adrengenics Flashcards
SYMPATHETIC NERVOUSSYSTEM
▪mediates Organ systems, blood pressure
▪Hormone (epi from adrenal medulla) vs. neurotransmitter (NE)
rate limiting step NE release
Tyr to dopa
NEUROTRANSMITTER TERMINATION NE vs Ach
▪Acetylcholine: ACh-esterase, 150ms FAST
▪Norepinephrine: Reuptake
▪Monoamine oxidase (Pregang)
▪Catechol-OMethyltransferase (postgang)
direct sympathetic agonists
effects depend on?
bind to receptors
effect depends on: route, affinity, expression of receptor subtypes
indirect sympathetic agonists mechanisms
▪Indirect: Catecholamine displacement (Amphetamines)
▪Decreased NE clearance: Reuptake inhibition
ADRENERGIC RECEPTORS
▪α1 α2
▪β1 β2
▪Dopamine
▪Sympathomimetic (sym effects) vs sympatholytic (opposes sym effects)
states dowregulating adrengenic receptors
▪Congestive Heart Failure (CHF)
▪Acidosis
▪Hypoxia
and sepsis
A1 functions
works at peripheral vas beds, sympathomimetic
▪Vasoconstriction=Blood pressure increased
▪Mydriasis (dilated pupils)
▪Urinary sphincter constriction
A2 functions
symphatolytic
▪In the vasculature
▪Inhibition of NE and ACh
▪Decreased sympathetic tone
▪Decreased BP
▪Sedation
B1 functions
sympathetimetic
▪Cardiac excitation
▪Increased rate, contractility, conduction (chronotrophy and ionotrophy with increased Ca)
B2 functions
sympathetlytic
▪Bronchodilation
▪Smooth muscle relaxation
▪Skeletal muscle vasodilation
▪Decreased vascular resistance
Dopa receptor function
▪Resistance vessel vasodilation to increase blood flow at:
▪Renal
▪Splanchnic
▪Coronary
▪Cerebral
catecholamines
1 ones?
where each is from?
▪Dopamine (DA) and norepinephrine (NE)= Primary catecholamines
▪DA – Brain and kidney
▪NE – Sympathetic nerve endings
▪Epinephrine – Adrenal medulla
NE binding affinties?
A1>B1>B2
NE
▪Primary neurotransmitter at?
▪Maintenance of?
BP?
▪ cardiac output changes
▪ chronotropic changes
▪ coronary blood flow
▪Endogenous
▪Primary neurotransmitter at sympathetic nerve endings
▪Maintenance of sympathetic tone
▪⇧BP
▪No cardiac output changes
▪Minimal chronotropic changes
▪Increased coronary blood flow
NE uses
spetic shock or hypotensive pts with fluids administered first
NE caution
porlonged use: cardiac cell death
Epi
▪Only released by
▪ released for?
coronary blood flow effect?
▪Caution?
▪Endogenous
▪Only released by adrenal medulla
▪Stress preparation
▪⇧coronary blood flow
▪Caution prolonged infusions
epi affinities
A1 at high doses and B1/2 at lower doses
epi uses based on dosage?
can be used for?
high doses: increase bp and hr
lower doses; beta effects
can be used for anaphylaxis and with LA
DA
▪Endogenous
▪NE precursor
DA affinities
- DA receptor
- A1,B1,B2 all similar
DA Dose-specific effects
▪Low dose (0.5 – 3 mcg/kg/min): DA effects
▪Intermediate (3 – 10 mcg/kg/min): B effects
▪High (10 – 20 mcg/kg/min): A effects
DA uses
can bes used as a NE reuptake inhibitor at intermediate doses to increase iono/chrono at heart and increase BP
caution with DA
can increase risk of V fib
dobutamine
▪ from?
▪Augments?
▪Dose-dependent increase in?
▪Alpha effects?
▪Beta-mediated effect? dose?
▪High dose increases?
▪Synthetic
▪Augments myocardial contractility
▪Dose-dependent increase in stroke volume and cardiac output
▪Alpha agonist AND antagonist
▪Beta-mediated vasodilation (low dose)
▪High dose increases myocardial O2 consumption
dobutamine affinity
- B1
- B2
- A1
dobutamine uses
B1 agonist used for cardiac stress test, unstable cardiogenic shock (short t1/2)
phenylephrine
▪made?
▪ A/B?
▪ metab?
▪HR?
▪Push dose?
▪Synthetic
▪All alpha, no beta
▪Not a catechol derivative, not metabolized by COMT BUT still by MAO
▪Can lead to baroreceptor mediated decrease in HR
▪Push dose pressor for short-term hypotension
phenylepherine affinity
A1
phenylepherine uses
push dose pressor for short term hypotension and as a nasal decongestant
milrinone
▪ inhibitor?
▪Inhibits breakdown of?
▪inotropy?
▪ vaso effect?
▪Increased?
▪Reduced?
▪Good in the setting of?
▪Phosphodiesterase-3 inhibitor
▪Inhibits breakdown of cAMP
▪Positive inotropy
▪Potent vasodilator
▪Increased diastolic relaxation
▪Reduced preload and afterload
▪Good in the setting of receptor downregulation
milrinone affinity?
no binding but has:
1. B1 like effects
2. B2 like effects
milrinone use
HF
vasopressin
▪AKA
▪Stored in?
▪Released when?
▪receptor agonist?
▪Neutral to negative impact on?
▪Dose dependent effects?
▪Not affected by?
▪AKA: antidiuretic hormone
▪Stored in posterior pituitary
▪Released when plasma osmolality increases or BP drops
▪V1 (vasoconstrict) and V2 (retain volume) receptor agonist
▪Neutral to negative impact on CO
▪Dose dependent SVR and vagal tone increase
▪Not affected by pH
ADH affinity? resembles effects of what receptor?
V1 and 2: A1 like effects
ADH uses
pts with acidosis to increase bp
A2 selective agonists
Clonidine
Dexmedetomidine
Guanfacine
Methyldopa
Clonidine, Dexmedetomidine, Guanfacine, Methyldopa
▪bp?
▪Effective?
▪Class effect =
▪Drop BP by reducing sympathetic tone
▪Effective antihypertensive
▪Class effect = sedation
A2 AGONISTS
long term clonidine oral effect
candidasis
Dexmedetomidine effects
no effects on bp, all sedative
A2 agonist
guanfacine use
ADHD; activates A2 in PF cortex to incrase focus
methyldopa key use
HTN tx during pregnancy
INDIRECT ACTING
SYMPATHOMIMETICS
mechanisms
▪Displacers of stored NE
▪Reuptake inhibition
increasing effects of endogenous NE
▪Amphetamine
▪ CNS uptake
▪effect?
▪Effects mediated by?
▪Rapid CNS uptake
▪Stimulant
▪Effects mediated by NE and DA (indirect sympathetomeitic)
▪Methylphenidate (Ritalin)
▪ variant?
▪ effect?
▪Use:
▪Caution?
teeth/drug tests?
▪Amphetamine variant/ amphetamine like molecule
▪Similar effect and abuse potential to amphetamine
▪Use: ADD-spectrum
▪Caution - UDS
no effects on teeth
postive on drug tests
amphetamine oral effects
destroys teeth
▪Modafinil (Provigil)
▪role?
▪Totally different from?
▪NE, DA?
▪NE, DA, 5-HT3, glutamate?; GABA?
▪Use:
▪Psychostimulant
▪Totally different from amphetamine but a amp like molecule
▪NE, DA reuptake inhibition
▪NE, DA, 5-HT3, glutamate increase; GABA decrease
▪Use: narcolepsy
▪Straterra
▪ MOA
▪CV effects
▪similar effects as what other drug?
▪Use:
▪Selective NE reuptake inhibition
▪No CV effects
▪Clonidine-like effect
▪Use: ADD
▪Cocaine
▪Local?, peripheral?
▪mechanism?
▪sign of abuse (mental)
▪Avoid?
▪Use:
▪Local anesthetic, peripheral sympathomimetic
▪Reuptake inhibition,especially dopamine
▪Excited delirium
▪Avoid concurrent betablockade
▪Use: epistaxis
Excited delirium
seen with cocaine abuse, increased DA in brain can lead to aggression ith increased temp folllowed by sudden res/cardaic arrest
goal would be to get pt sedated
why avoid betablockade with coke
increased risk MI, HR will decrease but A effects of coke active=vasoconstrict
Beta agonism and asthma
BETA-? AGONISM
▪Commonality?
▪Triggered by?
▪Angioedema?
BETA-2 AGONISM
▪Key to management of acute asthma
▪Common “allergy” in dentistry (7.9%)
▪Triggered by allergens, stress, food, drugs
▪Angioedema = similar but different
short acting beta agonsits (SABA)
Albuterol
Levalbuterol
Terbutaline
SABA used for:
short term control with fast onset and short duration
albuterol
acute managment, B2 agonist but also B1 so HR may increase (can pt handle?)
Levalbuterol
L sterioisomer of albuterol
used instead of albuterol for no B1 effect
terbutaline
SABA used in severe cases: IV/IM administration
LABAs
Formoterol
Salmeterol
LABA use
▪used in conjunction with?
▪Blocks receptors for?
▪NOT FOR?
▪Longer term control, used in conjunction with SABA/steroids
▪Blocks receptors 12-18h
▪NOT FOR ACUTE ATTACKS