Adrenergic Lecture Flashcards
what does the sympathetic nervous system control
- organ systems
- blood pressure
what is the NT for the SNS
NE
what is the mechanism of adrenergic transmission
NE starts as tyrosine (rate limiting step -> dopamine -> NE -> calcium triggers NE release and it binds
what is Ach broken down by and how long does it take
- ACh- esterase
- 150ms
how is NE broken down
- has to be reuptaked
- if it it reuptaken into where it came from then it is broken down by monoamine oxidase (MAO)
- if it is reuptaken into post site it is broken down into Catechol-O- Methyltransferase (COMT)
what are the types of sympathetic agonists
- direct
- indirect
what are the 2 mechanisms of indirect sympathetic agonists
- catecholamine displacement: amphetamines
- decreased NE clearance through reuptake inhibition
what are the adrenergic receptors and what are the two types of adrenergic receptors
- alpha 1 and alpha 2
- beta 1 and beta 2
- dopamine
- sympathomimetic vs sympatholytic
when can adrenergic receptors be downregulated
- CHF
- acidosis
- hypoxia
where are alpha 1 receptors located and what do they do
- peripheral vascular beds
- excitatory
- sympathomimetic
- vasoconstriction
- blood pressure increased
- mydriasis
- urinary sphincter constriction
what do alpha 2 receptors do and where are they located
- inhibitory
- sympatholytic
- in the vasculature
- decreased sympathetic tone
- decreased BP
- sedation
what do beta 1 receptors do and where are they located
- excitatory
- cardiac excitation
- increased rate, contractility, and conduction
- sympathomimetic
- the heart
what do beta 2 receptors do and where are they located
- bronchodilation
- smooth muscle relaxation
- skeletal muscle vasodilation
- decreased vascular resistance
- sympatholytic
- lungs
what does dopamine do
- resistance vessel vasodilation in renal, splanchnic, coronary, and cerebral vessels
what are the primary catecholamines
dopamine and NE
what do catecholamines mainly do
excitatory and are endogenous
where does dopamine act
brain and kidney
where does NE act
sympathetic nerve endings
what receptors does NE bind in order of most to least
-alpha 1
- beta 1
- beta 2
what is epinephrine released from
ONLY the adrenal medulla
what are the direct acting sympathomimetics
- NE
- epi
- dopamine
- dobutamine
- phenylephrine
- milrinone
- vasopressin
- alpha 2 selective agonists
what does NE do
- endogenous
- primary NT at sympathetic nerve endings
- maintenance of sympathetic tone- vasoconstriction
- increased BP
- no CO changes
- minimal chronotropic changes
- increased coronary blood flow
- caution with prolonged infusions
what are the uses of NE
- preferred vasoconstrictor
- first line therapy for spetic shock and hypotensive after fluids are given
what are the receptors epinephrine binds when given exogenously at different dosese
- at higher doses: alpha 1
- at lower doses: Beta 1
- at lower doses: beta 2
what does epinephrine do
- endogenous
- stress preparation
- increased coronary blood flow
- caution with prolonged infusions
what receptors does dopamine bind
- mostly dopamine
- alpha 1
- beta 1
- beta 2
describe dopamine
- endogenous
- NE precursor
what are the dose specific effects of dopamine
- low dose (0.5-3mcg/kg/min)
- intermediate (3-10mcg/kg/min) : increases BP
- high (10-20 mcg/kg/min)
what are the receptors that dobutamine binds in order of greatest to least
- beta 1
- beta 2
- alpha 1
describe dobutamine
- 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
what are the uses for dobutamine
- low dose: decreases BP
- mid range: increases ionotropy
- high doses: increases O2 consumption, vasoconstriction
- cardiogenic shock- usually combined with NE
what receptor does phenylephrine bind to
alpha 1
describe phenylephrine and what it does
- synthetic
- all alpha no beta
- not a catechol derivative, not metabolized by COMT
- metabolized by MAO
- can lead to baroreceptor mediated decrease in HR
- push dose pressor
what is phenylephrine used for
- transient hypotension
what receptor effect does milrinone have order of greatest to least
- B1
- B2
what does milrinone do
- 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
what is milrinone used for
in patient with heart failure without hypotension
what receptor does vasopressin mimic and what is another name for it
- alpha 1
- ADH
what are the direct acting sympathomimetics that dont directly bind the receptor they just mimic their effects
milrinone and vasopressin
where is vasopressin stored and when is it released
stored in posterior pituitary and released when plasma osmolarity increases or BP drops
what does vasopressin do
- V1 and V2 receptor agonist
- neutral to negative impact on CO
- dose dependent SVR and vagal tone increase
- not affected by pH
what is vasopressin used for
septic shock with acidosis
- 3rd or 4th line of treatment for BP control
what are the alpha 2 selective agonists
- clonidine
- dexomedetomidine
- guanfacine
- methyldopa
what do alpha 2 selective agonists do
- drop BP by reducing sympathetic tone
- effective antihypertensive
- sedation
what does clonidine used for
- 2nd line anti-hypertensive
- used in pain
- used in opioid and nicotine withdrawals
what is dexmedetomidine used for
same as clonidine but doesnt have BP effects
what is guanfacine used for
ADHD
what is methyldopa used for
drug of choice with HTN during pregnancy
what is the downside of long term use of alpha 2 selective agonists in dentistry
can lead to oral candidiasis and increased risk of dental caries due to decreased salivary gland activity
what are the 2 mechanisms of indirect acting sympathomimetics
- displacers
- reuptake inhibition
what are the indirect acting sympathomimetics
- amphetamine like agents: amphetamine, methylphenidate (ritalin), modafinil(provigil)
- catecholamine reuptake inhibitors: straterra, cocaine
describe amphetamines
- rapid CNS uptake
- stimulant
- effects mediated by NE and DA
describe methylphenidate( ritalin), what is it used for and what is the caution
- amphetamine variant
- similar effect and abuse potential
- use: ADD spectrum
- caution: UDS
describe modafinil (provigil), its mechanism, what it does and its use
- psychostimulant
- NE, DA reuptake inhibition
- NE, DA, 5-HT3, glutamate increase, GABA decrease
- use: narcolepsy
describe straterra and its use
- selective NE reuptake inhibition
- no CV effects- clonidine like effect
- Use; ADD
describe cocaine and what it is used for
- local anesthetic, peripheral sympathomimetic
- reuptake inhibition especially dopamine
- use: epistaxis
what can excessive cocaine use cause
excited delirium which manifests as aggression followed by respiratory or cardiac arrest
what should you avoid with cocaine use
concurrent beta blockade
describe beta-2 agonism
- key to management of acute asthma
- common allergy in dentistry is actually asthma 7.9% of the time
- triggered by allergens, stress, food and drugs
what drugs are used for short term control of asthma
- short acting beta agonists (SABA)
- albuterol
- levalbuterol
- terbutaline
what is used for long term control of asthma
- long acting beta agonists (LABA)
- formoterol
- salmeterol
how long go LABA drugs work
12-18 hours
LABA drugs must be used with:
steroids
what is advair made of
salmeterol + fluticasone
what is symbicort made of
formoterol + budesonide
what is dulera made of
formoterol + mometasone
what is the protocol for patient management with asthma in the dental settign
- minimize likelihood of exacerbation
- talk to your patient to learn their management strategies
- instruct patient to bring albuterol inhaler to all appointments
- decrease stressors
- drug considerations
what are the drug considerations in patients with asthma
- no ASA or NSAIDs
- avoid histaminic drugs
- avoid antihistamines
- avoid cholinergics
what do you do in an emergency with an asthma patients
- supplemental O2 immediately
- consider epi: 0.3mg IM or use epipen
what are the two types of alpha receptor antagonists
- reversible and irreversible
describe reversible alpha receptor antagonists
- concentration dependent
- duration dependent on half life
describe irreversible alpha receptor antagonists
- body has to regenerate new receptors
- drug effect can persist even after drug is cleared
- longer recovery process
what are the pharmacologic effects of alpha antagonists
-cardiovascular: alpha 1 blockade blocks vasoconstriction, orthostatic hypotension
- miosis, nasal stuffiness
- decreased resistance to urinary flow
what are the alpha receptor antagonist drugs
- phentolamine
- prazosin, terazosin, doxazosin
- tamsulosin
what does phentolamine do
- blocks alpha 1 and alpha 2
- decreased PVR and cardiac stimulation
- can lead to CV adverse reactions
what are the uses of phentolamine
- pheochromocytoma
- mainly used for extravasation reactions
what do prazosin, terazosin and doxazosin do and what are they used for
- selective alpha 1
- arterial and venous vascular smooth muscle relaxation and prostate relaxation
- 50% bioavailability- first pass effect
- use: BPH
what drugs cause orthostatic hypotension
- prazosin
- terazosin
- doxazosin
what does tamsulosin do
- competitive alpha 1 blocker
- high bioavailability
- more specific to prostate
- less orthostatic hypotension
what is tamsulosin used for
best drug for BPH
what do beta receptor antagonists do
- antagonize effects of catecholamines and beta agonists
- differ in affinity for beta 1 and beta 2
- beta 1 specificity decreases as dose increases
- end in -lol
what receptors do beta blockers ending in -olol act on
beta receptors only
what receptors do beta blockers ending in -ilol act on
mostly beta and some alpha receptors
what receptors do beta blockers ending in -alol act on
mostly beta and some alpha receptors
what affinities do labetalol and carvedilol have
B1 = B2 > alpha 1 > alpha 2
what affinities do metoprolol, betaxolol, acebutolol, esmolol, atenolol, nebivolol have
B1»_space;» B2
what affinities do propanolol, carteolol, penbutol, pindolol and timolol have
B1 = B2
what are the beta specific beta antagonists - “be a man”
- Betaxolol
- Esmolol
- Acebutol
- Metoprolol
- Atenolol
- Nebivolol
describe esmolol
- beta 1 selective
- short half life
- quick onset
- requires central line for administration
- great for tight BP control
- used for aortic dissection
describe labetalol
- beta and alpha blockade
- 3:1 ratio orally
- 7:1 ratio Iv
- dose dependent duration of action- up to 20 hours
what beta blocker drugs are safer for asthmatic patients
beta 1 specific
caution with non specific beta blockers and:
epi
