Adrenergic Agonists (8-19/20/21-15) Flashcards
Epinephrine
- Indication: Anaphylaxis, shock, cardiac arrest & heart block
- MOA: a1, a2, B1, B2 agonist (low dose: B1/B2; high dose: B1 + A1/A2)
- Elimination: COMT - urine
- 1/2 life: short
- Contraindications: Late term pregnancy due to unpredictable effects on blood flow
- Toxicity/side-effects: Arrhythmias
low dose: B effects predominate, B1 = + ionotropic and chronotropic effects (higher systolic (CO)), B2 = vasodialtion (lower diastolic (TPR)) and bronchodilation; high dose: A1 vasoconstriction (inc TPR) and decrease bronchial secretions
Low dose: inc PP
High dose: same PP
Norepinephrine
- Indication: Acute HYPOtension due to VASODILATORY shock (treat hypotension; septic shock)
- MOA: a1, a2, B1 agonist (stimulates A1/A2 and B1, NOT B2 (therefore no effect on bronchioles))
- Elimination: MOA & COMT - urine
- 1/2 life: short
- Contraindications: Pre-existing excessive vasoconstriction and ischemia
- Toxicity/side-effects: Ischemia
B1: increased inotropic and chronotropic effects on heart (systolic, CO); A1: vasoconstriction (inc diastolic, TPR), Decrease HR (baroreflex), Overall increase in MAP
Dopamine
- Indication: HYPOtension due to low cardiac output during CARDIOGENIC SHOCK
- MOA: B1, B2 agonist; D1, D2 agonist; some a1, a2 agonist activity (D1/B1 at low dose, see A1/A2/B1 at high dose)
- Elimination: MOA and COMT
- 1/2 life: ~2 mins
- Contraindications:
- Toxicity/side-effects: low infusion rate=low BP due to D1 effect; high infusion rate= Ischemia
low dose: D1 decrease TPR; medium dose: B1 increase CO and HR; at higher dose: A1/A2 increase BP and TPR (binds D1/2, B1, A1/2)
low dose D1 actions make it not entirely like NE
Isoproterenol
(Sympathomimetic)
- Indication: Transient heart block; bronchospasm during anesthesia
- MOA: B1, B2 agonist (non-selective)
- Elimination: COMT - urine
- 1/2 life: short
- Contraindications: Angina, particularly with arrhythmias
- Toxicity/side-effects: Tachyarrhythmias
(Infrequently used because of available better selective B2 agonists)
Potent B-receptor agonist with no appreciable affinity for a-receptors. Catecholamine structure -> susceptible to degradation. Cardio effects: B2-receptor activation promotes peripheral vasodilation, decreased diastolic BP; B1-receptor - positive inotropy and chronotropy -> transient increased systolic BP. Overcome by vasodilatory effect.
- Overall: small decrease in MAP which may contribute to further reflex HR increase. Bronchiole effects: B2-receptor - bronchodilation.
- Note on use: cardiac stimulation during bradycardia or heart block when peripheral resistance is high.
Dobutamine
(Synthetic catecholamine; sympathomimetic)
- Indication: Short term rx for low cardiac contractility (also, heart failure & cardiogenic/septic shock)
- MOA: B1 agonist (selective; B1 > B2 > a)
- Elimination: COMT - urine
- 1/2 life: 2-3 mins (so given by IV)
- Contraindications: ???
- Toxicity/side-effects: Arrhythmias, hypotension (vasodilation), HTN (inotropic & chronotropic effects)
Rapidly degraded by COMT. Cardio effects: increased CO, usually little effect on peripheral vasculature or lung; unique in that positive inotropic effect > positive chronotropic effect due to lack of B2-mediated vasodilation & reflex tachycardia. However, no agonist is purely selective -> at higher doses, B2-agonist activity may cause hypotension w/ reflex tachycardia.
Terbutaline
(Sympathomimetic)
*Indication: Prevent and reverse bronchospasm in asthma, bronchitis and emphysema
*MOA: B2 agonist (selective)
Elimination: Urine
1/2 life: 2.9 hrs
*Contraindications: none given, remember that B2 is also found on MN terminals
*Toxicity/side-effects: Tachycardia, tolerance, activation of B2-receptors expressed on pre-synaptic nerve terminals of cholinergic somatomotor neurons increases release of neurotransmitter -> can lead to a muscle tremor, a side-effect of B-agonist therapy.
Cardio effects: negligible in most pts due to lack of B1 activity. However, can cause some B1 agonist-like response. Bronchioles: bronchodilation. Pregnant uterus: relaxation.
tremor: B2 expressed on pre-synaptic nerve terminals of cholinergic somamtomotor neurons causing inc NT release
Albuterol
(Sympathomimetic)
*Indication: Bronchial SM relaxation
*MOA: B2 agonist (selective)
Elimination: Urine
1/2 life: 5 hrs
*Contraindications: none given, remember that B2 is also found on MN terminals
*Toxicity/side-effects: Tachycardia, tolerance, activation of B2-receptors expressed on pre-synaptic nerve terminals of cholinergic somatomotor neurons increases release of neurotransmitter -> can lead to a muscle tremor, a side-effect of B-agonist therapy.
Cardio effects: negligible in most pts due to lack of B1 activity. However, can cause some B1 agonist-like response. Bronchioles: bronchodilation. Pregnant uterus: relaxation.
tremor: B2 expressed on pre-synaptic nerve terminals of cholinergic somamtomotor neurons causing inc NT release
Phenylephrine
(NOT a catecholamine)
*Indication: Pressor agent for anethesia; nasal congestion; dilate pupil for eye exam; supraventricular tachycardia (SVT)
*MOA: a1 agonist (selective)
Elimination: MAO
*1/2 life: LONGER DOA)
*Contraindications: HTN
*Toxicity/side-effects: HTN
Peripheral vasoconstriction and increased BP; activates baroreceptor reflex and therby decreases HR. Dilates pupil. Decreases bronchial (and upper airway) secretions. **Note on use: hypotension during anesthesia or shock, paroxysmal SVT, mydriatic agent, nasal decongestant. Also, bc it is NOT a catecholamine: NOT SUBJECT to rapid degradation by COMT -> metabolized more slowly -> much longer duration of action than endogenous catecholamines.
Clonidine
(Sympathomimetic)
*Indication: HTN (when cause is due to excess sympathetic drive); analgesia
*MOA: a2 agonist (selective)
Elimination: Urine
1/2 life: 12-16 hrs
*Contraindications: ???
*Toxicity/side-effects: Dry mouth, sedation, bradycardia, withdrawal after chronic use can result in life-threatening HTN crisis (increases sympathetic activity)
Peripherally causes mild vasoconstriction & slight increase in BP; also crosses BBB to cause reduced sympathetic outflow -> reduces vasoconstriction and BP. The loss of sympathetic activity predominates over the direct vasoconstrictor effects of the drug, leading to overall reduction in BP. Activation of a2-receptors on pre-motor neurons that normally provide tonic activation of sympathetic pre-ganglionic cells reduces pre-motor neural activity by unknown mechanism. Reduction of tonic excitatory input to the sympathetic cells reduces sympathetic output to the vascular smooth muscle.
Amphetamine
(ADDERRALL) (Indirect sympathomimetic)
*Indication: ADHD
*MOA: Indirect sympathomimetic
Elimination: Urine
1/2 life: 10-13 hrs
*Contraindications: HTN, severe atherosclerosis, hx of drug abuse, Rx with MAO inhibitors w/in past 2 wks
*Toxicity/side-effects: Anxiety, tachycardia
(Enters CNS readily & has stimulant activity)
Increase concentration of endogenous catecholamines in the synapse and circulation -> activation of adrenergic receptors. This occurs via either 1) release of cytoplasmic catecholamines or 2) blockade of reuptake transporters. Most are resistant to degradation by COMT and MAO -> have relatively long 1/2 lives (except for tyramine). Amphetamine-like drugs are taken up by reuptake proteins and subsequently cause reversal of the re-uptake mechanism -> release of NT in a Ca-independent manner -> increase in synaptic NE. Readily cross the BBB -> high abuse potential due to reinforcing effects of central dopamine release. Cardio effects: due to NE release, a-adrenergic receptor activation causes peripheral vasoconstriction and increased diastolic BP; B-receptor activation of heart leads to positive inotropy and increased conduction velocity and increased systolic BP; increased BP can cause decreased HR due to baroreceptor activation, but this can be masked by direct chronotropic effect. CNS effect: stimulant, anorexic agent.
*Note: drugs in this category are sometimes also used for narcolepsy.
Methylphenidate
(RITALIN) (Indirect sympathomimetic)
*Indication: ADHD
*MOA: Indirect sympathomimetic
Elimination: Urine
1/2 life: 2-3 hrs
*Contraindications: HTN, severe atherosclerosis, hx of drug abuse, Rx with MAO inhibitors w/in past 2 wks
*Toxicity/side-effects: Anxiety, tachycardia
(Enters CNS readily & has stimulant activity)
Increase concentration of endogenous catecholamines in the synapse and circulation -> activation of adrenergic receptors. This occurs via either 1) release of cytoplasmic catecholamines or 2) blockade of reuptake transporters. Most are resistant to degradation by COMT and MAO -> have relatively long 1/2 lives (except for tyramine). Amphetamine-like drugs are taken up by reuptake proteins and subsequently cause reversal of the re-uptake mechanism -> release of NT in a Ca-independent manner -> increase in synaptic NE. Readily cross the BBB -> high abuse potential due to reinforcing effects of central dopamine release. Cardio effects: due to NE release, a-adrenergic receptor activation causes peripheral vasoconstriction and increased diastolic BP; B-receptor activation of heart leads to positive inotropy and increased conduction velocity and increased systolic BP; increased BP can cause decreased HR due to baroreceptor activation, but this can be masked by direct chronotropic effect. CNS effect: stimulant, anorexic agent.
*Note: drugs in this category are sometimes also used for narcolepsy.
Ephedrine
(Indirect sympathomimetic)
*Indication: Pressor agent with anesthesia (Also used to tx chronic orthostatic HYPOtension)
*MOA: Indirect sympathomimetic
Elimination: Urine
1/2 life: 3-6 hrs (Resistant to degradation by COMT & MAO -> longer DOA)
*Contraindications: HTN, severe atherosclerosis, hx of drug abuse, Rx with MAO inhibitors w/in past 2 wks
*Toxicity/side-effects: Anxiety, tachycardia
(Continued use -> tachyphylaxis may develop; also, penetrates the brain -> CNS stimulation!)
Increase concentration of endogenous catecholamines in the synapse and circulation -> activation of adrenergic receptors. This occurs via either 1) release of cytoplasmic catecholamines or 2) blockade of reuptake transporters. Most are resistant to degradation by COMT and MAO -> have relatively long 1/2 lives (except for tyramine). Amphetamine-like drugs are taken up by reuptake proteins and subsequently cause reversal of the re-uptake mechanism -> release of NT in a Ca-independent manner -> increase in synaptic NE. Readily cross the BBB -> high abuse potential due to reinforcing effects of central dopamine release. Cardio effects: due to NE release, a-adrenergic receptor activation causes peripheral vasoconstriction and increased diastolic BP; B-receptor activation of heart leads to positive inotropy and increased conduction velocity and increased systolic BP; increased BP can cause decreased HR due to baroreceptor activation, but this can be masked by direct chronotropic effect. CNS effect: stimulant, anorexic agent.
*Note: drugs in this category are sometimes also used for narcolepsy.
Pseudoephedrine
(SUDAFED) (Indirect sympathomimetic)
*Indication: Nasal decongestion
*MOA: Indirect sympathomimetic
Elimination: Liver
1/2 life: 4.3-8 hrs
*Contraindications: HTN, severe atherosclerosis, hx of drug abuse, Rx with MAO inhibitors w/in past 2 wks
*Toxicity/side-effects: Anxiety, tachycardia
(Isomer of ephedrine)
Increase concentration of endogenous catecholamines in the synapse and circulation -> activation of adrenergic receptors. This occurs via either 1) release of cytoplasmic catecholamines or 2) blockade of reuptake transporters. Most are resistant to degradation by COMT and MAO -> have relatively long 1/2 lives (except for tyramine). Amphetamine-like drugs are taken up by reuptake proteins and subsequently cause reversal of the re-uptake mechanism -> release of NT in a Ca-independent manner -> increase in synaptic NE. Readily cross the BBB -> high abuse potential due to reinforcing effects of central dopamine release. Cardio effects: due to NE release, a-adrenergic receptor activation causes peripheral vasoconstriction and increased diastolic BP; B-receptor activation of heart leads to positive inotropy and increased conduction velocity and increased systolic BP; increased BP can cause decreased HR due to baroreceptor activation, but this can be masked by direct chronotropic effect. CNS effect: stimulant, anorexic agent.
*Note: drugs in this category are sometimes also used for narcolepsy.
Tyramine
(Indirect sympathomimetic)
*Indication: n/a, in diet; NOT THERAPEUTIC
*MOA: Displaces NE -> increases concentration of NE in synapse & circulation
Elimination: MAO
*1/2 life: Normally very short
*Contraindications: HTN, severe atherosclerosis, hx of drug abuse, Rx with MAO inhibitors w/in past 2 wks
*Toxicity/side-effects: Anxiety, tachycardia
Increase concentration of endogenous catecholamines in the synapse and circulation -> activation of adrenergic receptors. This occurs via either 1) release of cytoplasmic catecholamines or 2) blockade of reuptake transporters. Amphetamine-like drugs are taken up by reuptake proteins and subsequently cause reversal of the re-uptake mechanism -> release of NT in a Ca-independent manner -> increase in synaptic NE. Readily cross the BBB -> high abuse potential due to reinforcing effects of central dopamine release. Cardio effects: due to NE release, a-adrenergic receptor activation causes peripheral vasoconstriction and increased diastolic BP; B-receptor activation of heart leads to positive inotropy and increased conduction velocity and increased systolic BP; increased BP can cause decreased HR due to baroreceptor activation, but this can be masked by direct chronotropic effect. CNS effect: stimulant, anorexic agent.
