#9 & #10 Adrenergic Pharmacology Flashcards
Ionic composition of blood is similar to _____.
Sea water
What is the minor component in establishing a resting potential?
ionic flux form Na+ K+ ATPase pump activity
What is the major component in establishing a resting potential?
the potential arising from the different membrane permeabilities
K+ is _____ times more permeable than Na+, Why is this important?
100x
* Important because, the net efflux of K+ continues until the chemical force leading K+ outside is balanced by the electrical force bringing it back!
What would happen in a cell if it suddenly became permeable to Na+ at one location?
At the site, the Na+ current would counteract the K+ current, leading to depolarization (Remember that permeability of K+ produced hyper-polarization in the first place) Yet further away from the perturbation , the effect is lost.
*THIS IS TRUE WITH NON -EXCITABLE CELLS?
AP’s in cardiac tissue are much _____ than in nerve or muscle.
Slower *KNOW THE GRAPHS!
_______ Projects from the CNS to targets and elicits an appropriate response from the target (like raise in BP)
Efferent division (of peripheral nervous system)
__________ Projects from target to CNS and provides sensory info.
Afferent division of PNS
What is Homeostasis?
The tendency of a higher animal to maintain internal stability in response to stimulus that would the to disrupt its normal condition or function
____ and ____ are primarily responsible for maintaining homeostasis.
Autonomic nervous system and the endocrine system.
*Boatloads of drugs developed to augment or block process.
Autonomic nervous system regulates and coordinates what 3 things?
- Smooth muscle
- Heart
- Secretory glands * can actually regulate themselves but affected by the ANS
Sympathetics come from the ____ region.
Thoracolumbar
Parasympathetics come from the _____ region.
Craniosacral
At the effector site, what are the main neurotransmitters of the sympathetic system?
Epinephrine and Norepinephrine
At the Effector site, what are the main neurotransmitters of the Parasympathetic system?
Acetylcholine (Muscarinic receptors)
At the Effector site, what are the main near transmitters of the Somatic system?
acetylcholine (nicotinic receptors)
Localized depolarization leads to ______.
Resumption of AP
What happens to neurotransmitter in adrenergic transmission?
Transmitter is transported back into the presynaptic terminus
What happens to the neurotransmitter in Cholinergic Transmission?
Neurotransmitter is hydrolyzed in the synapse
Tyrosine leads to _______ to ______ to _______ to ______.
Tyrosine -> dopamine -> Norepinephrine -> Epinephrine
What are the types of Dopamine receptors?
D1-D5
Where are dopamine receptors found?
In the CNS and Periphery (kidneys and some smooth muscle)
What are the 3 major adrenergic receptors?
Alpha 1 and 2 (a,b and c) in each type
Beta (1,2 and 3)
Where are adrenergic receptors found?
In the CNS and target organs of the sympathetic PNS.
What is the relationship between structure and function?
Changes in structure can lead to changes in function.
What do Alpha 1 receptors do on smooth muscle cells?
- Increase Ca++
- Increase activity of myosin light chain kinase
- Increase myosin light chain phosphorylation
- increase muscle contractility
What is phosphorylated myosin light chain essential for?
Muscle contraction
IMPORTANT: Agents increasing Ca++ in the smooth muscle cells will act as _________.
Smooth muscle constrictors
What do Alpha 2 receptors do?
Act at the presynaptic termini:
- Inhibit epinephrine and Norepinephrine release (CNS and PNS)
What happens when you activate Alpha 1 Receptors?
Vasoconstriction (raise) BP)
*Blocking Alpha 1 will lower BP
Alpha2 agonists will ______.
- Decrease heart rate
- Attenuate CNS response
- Vasodilator
Alpha2 antagonist will _____.
- Increase heart rate
- enhance CNS response
- Vasoconstrictor
What do Beta 2 receptors do on smooth muscle?
- increase PKA
- Phosphorylate and inhibit myosin light chain kinase
- diminish Ca++ levels
- Decrease muscle contractility
What does cAMP do?
Activates PKA which inhibits MLCK, which dimities myosin light chain phosphorylation and diminished smooth muscle contraction.
Where do we find Beta1 receptors?
Cardiac muscle
What do Beta1 receptors do?
- Activate PKA
- Activate L type Ca++ Channels
- Increase Ca++ levels
- Increase muscle contractilltiy
Drugs that activate the Beta 1 receptor have what effect?
Improve the contractility of the heart.
- increase HR
What happens when Beta2 receptor is activated?
- Smooth muscle (vascular and nonvascular) muscles relax
- Reduce BP
- Broncho dilation
What receptors will Epinephrine activate?
Alpha and Beta1 and Beta2 *Norepinephrine does NOT activate Beta2!
What are the effect of Epi. and Nore. on salivary glands?
Mainly affect A1 and B1 (Stimulates protein secretion) *net effect is modest secretion with high protein concentration.
How does Epi. and Nore. effect non vascular smooth muscle?
Usually relaxation mediated by B2 *Alpha receptors mediate sphincter contraction.
What is anaphylaxis?
Severe whole body allergic response
- vasodilation
- smooth muscle contraction
- increased vascular permeability
What is used to treat Anaphylaxis?
Epi. via intramuscular injection
- Stimulates Alpha receptors = increase BP
- Stimulates B1 = positive cardiac effects
- Stimulates B2 = bronchodilation
What are drug examples of A1 receptor agonists?
methoxamine phenylephrine Levonordefrin = sometimes used as vasoconstrior with local anesthetic. midodrine oxymetazoline metaraminol
What is the importance of Vasoconstrictors such as Epi and Levonordefrin in denstitry?
They are used in conjunction with local anesthetic to:
- Prolong duration of nerve block
- Diminish system toxicity of anesthetic
- Minimize blood loss during the surgical procedure.
What do A2 receptor agonist do?
Primarily drugs that act in the CNS by inhibiting epinephrine and Norepinephrine release from presynaptic termini.
*Some are used to treat hyper tension via autonomic regulation, others are used to treat ADHD
What do B1 receptor Agonists do?
These drugs are primarily using in the treatment of heart failure and cardiogenic shock via direct stimulation of B1 receptors.
What do B2 Receptor Agonists do?
These Drugs Produce smooth muscle relaxation. they are used primarily to treat respiratory disease, but can also be used to produce vasodilation in muscle and liver to produce relaxation of uterine tissues.
What are some possible adverse possibilities with administration of epinephrine?
- too large of a dose
- accidental intravascular injection
- heightened sensitivity
- Patient with cardiovascular disease
What are the therapeutic uses of A1 receptor antagonist?
Therapies all relating to antagonism of vascular smooth muscle constriction:
- Hypertension
- Pulmonary tension
- Hemodynamic shock
- Raynaud’s disease
- Conditions associated with increase sympathetic activity
- Antagonism of bladder smooth muscle constriction
Tell me about Prazosin…
Non selective Alpha antagonist, not useful to treat hypertension
Tell me about Alfuzosin….
Specific Alpha antagonist that acts primarily on smooth muscle of prostate (BPH drug). Likely to reflect selective accumulation in prostate tissue.
Tell me about Tamulosin….
Specific for Alpha1a and Alpha1d receptor (Not Alpha1b) and selective for prostate. Effective to treat BPH. does not increase blood pressure.
Why is Alfuzosin better for prostate hyperplasia than the other drugs?
B/c of accumulation in prostate tissue
Tell me abut Phentolamine….
Non-selective alpha antagonist that has limited utility (due to side effects) such as reflex tachycardia due to alpha 2 blockage of feedback loop)
What is Phentolamine good for?
Intravenous infusion to control acute episodes of hypertension during surgery of patients with phenochromocytoma.
*Used to reverse soft tissue numbness after administration of local anesthetics!
Tell me about Phenoxybenzamine….
Also has limited utility due to Irreversible blocker of alpha1 and alpha2 receptors.
*Used to treat patients with Phenocromocytoma (Dampen down responses)
Are there any clinical uses for Beta3 antagonists?
No
What do agonist of B3 do?
- produce vasodilation
- stimulate lipolysis
Blockade of B2 adrenergic receptors is generally undesirable where?
in airway smooth muscle, vascular smooth muscle and endocrine cells.
*Hence presently used B blockers are either non-selective (B1 +B2) or B1 selective. *B1 selective antagonist are generally preferred.
______ decrease heart rate and force of contraction.
Beta Blockers
Beta blockers will diminish _____ release form kidney.
Renin
Decrease in renin release causes ______.
Decrease in Blood pressure
What are the therapeutic uses of Beta blockers?
- Hypertension
- Ischmeic Heart disease (reduced oxygen consumption by reducing cardiac output)
- Post myocardial infarction (Reduce oxygen consumption by reducing cardiac output)
- Congestive heart failure
- Treat arrhythmias
B blockers are also reduce ______ and are used in the treatment of glaucoma.
Vitreous humor production
B blockers that get in the CNS are used to treat _________.
Migraine and tremor associated with anxiety
What are 2 B blockers that are both Alpha and Beta receptor antagonists?
Labetalol = 7x more potent as a B blocker, used in long term management of Hypertension. (ISA activity)
Carvedilol = No ISA activity, effective in treatment of congestive heart failure, antioxidant activity.
What are some of the adverse side effects of Beta blockers?
Many are logical extensions of their pharmacological activities:
Heart = Bradycardia, AV block. Withdrawal can lead to angina, myocardial infarction or death.
Smooth muscle: non-selective blockers can reduce vasodilatory responses, increase bronchospasms.
CNS: the usual suspects, depression, fatigue, sleep disturbances. hallucinations, dizziness
In dental practice, Alpha blockers can cause _______.
Orthostatic hypotension
A patient taking a non selective B blockers is at more risk of a hypertensive episode when?
After receiving local anesthetic with a vasodilator.
_______ can cause xerostomia.
Clonidine
