CV Autonomic Pharmacology Flashcards
What autonomic system & respective receptors respond to norepinephrine? Epinephrine? Acetylcholine?
- Sympathetic
- norepinephrine
- alpha1, alpha2, beta1
- epinephrine
- alpha1, alpha2, beta1, beta2
- norepinephrine
- Parasympathetic
- Acetylcholine
- M, N
- Acetylcholine
Cardiovascular response to activation of the autonomic nervous system depends on what factors?
- location adn proportoin of the receptors
- baroreflex and adjustments
- predominant tone
Fill out the provided table with regards to receptor location and proportion on CV response to activation of parasympathetic nervous system (M2)
Fill out the provided table with regards to receptor location and proportion on CV response to activation of sympathetic nervous system
Describe the sympathetic, parasympathetic & physiolgical responese to baroreceptors
- Baroreceptor response occurs in reaction to acute changes in pressure - (Blood Pressure)
- purpose is to maintain acceptable blood pressure
- direct relationship w/ parasympathetic & indirect relationship with sympathetic
- Increase in pressure
- decrease sympathetic activity
- increase sympathetic
- = decrease in HR & contractility
- Decrease in pressure
- increase in sympathetic
- decrease in parasympathetic
- = increase in HR & contractility
What is the predominant ANS tone for the following structures:
arterioles
veins
heart & ventricular muscle
SA node
- arterioles
- SNS
- veins
- SNS
- heart & ventricular muscle
- SNS
- SA node
- PNS
How does this graph demonstrate the concept of predominant tone?
What happens when a medication blocks innervation by either sympahetic or parasympathetic systems?
If the intrinsic heartrate without any autnomic innervation is around 100-110 bpm, but our normal resting heart rate is 60-80 bpm, then our normal resting heart rate is mostly controlled by the parasympathetic nervous system
- Parasympthetic blocked
- heart rate will increase
- Sympathetic blocked
- heart rate will decrease
What are 2 examples of clinical uses of atropine? What type of drug is this?
- Muscarinic antagonist
- Clinical uses
- sinus bradycardia or AV block in patients with MI
- severe bradycardia and syncope caused by hyperative carotid sinus reflex
Explain how the different type of indirect adrenergic agonists work & provide examples for each type
- cocaine & tricyclic antidepressants
- inhibiting NE reuptake into presynaptic nerve
- tolcapone
- blocking metabolism of NE by catechol methyltransferase
- rasagiline
- blocking the metabolism of NE by monoamine oxidase in presynaptic neuron
- amphetamine tyramine
- promoting release of NE by presynaptic nerve terminals
- ephedrine
- mixed acting
- indirect agonist: promote release of NE by presynaptic nerve terminals
- can also bin to post synaptic nerve
Fill out the provided table regarding clasfication of adrenergic agonists based on receptor selectivity
- Selectivity is dose dependent
- become less selective as dosage increases
*
- become less selective as dosage increases
What are the 3 clinical uses of alpha1-selective receptor agonists?
Name of the drugs?
- Phenylephrine (alpha1>alpha2) and midodrine (alpha1)
- Through vasoconstriction, can be used for the following clinical uses:
- Reduce bleeding
- Hypotension
- via increasing blood pressure
- Nasal congeestion
- via increased nasal cavity
What are the clinical uses of alpha2 agonists?
Drugs & mechanism of action?
-
Methyldopa – pro-drug (alpha-methyl-NE)
- decreases sympathetic outflow by stimulating alpha2 receptors in the CNS
- this decreases blood pressure
- clinical use: hypertension
- ** safe for pregnant women
-
Clonidine
- SAME as methyldopa
- ALSO, stimulates alpha2 receptors on neurons to decrease NE release
- decreasing blood pressure
- Clinical use: hypertension
Clinical uses of beta-adrenergic receptor agonists?
Drug names?
-
Dobutamine: beta1 receptors (beta1 > beta2, alpha)
- Low cardiac output states
- severe decompensated heart failure
- cardiogenic shock
- AV block
- Low cardiac output states
-
Dopamine (D1=D2>B1>a1) – dose dependent
- low dose
- activation DA1 in kidneys
- induces diuresis
- intermediate dose
- activation B1 reeptors in heart
- increase in contractile force
- high dose
- alpha receptors = increase peripheral resistance
- increases work of the heart
- could lead to arrhythmias
- Clinical uses
- septic shock
- severe decompensated heart failure
- cardiogenic shock
- AV block
- low dose
-
Fenoldopam- DA-1 agonists
- Hypertensive crisis
- may cause reflex tachycardia
Clinical uses of nonselective beta-receptor agonists?
Drug names?
-
Isoproterenol (B1=B2)
- severe decompensated heart failure
- cardiogenic shock
- AV block
- In conjuction with others: septic shock
- bronchospasm occurring during anesthesia
- stimulation B2 can open airway
Explain the clinical uses of epinephrine & mechanism of action
-
Epinephrine (a1, a2, B1, and B2, B>a)
- co-administered with local anesthetics to prolong the duration of anesthesia
- activate alpha1 receptors & constric blood vessels at site of local injection to prevent the body from carryign the anesthesia to different parts of the body
- anaphylactic shock: the drug of choice
- allergic attack = production IgE – will bind to surface of mast cells & basophils
- leads to degranulation & release of histamine, cytokines & leukotrienes
- Respiratory system
- increase bronchospasm, mucus secretion, pulmonary edema (b/c capillary permeability)
- obstruction of airway
- Cardiovascular system
- increase capillary permeability (fluid loss) & vasodilation, decrease cardiac contractility
- hypotensive shock
- allergic attack = production IgE – will bind to surface of mast cells & basophils
- co-administered with local anesthetics to prolong the duration of anesthesia
- Mechanism of Action
- (1) by activating vascular a1 receptors, decrease capillary permeability
- relieve pulmonary edema & reduce fluid loss
- (2) by activating vascular a1 in smooth muscle can cause vasoconstriction
- increase blood pressure (prevent shock)
- (3) B1 receptors in heart increasing contractility
- increase heart rate & cardiac output
- increase blood pressure (prevent shock)
- (4) activating B2 in ariway, can cause vasodilation
- increase airway
- (5) activating a1 in mucus gland can reduce mucus secretion
- clear airway
- (6) activate B2 receptors on the surface of mast cells & basophils, inhibiting their degranulation
- (1) by activating vascular a1 receptors, decrease capillary permeability
What are the adverse effects of adrenergic agonists & the associated receptor to each effect?
- Tachycardia (B1)
- Cardiac Arrhythmias (B1)
- Hypertenzive Crisis (a1)
- Dry mouth, sedation, mild depression (a2)
- Exacerbate urinary retention in patients with benign prostatic hyperplasia (BPH, a1)
- exacerbate closed-angle glaucoma (a1)
- iris has circular muscle (M) & radial (a1)
- stimulating a1 will pull muscle back to trabecular meshwork & open pupil
- closed-angle glaucoma, can be caused by the iris muscle being pathologically positioned against the trabecular meshwork, this prevents an outflowof vitreous humor to the venous system don’t have outflow of atreous humor to venous system
- this will increase intraocular pressure, leading to glaucoma
Describe the mechanism of action for non-selective alpha eceptor antagonists
- Blocking a1 in smooth muscle will prevent lead to vasodilation
- decrease blood pressure
- the decrease in blood pressure stimulate baroreceptors in the brain to stimulate the sympathetic nervous system to release more NE
- Blocking a2 receptors in presynaptic nerve terminals, interrupting the synaptic feedback control of NE, and can lead to increased NE release
- NE will act on the heart to increase HR contractility
- Clinical Results
- vasodilation & cardiatc stimulation
What are the two major non-selective a receptor antagonists?
What are their clinical uses?
-
Phenoxybenzamine: Pheochromocytoma
- competitive, irreversible
- normal adrenal medulla: EPI:NE= 80:20
- Pheochromocytoma: EPI:NE=20:80
- major problem is hypertension
- Receptor selectivity of NE: a1=a2, B1>B2
- Phentolamine
- Phentolamine
- Reversal of local soft tissue anesthesia
- compete with the epinephrine that was injected with the anesthesia, causing relaxation & blood flow
- a1 agonist overdose
- hypertensive crisis associated with monoamine oxidase inhibitor (MAOI)
- NE can be metabolized by MAO in presynaptic nerve terminals
- Tyrosine can be used to synthesize NE via dopamine
- Tyrosine can also be converted to tyramine (indirect adrenergic agonist) via bacterial decarboxylation
- have MAO in GI that converts tyramine to P-hydroxyphenylacetic acid
- MAOI will inhibit MAO in both the presynaptic nerve terminals & in the GI system
- release of a lot of NE in the blood stream which can leave to hypertensive crisis
What are the a1-selective receptor antagonist drugs?
Describe their mechanism of action.
- All are competitive, reversible antagonists
- Prazosin
- Terazosin
- Doxazosin
- Tamsulosin
- Mechanism of Action
- block peripheral a1 receptors
- vasodilation, leads to decrease in BP
- decrease baroreflexive response, so does NOT stimulate sympathetic system & does NOT induce NE release
- since a2 are not blocked, NE concentration decreases
-
Decreased heart rate & decreased cardiac contractility
- further decreases blood pressure
- Also reduce LDL & TG and increase HDL levels, but mechansim is not uderstood
- block peripheral a1 receptors
Clinical uses of a1-selective receptor antagonists
Adverse effects?
- Clinical uses
- Pheochromocytoma
- Chronic hypertension: not commonly used
- Chronic hypertension with benign prostatic hyperplasia (BPH)
- Urinary retention in men with benign prostatic hyperplasia (BPH)
- block a1 in urinary tract, relaxing urinary track improving urination & reducing urinary retention
- Adverse effects
- Apply to all: hypotension, dizziness, fainting
- Reflex tachycardia
- mainly apply to non-selective
- First-dose syncope (selective a1)
- prevented by:
- reducing dose, increasing dose slowly, and add additional antyhypertensive drug cautiously
- prevented by:
Describe the mechanism of action for the B-receptor antagonists
- Physiological effect
- lower BP and reduce O2 consumption
- By blocking B1 receptors in the heart,
- heart reate contractility decreases
- decreasing cardiac work load & decreasing O2 consumption
- CO consumption decreases
- BP decreases
- heart reate contractility decreases
- Blocking B1 in the renal system can block the release of Renin, preventign the vasoconstriction & aldosterone production that increases BP
What are the adverse effects of all B-receptor antagonists & non-selective B-receptor antagonists?
- All B receptor antagonists
- Bradycardia
- Precipitation of acute heart failure
- metabolic effects
- augmenttion of hypoglycemic action of insulin
- blocks beta receptors, messing with the B3/B2 glucose feedback system
- not able to monitor heart rate as indicator insulin overdose b/c tachycardia is blocked by blocking B receptors
- altered plasma lipid levels
- worsen serum lipid profile (VLDL and HDL)
- augmenttion of hypoglycemic action of insulin
- CNS: mental depression, insomnia, fatigue, and dreams
-
Sudden discontinuation of B receptors can exacerbate angina and cause death
- ALWAYS taper
- Non-selective B receptor antagonists
- Bronchospasm (blocking B2 in lungs)
- in patients with asthma or COPD
- cold extremities (blocking B2 in vasculature)
- Raynaud’s disease (blocking B2 in vasculature)
- Metabolic effects
- selective B1 = improve serum lipid profile
- Bronchospasm (blocking B2 in lungs)
