Pharm2Final Flashcards
What are the three naturally occurring catecholamines?
- epinephrine
- norepinephrine
- dopamine
What are the two synthetic catecholamines?
- isoproterenol
2. dobutamine
What are the six steps of cholinergic transmission?
- synthesis
- storage
- release via Ca++ mediated exocytosis
- binding
- degradation
- recycling
Sympathomimetic drugs have their effect on adrenergic receptors located in the _____ and _____.
CNS and the ANS
What is the nuerotransmitter for pre-ganglionic adrenergic neurons in the SNS?
Ach
What are the required neurotransmitters for sympathomimetic receptor types alpha and beta?
epi or norepi
What is the effects of alpha 1 stimulation and where are the receptors found at?
POST SYNAPTIC
vasoconstriction, mydriasis, relaxation of GI, contraction of GI sphincters, contraction of bladder sphincters
What is the effects of alpha2 stimulating and where are the receptors found?
PRESYNAPTIC-inhibition of NE
POSTSYNAPTIC-platelet aggregation, hyper polarization of cells in the CNS, sedation
Adrenergic receptors specifically bind to what two neurotransmitters?
epi and NE and they are activated by them
What is the selected agonist action of Beta 1?
increased myocardial contractility
What are 4 agents with beta 1 properties?
- isoproterenol
- dobutamine
- epi
- NE
What are 2 beta 1 antagonist?
- metoprolol
2. atenolol
What is the selected Beta 3 agonist action?
lipolysis—>”burn fat”
How is the action of catecholamines terminated?
by repute into the postganglionic sympathetic nerve endings
Sympathomimetics mimic actions of…..?
endogenous neurotransmitters, epi, NE and dopamine
Direct acting sympathomimetic agonist act on what receptors?
post-synaptic
Synthetic non-catecholamines activate adrenergic receptor how?
by evoking release of NE from POST GANGLIONIC sympathetic nerve endings
elicit mostly a and b-1 as NE is a weak b-2 agonist
Indirect acting sympathomimetics require _____ _____ to produce effect.
endogenous catecholamines; little activity if catecholamines are depleted
Do direct acting sympathomimetics require endogenous catecholamines to produce effect?
no; they activate even if catecholamines are depleted
Where is the location of the adrenergic receptors that direct acting sympathomimetics act upon?
post-synaptically on adrenergic receptors
Direct acting sympathomimetics include catecholamines and synthetic non-catecholamines(T/F)?
true
What are three uses of alpha 1 agonist?
- hypotension-to increase BP during anesthesia
- ophthalmic preparations-to induce mydrasis
- cough and cold preparations-induces constriction of nasal mucosa, decreases resistance to air flow
T/F-Direct acting alph agents-synthetic agents that directly activate alpha-1 adrenergic receptors?
true
What is the dose of Precedex?
1 mcg/kg bolus for 10 minutes
0.2 - 1 mcg/kg/hour maintenance
What are four examples of direct acting beta-1 agonist?
- dopamine
- dobutamine
- epinephrine
- isoproterenol
Stimulation of beta-1 receptors induces positive(3) effects?
- chronotropic
2, dromotropic - inotropic
How is epinephrine synthesized?
tryosine—>DOPA—>dopamine—>NE—>epi
How is epi released?
- SNS acting vai splanchnic nerves to the adrenal medulla stimulate the release of epi
- calcium triggers exocytosis of chromatin granules and realize of epi and NI into the bloodstream
Do indirect sympathomimetics act upon beta-2?
nope
What is THE adrenergic neurotransmitter?
norepinephrine
Where is NE released from?
released from presynaptic vesicles of postganglionic sympathetic nerve endings
What is the effects of NE release?
- equal to epi at beta-1 with very little beta-2 action
- potent alpha-1 producing intense vasoconstriction in arterial and venous vascular beds
- causes >SBP, >DBP, >MAP
- has no bronchodilating effects
By what action does NE increase BP?
primarily by increasing the SVR
What can be a reflex triggered by NE induced increase in SVR?
reflex bradycardia
What types of receptors does NE bind to causing stimulation of alpha and beta?
adrenergic receptors
What structure is the origin of most NE pathways in the brain?
Locus ceruleus
Is norepi released from pre-ganglionic SNS neurons or post-ganglionic?
post-ganglionic
Ach is released pre-ganglionic
What is the steroisomer of NE?
Levophed
How is NE synthesized?
synthesized in te adrenal medulla from the amino acid tyrosine
tyrosine—>L-dopa—>dopamine—>NE
How is the action of NE terminated?
either by degradation of NE or by NE UPTAKE BY SURROUNDING CELLS
After being released into the synaptic cleft, NE acts upon what type of receptors?
adrenergic
What is two ways uptake is done with NE?
- pre-synaptically
2. by non-neuronal cells in the vicinity
What is NE mechanism of action?
acts on target cells by binding to and activating adrenergic receptors.
unlike ep, NE does not activate beta-2 receptors—>just alpha-1, alpha-2 and beta-1
T or F: NE has different actions based on different cell types?
true
What types of patients is NE useful with?
NI is used to treat patients in vasodilatory shock states such as septic shock and neurogenic shock
Dopamine is a CNS neurotransmitter that is a _____ derivative.
phenethylamine
There are five types of dopamine receptors, how many of them have clinical significance?
only 2, D1,D2
Does dopamine have direct or indirect adrenergic action?
both
At what part of the NMJ does dopamine1 act and what is the affect?
POST-SYNAPTIC: vasodilation of renal, mesenteric, coronary and cerebral blood vessels
At what part of the NMJ does dopamine2 act and what is the affect?
PRE-SYNAPTIC: inhibits the release of NE
POST-SYNAPTIC: weak vasoconstricton
Dopamine actions include?
> CO
HR
SBP
Can dopamine cross the BBB?
nope
To increase dopamine in brains of patients with diseases such as Parkinson’s and dopa-responsive dystonia, _____ can be given because it crosses the BBB.
L-DOPA(levo-dopa)
Describe dopamine synthesis
synthesized by adrenal medulla —>tyrosine—>L-DOPA—>dopamine
How is dopamine stored and released?
In neurons, dopamine is packaged after synthesis into vesicles, released into synapses in response to pre-synaptic action potentials
How is dopamine inactivated?
by repute via dopamine transporter DAT
How is dopamine broken down?
by catechol-o-methyl transferase(COMT) and monoamine oxidase(MAO)
dopamine not broken down is repackaged into vesicles for reuse
Dopamine dosing?
-2-5 mcg/kg/min:
binds D1 receptors, dilating blood vessels, increasing blood flow to renal, mesenteric, coronary and cerebral arteries
-5-10 mcg/kg/min:
postitive inotropic and chronotropic effects via increased beta-1 receptor activation. Used in patients with shock or heart failure to increase CO and BP.
-10-20 mcg/kg/min:
dopamine causes vasoconstriction, increases SVR and increases BP through alpha-1 receptor activation.
By what effect does “renal dose” dopamine prob work?
by increasing the CO
McCarver not a believer in renal dose dopamine
What is the most potent activator of beta adrenergic receptors?
Isoproterenol
Does Isoproterenol directly affect the BP?
NO-has no alpha affect!
increased SBP is indirectly from greater CO, will see lower MAP and decreased DBP due to reduced SVR
What is Isoproterenol used for?
- greater HR
- increased myocardial contractility
- cardiac automaticity
- bronchodilation
- reduction in PVR
use with post heart transplant patients due to deinnervation of the orthotropic heart transplant
mostly seen in heart blocks now
What particular caution should be observed when using Isoproterenol?
caution with low DBP and reduced coronary perfusion since increased HR causes increased myocardial oxygen consumption
What is the primary use of Isoproterenol?
bradycardia and heart blocks
- resistant bradyarrhythmias when pacing is not available
- pharmacologic pacing for torsade de pointes(polymorphic ventricular tach)
can also be used as a bronchodilator(very rare)
Isoproterenol caused what three effects?
- chrontropic
- dromotropic
- inotropic
What are some contraindication for use of Isoproterenol?
angina, pre-existing arrhythmias, tachycardia or AV block caused by cardiac glycoside intoxication. Ventricular arrhythmias due to AV nodal block
*significantly increased myocardial oxygen demand—>can cause vasodilation(beta-2 effect)
What is the dose for Isoproterenol?
usual effective dose 0.-2 mcg/kg/min
What type of catecholamine is Dobutamine?
synthetic
What is Dobutamine used to treat?
Sympathomimetic used to treat CHG and cariogenic shock.
-Used to treat acute and chronic heart failure as with heart surgery, sepsis and cardiogenic shock
What is the primary action of Dobutamine?
direct stimulation of beta-1 receptors
In what specific scenario is dobutamine not useful and why?
not useful in ischemic heart disease because it may increase HR, potentially increasing myocardial oxygen demand
also: +dromotrope so be careful with atrial fibrillation as HR may markedly increase—>so prob is contraindicated in patients with A-fib
Dobutamine best used in combo with other drugs like _____ in the presence of _____.
vasodilators; increased afterload
What are the results of using dobutamine?
increased CO
decreased atrial filling pressure
increased HR
increased SBP
allegedly a coronary artery vasodilator with no endogenous catecholamine release like dopamine
Describe the racemic mixture of dobutamine.
Dobutamine is given as a racemic mixture for both + and - isomers.
-The + isomer is a potent beta-1 agonist
-the - isomer is an alpha-1 agonist
Dobutamine also has mild beta-2 agonist activity
What are the specifics on Dobutamine dosing?
- Infusion should be started at low rates, 0.5-1.0 mcg/kg/min and titrated by patients response including SBP, HR and invasive monitoring
- Optimal infusion rates typically 2-10 mcg/kg/min
- use the lowest rate you can get away with*
What are some results are usually seen with dobutamine?
- a 10-20 mm increase in SBP and increase in HR of 5-15 beats/min
- 5% of patients experience PVC’s-dose related
What is the drug classification of phenylephrine?
Synthetic non-catecholamine
What is the principal effect of phenylephrine?
- direct alpha-1 effect with only a small part via indirect release of NE
- minimal if any beta effect
venoconstriction > arterial constriction
mimics NE but is less potent and longer lasting
What cardohemodynamic effects are seen with the use of phenylephrine?
- increases SBP
- decreases CO
- lowers HR(reflex)
- raises PAP
- reduced CO most likely from baroreceptor-mediated reflex bradycardia rather than increases in after load*
- may impair LV global function when given rapidly to anesthetized patients(1mcg/kg)*
- can be used to treat SVT(500 mcg bolus)
Describe phenylephrine dosing
- IV infusion(usual initial rate): 100-180 mcg/min
- Usual maintenance rate: 20-60 mcg/min
- Max rate: infusion rates as high as 10 mcg/kg,min may be required in shock
- Adult IV bolus therapy: usual dose is 100 mcg and repeat as needed
- SVT(PSVT): 0.5 mg(500 mcg) rapid IV push, subsequent doses may be increased in increments of 0.1-0.2 mg
wean as soon as possible as will hurt end organ perfusion
What is the novelty of Precedex?
unusual in its ability to provide sedation without causing respiratory depression
What type of agonist is Precedex?
like clonidine it is an alpha-2 adrenergic agonist
By what mechanism does Precedex decrease BP?
decreases sympathetic tone, with attenuation of neuroendocrine and hemodynamic responses to surgery
reduces anesthetic and opioid requirements
What type of compound is Precedex?
imidazole compound
What type of pharmacological active isomer is Precedex?
pharmacologically active dextroisomer of medetomidine
The pharmacological isomer of Precedex causes?(4)
- hypotension
- bradycardia
- sedation
- analgesia
Other responses to the activation of alpha-2 receptors by Precedex include….
- decreased salivation, decreased secretion and decreased bowel motility
- contraction of vascular and other smooth muscle
- inhibition of renin release
- increased glomerular filtration and increased secretion of sodium and water in the kidney
- decreased intraocular pressure
- decreased insulin release from the pancreas
What are the indications for Precedex?
- indicated for sedation of critically ill and nonintubayted patients requiring sedation for surgery or procedures short-term.
- useful as an adjunct for sedation and general anesthesia
What are the contraindications of the use of Dexmedetomidine?
- no absolute contraindications
- Very expensive
- caution with boluses due to peripheral alpha-2 receptor stimulation with resulting hypertension and bradycardia(may see hypotension with loss of sympathetic tone)
- high cost relative to generic medications
Individual variablity in HR and BP effects, as well as the sedative effects of the drug
Describe the drug Methoxamine, its classification, what receptors it stimulations and why its used
- direct acting synthetic non-catecholalmine
- alpha agonist
- used in cath lab and tx for SVT
Describe the drug Clonidine, its classification, what receptors it stimulations and why its used
- direct acting
- selective alpha-2 agonist
- used for the treatment of HTN and opioid withdrawal
Describe the drug Terbutaline, its classification, what receptors it stimulations and why its used
- direct acting
- beta-2 agonist
- treatment of asthma and to slow uterine contractions
Describe the drug Albuterol, its classification, what receptors it stimulations and why its used
- direct acting
- beta-2 agonist
- acute bronchospasm
Describe the indirect adrenergic agonist Amphetamines
- resemble ephedrine in their alpha and beta receptor stimulation, however differ in their intense CNS activity
- reflects the release of NI stores in the CNS
- clinical uses include ADD, anoretics, troops in combat
- Tyramine found in fermented foods(cheese) metabolized by MAO and may cause hypertensive crisis in patients with MaOI
Is Ephedrine a direct acting synthetic non-catecholamine, or an indirect acting synthetic non-catecholamine and why?
Ephedrine is a mixed acting synthetic non-catecholamine.
- endogenous release of NE(indirect)
- Direct stimulation of adrenergic receptors
**stimulates alpha and beta receptors
What are the two affects responsible for prolonged duration of Ephedrine?
- slow inactivation
2. slow excretion
Where on the NMJ is Ephedrine active?
presynaptically causing the release of NE—>primary beta effects
What are two things that Ephedrine may cause besides the intended affects?
- mydriasis
2. CNS stimulation
Can Ephedrine be given IM?
yes
Does Ephedrine have good absorption from the stomach?
yes
The ____ of Ephedrine will be the best due to ______.
first, endogenous catecholamine depletion
What hemodynamic affects will be seen with Ephedrine administration?
- CV effects are similar to Epi except milder
- SBP increased are less intense but last 10 times longer, takes 250X an ephedrine dose to equal an epi dose
- increased SBP, DBP, HR & CO
- Renal and splanchnic blood flows are decreased(due to alpha effect), coronary and skeletal muscle blood flows are increased
What is the principle mechanism for the CV effects of Ephedrine?
- principle mechanism of CV effects is increased myocardial contractility due to activation of beta-1 receptors
- in the presence of beta blockage, predominant CV effect may be a receptor stimulation
In the beta blocked patient what effect will you primarily see when administering Ephedrine?
alpha cause they are beta blocked
Is Vasopressin an adrenergic agent? Does it bind to alpha or beta receptors?
No it is a:
- peptide hormone derived from pre-prohormones synthesized in the hypothalamus
- stored in the posterior pituitary for the release into the bloodstream or directly into the brain
What is the dose of Vasopressin and why give it?
- given as single IV dose of 40 units
- Given as an alternative to epi for treatment of shock-resistant v-fib or pulseless v-tach
used to increase SVR
What are the three arginine Vasopressin receptor types?
- AVPR1A-vasoconstriction, gluconeogenesis, platelet aggregation, coagulation
- AVPR1B-ACTH secretion in response to stress
- AVPR2-anti diuretic effect
Where are Vasopressin receptors present in the body?
brain, liver, kidney and vascular
What effect does Vasopressin have on the body?
- Vasopressin is released when the body is dehydrated, causing kidneys to conserve water by decreasing UOP
- In higher {}, vasopressin raises BP by increasing SVR
- Vasopressin increases permeability to water of distal convoluted tubules and collecting tubules in nephrons allowing water reabsorption and excretion of small volumes of more {} urine
- ANTI-DIURETIC drug
What are the hemodynamic reasons to use Vasopressin?
for hemodynamic support in septic shock
What is the dose for vasopressin?
- For shock, bolus of 0.5-20 units followed by an IV infusion rate of 0.01-0.4 units/minute
- doses above 0.04 units/minute do not consistently improve hemodynamics and may contribute to adverse events
- adding vasopressin to NE may allow reduction of NI doses
What is the blood-gas partition coefficient of Isoflurane?
1.46
