andrenoceptor activating drugs
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Adrenoceptor*Agonists*and*Sympathomimetic*Drugs*|*Pharmacology*!
!Aleyssa |"Jeng
DIVISIONS OF HUMAN NERVOUS SYSTEM
NERVOUS SYSTEM
The SNS is an important regulator of virtually ALL organs Mediated by norepinephrine release !
activates adrenoceptors on postsynaptic sites Epinephrine is released from the adrenal
medulla in response to stress ! Norepinephrine acts as a neurotransmitter ! Epinephrine acts as a hormone
SYMPATOMIMETIC DRUG CLASSIFICATION:
1. Direct Agonists directly interact with and activate adrenoceptors Pharmacologic effects depend on: route
of administration, relative affinity for adrenoceptor subtypes, and relative expression of receptor subtypes in target tissues
2. Indirect Agonists actions depend on its ability to enhance the actions of endogenous catecholamines Displace stored catecholamines, or
decrease clearance of released NE Inhibit reuptake Prevent metabolism (MAO, COMT) Greater effects under conditions of
increased sympathetic outflow
3. Mixed-Acting leads to some or all of the characteristic effects of endogenous catecholamines
SYMPATHETIC NERVOUS SYSTEM FIGHT OR FLIGHT RESPONSE RESULTS IN:
1. Increased BP 2. Increased blood flow to brain, heart and
skeletal muscles 3. Increased muscle glycogen for energy 4. Increased rate of coagulation 5. Pupil dilation
Human!Nervous!System!Central!Nervous!System!
Peripheral!Nervous!System! Autonomic!Nervous!System!
With!Neurotransmitter!NOREPI!&!ACETYLCHOLINE!
Either!"FIGHT!&!FLIGHT"!or!"REST!&!DIGEST"!!
Includes!NEURONS!&!GANGLIA!outside!of!the!brain!&!spinal!cord! Peripheral!NS!Autonomic!NS!(Involuntary)!
Sympathetic!NS!(Adrenergic)! Para!sympathetic!NS!(Cholinergic)!
Somatic!NS!(Voluntary)!
Sympathomimetic!Direct!Agonist!(Epi/NE)!
Indirect!Agonist!
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PRECURSOR Tyrosine: Amino acid found in many foods including cheese and dairy products BIOSYNTHESIS
Rate Limiting (TH): Controls production, found in axons L-DOPA: L-3-4-dihydroxyphenylalanine NOREPINEPHRINE SYNTHESIS
Tyrosine transported into Noradrenergic ending
by a Na-dependent carrier
Tyrosine converted to Dopamine and transported into the vesicle by VMAT (which can be blocked by reserpine)
Dopamine is converted to NE in the vesicle by Dopamine-B-hydroxylase
Physiologic release of transmitter occurs when an action potential opens voltage-sensitive calcium channels and increases intracellular calcium.
Fusion of vesicles results in expulsion of NE, cotransmitters, and dopamine-B-hydroxylase (blocked by guanethidine and bretylium)
After release NE diffuses out or is transported into the cytoplasm by NET (can be blocked by cocaine and TCA)
Regulatory receptors are present on the presynaptic terminal. SNAPs, synaptosome-associated proteins; VAMPs, vesicle-associated membrane proteins
REGULATION The actions of catecholamine are terminated by: (1) Reuptake into nerve terminals by NET (2) Dilution by diffusion out of the junctional cleft and uptake at extraneuronal sites by ENT, OCT1, and OCT2 (3) Metabolic transformation (1) Reuptake into nerve terminals by NET Once released, NE will interact with the
receptors. If there is excess NE, the body will balance &
regulate it release by NET (norepinephrine transporter) & alpha-2
NET (NE transporter) is a Na-dependent transporter, which needs high Na+ concentration entering the presynaptic fiber. NET has higher affinity to NE but highest with DOPAMINE & low affinity to EPI. (D>NE>Epi)
NET primarily responsible in terminating the activity of NE because it removes 90% of NE in synaptic cleft area. Thus, increasing the re-uptake of NE.
NET can be inhibited by tricyclic antidepressants & cocaine. Thus, NE is still high in the synaptic cleft.
There are certain substances that can be taken up by NET (not only NE, Dopa, Epi) like mixed sympathomimetic agents (ex. Amphetamine, Ephidrine & Tyramine). Once they are taken, it will enter the presynaptic fiber. As it enters, it will be transported by VMAT going inside the storage vesicle. If the mixed sympathomimetic drug is inside the vesicle, it will NOT allow the NE to go inside the vesicle causing
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Adrenoceptor*Agonists*and*Sympathomimetic*Drugs*|*Pharmacology*!
!Aleyssa |"Jeng
displacement of NE in synaptic cleft. If the mixed sympathomimetic drug is given repeatedly at close interval. NE stores will be depleted causing lesser sympathetic effect.
Alpha-2 is an autoreceptor, which prevents NE release. When there is excess NE in the synaptic cleft that occupies ALL the post-synaptic receptors. The excess NE will occupy the alpha-2 receptor. Hence, preventing the release of NE.
Summary: (responsible in regulation the AMOUNT of NE) o NET increase re-uptake of
neurotransmitters. It is the major pathway in terminating the activity of NE (90%)
o Alpha-2 decrease/prevent the release of neurotransmitters
Other mechanisms in regulation of NE release:
1] Up & down regulation The receptors are the one being regulated. If up-regulated the response of the
receptor of the agonist will be greater. Thus, effects are increase.
If down-regulated the response of the receptor of the agonist will be diminished. o Most of the time, down-regulation is a
result of loss of receptors (ex. If all the receptors are occupied & thus, there will be NO available receptors for the next batch of the transmitters)
2] Post-synaptic excitatory potential (NOT sympathetic in nature) This is inhibited by GABA
(3) Metabolic transformation - Metabolism, thru enzymes MAO & COMT Both MAO & COMT are distributed widely throughout the body, including the brain; the highest concentrations of each are in the liver and the kidney.
DESENSITIZATION Occurs after exposure to almost all
sympathomimetics Tolerance, refractoriness, and tachyphylaxis
Covalent bond in receptor irreversible
HOMOLOGOUS when the receptor is repeatedly activated by the same agent that activates it
HETEROLOGOUS - when there is diminished in the response of the receptors by other agonist
CHEMICAL STRUCTURE
Substitution on the Benzene Ring
Hydroxyl group at the 3rd and 4th position will tell whether the agent has a good alpha or beta activity
o Absence of hydroxyl group = will reduce the drug effect
2 functions of hydroxyl group: o Maximal alpha & beta activity o Recognition of COMT
Hydroxyl group at phenyl ring will be the one that will be recognized by COMT. If absence or lack 1 of hydroxyl group, COMT will NOT degrade the agent. Causing inc./greater the bioavailability. ! Phenylephrine has greater bioavailability than Epinephrine
Phenylephrine o Lack the hydroxyl group at both
positions o Has lesser potency than EPI in terms of
alpha activity & negligible beta activity o Lesser effect BUT delay degradation by
COMT ! stays in the system longer
Adrenergic!Receptors!Alpha!1,2!
Beta!1,2,3! Dopamine!1S5!
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Epinephrine
o Has a complete hydroxyl group at 3rd & 4th position ! greater effets, shorter action
Alkyl substituents in Amino Group
A drug that has an alkyl substituent in amino group has increased BETA-receptor activity
The bulkier the alkyl substituent the greater effect of BETA activity
EPI has better BETA activity than NE (none)
ISOPROTERENOL has the greatest B-activity because it has bulkier/larger group of substituents ! weak at alpha-receptors
Substitution on the A-carbon Substitution at alpha carbon will delay
oxidation by MAO Phenylephrine will be degraded easily by
MAO d/t absence of substitution at alpha carbon
Alpha-methyl compounds ! phenylisopropylamine ! some have enhanced ability to displace catecholamines from their storage sites in noradrenergic nerves. This means that a portion of their activity is dependent on the presence of normal NE stores (indirect sympathomimetics)
Substitution on the B-carbon
If there is hydroxyl group at B-carbon, it implies that the agent can directly act on the receptors.
ADRENERGIC RECEPTORS AFFINITY FOR ALPHA RECEPTORS: Epinephrine > Norepinephrine >> Isoproterenol FOR BETA RECEPTORS: Isoproterenol > Epinephrine > Norepinephrine 1 receptors have equal affinity for epinephrine
and norepinephrine 2 receptors have a higher affinity for
epinephrine than for norepinephrine
ADRENOCEPTOR TYPES & SUBTYPES
Rec
epto
r
Ago
nist
Ana
goni
st
Effects
Gen
e on
C
hrom
osom
e
1 Type
Penyl ephrine
Prazosin
IP3, DAG common to all
1A C5 1B C8 1D C20
2 Type
Clonidine
Yohimbine
cAMP common to all
2A Oxymeta zoline
C10
2B Prazosin C2 2C Prazosin C4 Type
Isopro terenol
Propra nolol
cAMP common to all
1 Dobu tamine
Betaxolol C10
2 Albuterol Butox amine
C5
3 C8
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Adrenoceptor*Agonists*and*Sympathomimetic*Drugs*|*Pharmacology*!
!Aleyssa |"Jeng
ORGAN SYSTEM EFFECTS TYPE TISSUES ACTION - 1
Most vascular smooth muscles (innervated)
Contraction
Pupillary dilator muscle
Dilates Pupil
Pilomotor smooth muscle
Erects Hair
Prostate Contraction Heart
Increase Force of Contraction
- 2
Postynaptic CNS adrenoceptor
Mutliple
Platelets Aggregation Adrenergic/Cholinergic nerve terminals
Inhibition of release of transmitter
Some vascular muscles
Contraction
Fat cells Inhibition of Lypolysis
- 1
Heart Increase force & rate of contraction
Juxtaglomerular cells Increase Renin release
- 2
Respiratory Uterine Vascular smooth muscles
Relaxation
Skeletal muscles Promotes Potassium Uptake
Human Liver Glycogenolysis - 3 Fat cells Activates
Lipolysis D 1 Smooth muscles Dilates vessels
(Renal) D 2
Nerve endings
Modulates Transmitter Release
CARDIOVASCULAR SYSTEM ALPHA RECEPTORS Increase arterial resistance Alpha, agonists decrease blood pressure by
actions in the CNS, through their direct effect on a blood vessel may be constriction
Alpha, agonists are useful in the treatment of hypertension
BETA RECEPTORS Beta-1 has direct effect on the heart more than
Beta-2 1 selective agonists do not induce
vasodilatation, so they increase cardiac output with less reflex tachycardia
Beta-2 decreases arterial resistance CATECHOLAMINES Cathecol + amine (NH2) Members:
o Dopamine o Norepinephrine (Noradrenaline) o Epinephrine (Npepinephrine)
STRUCTURE ACTIVITY RELATIONSHIP OF SYMPHATOMIMETIC DRUGS
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Maximal alpha & beta activity -OH group at 3,4 position on benzene ring Absence OH at C-3 reduce potency
: Blocks oxidation by MAO prolonged action : -OH facilitates activation of receptor important
for storage in neutral vesicles SPECIFIC DRUGS CATHECHOLAMINES & SYMPHATOMIMETIC
DRUGS
DIRECT ACTING SYMPATHOMIMETICS ALPHA-1 SELECTIVE
o Phenylephrine o Midodrine o Methoxamine
ALHA-2 SELECTIVE o Clonidine o Methyldopa o Guanfacine o Guanabenz o Dexmedetomidine o Xylometazoline & Oxymetazoline
BETA-1 SELECTIVE o Dobutamine o Prenalterol
ENDOGENOUS CATECHOLAMINES EPINEPHRINE
o Primary hormones secreted by the adrenal medulla in mammals
NOREPINEPHRINE o Major neurotransmitter in the peripheral
sympathetic nervous system (postganglionic adrenergic erves)
DOPAMINE o Found predominantly in the basal ganglia of
the CNS EPINEPHRINE POTENT STIMULANT: BOTH
o Effects on target organ-complex POWERFUL CARDIAC STIMULANT
o Predominantly on -1 receptors of the myocardium
o Cells of pacemaker IT AFFECTS RESPIRATION
o Primarily by relaxing bronchial muscle DIRECT RESPONSES
o in contractile force o Accelerated rate of rise of isometric tension o Enhanced rate of relaxation o time to peak tension o excitability o Acceleration of the rate of spontaneous
beating o Induction of automaticity in specialized
regions of the heart o GIT smooth muscle is relaxed due to
activation of both & adrenergic receptors
o Intestinal tone and the frequency and amplitude of spontaneous contractions are reduced
o Stomach is relaxed o Pyloric and ileocecal sphincters are
contracted o Response of uterine muscles vary with
species, phase of sexual cycle, state of gestation and dose given
o Inhibits uterine tone & contractions during the last trimester
Endogenous!Cathecolamines!Epinephrine!
Norepinephrine!Dopamine!
Direct!Acting!Sympathomimetics!AlphaS2!Selective!BetaS1!Selective!BetaS2!Selective!
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Adrenoceptor*Agonists*and*Sympathomimetic*Drugs*|*Pharmacology*!
!Aleyssa |"Jeng
METABOLIC EFFECTS o Insulin secretion is inhibited through an
interaction with 2 receptors and enhanced by activation of 2 receptors
o Glucagon secretion is enhanced by an action on the receptors of the cells of pancreatic islets
o Decreases the uptake of glucose by peripheral tissues
UNTOWARD EFFECTS o May cause restlessness, apprehension,
headache, and tremor which may be secondary to the effects on the CV system, skeletal muscles & intermediary metabolism
INJECTIONS o 1:1000 o 1:10,000 o 1:100,000
DOSE o Usual SC adult: 0.3-0.5 mg o IV (cardiac arrest): 0.25 mg o INH 1:100 1% formulation
NOREPINEPHRINE LACK THE METHYL SUBSTITUTION IN THE AMINO
GROUP o 10% - 20% of the catecholamine content of
human adrenal medulla A POTENT AGONIST AT RECEPTOR
o Less potent than epinephrine on the receptors of most organs
INCREASE IN CORONARY BF o Indirectly induced coronary dilation and to
elevated BP DOPAMINE CENTRAL NEUROTRANSMITTER
o D1 receptors in vascular beds which leads to vasodilation
o Also activates 1 receptors in the heart o Low doses peripheral resist. o At higher doses activates receptors
leading to vasoconstriction o High rates of infusion of dopamine mimics
actions of epinephrine DOPAMINE RELATED DRUGS
o Fenoldopam " D1-receptor-selective agonists " Lowers BP in severe hypertension
o Dopexamine " Synthetic analog related to dopamine
with intrinsic activity at dopamine receptors as well as at the 2-adrenergic receptors
" Used in pts with severe CHF, sepsis, & shock
EPI Nor
EPI DOPA
Bronchospasm
Shock
CHF w/ oliguria & low or normal peripheral resist
Hypersensitivity Low BP
Cardiogenic & septic shock
Cardiac Arrest Post-intubation Infectious Croup ADRENERGIC AGONIST
2-SELECTIVE
O Metaproterenol O Albuterol O Pirbuterol O Fenoterol O Procaterol O Ritodine O Terbutaline O Isoetharine O Bitolterol O Formoterol O Salmeterol
!Adrenergics!Agonists!1!Selective!!
Isoproterenol! Dobutamine!Penalterol!2!Selective!Metaproterenol!Albuterol!Pirbuterol!
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MIXED ACTING Ephedrine Pseudoephedrine Phenylpropanolamine
INDIRECT ACTING ANDRENERGIC AGONIST RELEASING AGENTS
o Amphetamine " CNS stimulants & readily enters CNS " Peripheral actions mediated through
catecholamine release " Moderate doses: restlessness, insomnia
anxiety " High dose: paranoid state " Alerting, sleep deferming acion, improve
attention " Loss of apetite weight loss but long
term cannot achieve the goal " Therapeutic application: NARCOLEPSY " MODAFINIL
Amphetamine substitute used for narcolepsy
" METHAMPHETAMINE Higher ratio of CNS to peripheral
actions than amphetamine " PHENMETRAZINE
Amphetamine like effect used as ANOREXIANT
" METHYLPHENIDATE (RITALIN) Amphetamine variants used in
children with ADHD o Tyramine
" By product in the body metabolized by MAO.
" It is found in high concetrations in fermented foods such as cheese
" It releases stored catecholamines and has a noradrenaline like effect
" In patients treated with MAO inhibitors effect of Tyramine may be greatly intensified
" In patient taking an irreversible MAO inhibitor drug, 20-50 mg of Tyramine increases the BP significantly
" Cheese, sausage, pickled fish, & yeast supplements contain sufficient Tyramine to be dangerous
FOODS REPUTED TO HAVE A HIGH CONTENT OF TYRAMINE & OTHER SYMPATHOMIMETIC AGENTS
FOOD TYRAMINE CONTENT (Average Serving) Beer No data Broad beans, Fava Negligible (but contains
beans dopamine) Cheese, natural or aged Nil to 130 mg Chicken Liver Nil to 9 mg Chocolate
Negligible (but contains Phenylethylamine)
Sausage, fermented (salami, pepperoni, summer sausage)
Nil to 74 mg
Smoked/pickled fish Nil to 198 mg Snails No data Wine (Red) Nil to 3 mg Yeast (dietary brewers yeast supplements)
2-68 mg
UPTAKE INHIBITOR
o Cocaine " Local anesthetic that also inhibits
norepinephrine reuptake " It produces an AMPHETAMINE-LIKE
EFFECT that is shorter lasting and more intense
" The major action of cocaine in the CNS is to inhibit dopamine reuptake into the neurons in the pleasure centers of the brain
" Cocaine may precipitate convulsions, cerebral hemorhhage, arrythmias or myocardial infarction
MAO/COMT INHIBITORS o Pargyline o Entacapone
SHOCK Although sympathomimetic drugs have been
used in the treatment of virtually all forms of shock, their efficacy is unclear
In most forms of shock, vasoconstriction mediated by the sympathetic NS is already intense
Indeed, efforts aimed at reducing rather than increasing peripheral resistance may be more fruitful
A decision to use vasoconstrictors or vasodilators is best made on the basis of information about the underlying cause
HYPOTENSIVE SHOCK If cerebral, renal, cardiac perfusion is
maintained, hypotension itself does not usually require vigorous direct treatment
The use of sympathomimetic drugs merely to elevate a BP that is not an immediate threat to the patient may increase morbidity
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Adrenoceptor*Agonists*and*Sympathomimetic*Drugs*|*Pharmacology*!
!Aleyssa |"Jeng
Direct-acting agonists such as norepinephrine, phenylephrine, methoxamine have been utilized in this setting
For the treatment of chronic orthostatic hypotension, oral ephedrine has been the traditional therapy
ANAPHYLACTIC SHOCK EPINEPHRINE, 0.3-0.5 mg (0.3-0.5 mL of 1:1000
epinephrine solution) is the drug of choice Intramuscular injection may be preferred In patients with impaired cardiovascular
function, intravenous injection of epinephrine is required
Glucocorticoids and antihistamines (bot H1 & H2 antagonists) may be useful as secondary therapy.
CARDIOGENIC SHOCK Positive inotropic agents such as dopamine or
dobutamine may have a role in this situation In low doses, these drugs may increase cardiac
output & cause little peripheral vasoconstriction The goal of therapy in shock should be to
optimize tissue perfusion, not BP OTHER CARDIAC PROBLEMS Epinephrine may be useful in cardiac arrest by
redistributing blood flow to coronaries and to the brain
Heart failure may respond to the positive inotropic effects of drugs such as dobutamine
Development of tolerance is a major limitation to the use of catecholamines in heart failure
EYE Alpha adrenergic drugs (phenylephrine) cause
mydriasis antagonists decrease the production of
aqueous humor Glaucoma responds to a variety of
sympathomimetic & sympathoplegic drugs Apraclonidine & brimonidine are 2 selective
agonists used in glaucoma
GENITOURINARY TRACT 1A receptor mediated constriction of the
bladder base & prostate The 2 receptors of the bladder wall mediate
relaxation Ejaculation depends on normal receptor (and
purinergic receptor) The detumescence of erectile tissue is brought
about by norepinephrine (and neuropeptide Y) released from sympathetic nerves
MISCELLANEOUS The sweat glands, located on the palms of the
hands increase sweat production These are glands associated with psychologic
stress Renin secreton is stimulated by 1 and inhibited
by 2 receptors In high concentrations, epinephrine and related
agents cause leukocytosis TOXICITY Marked elevations in BP Cardiac ischemia & failure Sinus tachycardia & even serious ventricular
arrythmias Myocardial damage, particularly after prolonged
infusion If an adverse sympathomimetic effect requires
urgent reversal, a specific adrenoceptor antagonist can be used
You$are$going$to$want$to$give$up.$Dont.$
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EGBautistaII 4
. Dru
gs
CLASS
DRUGS
PHARMACOLOGICAL
ACTIONS
THERAPEUTIC APPLICATIONS
UNTOW
ARD EFFECTS
COMM
ENTS
DIR
EC
T-A
CT
ING
(SE
LE
CT
IVE
)
A1-selective
Phenylephrine M
idodrine M
ethoxamine
Xylom
etazoline O
xymetazoline has alpha2 also
Mephenterm
ine M
etaraminol
Vasoconstriction
Nasal congestion (used topically)
coz vessels are dilated
Pupillary dilation Postural hypotension (m
idodrine)
Hypertension
Reflex bradycardia
Dry m
outh, sedation, rebound hypertension upon abrupt w
ithdrawal
Mephenterm
ine and m
etaraminol also act indirectly
to release NE
Midodrine is a prodrug
converted in vivo to an active com
pound
A2-selective
Clonidine
Methylnorepinephrine
Guanfacine
Guanabenz
Methyldopa
Decrease sym
pathetic outflow from
brain to periphery resulting in decreased PV
R and blood pressure
Decrease nerve-evoked release of
sympathetic transm
itters D
ecrease production of aqueous hum
or
Adjunctive therapy in shock
Hypertension
To reduce sympathetic response
to withdraw
al from narcotics,
alcohol, and tobacco G
laucoma
Apraclonidine and brim
onidine used topically for glaucom
a and ocular hypertension M
ethyldopa is converted in CN
S to a-m
ethyl NE, an
effective a2 agonist
B1-selective
Dobutam
ine Increase in contractility Som
e increase in heart rate Increase in A
V conduction
Short-term
treatment of cardiac
decompensation after surgery, or
patients with C
HF or M
I
Increase in blood pressure and heart rate.
Use w
ith caution in patients w
ith hypertension or cardiac arrhythm
ias U
sed only IV
B2-selective
Albuterol
Bitolterol
Fenoterol Procaterol M
etaproterenol Terbutaline Ritodrine
Isoetharine
Relaxation of bronchial sm
ooth m
uscle Relaxation of uterine sm
ooth m
uscle Activation of other B
2 receptors after system
ic administration
Bronchodilators for treatm
ent of asthm
a and CO
PD
Short/interm
ediate-acting drugs for acute bronchospasm
Ritodrine, to stop prem
ature labor
Skeletal m
uscle tremor
Tachycardia and other cardiac effects seen after system
ic adm
inistration (much less w
ith inhalational use)
Use w
ith caution in patients w
ith CV
disease (reduced by inhalational adm
inistration) M
inimal side effects
Non-selective
(B1+B
2) Isoproterenol (B
1=B2)
Increase in contractility Som
e increase in heart rate Increase in A
V conduction
Short-term
treatment of cardiac
decompensation after surgery, or
patients with C
HF or M
I
Increase in blood pressure and heart rate.
Use w
ith caution in patients w
ith hypertension or cardiac arrhythm
ias U
sed only IV
M
ixed (alpha &
beta) Epinephrine A
1=A
2; B1=
B2
Increase in heart rate Increase in blood pressure Increased contractility Slight decrease in PV
R
Increase in cardiac output Vasoconstriction (viscera)
Open-angle glaucom
a W
ith local anesthetics to prolong action Anaphylactic shock
Com
plete heart block or cardiac arrest
Palpitation Cardiac arrhythm
ias Cerebral hem
orrhage H
eadache Trem
or Restlessness
Not given orally
Life saving in anaphylaxis or cardiac arrest
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EGBautistaII
Vasodilation (skeletal m
uscle) Increase in blood glucose and lactic acid
Bronchodilator in asthm
a
N
orepinephrine A
1=A
2; B1>
>B
2
Increase in systolic and diastolic blood pressure Vasoconstriction
Increase in PVR
Direct increase in heart rate and
contraction Reflex decrease in heart rate
Hypotension
Sim
ilar to Epi H
ypertension
Not absorbed orally
Dopam
ine D
opamine (D
1=D
2) Fenoldopam
(D1>
D2)
Improve renal blood flow
D
ilates blood vessel, inhibits sym
pathetic discharge
It dilates renal vasculature U
sed for malignant H
PN
(Fenoldopam)
MIX
ED
AC
TIN
G
Ephedrine
Pseudoephedrine
Appetite stim
ulant
Associated w
/ hemorrhagic
strokes
Phenylpropanolam
ine
IN
DIR
EC
T A
CT
ING
A
mphetam
ine-like d
isplace
rs
Am
phetamine
Metham
phetamine
Phenmetrazine
Methylphenidate
Modafinil
Tyramine
promotes N
E release; mostly
used for weight reduction
Modafinil inhibit both N
E &
dopamine transporter
Tyramine displace N
E from
storage vesicle & prom
ote NE
release
Catecholam
ine R
euptake Inhibitors in
hibit N
ET
Satom
oxetine Reboxetine
Sibutram
ine D
uloxetine Cocaine
Sibutram
ine only appetite suppressant approved by FD
A;
also (-) reuptake of serotonin D
uloxetine - antidepressant
A/E: tachycardia
for ADHD ( down regulation )
for depression
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