Sympath- Adrenergic Agonists- Endogenous Catecholamines Flashcards
What are the three types of Adrenergic Agonists?
1) Direct Acting ( selective and non selective)
2) Mixed acting
3) Indirect Acting
What is the Mixed Acting Adrenergic agonist?
Ephedrine
What are the 4 indirect acting Adrenergic agents?
Releasing Agents (amphetamine, tyramine)
Uptake inhibitors (cocaine)
MAOI Inhibitors (selegiline)
COMT Inhibitors (entacapone)
What are the Direct acting adrenergic Agonist groups?
Endogenous catecholamines Beta Agonists (nonselective) Beta 2-selective agonists (Short-acting) ( Long acting) (Very Long acting) Beta 3-selective agonists Alpha 1-selective agonists
What are the important direct acting Endogenous catecholamines?
Epinephrine
Norepinephrine
Dopamine
What are the important direct acting beta agonists?
Isoproterenol
Dobutamine
( non selective)
What are the beta 2 selective agonists that are short acting?
Albuterol
What are the beta 2 selective agonists that are long acting?
Sametrol
Formoterol
What are the Beta 2 selective agonists that are very long acting?
Inadacterol
Vilanterol
Olodaterol
What are Beta 3 selective agonists?
Mirabegron
What is an Alpha 1 selective agonist?
Phenylephrine
What is a mixed acting Andrenergic Agonist?
Pseudoephedrine
Ephedrine
What are indirect acting Adrenergic Agonists
Amphetamine
Dextroamphetamine
Methylphenidate
*cocaine and methamphetamine
Go over mean arterial pressure, cardiac output, and baroceptor reflex.
MAP
CO
Baroceptor Reflex
How do Adrenergic receptors affect the vasculature?
Activation of Alpha 1 =vasoconstriction
Skin,splanchnic, nasal mucosa, skeletal muscle
Activation of Alpha 2
=minor vasoconstriction
Activation of Beta 2
=vasodilation in skeletal muscle
How do adrenergic receptors affect the heart?
Beta Receptors: Beta 1 Primary
Beta 2 important in heart failure
activation leads to: increased pacemaker/ heart rate, conduction velocity, contractility. Increased cardiac output.
Alpha receptors: myocardium functionally important in heart failure.
Minor increase in contractility
Go over localization of adrenergic receptors.
Slide 12
Describe the mechanism of action of Epinephrine.
Epinephrine is an adrenergic agonist and stimulates both alpha and beta receptors.
It is a potent vasoconstrictor
What are the cardiovascular effects of Epinephrine?
Blood Pressure: increased systolic pressure/ Decreased diastolic pressure
Heart: Increased heart rate, contractile force, cardiac output.
Vasculature: construction of most vascular beds
Dilation of skeletal muscle blood vessels
See tables on slide 14/15
What are the effects of Epinephrine on the respiratory system?
Bronchodilation
What are the metabolic effects of Epinephrine
Hyperglycemia
- stimulates gluconeogenesis
Lypolysis- increased free fatty acids
What are the adverse effects of Epinephrine?
Cerebral hemorrhage because increase in BP.
Cardiac arrhythmia
Angina- in patients with coronary artery disease.
What are the contraindications of Epinephrine?
Do not give to patients on non-selective beta blockers.
Results in unopposed activation of vascular a1 receptors.
Leading to severe hypertension and cerebral hemorrhage.
What are the therapeutic uses for Epinephrine?
Hypersensitive reactions due to allergy. Epi Pen
Co-administration with local anesthetics
Increases duration of action by increasing local blood flow. ( tooth)
Bradyarrhythmias - restore rhythm in patients with cardiac arrest.
Ophthalmic uses
Mydriatic agent for ocular surgery
Glaucoma
What is the mechanism of action in Norepinephrine?
Similar to Epinephrine
Little to no action on beta 2 receptors
What are the cardiovascular Effects of Norepinephrine?
Blood pressure: increased systolic and diastolic pressure.
Heart: decreased heart rate
Increased contractile force
CARDIAC OUTPUT IS UNCHANGED
Vasculature: construction of vascular beds
Increased peripheral vascular resistance. Alpha1)
What are the adverse effects of Norepinephrine?
Bradycardia
Cardiac Arrhythmias
Severe hypertension
Necrosis at injection site ( imparted circulation)
Peripheral vascular insufficiency
- Reduced blood flow to organs
What are the therapeutic uses for Norepinephrine?
Vasoconstrictor in intensive care situations to raise or support blue pressure
Neurological injury and spinal anesthesia to raise or support blood pressure.
What is dopamine?
A Metabolic Precursor of NE and Epinephrine
An Neurotransmitter in the CNS
-Important in the regulation of movement.
What is the Mechanism of Action for Dopamine?
In low concentrations it’s an Agonist of D1 receptors
In high concentrations
Agonist of beta 1 and alpha 1 receptors
What are the cardiovascular effects of Dopamine?
Low dose: vasodilation of kidney, mesenteric, and coronary vasculature D1
Intermediate dose: beta 1
Increased heart rate and contractility
Increased systolic pressure
High dose: alpha 1
Vasoconstriction and increased peripheral vascular resistance
What are the therapeutic uses of Dopamine:
1) Severe decompensated heart failure
2) cardiogenic shock
3) septic shock
What is the mechanism of action for isoproterenol?
Potent, non selective beta agonist
Very low affinity for alpha receptors
What are the cardiovascular effects of isoproterenol?
Blood pressure: Increase the diastolic pressure
MAP will decrease
Heart: increase heart rate, contractile force, cardiac output
Vasculature: Decrease peripheral resistance
Primary in skeletal muscle and vasculature
Respiratory: Bronchodilation
What are the adverse effects of Isoproterenol?
Palpitations
Tachycardia
Headache
Flushing
Cardiac ischemia and arrhythmias more common in patients with underlying coronary artery disease
What are the therapeutic uses for isoproterenol?
Emergency stimulation of heart rate
Patients with bradycardia or heart block.
What is the mechanism of action of Dobutamine?
-isomer is an alpha1 agonist
+isomer is an alpha 1 antagonist
Both are agonists of beta receptors with the positive isomer being 10xs more effective
A race mic mixture is beta agonist
Cardiovascular effects dobutamine
Blood pressure: minor effect
Heart: increased cardiac output and contractility
Vasculature: Minimal effect on peripheral resistance
What are the adverse effects of dobutamine?
Blood pressure and heart rate may increase significantly.
Patients with Afibrillation are at risk for ventricular response.
What are the therapeutic uses for Dobutamine?
Short-term management of patients with cardiac decompensation after heart surgery, congestive heart failure, acute myocardial infarction.
What are the mechanism of action for Beta 2 selective Adrenergic receptor agonists?
Selective agonist of beta 2 receptors ( selectivity is lost at high concentrations)
Treat asthma and COPD
Administered by inhalation.
Pulmonary effects: Bronchodilation
Reduced airway inflammation
What are the adverse effects for Beta 2 selective Adrenergic receptor agonists?
Tremor
Anxiety
Tachycardia
Arrhythmia *maoi increases this
Note: likelihood of adverse effects is reduced by inhalation administration.
Name and Describe a short-acting beta 2 selective agonist.
Albuterol
Duration of action 3-6 hours
Onset of action: Bronchodilation within 15 min
Therapeutic use: Asthma
Name and describe long acting Beta2 selective agonist?
Salmetrol and Formoterol
Duration of actions 12+ hours after inhaled
Onset of action Salmeterol: slow
Formoterol: Bronchodilation in minutes
Therapeutic uses: COPD Asthma
Name and describe a beta 3 selective agonist?
Expressed in brown fat GI and bladder.
Mechanism of action: relaxation of the detrusor muscle. ( increased bladder capacity )
Adverse effects: hypertension, UTI, headache
Therapeutic use: urinary incontinence
What are **Phenylephrine and Midodrine?
Alpha 1 selective agonist:
Mechanism of action: potent, direct-acting alpha 1 Adrenergic agonist
Cardiovascular effects: increased blood pressure
Decreased heart rate
Vasoconstriction and decreased blood flow
What are the therapeutic uses of phenylephrine?
Hypotension
Nasal decongestant
Ophthalmic - Mydriatic agent
Know slide 44
Read slide 44
What is Ephedrine
Both a direct and indirect sympathomimetic:
Alpha and beta adrenergic receptor agonist
Enhances release of NE from sympathetic neurons
What are the effects of Ephedrine?
Increases blood pressured Stimulates heart rate and cardiac output Increases peripheral resistance Increase resistance to outflow of urine (alpha receptors in the base of the bladder) Bronchodilation Potent CNS stimulant
What are the adverse effects of ephedrine?
Hypertension
Insomnia
Serious adverse cardiovascular effects for this with diseases or predisposed heart conditions
What is pseudoephedrine?
A mixed acting sympathomimetic like ephedrine.
It is a direct Alpha 1 agonist.
Therapeutic use: nasal decongestant
Precursor to methamphetamine
What are indirect acting sympathomimetics?
Cocaine : Schedule 2
Amphetamine: CNS Stimulant
Describe Cocaine:
Mechanism of action: inhibits reuptake of biogenetic amines from the synaptic cleft.
Increases Blood pressure
Increases heart rate
Adverse effects: cardiac arrhythmia, myocarditis, aortic dissection, cerebral vasoconstriction
Therapeutic use: topical anesthesia of the upper respiratory tract.
What is Amphetamine and what is the mechanism of action?
Powerful CNS stimulant with peripheral sympathomimetic actions.
Mechanism of action: release biogenic amines from storage vesicles in CNS and peripheral sympathetic nerve terminals.
Inhibits vesicular monoamine transporter
VMAT
What are the cardiovascular effects of amphetamine:
Increased systolic and diastolic pressure.
Slow heart rate
Other smooth muscles: Contraction of urinary sphincter
Unpredictable GI effects
What is the therapeutic use of Amphetamines:
treatment of narcolepsy and ADHD
What are similar drugs to methamphetamine?
Methamphetamine
Methylphenidate
All are schedule 2
Narcolepsy and ADHD
