Adrenergics Flashcards
1
Q
Sympathomimetics
- Definition
- Catecholamines
- Non-catecholamines
- Direct-acting sympathomimetics
- Indirect-acting sympathomimetics
- Mixed-acting sympathomimetics
A
- Definition
- Drugs that produce effects similar to the SNS
- Potentiate noradrenergic neruotransmission or stimulate adrenergic receptors at effector organs
- Catecholamines
- Contain a catechol nucleus (benzene ring w/ 2 hydroxyl groups) & an amine-containing sidechain (Epi, NE, & DA isoproterenol)
- Potent agonists
- Susceptible to oxidation/autoxidation
- If given orally, almost completely metabolized before reaching systemic circulation
- Non-catecholamines
- Stable
- Given orally
- Not metabolized
- Direct-acting sympathomimetics
- Adrenergic agonists acting on alpha, beta, or both adrenergic receptors
- Indirect-acting sympathomimetics
- Act pre-synaptically
- Increase catecholamine availability by…
- Releasing/displacing NE from sympathetic nerve varicosities
- Blocking the transport of NE into sympathetic neurons (e.g., cocaine)
- Blocking metabolizing enzymes (MAO, COMT)
- Mixed-acting sympathomimetics
- Release NE & act directly on adrenergic receptors (e.g., ephedrine, dopamine)
2
Q
Sympathomimetic drugs
- Direct-acting
- Non-selective (4)
- Selective (4)
- Indirect-acting (4)
- Mixed-acting (2)
A
- Direct-acting
- Non-selective
- Epinephrine (alpha1, alpha2, beta1, beta2)
- Norepinephrine (alpha1, alpha2, beta1, beta2)
- Oxymetazoline (alpha1, alpha2)
- Isoproterenol (beta1, beta2)
- Selective
- Phenylephrine (alpha1)
- Clonidine (alpha2)
- Dobutamine (beta1)
- Trebutaline (beta2)
- Non-selective
- Indirect-acting
- Releasing agent (amphetamine, tyramine)
- Uptake inhibitor (cocaine, SNRI)
- MAOIs (TCA)
- COMT inhibitors (entacapone)
- Mixed-acting
- Ephedrine (alpha1, alpha2, beta1, beta2, releasing agent)
- Dopamine (DA, beta, high dose alpha, releasing agent)
3
Q
Catecholamines
A
- Catechol + amine group
- Catechol group: high potency
- Amino group: activity
- Acute inotropes / vasopressors
- Rapid inactivation
- Metabolism or reuptake
- Short half-life
- Poor penetration into the CNS
- May have some CNS effects
4
Q
Epinephrine (Epi, adrenaline)
- Drug
- Receptors
- Pharmacological dose
- Use
- Pharmacological response depends on…
A
- Drug
- Direct-acting, non-selective
- Receptors
- beta2 >= beta1 > alpha1 >= alpha2
- Low dose: beta effects only
- Increases contractility & heart rate
- Induces bronchodilation
- Minor effects on mean BP
- High dose: alpha effects
- For cardiac arrest
- Pharmacological dose
- Increases systemic vascular resistance & diastolic BP
- Critical for perfusion of organs during CPR
- Decreases non-vital organ perfusion (splanchnic, intestinal, renal & skin)
- Use
- Initial CPR (bolus) & post-CPR stabilization (infusion)
- Anaphylactic shock
- Acute severe asthma
- Glaucoma
- Mixed w/ local anesthetics to prolong their effects
- Pharmacological response depends on…
- Ratio & sensitivity of receptors
- Penetration of circulating Epi into target organ
- Concentration fo Epi at site of action
- Level of activation at ANS
5
Q
Norepinephrine (NE, noradrenaline)
- Drug
- Receptors
- Effects
- Use
- Administration
A
- Drug
- Direct-acting, non-selective
- Receptors
- beta1 > alpha1 > alpha2
- Effects
- Arterial & venous vasoconstrictor
- Reduces renal, cutaneous, & muscle blood flow
- Little to no effect on splanchnic blood flow
- Use
- Restoration of BP in severe, acute hypotension
- Post pheocrhomocytomectomy, sympathectomy, or spinal anesthesia
- Septic shock
- Adjunctive treatment in cardiac arrest
- Restoration of BP in severe, acute hypotension
- Administration
- Only via central venous catheter b/c extravasation causes severe local tissue damage
6
Q
Dopamine (DA)
- Drug
- Receptors
- Use
- Selective agonist
A
- Drug
- Mixed-acting
- Precursor of NE + releaser of NE from nerve endings
- Receptors
- DA > beta1 >> alpha1
- Low dose: D1
- Increase splanchnic, cerebral, coronary, & renal blood flow
- Inhibit NE release
- Mid dose: beta1
- Increase cardiac contractility
- Little/no effect on BP or HR
- High dose: alpha1
- Increase BP & HR (marked tachycardia)
- Vasoconstriction
- Decrease renal & splanchnic blood flow
- Use
- Shock syndrome
- Chronic heart heart failure w/ oliguria & low/normal vascular resistance
- Selective agonist
- Fenoldopam
- Antihypertensive agent used in hypertensive crisis
7
Q
Isoproterenol (Iso)
- Drug
- Receptors
- Effects
- Use
A
- Drug
- Direct-acting, non-selective
- Receptors
- beta1 > beta2
- Effects
- Increases myocardial oxygen demand
- Unfavorable balance for O2 supply vs. demand
- Since also vasodilates & decreases diastolic pressure, may decrease coronary perfusion & provoke myocardial ischemia
- Bronchodilator
- Chronotropic: increases HR, potentiates AV conduction
- Inotropic: increases contractility & cardiac output
- Increases myocardial oxygen demand
- Use
- Beta blocker overdose
- After cardiac surgery in patients w/ prior beta-blockade
- Low contractility, low HR, high peripheral resistance
8
Q
Dobutamine
- Drug
- Receptors
- Effects
- Use
A
- Drug
- Direct-acting, selective
- Receptors
- beta1 > beta2 >> alpha1
- Effects
- Hemodynamic: increase contractility, HR, & vasodilation
- More prominent inotropic than chronotropic effects (than Iso)
- minimal effects on myocardial oxygen demand
- Favorable balance for O2 supply vs. demand
- No direct effects on renal or splanchnic blood flow
- Use
- Inotropic support in short-term treatment of cardiac decompensation
9
Q
Bronchodilators
- Drug
- Receptors
- Short-acting
- Long-acting
- Use
A
- Drug
- Selective beta2 adrenergic receptor agonists
- Receptors
- beta2
- Short-acting
- Terbutaline & albuterol
- Given via inhalation “as needed”
- Long-acting
- Salmeterol, formoterol, arfomoterol
- Given via adjunctive therapy twice a day
- Use
- COPD
- Asthma
10
Q
Tocolytic agents
- Drug
- Receptors
- Examples
- Use
- Side effects
A
- Drug
- Selective beta2 adrenergic receptor agonists
- Receptors
- beta2
- Examples
- Ritodrine
- Activates adenylyl cyclase –> increases cAMP production –> enhances Ca2+ efflux from vascular smooth muscle cells
- Decreases intensity & frequency of uterine contractions
- Terbutaline
- Ritodrine
- Use
- Delay / control premature labor
- Allow maternal transport/adminsitered steroids to work
- Don’t prevent pre-term labor
- Side effects
- Maternal & fetal tachycardia
- Palpitations
- Hypokalemia
- Hyperglycemia
- Cardiac ischemia
11
Q
Phenylephrine
- Drug
- Receptors
- Effects
- Use
- Administration
- Side effects
A
- Drug
- Direct-acting, selective
- alpha1 adrenergic agonist
- Receptors
- alpha1
- Effects
- Arterial vasoconstriction
- Vasopressor
- Use
- Nasal, mydriatic, & ophthalmic decongestant
- Administration
- IV
- Side effects
- Hemorrhoid discomfort
- Hypertension
12
Q
Clonidine
- Drug
- Receptors
- Effects
- Use
A
- Drug
- Direct-acting, selective
- Selective central alpha2 adrenergic agonist
- Receptors
- alpha2
- Effects
- Acts in vasomotor center (rostral ventrolateral medulla, RVLM) to regulate/inhibit SNS
- Sympathoinhibitory effects: reduce central sympathetic outflow & vasomotor tone
- Decreases NE releaes by activating alpha2 receptors
- Use
- Hypertension
- Hypertensive urgency
- Severe pain
- Opioid or nicotine withdrawal
13
Q
Indirectly Acting Sympathomimetics
- Mechanism
- Effects in peripheral organs
- Effects in CNS
- Use
- Releasing agents
- Uptake inhibitor
- MAOIs
- COMT inhibitors
A
- Mechanism
- Enter presynaptic nerve terminal –> activate neurotransmitter release –> increase concentrations of catecholamines in synaptic clefts –> increased sympathetic response
- May bind to an adrenergic receptor (direct agonistic activity)
- Effects in peripheral organs
- When drug doesn’t cross BBB
- beta1: induce cardiac stimulation (beta1) w/ increased contractions, tachycardia, & palpitations
- alpha1: induce vasoconstriction to increase peripheral resistance & BP, mydriasis, difficulty in micturition
- beta2: bronchodilation
- Effects develop more slowly, last longer, & attenuate w/ reptitive administrations (tachyphylaxis)
- Effects in CNS
- Increase NE –> antidepressant, vigilance, anorectic effect
- Increase DA –> antiparkinson or antidepressant effects, induce addiction
- Use
- Vasoconstrictors
- CNS stimulants
- Appetite suppressants
- Antidepressants
- Antiparkinsonism
- Releasing agents
- Amphetamine, tyramine
- Uptake inhibitor
- Cocaine, SNRI
- Drugs for ADHD
- Tricyclic antidepressants (TCA)
- MAOIs
- Selegiline
- COMT inhibitors
- Entacapone
14
Q
Drugs to Treat ADHD
- Drugs
- Adverse effects
A
- Methylphenidate (Ritalin)
- Blocks reuptake of NE & DA
- Stimulates cerebral cortex
- Dexamphetamine
- Promotes release of catecholamines (NE & DA)
- Inhibits catecholamine reuptake
- Buproprion
- Inhibits neuronal uptae of NE & DA
- Atomoxetine
- Inhibits NE reuptake
- Adverse effects (cardiovascular)
- HTN
- Arrhythmias
- QT interval prolongation
- Sudden death
15
Q
Adrenergic Crisis
- Definition
- Life-threatening because…
- Most common cause
- Other causes
- Hyper-adrenergic state is caused by…
A
- Definition
- Sudden & marked increase in circulating & extracellular levels of catecholamines (EPI = NE > DA)
- Main sources: adrenal gland & sympathetic nerve terminals
- Life-threatening because…
- Extreme tachycardia
- Severe elevation in BP (hypertensive crisis
- Most common cause
- Cocaine overdose
- Other causes
- Intoxication w/ amphetamine & other central sympathetic stimulants
- Pheochromocytoma (uncontrolled, paroxysmal hypertension)
- Ingestion of tyramine while receiving MAOIs
- Clonidine, beta blocker, opiate, & alcohol withdrawal
- Hyper-adrenergic state is caused by…
- Subarachnoid hemorrhages
- Severe pain
- Panic attack
- Myocardial infarction
