Avoids orthostatic hypotension in most |
|
uses of beta antagonists
|
Cardiovascular
Hypertension Angina Arrhythmias Myocardial infarction Heart failure CV Symptoms of Hyperthyroidism Pheochromocytoma Aortic aneurysm Migraine headache Non-cardiovascular Glaucoma Somatic symptoms of anxiety (e.g. stage fright) Fine muscle tremors |
|
what is the prototype of beta antagonists?
|
propanolol
Pure antagonist, no Intrinsic Sympathomimetic Activity (i.e. not a partial agonist) Nonselective to subtypes High lipid solubility - Enters gut & CNS High first pass metabolism - causing low bioavailability Has membrane-stabilizing activity Quinidine-like effects, Na+ channel blockade, (local anesthetic) Avoid for topical administration to eye (glaucoma Tx) |
|
what are the nonselective beta antagonists
|
Propranolol
Nadolol: long half-life Timolol: low local anesthetic action - use in glaucoma Pindolol: ISA |
|
selective beta 1
|
Atenolol: low lipid sol.
Betaxolol: opthal. Esmolol: short half-life Metoprolol |
|
adverse effects of beta antagonists
|
Cardiovascular
Induce CHF or bradycardial arrhythmia Sudden withdrawal - in anginal patients may cause sudden death (probably due to receptor supersensitivity) Cholesterol levels Bronchiospasm CNS - sleep disturbance, depression (Lacking recognition of hypoglycemia) |
|
benefits of beta antagonists
|
In hypertensive (1st choice if stable angina present)
Decrease blood pressure & protects heart Less effective than other anti-HT in blacks In older patients with isolated systolic HT – often used with diuretics as 1st choice In angina In heart failure – both acute (MI) & chronic Decrease heart work & protect against arrythmias |
|
problems with beta antagonists
|
Asthma or other bronchospasm -cause bronchoconstriction
Diabetes – until recently many felt caution needed - still caution in persons with frequent hypoglycemia (mask symptoms of insulin-induced hypoglycemia & glycogenolysis inhibited) (augment insulin-induced hypoglycemia) Raise VLDL and lower HDL cholesterol levels (not clear why this happens) |
|
clinical uses of phenoxybenzamine
|
alpha antagonist
symptomatic management of pheochromacytoma - treatment of hypertensive crisis caused by sympathomimetic amines - micturition problems *decreased vasoconstriction by epi and NE IRREVERSIBLE alpha antagonist |
|
adverse effects of phenoxybenzamine
|
decreased BP
GI postural hypotension reflex CV stimulation pupil constriction partial agonist/antagonist at 5HT2A |
|
contraindication of phenoxybenzamine
|
drug sensitivity
|
|
list the nonselective beta antagonists
|
propanolol
nadolol - low half life timolol - low local anesthetic action/tx gaulcoma pindolol |
|
list the selective beta antagonists
|
atenolol - low lipid solubility
betaxolol - ophthal esmolol -short half life metoprolol |
|
CV benefits of beta antagonists (beta blockers)
|
1. hypertension: decrease BP, protects heart
less effective than other anti=HT in blacks isolated systolic HT: used with diuretics as 1st choice 2. in angina 3. in heart failure: both acute and chronic - decreases heart work and protects against arrhythmias |
|
problems with beta antagonists
|
1. asthma/bronchospasm: cause bronchoconstriction
2. Diabetes: caution with pts with frequent hypoglycemia 3. raise VLDL and lower HDL cholesterol levels |
|
Ach is an established NT that acts at what sites in the body?
|
1. autonomic effector sites innervated by postganglionic sympathetic fibers
2. autonomic ganglia 3. adrenal medulla 4. motor endplate region of NMH 5. sweat glands |
|
2 basic types of ACh release
|
1. spontaneous: Ca2+ independent
2. evoked: Ca2+ depdent occurs from synaptic vesicles by exocytosis |
|
muscarinic receptor mediated responses are...
|
slow, long lasting, either excitatory or inhibitory
|
|
atropine
|
competitive muscarinic inhibitor
|
|
do known muscarinic agonist discriminate between muscarinic receptor subtypes?
|
nope
|
|
pirenzepine
|
competitive muscarinic antagonist for M1 receptor
acts on M1 receptor in myenteric plexus and cerebral cortex |
|
nicotinic receptor
|
quick
short lived always excitatory |
|
nicotinic receptors are located on
|
autonomic ganglia
adrenal medulla motor endplate region |
|
muscarinic receptors are located on
|
SM, glands, heart
|
|
nicotinic receptors in ganglia are stimulated by
|
dimethyl 4-phenyl piperazinium
|
|
classical nicotinic receptor antagonist at ganglia
|
hexamethonium which acts competitively
|
|
classical nicotinic receptor antagonist at motor endplate region
|
d-tubocurarine
|
|
is ACh used therapeutically?
|
not useful bc of short duration
|
|
what M receptor agonist?
1.hydrolyzed by true but not pseudocholinesterase 2. mainly a muscarinic agonist 3. used to diagnose bronchi hyperactivity and asthmatic conditions 4. used to diagnose achalasia (causes induced swallowing) |
methacholine
|
|
what muscarinic agonist?
1. longer duration of action bc not broken down by either true or pseudocholinesterase 2. nicotinic and muscarinic activity 3. can be used topically in the eye for wide angle glaucoma the cause of open angle glaucoma is unknown --chronic problem |
carbachol
|
|
muscarinic receptor agonist
1. best among three synthetic drugs 2. not broken down by pseudo or true AChE 3. PURE muscarinic agonist 4. stimulates SM of bladder and GI preferentially over heart 5. used to treat posteroperative distension, gastric atony, urinyar retention, reflux esophagitis 6. adverse risks can cause gastric distress and bronchiole constriction |
bethanechol (is the best)
|
|
1. naturally occuring muscarinic agonist which is NOT charged
2. longder duration of action bc not broken down by true or pseudo AchE 3. cholinergic drug of choice for WIDE ANGLE GLAUCOMA 4. use to treat narrow angle glaucoma until surgery combined with physostigmine 5. now used to treat xerostomia that follow head and neck radiation treatments 6. CNS side effects, irritability, restelssness |
pilocarpine
|
|
xerostomia
|
autoimmune disease that decreases salivary secretions
|
|
Cevimeline (Evoxac)
|
relatively new drug used to treat dry mouth associated with Sjogren's syndrome
|
|
side effects of muscarinic stimulants
|
1. extension of actions at muscarinic receptor sites on SM, glands, heart
2. urinary frequency, diarrhea, bronchiole constriction, salivation 3. use of cholinergic stimulant contraindicated in ASTHMA, HYPERTHYROIDISM, PEPTIC ULCERS |
|
what is the best drug for motion sickness?
|
Scopolamine
|
|
used to treat bedwetting
|
Scopolamine
|
|
what is homatropine used for?
|
retinal examination in adults - shorter acting than atropine
|
|
what is tropicamide used for?
|
retinal examination inf adults- shorter acting than atropine or homatropine
|
|
atropine used for?
|
retinal examination produces mydriasis and loss of accomodation
antidote for organophosphate intoxication adjunct for myasthenia gravis to reduce muscarinic side effects due to AchE inhibition at GI tract and bladder |
|
what drugs are used for irritable bowel syndrome?
|
methantheline
propantheline |
|
methantheline
propantheline - function |
block ganglionic transmission and antagonize Ach at muscarinic receptors
|
|
antimuscarinic drugs can be very dangerous in what condition? why?
|
narrow angle glaucoma?
antihistamine, phenothiazines, antidepressants cause atropine-like toxicity |
|
what are the contraindication for antimuscarinic drugs?
|
prostatic hypertrophy
achalasia intestinal atony |
|
atropine flush
|
indicative of atropine toxicity and especially dangerous in young children
body temp must be reduced physostigmine was one used to counteract atropine intoxication bc it builds up ACh but centrally and peripherally but considered TOO dangerous bc of convulsions! |
|
primary pathway of ganglionic transmission
|
mediated by nicotinic receptors on ganglia-activation, leads to fast excitatory potential
|
|
secondary pathway of ganglionic transmission
|
slow excitatory potential produced by action of ACh on M1 receptor
slow inhibitory potential produced by release of ACh from preganglionic nerve terminal, activation of M2 receptor on: SIF cell, release od NE or dopamine which hyperpolarize ganglia metoclopramide blocks dopamine action at ganglia - will increase GI tract motility without stimulating HCl secretion |
|
are ganglionic stimulants used therapeutically?
|
no
|
|
nicotine in low doses
|
considered a nonselective nicotinic receptor agonist
activates autonomic ganglia, stimulate tranmission through both parasympathetic and sympathetic ganglia |
|
CV effects of nicotine
|
ELEVATE BP
naive individual can increase TPR stimulate sympathetic ganglia controlling ventricular contraction stimulate ganglia controlling venous return |
|
ganglionic stimulants on respiratory system
|
activate chemoreceptors in aortic arch and carotid body to increase respiration
some direct action on medulla to increase respiration |
|
ganglionic stimulants on GI tract - parasympathetic has dominant tone in GI tract
|
increase GI tract motility and HCl release
|
|
central effects of ganglionic stimulants
|
can cause emesis by acting at chemoreceptor trigger zone
increases ADH release to cause fluid retention |
|
toxic effects of nicotine
|
ganglionic blocker at HIGH DOSES
rapidly asborbed through skin and enter placenta readily kills by causing RESPIRATORY ARREST desensitize nicotinic receptors at medulla oblongata to stop breathing desensitized nicotinic receptors at motor endplate region to cause paralysis of diaphragm and intercostal muscles |
|
DMPP
|
dimethyl 4 phenyl piperazinium ion
-stimulates ganglionic transmission without causing receptor desensitization, only used as lab tool -specific nicotinic Rc's autonimc ganglia and at the adrenal medulla not the NMJ -CV effects basically same as nicotine |
|
tetraethylammonium TEA
|
ganglionic blocker
positively charged does not cross BBB short duration of action |
|
hexamethonium
|
ganglionic blocker
positively charged does not cross BBB long duration of action not well absorbed |
|
trimethaphan
|
positively charged so doesn ot cross BBB
short acting inactive orally and given by IV |
|
what WERE ganglionic blockers used for?
|
lowering BP
only used to chronically control BP in patients with acute dissecting aortic aneuysm ideal bc they inhibit sympathetic reflexes and reduce rate of rise of blood pressure at site of tear |
|
what are the side effects of ganglionic blockers?
|
interfere with body's ability to maintain homeostasis
-abolish autonomic reflexes such miosis/accomodation -reduces transmission through division of ANS which is dominant to produce physiological responses also GI tract motility is inhibited causing constipation -orthostatic hypotension -urinary retention impotence due to block in both para and symp: control of erection and ejaculation |