Adrenergic Drugs Flashcards
What is the precursor for catecholamines (dopamine, nor-epinephrine, epinephrine)?
what is the rate limiting enzyme for synthesis of these?
tyrosine
tyrosine hydroxylase
dopa is converted to dopamine through which enzyme?
dopa decarboxylase
dopamine is converted to nor-epinephrine through which enzyme?
dopamine ß decarboxylase
what can inactivate nor-epinephrine?
Monoamino oxidase
how is nor-epinephrine’s effect terminated?
by reuptake
Norepinephrine is degraded to metabolites by two main enzymes, what are they? and where do we find these?
in what form are catecholamines excreted from the body?
- Catechol-O-methyltransferase (COMT): cytosolic enzyme found mostly in liver
- Monoamine oxidase (MAO): localized to the outer surface of mitochondria
Vanillylmandelic acid (VMA)
what do MAO inhibitors do?
increase in the pre-junctional levles of NE
what do displacers do?
indirect acting sympathomimetics that displace the stored NE
what do reuptake inhibitors do?
indirect acting sympathomimetics inhibit the uptake into nerve cell (increases postjunctional levels/actions of NE)
what type of G protein do each of these use?
alpha 1 receptors
alpha 2 receptors
beta receptors
D1 receptors
alpha 1 receptors: Gq
alpha 2 receptors: Gi
beta receptors: Gs
D1 receptors: activates adenyl cyclase
alpha 1 receptors are mostly found where?
and what effect will it have in these places?
- vascularly: vascoconstriction (increase TPR, BP)
- pupillary dilator muscles: contraction
- prostate: contraction
alpha 2 receptors are mostly found where?
and what effect will it have in these places?
- Postsynaptic CNS adrenoceptors
- Presynaptic nerve terminals: inhibition of transmitter release (decreases sympathetics)
- vascular smooth muscle (nasal mucosa): nasal decongestion
- Fat cells: inhibits lipolysis
Beta 1 receptors are mostly found where?
What effect will it have in these places?
heart: increase FOC
JGA: release renin
D1 receptors are mostly found where?
and what effect will it have in these places?
smooth muscle: Dilates renal blood vessels
Sympathomimetics are categorized by mode of action and by the spectrum of receptors that they activate, what are these categories?
Give example of each.
- direct agonist: NE and Epinephrine, they directly activate adrenoreceptors
- indirect agonist: their actions are dependent on the release of endogenous catecholamine.
there are Two types of drugs, that are indirectly acting, which involve what?
- Displacement of stored catecholamines from the adrenergic nerve ending
* Ex: amphetamine, methamphetamine and tyramine - Inhibition of reuptake of catecholamine’s already released
* Ex: cocaine and Tricyclic antidepressant
**Drugs that have both, direct and indirect actions
Ex: ephedrine, pseudoephedrine
The net effect of a given drug in the intact organism depends on what?
- Its relative receptor affinity (α or β)
- Intrinsic activity of the drug
- The compensatory reflexes evoked by its direct actions
Name 2 alpha agonist drugs that prefer alpha 1 receptors
phenylephrine
methoxamine
Name 2 alpha agonist drugs that prefer alpha 2 receptors
Clonidine
methylnorepinephrine
Name a alpha (both 1 and 2) and beta agonist drug that prefer beta 1 receptors
norepinephrine
Name a alpha (both 1 and 2) and beta (1 and 2) agonist drug that has equal affinity for types of receptors in both type of agonist
epinephrine
name a beta agonist that has more affinity for beta 1
dobutamine
name a beta agonist that has equal affinity for beta 1 and 2
isoprotenerol
name a beta agonist that has more affinity for beta 2
terbutaline, metaproterenol, albuterol, ritodrine
name a dopamine agonist that has equal affinity to D1 and D2
dopamine
what is the Net Cardiovascular effect of sympathomimetics and baroreceptor reflexes?
Sympathomimetics with both α and β1 effects can cause a reflex increase in vagal nerve by increase in blood pressure and evoke the baroreceptor reflex.
the effect may dominate any direct beta effects on the heart rate, so that a slow infusion of norepinephrine typically causes increased blood pressure and bradycardia .
what will a pure α agonist do?
what will a pure ß-agonist do?
routinely slows heart rate via the baroreceptor reflex
almost always increases the rate.
what is the effects of sympathomimetics in blood vessels?
- alpha 1 stimulation in the skin & splanchnic vessels:
- increases peripheral vascular resistance – increasing BP
- Β2 stimulation in vascular beds in skeletal muscl:
- dilate and hence decreases BP.
- Dopamine (D1) stimulation at low doses:
- causes vasodilation in the splanchnic and renal vascular beds.
what is the effects of sympathomimetics in heart?
Direct effects on the heart are determined largely by β1 receptors
- Beta 1 receptor activation results in increased calcium influx in cardiac cells.
- positive inotropic effect
- positive chronotropic effect
- Conduction velocity in the atrioventricular node is increased
What is the effects of sympathomimetics in the CNS?
Catecholamines do NOT enter the CNS effectively
Non catecholamines enter the CNS and produces stimulant effects:
- Increased allertness, reduced fatigue, anorexia, euphoria and insomnia
- Very high doses-aggressiveness, marked anxiety and convulsions
what is the effects of sympathomimetics in the eye?
The radial pupillary dilator muscle of the iris contains α receptors
- Activation will mydriasis
α agonists can be used in treatment of what eye condition? why?
what b antagonist can be used in the same condition?
glaucoma;
- Non-selective (epinephrine) increase the outflow of aqueous humor via uveocleral veins(obsolete)
- α 2 selective agonists (Apraclonidine, brimonidine)- ↓ aqueous secretion
β antagonists (timolol) decrease the production of aqueous humor- hence can be used in treatment of glaucoma
what is the effects of sympathomimetics in lungs?
Alpha receptors:
Decongestant action of adrenoceptor stimulants
β2 receptor:
Bronchial smooth muscle causes bronchodilation
what is the effects of sympathomimetics in Genitourinary tract?
- β2 receptors in uterus: relaxation
- *good for premature labour
- bladder base, urethral sphincter, and prostate contain α (α1A) receptors:
- mediate contraction and therefore promote urinary continence.
- β2 receptors of the bladder wall: relaxation
- α-receptor activation in ductus deferens, seminal vesicles, and prostate:
- plays a role in normal ejaculation
What is the effect of activating Beta 3 receptors in fat cells?
increased lipolysis
what type of receptors can we find in pancreatic islets cells? what is the effect?
β receptors: increase release of insulin
α2 receptors: decrease release of insulin
what is epinephrine?
why is there a rise in systolic blood pressure after epinephrine is released?
A very potent vasoconstrictor and cardiac stimulant.
due to its positive ionotropic (↑FOC) and chronotropic (↑HR) actions on the heart (predominantly β1 receptors) and the vasoconstriction induced in many vascular beds (α1 receptors).
why can epinephrine cause a fall in diastolic pressure ?
Epinephrine also activates β2 receptors in skeletal muscle blood vessels, leading to their dilation. Consequently, TPR may fall
what is the dose dependent effect of epinephrine?
low epinephrine concentration:
- beta 2 agonist receptors get activated
- cause relaxation
high epinephrine concentration:
- alpha 1 agonist receptors get activated
- vascular smooth muscle contraction
what are some uses of epinephrine?
- drug of choice for treatment of acute anaphylactic reactions
- secondary drug for treatment of acute asthmatic attacks to relieve bronchospasm
- cardiac arrest and attacks of transitory atrioventricular (A-V) heart block with syncopal seizures (stokes-adams syndrome)
- Epi is combined with Lidocaine (local anesthetic) to reduce the systemic absorption of anesthetic, and increase their duration of action.
Norepinephrine will stimulate what receptors?
what happens when give through I.V?
What is the effect of ß1 stimualtion of norepinephrine?
- Stimulate α1, α2 and β1 adrenergic receptors
- increases both total peripheral resistance, as well as systolic and diastolic blood pressure, but Compensatory baroreflex activation tends to overcome the direct positive chronotropic effects of NE
- causes Positive inotropic (↑ Force of contraction or contractility) effects on the heart
what are the 2 clinical uses of norepinephrine?
- For blood pressure control in certain acute hypotensive states (e.g., pheochromocytomectomy, sympathectomy poliomyelitis, spinal anesthesia, myocardial infarction septicemia, blood transfusion, and drug reactions)
- As an adjunct in the treatment of cardiac arrest and profound hypotension
What will Isoprotenerol do?
what receptors does it target?
lowers peripheral vascular resistance, primarily in skeletal muscle but also in renal and mesenteric vascular beds.
both β1 and β2 adrenergic receptors
When is isoprotenerol used?
- cardiac arrest until electric shock or pacemaker therapy are available
- mild or transient episodes of heart block
- For bronchospasm occurring during anesthesia
What are the effects of taking isoprotenerol?
- Diastolic pressure falls.
- Systolic blood pressure may remain unchanged, rise or fall (depending on the dose)
- Mean arterial pressure typically falls;
- Cardiac output is increased because of the positive inotropic and chronotropic effect
what is dobutamine?
why is it used?
It is relatively β1-selective adrenergic agonist
inotropic support in the short-term treatment of patients with cardiac decompensation due to depressed contractility resulting either from organic heart disease or from cardiac surgical procedures
What is the effect of low dose dopamine?
- it selectively activates D1 receptors in several vascular beds (e.g. kidney) resulting in vasodilation.
- This increase in renal blood flow is of clinical significance in the treatment of shock
What is the effect of low intermediate dopamine?
dopamine activates β1 receptors in the heart.
What is the effect of low high dopamine?
dopamine activates α receptors leading to vasoconstriction
when is dopamine used as a drug?
correction of hemodynamic imbalances present in shock due to myocardial infarction, trauma, endotoxic septicemia, open-heart surgery, renal failure, and chronic cardiac decompensation as in congestive failure
what is Phenylephrine?
pure α1 agonist
what are the uses of Phenylephrine?
- Nasal decongestant to reduce the discomfort of hay fever & the common cold
- To maintain BP during spinal and inhalation anesthesia
- Used as a mydriatic.
Xylometazoline and oxymetazoline are what type of drugs?
for what are they used?
- Directly-acting α agonists.
- These drugs are used as topical decongestants because of their ability to promote constriction of the nasal mucosa.
what type of drug is Clonidine and alpha methyldopa?
α2 Selective Agonists
for what is clonidine used for?
for what is alpha methyldopa used for?
what are the side effects for both?
clonidine = Hypertension, narcotic addicts and to treat diazepam withdrawal
alpha methyldopa = Hypertension in pregnancy
Side effects: Postural hypotension, dry mouth, sedation, rebound hypertension
what are 2 derivatives of clonidine?
when are they used?
Apraclonidine, Brimonidine
Used in glaucoma
Albuterol, terbutaline, Salmeterol are what type of drugs?
which is long lasting?
what are these drugs used for?
what are the side effects of these drugs?
how are these drugs administered? (what forms?)
Selective β2 agonist
salmeterol
- To produce bronchodilation in treatment of Bronchial asthma and COPD
- Premature labor, threatened abortion
1. tremors
2. Hypokalemia
3. tachycardia
oral or aerosol
What type of drugs are amphetamines?
what effect can they have?
what do amphetamines do? (PRIMARY MECHANISM)
Give 3 examples of these drugs?
Indirect acting sympathomimetics
It has marked stimulant effects on mood and alertness and a depressant effect on appetite.
increases the release of monoamines (norepinephrine & dopamine) from their storage sites.
- Modafanil
- Dextroamphetamine (Adderall)
- Methylphenidate (Ritalin)
what are the Therapeutic uses of CNS stimulant sympathomimetics?
Narcolepsy - modafinil
Attention-deficit hyperactivity disorder (ADHD) -Methylphenidate
What is a Indirect acting sympathomimetics: Reuptake inhibitor?
cocaine
what is cocaine?
how does it work?
local anesthetic with a peripheral sympathomimetic action
inhibition of transmitter reuptake at noradrenergic synapses.
Readily enters the CNS and produces an amphetamine-like effect that is shorter lasting and more intense.
what is the main effect of cocaine in the CNS?
inhibit dopamine reuptake into neurons in the “pleasure centers” of the brain.
Give examples of Mixed-Acting Sympathomimetics?
- Ephedrine
- Tachyphylaxis
- Pseudoephedrine
- Tyramine
where do we find Pseudoephedrine?
available over the counter as a component of many decongestant mixtures.
how does tyramine get inside nerve terminals?
what happens once inside?
where can tyramine be found generally?
What happens if tyramine is taken with MAO inhibitors?
- Tyramine is taken up into nerve terminals by NET
- once inside the nerve terminal causes the release of catecholamines
- cheese, sausage, pepperoni, salami, pickled or smoked fish & yeast
- it produces effects similar to norepinephrine, and can possibly cause a hypertensive crisis (cheese reaction)
