Test 2 Lectures 2-4 Flashcards
Which is the craniosacral vs. thoracolumbar division of the spinal cord? Which has longer post- or pre-ganglionic neurons?
- Sympathetic - thoracolumbar division (short pre-ganglionic cells and long-post
ganglionic cells) - Parasympathetic - craniosacral division (long pre-ganglionic cells and short
post-ganglionic cells)
A .Pre-ganglionic fibers release __________.
B. Post-ganglionic parasympathetic fibers release _________.
C. Post-ganglionic sympathetic fibers release _________.
D. Adrenal medulla releases _________and ________ (to a lesser extent) into
the circulation
E. Exceptions: Post-ganglionic sympathetic fibers that innervate sweat glands
and some skeletal muscle blood vessels that release _________.
- ACh
- ACh
- NE
- Epi, NE
- ACh
Is accommodation regulated by symp or parasymp?
Parasymp
Describe the 4 autonomic influences on the eye (symp vs. parasymp and their function)
Dilator: constrict it to open the pupil (symp)
- Could prevent aqueous humor from draining effectively or to visualize eye
Sphincter contraction would release pressure (parasymp)
- Parasymp agonists help flatten iris–aqueous humor drainage
Ciliary mm. (parasymp)
- Helps change of lens to promote accommodation
- Also helps w/promoting drainage!
Ciliary epithelium (symp)
- Makes aqueous humor
How does sympathetic activation affect HR? (what currents are affected and how?) (what phase # does this take place during?)
Sympathetic activation increases inward calcium current and the funny current to promote faster spontaneous depolarization during phase 4 of sinoatrial node action potential and lower threshold for activation
How does sympathetic activation affect heart contractility?
Sympathetic activation also stimulates greater calcium influx into myocytes during depolarization culminating in greater contractile force of the heart.
What enzyme converts dopamine to NE in vesicles?
Dopamine beta-hydroxylase
What are the 3 routes of termination of an action potential in a sympathetic neuron?
1) re-uptake into nerve terminals or post-synaptic cell
2) diffusion out of synaptic cleft
3) metabolic transformation
Where are alpha-1 receptors expressed?
What are the effects?
- Most vascular smooth muscle
- Pupillary dilator muscle
- Contracts (^ vascular resistance)
- Contracts (mydriasis)
Where are alpha-2 receptors expressed?
What are the effects?
- Adrenergic and cholinergic nerve terminals (pre-synaptically)
- Some vascular smooth muscle (like alpha-1)
- Inhibits NT release
- Contracts (^ vascular resistance)
Where are beta-1 receptors expressed?
What are the effects?
- Heart
- Juxtaglomerular cells
- Stimulates rate and force
- Stimulates renin release
Where are beta-2 receptors expressed?
What are the effects?
- Respiratory, uterine, and vascular smooth muscles
- Somatic motor nerve terminals (voluntary muscle)
- Relaxation (unlike alpha-1/2)
- Causes tremor
Where are dopamine-1 receptors expressed?
What are the effects?
- Renal and other splanchnic blood vessels
1. Relaxes (reduces resistance)
Eye – activation of dilator muscle causes ___________ (mydriasis vs miosis), innervation of ciliary epithelium
regulates production of ____________.
- mydriasis
- Aqueous humor
Constricting pupillary dilator muscle __________ drainage, while relaxation __________ drainage.
- Prevents
- Promotes
Describe the pharmacological mechanism of action of alpha-1 adrenergic receptors produces smooth m. contraction.
Binding -> Gq -> PLC -> PIP2 -> DAG + (soluble) IP3 -> Ca2+ release -> smooth m. contraction
Describe the pharmacological mechanism of action of alpha-2 adrenergic receptors reduce presynaptic NT release.
Binding -> Gi -> inhibits AC/cAMP/PKA -> reduced P’lation of presynaptic N-type Ca2+ channel -> reduced Ca2+ release -> reduced NT release (presynaptically)
Describe the pharmacological mechanism of action of beta-1 adrenergic receptors produce their effects on the heart.
Binding -> Gs -> AC/cAMP/PKA -> increased Na+ (funny current) and P’lation of L-type Ca2+ channels -> increased sarcoplasmic Ca2+ storage + release -> chronotropy (SA node cells) and inotropy (cardiomyocytes)
Describe the pharmacological mechanism of action of beta-2 adrenergic receptors reduce smooth m. contraction in the uterus, bronchioles, and vascular smooth m.
Binding -> Gs -> AC/cAMP/PKA -> P’lates (and inhibits) MLCK -> reduced affinity for Ca/calmodulin -> decreased P’lation of myosin -> reduced smooth m. contraction.
Describe the pharmacological mechanism of action of alpha-2 adrenergic receptors produce peripheral vasoconstriction.
Binding -> Gi -> inhibits AC/cAMP/PKA -> decreased P’lation of MLCK -> increased affinity for Ca/calmodulin -> P’lation of myosin -> smooth m. contraction
What are the 3 endogenous ligands for adrenergic receptors?
NE, EPI and dopamine (DA)
Recall: what degrades each of the catecholamines (NE, epi, DA) after their release?
COMT: Epi, NE, DA
MAO: NE, DA
Give the relative affinity for the alpha1 adrenergic receptor of NE, EPI, and isoproterenol
Epi ≥ NE»_space; isoproterenol (negligible binding)
Give the relative affinity for the alpha2 adrenergic receptor of NE, EPI, and isoproterenol
Epi ≥ NE»_space; isoproterenol (negligible binding)
Give the relative affinity for the beta1 adrenergic receptor of NE, EPI, and isoproterenol
Isoproterenol > epi»_space; NE
NE lacks ability to relax smooth m.
Give the relative affinity for the beta2 adrenergic receptor of NE, EPI, and isoproterenol
Isoproterenol > epi = NE
MAP =
CO x TPR
CO =
HR x SV
TPR has a predominant effect on __________ (systolic/diastolic) pressure, while CO has a predominant effect on ___________ (systolic/diastolic) pressure.
- diastolic
- systolic
What adrenergic receptors does epi have affinity for?
alpha1, alpha2, beta1, beta2
What are the BP effects of epi at LOW doses? (explain)
What are the BP effects of epi at HIGH doses? (explain)
- Epi has higher affinity for beta2 relaxing receptors (vs. alpha1 constrictors)
- Therefore, TPR slightly decreases at low dose, decreasing BP
- At high dose, there is still some beta2 receptor binding, but there are way more alpha1 (and alpha2) receptors
- Leads to robust increase in TPR and hence, BP
What are the CO effects of epi at low and high doses? (explain)
- Low dose: although TPR slightly decreases, increased Na+ (funny) and L-type Ca2+ channel release leads to increased Beta1 activation, increased chronotropy, as well as inotropy, leading to increased CO
- High dose: further increase BP (due to alpha1/2 activation) leads to further increase in CO thru same mech as above
Briefly state the bronchiolar effects of epi and what receptor they are due to.
- Bronchodilation (beta2)
2. Decreased bronchial secretions (alpha1)
Toxic effects of epi? (1)
Arrhythmia
Therapeutic uses of epi? (3)
- Anaphylaxis
- Cardiac arrest
- Bronchospasm
What adrenergic receptors does NE have affinity for?
Alpha1, alpha2, beta1
Is NE’s half-life long or short? How is it therefore administered?
- Short half-life
- Give by controlled infusion.
Explain the CV effects of NE.
- Primarily alpha1 receptor activation, leading to vasoconstriction and increased TPR (*more than w/epi because there is no vasodilating beta2 activation)
- Also inotropic and chronotropic effects due to beta1 activation
- Large increase in TPR leads to baroreceptor reflex (sinuses) that slows HR, but still overall increase in MAP
Toxicity of NE? (1)
Arrhythmia
Therapeutic use of NE? (1)
Vasodilatory shock
Contraindications of NE? (1)
Pre-existing ischemia
What receptors does DA bind?
(Looks like NE, but also binds its own receptors)
- D1, D2, alpha1, alpha2, beta1
Explain the physiological effects of DA at low, medium, and higher doses.
- Low: D1 activated, decrease in TPR
- Medium: Beta1 activated, increased contractility and HR
- High: Alpha receptors activated, further increasing BP and TPR
Dopamine:
Toxicity, therapeutic uses, and contraindications?
- Tox: hypotension (at low infusion rates), ischemia (at high infusion rates)
- Uses: Cardiogenic shock
- Contra: Tachyarrhythmias
What drug category is isoproterenol?
What degrades it?
Explain its effects.
- Non-selective beta-adrenergic agonist
- COMT
- Peripheral vasodilation (beta2), diastolic
- Transient increase in systolic BP due to positive inotropy and chronotropy (beta1, but offset by beta2 effects above)
- Bronchodilation (beta2)
Isoproterenol:
Toxicity, therapeutic uses, and contraindications?
- Tox: Tachyarrhythmias
- Uses: not often used
- Angina w/arrhythmias
What drug category is Dobutamine?
What degrades it?
Explain its effects.
- Selective beta1-adrenergic receptor agonist
- Rapidly degraded by COMT, must be infused
- Increased CO
Dobutamine:
Toxicity and therapeutic uses? (no contraindications)
Relative 1/2-life?
- Tox: hypotension
- Uses: short-term tx for CHF (1/2-life 2-3 min) or cardiogenic shock
What drug category are terbutaline and albuterol?
Explain their effects.
- Selective beta2-adrenergic agonists
- Bronchodilation (+ uterine relaxation in late pregnancy)
Terbutaline and albuterol:
Toxicity and therapeutic uses? (no contraindications)
- Tox: tachycardia (B1), muscle tremor (B2), tolerance (B2)
- Uses: bronchospams, chronic obstructive airway dz tx
What drug category is phenylephrine?
Explain its effects.
1/2-life?
- Selective alpha1-adrenergic agonist
- Increase TPR and BP
- Baroreceptor reflex decreases HR
- Dilates pupils
- Decreased bronchial and upper airway secretions
- 1/2-life less than 1 hr
Phenylephrine:
Toxicity, therapeutic uses, and contraindications?
- Tox: HTN
- Uses: Paroxysmal SVT, mydriatic agent, nasal decongestant (constricts leaky sinuses)
- Contra: HTN, V-tac
What drug category is clonidine?
Explain its effects.
- Selective alpha2-adrenergic agonist
- Peripherally, clonidine causes mild vasoconstriction and slight increase in BP
- Crosses BBB to cause reduced symp outflow, reducing vasoconstriction and BP
Clonidine:
Toxicity and therapeutic uses? (no contraindications)
- Tox: Dry mouth, hypertensive crisis (following acute withdrawal due to symp sensitization from the inhibition)
- Uses: HTN (when due to symp activation)
What are the 2 classes of indirect sympathomimetics?
- Releasing agents
2. Reuptake blockers
Name the 6 indirect sympathomimetic drugs that are known as “releasing agents”
- Amphetamine
- Methamphetamine
- Methylphenidate
- Ephedrine
- Pseudoephedrine
- Tyramine (in food)
Recall: when does tyramine cause its damaging effects?
How long is it’s 1/2-life?
Highly susceptible to degradation (Very short 1/2-life) by MAO and thus has little effect unless pt is taking MAO inhibitor (then NE builds up)
How do the 6 amphetamine-like drugs (releasing agents) work?
Amphetamine-like drugs are taken up by re-uptake proteins and subsequently cause reversal of the re-uptake mechanism resulting in release of NT in a Ca2+ independent manner.
(amphetamines P’late transpoter)
What are the CV effects of amphetamine, methamphetamine, methylphenidate,
ephedrine, pseudoephedrine, and tyramine?
- Increased TPR and diastolic BP (alphas)
- Positive inotropic and chronic tropic effects (beta1), increase systolic BP
- CNS: stimulant + anorexia
Amphetamine, methamphetamine, methylphenidate, ephedrine, pseudoephedrine, and tyramine:
Toxicity, therapeutic uses, and contraindications?
- Tox: Tachycardia (B1)
- Uses: ADHD, narcolepsy, nasal congestion (pseudoephedrine in sudafed)
- Contra: Tx w/MAOI in past 2 weeks
Name the drugs that are non-selective beta-blockers (B1 and B2), cardioselective beta blockers (B1), and partial agonists (B1 and B2)
- Non-selective: propranolol, timolol, nadolol
- Cardioselective: atenolol, metoprolol
- Partial agonists: Pindolol
(comes up again later)
Effects on HR/contractility of non-selective beta-blockers (B1 and B2), cardioselective beta blockers (B1), and partial agonists (B1 and B2)
- Non-selective: decrease
- Cardioselective: decrease
- Partial agonists: decrease, but less because of partial agonism
Effects on TPR of non-selective beta-blockers (B1 and B2), cardioselective beta blockers (B1), and partial agonists (B1 and B2)
- Non-selective: increase (unopposed constriction by alpha1)
- Cardioselective: little effect (beta2 still work to vasodilate)
- Partial agonists: may be slight decrease
Effects on renin release of non-selective beta-blockers (B1 and B2), cardioselective beta blockers (B1), and partial agonists (B1 and B2)
- Non-selective: decrease
- Cardioselective: decrease
- Partial agonists: decrease
Effects on bronchioles of non-selective beta-blockers (B1 and B2), cardioselective beta blockers (B1), and partial agonists (B1 and B2)
- Non-selective: bronchoconstriction (particularly in asthmatics)
- Cardioselective: less bronchoconstriction (but still not recommended)
- Partial agonists: Asthmatics have a reduced
capacity to dilate bronchioles.
Effects on glucose metabolism of non-selective beta-blockers (B1 and B2), cardioselective beta blockers (B1), and partial agonists (B1 and B2)
- Non-selective: masks sx of hypoglycemia (due to epi release)
- Cardioselective: little effect
- Partial agonists: reduced response to epi (since partial response)
What drug category are propranolol, nadolol, and timolol?
Explain their effects.
- Non-selective beta-blockers
- Decreased HR and contractility
- Reduced renin release (therefore reduced vasoconstriction)
- Inhibition of aqueous humor production
Propranolol, nadolol, and timolol:
Toxicity, therapeutic uses, and contraindications?
- Tox: Bronchospasm, masks sx of hypoglycemia (blocks epi), bradycardia, increased triglycerides
- Uses: HTN, angina, glaucoma, early to mod heart failure, arrhythmia
- Contra: Bronchospasm during asthma, sinus bradycardia, 2nd and 3rd degree heart block, cardiogenic shock
What drug category are metoprolol, atenolol, esmolol?
Explain their effects.
Which is short-acting?
- Cardioselective beta1 blockers (reduced resp side-effects)
- Decrease HR and contractility
- Reduced renin release
- Decreased symp activation
- Esmolol is short-acting (emergent use)
Metoprolol, atenolol, esmolol:
Toxicity, therapeutic uses, and contraindications?
- Tox: Hypotension, bradycardia
- Uses: HTN, angina, arrhythmia
- Contra: sinus bradycardia, 2nd/3rd degree heart block, cardiogenic shock
What drug category is pindolol? (when would you use it over other beta-blockers?)
Explain its effects.
- Partial agonist beta-blocker (*used when symp activity is high)
- Decrease BP
- Decrease contractility
- Reduced renin release
- Decreased symp activation
Pindolol:
Toxicity, therapeutic uses, and contraindications?
- Tox: hypotension
- Uses: HTN
- Contra: sinus bradycardia, 2nd/3rd degree heart block, cardiogenic shock
What drug category are phentolamine and phenoxybenzamine? (how are they different)
Explain its effects.
- Non-selective alpha-blockers (phentolamine is reversible, phenoxybenzamine is irreversible)
- Decrease BP (alpha blockage + unmasks beta effects)
- Increased chronotropy and inotropy
Phentolamine and phenoxybenzamine:
Toxicity and therapeutic uses? (No contraindications)
- Tox: prolonged HTN, reflex tachycardia
- Uses: HTN associated w/pheochromocytoma, vasoconstrictor-induced extravasation
What drug category are prazosin, doxazosin, and terazosin?
Explain its effects.
- Selective alpha1-receptor blockers
- Inhibit vasoconstriction (less cardiac stimulation than non-selective alpha-blockers cuz alpha2 still works)
- Prostate smooth m. relaxation
Prazosin, doxazosin, and terazosin:
Toxicity and therapeutic uses? (No contraindications)
- Tox: Orthostatic HTN
- Uses: HTN, BPH
List the two adrenergic receptors that are expressed on the pre-synaptic membrane of both noradrenergic and non-noradrenergic nerve terminals and describe how their activation influences NT release
- Alpha2 (inhibits NT release)
- Beta2 (causes tremor)
What are the relative 1/2-lifes of the catecholamines?
All short
How do the 1/2-lives of propranolol, nadolol, and timolol differ?
Propranolol and timolol: 4 hrs
Nadolol: 20-24 hrs
What’s another name for ephedrine?
What is the relative 1/2-life of ephedrine/norephedrine?
What degrades them?
Adrenaline chloride
- Relatively short 1/2-life
- COMT for ephedrine, COMT and MAO of norephedrine
