CHAPTER 6: ADRENERGIC AGONISTS Flashcards
direct acting, indirect acting, mixed acting, beta specific, and alpha specific
catecholamines vs. non-catecholamines
catecholamines: sympathomimetic amines that contain 2 OH on benzene rings
- high potency
-rapid inactivation by COMT
- poor penetration into CNS
non-catecholamines: lack catechol group
- poor substrate for MAO—> prolonged duration of action
- greater access to CNS
how does the affinity for B2 receptors increase?
as the group on the amine nitrogen gets larger, the affinity increases
ex: isoproterenol has more methyl groups than epinephrine on the amine
what is a natural endogenous drug? which drugs are natural endogenous drugs?
- naturally made in the body
- epinephrine and norepinephrine
mechanism of action: adrenergic agonists
- direct
- indirect
- mixed action
DIRECT: directly on a and B receptors
-epi, NE, isoproterenol, phenylepi
INDIRECT: block uptake of NE or ENHANCE release of NE from vesicles
- amphetamine, cocaine, tyramine
MIXED: mixed activity, acts both directly and indirectly
- ephedrine, pseudoephedrine
effect of adrenergic agonists on: HEART
- inotropic effect
- chronotropic effect
- dromotropic effect
what is inotropic effect? pos and neg?
- contractility of myocardium, depends on ions to contract
positive: drug increases strength of contractility
negative: drug dec strength of contractility
what is chronotropic effect? pos and neg?
- rate of contraction
positive: drug inc rate of contraction
negative: drug dec rate of contraction
what is dromotropic effect? pos and neg?
- rate of condution through AV node/ how fast the electrical signal goes to allow AV contraction
dromo=circuit
pos: drug inc rate of conduction
neg: drug dec rate of conduction
diastolic vs. systolic BP
systolic: contraction of vessels, a1 activation
diastolic: ventricular filling, BP slightly reduced, b2 receptors
EPINEPHRINE:
-mechanism of action (MOA)
-interacts with BOTH a and B
receptors
both receptors still engaged, both effects stimulated, but BALANCE each other
-LOW DOSES: B effects on vascular system (vasodilation)
-HIGH DOSES: a effects predominate (vasoconstriction)
epinephrine:
- actions
CARDIOVASC: inc cardiac output (B1)
RESPIRATORY: bronchodilation (B2)
HYPERGLYCEMIA: inc glycogenolysis in liver/ inc blood glucose (B2), inc release glucagon (B2), dec insulin release (a2)
LIPOLYSIS: stimulation B2 in adipose tissue
what does epinephrine do to peripheral resistance? inc or dec?
SLIGHTLY DECREASES peripheral resistance
why not increase? bc yes the alpha receptors are being activated (HIGH DOSE), BUT so are beta (LOW DOSE) so periph resistance will still be decreased.
epinephrine:
-therapeutic uses/indications
- bronchospasm
- anaphylactic shock
- cardiac arrest
- local anesthetics
- ADJUVANT to induce vasoconstriction
- allows prolonged anesthetic effect at area of
administration
epinephrine:
- pharmacokinetics
- RAPID onset
- BRIEF duration of action (rapid degradation)
ROUTES: IM anaphylaxis, IV emergencies, SC, endotracheal, inhalation
RAPIDLY metabolized by MAO and COMT enzymes, metabolites excreted in urine
epinephrine:
- adverse effects
CNS: anxiety, fear, tension, headache, tremor
CV: cardiac arrhythmias (especially if receiving DIGOXIN-cardiac disease drug)
- pulmonary edema due to inc afterload caused by vasoconstrictive properties of the drug
- inhalation anesthetics sensitize heart, lead to tachycardia
NOREPINEPHIRNE (NE):
- MOA
- neurotransmitter, NE stimulates ALL adrenergic receptors
- a receptor most affected in therapeutic doses
inc affinity for a1
norepinephrine:
- actions
little B1, NO B2
CARDIOVASCULAR:
- intense vasoconstriction (a1)
- baroceptor reflex/ vagal stimulation:
inc peripheral resistance, sends a message to brain that BP increased, response is REFLEX bradycardia
- tachycardia with atropine pretreatment
norepinephrine:
- therapeutic uses/indications
- septic shock (last stage of sepsis)
what is septic shock?
the last stage of sepsis, there is a generalized infection in the body w/ extremely low BP
- NE will inc the BP in this type of patient
norepinephrine:
- pharmacokinetics
- RAPID onset via IV (1-2 min DOA)
- metabolized by MAO and COMT, urine excretion
norepinephrine:
- adverse effects
- CNS disturbances
- cardiac arrhythmias
- pulmonary edema
- blanching to necrosis of skin IF extravasation occurs
what is extravasation?
veins constrict at the site of injection, and fluid (drug or vesicant fluids) leaks from vein into surrounding tissue
ISOPROTERENOL:
- MOA
- stimulates BOTH B1 and B2
- non-selectivity is a DISADVANTAGE/ rarely used therapeutically
isoproterenol:
- actions
CV: inc HR, contractility, and cardiac output (B1)
- dilate arterioles of skeletal muscle (B2)—->
DEC peripheral resistance (vasodilation)
RESPIRATORY: potent bronchodilator (B2)
isoproterenol:
- adverse effects
similar to B-receptor related side effects of EPINEPHRINE
DOPAMINE:
- MOA
can activate a and B
- HIGH DOSE: vasoconstriction (a1)
- LOW DOSE: stimulate B1 cardiac receptors
- D1 and D2 dopaminergic receptors: in peripheral mesenteric and renal vasc beds—-> VASODILATION, inc blood flow
- D2 on presynaptic adrenergic neurons, activation interferes w NE release
dopamine:
- actions
- CV (pos inotropic and chronotopic)
- renal and visceral—> INC blood flow to kidneys and viscera
dopamine:
- therapeutic uses/indications
- cardiogenic shock and septic shock
- hypotension
- severe congestive heart failure
dopamine:
- pharmacokinetics
rapidly metabolized by MAO and COMT enzymes
dopamine:
- adverse effects
SNS stimulation due to overdose
- short-lived effects: nausea, hypertension, arrhythmias
ALPHA specific direct-acting:
actions and list which drugs
- therapeutic effects from stimulation of a receptors within SNS
- phenylephrine, midodrine, clonidine, oxymetazoline
alpha specific: phenylephrine
- primarily a1
- cold and allergies, supraventricular tachycardia, hypotension
alpha specific: midodrine
- primarily a1
- orthostatic hypotension
( when changing body position, you feel dizzy, hard time adjusting BP, pressure inc in vessels)
alpha specific: clonidine
- centrally on a2 (presynaptic rec, dec NE, dec SNS)
- hypertension, withdrawal symptoms from opiates and benzodiazepines
alpha specific: oxymetazoline
- BOTH a1 and a2
- nasal congestion, eye redness
BETA specific direct acting:
SABAs and LABAs
SABAs: short-acting B2 agonists
LABAs: long-acting B2 agonists
SABAs: list which, indications, adverse effects
albuterol, metaproterenol, terbutaline
- manage acute asthma symptoms
- adv effects: tremor, tachycardia (B1), anxiety
LABAs: list which, indications
salmeterol, formoterol, indacaterol
- manage respiratory diseases (asthma, COPD)
INDIRECT ACTING: MOA, list which
MOA: release, inhibit reuptake, or inhibit degradation of epinephrine OR norepinephrine
-amphetamine, cocaine, tyramine
indirect-acting: amphetamine
- inc non vesicular release of catecholamines (dopamine, NE) from nerve terminals
- INC BP (a1), stimulate B1 effects on heart
indirect-acting: cocaine
- block NE transporter needed for cellular reuptake of NE into adrenergic neuron by staying in synaptic cleft
- enhance SNS activity
indirect-acting: tyramine
found in fermented food (cheese and wine)
MAOA and MAOB- tyramine metabolism in small intestine
MIXED ACTION
ephedrine:
- not catechol, poor COMT and MAO substrate, LONG duration of action
- good absorption orally, penetrate CNS
- unchanged in urine
- raise systolic and diastolic BP by vasoconstriction/cardiac stim, bronchodilation
- stimulate CNS mildly: alertness, dec fatigue, prevent sleep
pseudoephedrine:
- not catechol, poor COMT and MAO substrate, LONG duration of action
- fewer CNS effects
- incomplete hepatic metabolism before elimination in urine
- used orally, treat nasal and sinus congestion, congestion of eustachian tubes
(vessels are constricted=less congestion)
