Adrenergic Drugs Flashcards
How does the composition interstitial fluid compare to sea water?
Very similiar
How does the concentrations of solutes in the cytoplasm of a human cell compare to interstitial fluid and sea water?
Na much lower
K much higher
Ca exponentially lower
Cl lower (been replaced by proteins)
What is a minor component of the resting potential of a cell?
Ion flux from the NaK ATP-ase pump
What is a major component of the resting potential of a cell?
The different membrane permeabilities of Na and K
Is there more Na or K permeability in a cell?
K is 100x more permeable than Na
How long does the the efflux of K continue?
The net efflux of K+ out of the cell (due to the concentration gradient) continues until the electrical force leading K+ outside is balanced by the electrical force of Cl- bringing it back
What is the significance of membrane potential?
Changes in membrane potential in nerve and muscles above a threshold lead to an AP
What would happen in a cell, if it suddenly became permeable to Na in a location?
At that site, the Na channel would counteract the K current, leading to depolarization
Voltage gated channels
Special membrane proteins on excitable cells
Open or close based on the potential differences across the membrane
Do K or Na voltage gated channels respond quicker?
Na voltage gated channels respond quicker
K voltage gated channels respond slower
How do the rates of AP compare in cardiac tissue, nerves, or skeletal muscle?
Cardiac AP are much slower to prevent tetanic contraction
What are the steps of synaptic transmission?
1) AP reaches the terminal and Ca channels open
2) Ca entry leads to transmitter release
3) Receptors open Na channels and AP occurs on post-synaptic cell
What makes up the central nervous system?
Brain and Spinal cord
What makes up the peripheral nervous system?
Nerves and ganglia outside the brain and spinal cord
What are the divisions of the peripheral nervous system?
Efferent
Afferent
What are the divisions of the efferent nervous system?
Somatic nervous system
Autonomic nervous system
Somatic nervous system
Motor innervation of all skeletal muscles
Autonomic nervous system
Sympathetic and parasympathetic divisions
Motor innervation of smooth muscle, cardiac muscle, and glands
Efferent nervous system
Projects from the CNS to targets and elicits appropriate responses from the target
Afferent nervous system
Projects from the target to the CNS to provide information
What are the divisions of the afferent nervous system?
Somatic sensory
visceral sensory
Somatic sensory system
Senses the external environment
Made up of general and special divisions
Visceral sensory system
Senses the internal environment
What is homeostasis?
Ability of a higher animal to maintain internal stability
What divisions of the nervous system are responsible for maintaining homeostasis?
The autonomic nervous system and endocrine system
What are the differences in the regions of origin of the sympathetic and parasympathetic ns?
Sympathetic = thoracolumbar region Parasympathetic = Craniosacral region
What are the differences in the locations of ganglia of the sympathetic and parasympathetic systems?
Sympathetic = close to the spinal cord Parasympathetic = close to the target organs
What are the differences in the length of postganglionic fibers of the sympathetic and parasympathetic fibers?
Sympathetic = long Parasympathetic = short
What are the differences in the postganglionic branching of the sympathetic and parasympathetic fibers?
Sympathetic = lots, so multiple organs can be mobilized at once Parasympathetic = very little branching
What are the primary neurotransmitters of the sympathetic system? What do they target?
Epinephrine (via blood)
Norepinephrine (post-ganglionic neuron)
They target adrenergic receptors
What is the primary neurotransmitter of the parasympathetic system? What receptors do they target?
Acetylcholine
Targets muscarinic receptors
What is the primary neurotransmitter of the somatic system? What receptor is targeted?
Acetylcholine
Targets nicotinic receptors
T/F - Most organs have both sympathetic and parasympathetic innervation?
True - So multiple transmitters and classes of drugs that affect the functioning of the organ
This will influence the effect of a given autonomic drug on a given target organ
What happens to adrenergic transmitters in the synapse?
Transmitter is transported back in the postsynaptic terminus?
Drugs can prevent them from being brought back in
What happens to cholinergic transmitters in the synapse?
Neurotransmitter is hydrolyzed in the synapse
T/F - AP continues once it reaches the target organ?
False - Once the AP reaches the target, it’s going to make the organ do something
What are the major types of adrenergic amines?
Dopamine
Norepinephrine
Epinephrine
Where are dopamine receptors located?
CNS
Kidney
Smooth muscles in the periphery
What are the major types of adrenergic receptors?
a1, a2, B
What are the a1 receptor subtypes?
a1(A, B, D)
What are the a2 receptor subtypes?
a2(A, B, C)
What are the B receptor subtypes?
B1, B2, B3
What are the most important adrenergic receptors in the PNS?
a1, B1, B2
Where are adrenergic receptors located?
CNS
Target organs of the sympathetic ns
Where are a1 receptors located?
Smooth muscle cells
What do a1 receptors do when stimulated?
Increase Ca
This increases the activity of MLCK, which increases MLC phosphorylation
This all ultimately increases smooth muscle contractility
What do a2 receptors do?
They are most important on presynaptic termini
Inhibit epinephrine and norepinephrine release in the CNS and PNS
-they sense how much epi and norepi are around, if there’s too much, they prevent them from being released
What will an a2 agonist do?
Attenuate CNS response
Vasodilate
Decrease HR
What will an a2 antagonist do?
Enhance CNS response
Vasoconstrict
Increase HR
What will an a1 agonist do?
Vasoconstrict
Produce contraction of vascular smooth muscle
What will an a1 antagonist do?
Vasodilate
Where are B2 receptors located?
Smooth muscle cells
What will B2 receptors do when stimulated?
This will activate K channels, leading to hyperpolarization, a reduction of Ca, and muscle relaxation due to the activity of MLCK
Where are B1 receptors located?
Cardiac muscle cells
What will B1 receptors do when stimulated?
Activate PKA and L-type Ca channels - increasing Ca levels and muscle contractility
What will a B1 agonist do?
Improve contractility of the failing heart
Increase HR
What can excess of a B1 agonist cause?
Arrhythmias
What will a B2 agonist do?
Lead to vascular and non-vascular smooth muscle relaxation
Reduce BP, bronchodilation, reduce uterine contraction
What receptors does epinephrine activate?
a, B1, B2
What receptors does norepinephrine activate?
a and B1
does not activate B2
What does systemic effects of endogenous agonists depend on?
Administration and dose
A decrease in concentration leads to a decrease in receptor stimulation
What are the cardiac effects of epinephrine and norepinephrine?
Mainly B1 effects
What are the smooth muscle effects of epinephrine and norepinephrine?
Usually relaxation mediated by B2 receptors
GI decreased motility
Bronchodilation
However, a receptors mediate sphincter contraction
What are the effects on salivary glands of epinephrine and norepinephrine?
Modest secretion with a high concentration of protein
Mainly a1 and B1, but some B2 - protein secretion comes from B1
What are the effects of epinephrine and norepinephrine on the CNS, when administered peripherally?
Nothing - does not cross the blood-brain barrier
What is anaphylaxis?
Severe whole body response to an allergen
Includes smooth muscle constriction, vasodilation (severe hypotension), and increased vascular permeability
Why is epinephrine used to treat anaphylaxis?
Standard emergency treatment
Stimulates a receptors (increase BP)
Stimulates B1 receptors (positive cardiac effects)
Stimulates B2 receptors (bronchodilation)
What are major examples of a1 agonist drugs?
Levonordefrin
Metarminol
Levonordefrin
Sometimes used in conjunction with local anesthesia
Metarminol
Used to treat hypotension during surgery
Why is epinephrine or levonordefin used in conjunction with local anesthetics?
1) Prolong the duration of the nerve block, and improve the likelihood of its success
2) Diminish systemic toxicity of anesthesia
3) Minimize blood loss during surgical procedures
(these are all due to their hypertensive effects)
What can a2 agonist drugs be used for?
Treat hypertension via autonomic regulation of the cardio system
Muscle relaxants
ADHD treatment
Sedative
What conditions can B1 agonist drugs be used for?
Primarily heart failure and cardiogenic shock via direct stimulation of B1 receptors
What conditions can B2 receptor agonists be used for
Respiratory diseases (mainly) can also be used to produce vasodilation in muscle and liver, and relaxation of uterine tissue
What can dose related complications come from?
- Too large a dose
- accidental IV injection
- heightened sensitivity
- patient cardiovascular disease
What can a1 antagonists be used to treat?
Therapies relating to antagonism of vascular smooth muscle constriction
- hypertension
- pulmonary hypertension
- hemodynamic shock
- Rynaud’s disease
Antagonism of bladder smooth muscle contraction
-Benign prostatic hyperplasia
What are the major examples of a1 antagonists?
Prazosin Terazosin Doxazosin Alfuzosin Tamulosin
Why might Prazosin be more beneficial? Why might Terazosin or Doxazosin be more beneficial?
Prazosin is the first a-selective antagonist
Terazosin and Doxazosin have longer half lives and only need to be taken once a day
All are used to treat hypertension
Alfuzosin
Acts primarily on the smooth muscle of prostate (BPH drug)
Likely to reflect the selective accumulation in prostate tissue
Tamulosin
Specific for a1A and a1D receptors and selective for prostate
Effective to treat BPH
Does not increase BP
(a1 antagonist)
What do non-selective a-adrenergic receptor antagonist do?
Block the transmitter mediated feedback loop
What do agonists of B3 do?
Produce vasodilation
What do antagonists of B3 do?
No clinical use
Why are B-blockers either non-selective (B1 and B2) or B1 specific?
Blockage of B2 would be undesirable in airway smooth muscle, vascular smooth muscle, and endocrine cells
What is the cardiac effect of B-blockers?
Decrease HR and force of contraction of the heart
What is the blood pressure effect of B-blockers?
Diminish renin release form the kidney.
Renin is important in BP regulation, and therefore the diminish of renin drops BP
Cardiac effects may indirectly contribute to this drop as well
Intrinsic Sympathomimetic Activity (ISA)
Some B-blockers have a slight ISA, and the consequence is low B stimulation
They have a high affinity for B-receptors, but no or low capacity to activate the receptors
B-blockers without ISA
Decrease resting HR, plasma renin activity, and cardiac output
B-blockers + ISA
Do not depress cardiac function or plasma renin activity as well as without ISA
But they do attenuate against increases
What can B-blockers be used to treat?
Hypertension Ischemia Heart disease Post-MI Congestive heart failure Arryhthmias Glaucoma (In CNS) - Migraines and tremors associated with anxiety
T/F - some drugs are both a and B antagonists
True
Labetalol and Carvedilol
Labetalol
7x as potent as normal B-blocker
ISA activity
Used in long term management of hypertension
Carvedilol
No ISA affect
Effective treatment of congestive heart failure
Antioxidant activity
What are adverse effects of B-blockers on the heart?
Bradycardia
AV block
Withdrawal can lead to angina, myocardial infarction, or death
What are adverse effects of B-blockers on smooth muscle?
Non-selective blockers can reduce vasodilation responses
Increased bronchospasms
What are adverse effects of B-blockers on the CNS?
Depression Fatigue Sleep disturbance Hallucination Dizziness
What dental adverse effect can a-blockers have?
Orthostatic hypotension
-special care should be taken to prevent an accident
What should dentists be aware of with a patient taking B-blockers?
More at risk for hypertensive episode after receiving with vasoconstrictor
What adverse dental effect does Clonidine have?
Causes Xerostomia
