Autonomic Pharmacology Flashcards
What type of functions does the autonomic nervous system control?
- Visceral functions that occur without concious control
What is the “only organ” not innervated by the autonomic nervous system?
- Skeletal muscle
From where does the autonomic nervous system originate?
- The CNS/ lower brainstem
What are the 2 divisions of the ANS?
- Sympathetic
- Parasympathetic
What effect does the parasympathetic/ sympathetic nervous system have on the pupils?
Sympathetic: Dilates pupil
Parasympathetic: Constricts pupil
What effect does the parasympathetic/ sympathetic nervous system have on salivation?
Sympathetic: Inhibits salivation
Parasympathetic: Stimulates salivation
What effect does the parasympathetic/ sympathetic nervous system have on the heart?
Sympathetic: Accelerates the heart
Parasympathetic: Inhibits the heart
What effect does the parasympathetic/ sympathetic nervous system have on the bronchi?
Sympathetic: Dilates bronchi
Parasympathetic: Constricts bronchi
What effect does the parasympathetic/ sympathetic nervous system have on digestive activity?
Sympathetic: Inhibits digestive activity
Parasympathetic: Facilitates digestive activity
What effect does the parasympathetic/ sympathetic nervous system have on the kidneys and gallbladder?
Sympathetic: Stimulates glucose release by the liver
Parasympathetic: Stimulates the gall bladder
What effect does the parasympathetic/ sympathetic nervous system have on the bladder?
Sympathetic: Relaxes the bladder
Parasympathetic: Contracts the bladder
What effect does the parasympathetic/ sympathetic nervous system have on the rectum?
Sympathetic: Contracts the rectum
Parasympathetic: Relaxes the rectum
What effect does the sympathetic nervous system have on the kidneys?
- Secretion of epinephrine and norepinephrine
What is the main nerve to the heart?
- The vagus nerve
From which spinal segments do the sympathetic fibers originate from?
T1 - L3
From which part of the nervous system/ spinal segments do the parasympathetic fibers originate from?
- Midbrain
- Medulla oblongata
- Sacral portion of spinal cord
What is an autonomic ganglia?
- Specialized complex structure residing outside the spinal cord that contains axodendritic synapses between preganglionic and postganglionic neurons
Is the sympathetic nervous system closer, or farther away from the spinal cord?
- Sympathetic closer
- Parasympathetic farther away
What does an autonomic ganglion connect?
Preganglionic and postganglionic nerves
How do reactions propogate through ganglia?
Neurotransmitters
Which neurotransmitter is present in the autonomic ganglia of the sympathetic and parasympathetic nervous systems?
Acetylcholine
Why do drugs need to either stimulate or block at the level of the end organ?
There is no specificity
Where are receptors located typically?
Embedded into the target tissue (nerve, end organ, etc…)
What neurotransmitter is located at the neuro-effector junction of the parasympathetic division?
Acetylcholine
What two compounds are acetylcholine synthesized from? What enzyme facilitates this synthesis?
- Acetyl CoA and Choline
- Choline Acetyltranseferase
Where is Acetylcholine broken down?
Ganglionic junction or neuro-effector junction
Why can’t acetylcholine be used as a drug?
It is resorbed/ disposed of too quickly
What happens to ACh after it is synthesized?
- Stored in vesicle at the nerve terminal
What ions are involved in binding the ACh vesicle to the nerve terminal and releasing ACh into the synapse?
- Sodium
- Calcium
Where does norepinephrine function as a neurotrasmitter in the autonomic nervous system?
- Neuro-effector junction of sympathetic nervous system
What group of chemicals does norepinephrine belong to?
- Catecholamines
What 2 other chemicals are catecholamines?
- Dopamine
- Epinephrine
What chemical do the adrenal glands release?
- Epinephrine
What catecholamine is a precursor to norepinephrine?
- Dopamine
What is the main way that NE is removed from the synapse?
- Re-uptake by pre-synaptic fibers
What mediates re-uptake of norepinephrine?
Alpha-2 receptors
What are 2 methods of inactivation of NE?
Breakdown by:
- Monoamine oxidase
- Catechol-o-methyltransferase
What 2 factors of a cell can be affected by NE or ACh?
- Metabolism
- Ion channels
What is the presynaptic receptor in the sympathetic nervous system? What is its function?
- Alpha-2 receptor
- If activated by an excess of NE in the synapse, it sends a signal to the nerve terminal to decrease norepinephrine synthesis
What two subtypes of receptors mediate ACh’s effects?
- Muscarinic (M)
- Nicotinic (N)
Where are M receptors found?
- Neuro-effector junction in parasympathetic division
Where are N receptors found?
- Autonomic ganglia of both sympathetic and parasympathetic divisions of the ANS, and at the neuro-muscular junction
What is the source of the name of nicotinic receptors?
Nicotine
What is the source of the name of muscarinic receptors?
Mushrooms
What is meant by neuro-effector junction?
At the end organ
What type of reactions are muscarine receptors related to?
Parasympathetic
What type of reactions are nictonic receptors related to?
Both sympathetic and parasympathetic
What two subtypes of receptors mediate the effects of norepinephrine, and epinephrine?
Alpha and beta receptors
What are the 2 types of alpha receptors?
Alpha-1
Alpha-2
Where are alpha-1 fibers found, and what is their function?
- Present in arteriolar smooth muscles
- Activation causes vasocontriction
Where are alpha-2 fibers found, and what is their function?
- Found pre-ganglionically, and in the CNS
- Decreases sympathetic flow from the CNS
What neurotransmitter production is inhibited by alpha-2 stimulation?
- Norepinephrine
What are the 2 types of beta receptors?
Beta-1
Beta-2
Where are Beta-1 receptors found? What is their function?
- Found in the heart and kidney
- Increases heart rate, force of contration, and secretion of renin from kidney
Where are Beta-2 receptors found? What is their function?
- Found in smooth muscles of blood vessels and bronchi
- Vasodilates, and bronchodilates
What are adrenergic impulses?
- Norepinephrine reactions
- Sympathetic nervous system
What are cholinergic impulses?
- Acetylcholine reactions
- Parasympathetic nervous system
What is the function of adrenergic and cholinergic impulses on the radial muscle of the eye?
Adrenergic: Contraction/ Opens eyes
Cholinergic: No effect
What is the function of adrenergic and cholinergic impulses on the spincter muscles of the eye, iris?
Cholinergic: Contraction/ closes eyes
Adrenergic: No efefct
What is the function of adrenergic and cholinergic impulses on the ciliary muscles of the eye?
Adrenergic: Relaxation for far vision
Cholinergic: Contraction for near vision
What is the function of adrenergic and cholinergic impulses on the lacrimal glands of the eye?
Adrenergic: No effect
Cholinergic: Increased secretions/ tearing
What is the function of adrenergic and cholinergic impulses on the SA node of the heart?
Adrenergic: Increased heart rate
Cholinergic: Decreased heart rate/ vagal arrest
What is the function of adrenergic and cholinergic impulses on the atria of the heart?
Adrenergic: Increased contractility and conduction velocity
Cholinergic: Decreased contractility
What is the function of adrenergic and cholinergic impulses on the AV node of the heart?
Adrenergic: Increased conduction velocity and automaticity
Cholinergic: Decreased conduction velocity
What is the function of adrenergic and cholinergic impulses on the ventricles of the heart?
Adrenergic: Increased contractility
Cholinergic: Slight decrease in contractility
What is the function of adrenergic and cholinergic impulses on the coronary arterioles?
Adrenergic: Contriction with Alpha-1; Dilation with Beta-2
Cholinergic: (Contriction with endothelial damage)
What is the function of adrenergic and cholinergic impulses on the pulmonary arterioles?
Adrenergic: Constriction with Alpha-1; Dilation with Beta-2
Cholinergic: Dilation
What is the function of adrenergic and cholinergic impulses on renal arterioles?
Adrenergic: Constriction with Alpha-1; Dilation with Beta-2
Cholinergic: No effect
What is the function of adrenergic and cholinergic impulses on system veins?
Adrenergic: Constriction with alpha-1; Dilation with beta-2
What is the function of adrenergic and cholinergic impulses on the tracheal and bronchial muscles of the lungs?
Adrenergic: Relaxation with beta-2
Cholinergic: Contraction
What is the function of adrenergic and cholinergic impulses on the bronchial glands of the lungs?
Adrenergic: Decreased secretion by alpha-1; Increased secretion with beta-2
Cholinergic: Increased secretion
What is the function of adrenergic and cholinergic impulses on the motility and tone of the stomach?
Adrenergic: Decreased with alpha-1
Cholinergic: Increased
What is the function of adrenergic and cholinergic impulses on the sphincters of the stomach?
Adrenergic: Contraction with alpha-1
Cholinergic: Relaxation
What is the function of adrenergic and cholinergic impulses on the secretions of the stomach?
Adrenergic: Inhibition
Cholinergic: Stimulation
What is the function of adrenergic and cholinergic impulses on the motility and tone of the intestine?
Adrenergic: Decreased with alph-1
Cholinergic: Increased
What is the function of adrenergic and cholinergic impulses on the sphincters of the intestines?
Adrenergic: Contraction
Cholinergic: Relaxed
What is the function of adrenergic and cholinergic impulses on the secretions of the intestines?
Adrenergic: Inhibition
Cholinergic: Stimulation
What is the function of adrenergic and cholinergic impulses of the gallbladder and ducts of the intestine?
Adrenergic: Relaxation with beta-2
Cholinergic: Contraction
What is the function of adrenergic and cholinergic impulses on renin secretion in the kidney?
Adrenergic: increase with beta-1
Cholinergic: No effect
What is the function of adrenergic and cholinergic impulses on the sphincter of the urinary bladder?
Adrenergic: Contraction by alpha-1
Cholinergic: Relaxation
What is the function of adrenergic and cholinergic impulses of the water and potassium secretions of salivary glands?
Adrenergic: No effect
Cholinergic: Increased
What is the function of adrenergic and cholinergic impulses of amylase secretion of salivary glands?
Adrenergic: No effect
Cholinergic: Increased
What is the function of adrenergic and cholinergic impulses of nasopharyngeal glands of the salivary glands?
Aderenergic: No effect
Cholinergic: Increased secretion
What are parasympathomimetics?
- Drugs that mimic the effects of parasympathetic nerve stimulation
What is another name for parasympathomimetics?
- Muscarinic receptor agonists
What is the mechanism of action of direct-acting parasympathetics?
- Stimulation of M receptors at the neuro-effector junction with no or little N receptor stimulation
What are 4 therapeutic uses of muscarinic receptor agonists?
- GI disorders
- Urinary bladder disorders
- Xerostomia (dry mouth)
- Opthalamological (reduce acute narrow angle glaucoma attack)
What is the use of bethanchol in the GI tract?
- Stimulates gi tract following abdominal distension and gastric atony
How do indirect-acting parasympathomimetics work?
- Prolong duration of action of ACh by inhibiting ACh esterase
What are the therapeutic uses of indirect-acting parasympathetics?
- Similar to direct acting muscarinics
How are indirect-acting parasympathetics used to treat dementia?
- Donepezil manage the dementia associated with alzheimer disease
What are some examples of irreversible ACh esterase inhibitors?
- Paraxon
- Malaoxon
- Nerve gas sarin
- Insecticides
How is exposure to irreversible ACh inhibitors treated?
- Atropine (an M receptor blocker) and pralidoxime (2-PAM) given before binding of organophosorous compounds becomes permanent
What can used to treat serious toxic reactions to muscarinic agonists?
- Atropine sulfate administered by IV or subcanteously
- Epinephrine for cardiovascular or bronchoconstrictor responses
What are parasympatholytics?
Muscarinic Receptor Antagonists
What is the mechanism of action of muscarinic receptor antagonists?
- Competitive blocking of muscarinic receptors at neuro-effector sites on smooth muscle, cardiac muscle, gland cells, and in the CNS with little blockage of the effects of ACh at nicotinic receptor sites
Do muscarinic receptor blockers show selectivity towrads the muscarinic receptor subtypes?
- No, except for pirenzepine that are selective towards M1 receptors
How are muscarinic receptor anatogonists used in relation to the heart?
- Increases heart rate by blocking vagal nerve effects on M2 receptors on the SA nodal pacemaker
Do muscarinic receptor antagonists have an effect on blood vessels when administered in isolation? Why?
No, because, there is no parasympathetic control of the vascular system
What effect can muscarinic receptor antagonists have on choline esters?
- Block vasodilation induced by choline esters effects on endothelial M3 receptors
What roles does the parasympathetic nervous system play in the respiratory tract?
- Regulate bronchomotor tone/ constrict broncioles
- Facilitate secretions in the nose, pharynx and bronchi
What effect do muscarinic receptor antagonists have on the respiratory tract?
- Bronchodilation by means of blocking the M3 receptor
- Block secretions of the nose, pharynx, and bronchi
What is a danger of muscarinic receptor antagonists to the respiratory tract?
- May dry the lungs out to the point of irritation
What effect do muscarinic receptor antagonists have on the gastrointenstinal tract?
- Inhibit motility and secretions
- Inhibit gastric acid secretion
What effect do muscarinic receptor antagonists have on the urinary tract?
- Decrease the tone and amplitude of contractions of the bladder
What effect do muscarinic receptor antagonists have on sweat glands?
- Inhibition of sweating
- Skin can become hot and dry, raising body temperature
What determines a muscarinic receptor antagonists effect on the CNS?
- Its ability to cross the blood brain barrier
What effects can muscarinic receptor antagonists have on the CNS if they can cross the blood brain barrier?
- Depression of the CNS
- May be preceded by central excitation if atropine is used
What are the effects of muscarinic receptor antagonists on the eyes?
- Pupil dilation/ mydriasis
- Cycloplegia (lack of accomodation of the eye due to a paralysed ciliary muscles
What effect does atropine have at a 0.5 mg dose?
- Inhibition of sweating, some dryness of the mouth
What effect does atropine have at a 1 mg dose?
- Definite dryness of mouth
- Heart acceleration
- Mild pupil dilation
What effect does atropine have at a 2 mg dose?
- Rapid heart rate
- Palpitations
- Marked dilation of pupils
What effect does atropine have at a 5 mg dose?
- Inhibition of parasympathetic control of the GI, urinary bladder
- Inhibited gastric secretions and motility
- Increased dryness of mouth
- Heart acceleration
- Pupil dilation
- Palpitations
What effect does atropine have at a 10 mg dose?
Previously listed symptoms, and CNS symptoms:
- restlessness
- Excitement
- Hallucinations
- Delirium
- Coma
What is ipratropium bromide/ artrovent?
A muscarinic receptor antagonist that doesn’t influence the CNS. Its mostly used as a bronchodilator in COPD, but also in asthma
What is the effect scopolamine?
- Controls motion sickness
What are the therapeutic uses of atropine?
- Reduce salivary/ mucus hypersecretions
- Protect against reflex bradycardia
- Antidote for mushroom poisoning
What is tolterodine tartrate/ detrol used for?
Inhibit an overactive bladder
What is Fesoterodine fumarate/ Toviaz used for?
- Treats overactive bladder
What are 6 side-effects of muscarinic receptor antagonists?
- Mouth
- Urinary retention
- Anhydrosis
- Tachycardia
- Palpitations
- Constipation
What are sympathomimetic agents?
- Direct stimulators of the adrenergic receptors
What are the 3 endogenous sympathomimetic drugs?
- Epinephrine
- Norepinephrine
- Dopamine
What are the cardiac effects of epinephrine?
- B-1 receptors are stimulated, causing chronotropic, and postitive iontropic effects (stimulates heart)
What are the respiratory effects of epinephrie?
- B-2 receptor stimulation leads to potent bronchodilation (bronchial smooth muscles are relaxed)
Why does epinephrine have a short duration of action?
- It is rapidly metabolized by enzymes (MAO and COMT)
What may results from rapid intravenous injection of epinephrine? Why?
- Cerebral hemorrhage may occur due to the sharp rise in blood pressure May also undergo: - Tremors - Palpitations - Anxiety - Reslessness
What are the 2 therapeutic uses of epinephrine?
- Provide rapid relief to hypersensitivity reactions including anaphylaxis to drugs and allergens
- Restore cardiac rhythm in patients with cardiac arrest
What receptors does norepinephrine act most powerfully on? What is the effect of this?
- NE activates alpha-1 receptors powerfully, and weakly activates beta-2
What is the therapeutic use of norepinephrine?
- Can be titrated to desired pressor effect in treatment of hypotension (raises blood pressure due to vasocontriction)
By what route of administration is NE and epinerphrine not active?
The oral route
What is the effect of dopamine at lower doses?
- Increases renal, coronary, and mesenteric vasodilation due stimulation of dopamine receptors (D1)
What is the effect of dopamine at higher doses?
- Stimulates cardiac beta-1 receptors causing positive iontropic and chronotropic effects. (stimulating the heart)
In what pathway is dopamine involved?
The synthetic pathway to NE and epinephrine
What is the therapeutic use of dopamine?
- Treats severe congestive heart failure in patients with oligurea (low urine output) and low or normal peripheral vascular resistance
What is the effect of non-selective beta-agonists? What are their therapeutic effects?
- Increased cardiac output
- Dilation of muscle and mesenteric arteries
- Stimulates heart rate in patients with bradycardia or heart block in emergency situations
What would be the ideal selective beta-agonist for asthma? Why?
- Higher preferential affinity towards B2 receptor, and no affinity towards B1.
- Bronchodilation and vasodilation without cardiac effects
What types of drugs are used to treat asthma?
Beta-2-selective agonists
What are some short and long actin beta-2-agonists?
Short: - Albuterol/ Ventolin - Terbutaline/ Brethine Long: Salmetrol/ Serevent
How fast does a short acting beta-2-selective agonist onset? How do the effects last?
- Onsets in 15 minutes
- Lasts 4 - 6 hours
How long does a long-acting beta-2-selective agonist last?
- Up to 12 hours
How do alpha-adrenergic receptor agonists work?
- Stimulate either alpha-1 or alpha-2 receptors
What is a common use of alpha-1-selective agonists? How does it work?
- Nasal decongestant in allergic rhinitis
- Contricts blood vessels in the nasal tissue leading to decreased fluid accumulation
What can happen in chronic use of nasal decongestants?
- Loss of efficacy, and worsening of symptoms due to receptor desensitization
What drug is a common alpha-2-selective agonist? What is its effect?
- Clonidine/ Catapres selectively stimulates alpha-2 receptors to decrease central sympathetic outflow to lessen vasoconstrictive drive
What are some non-direct adrenergic agonists? What is their effect?
- Amphetamine, dextroamphetamine, and methylpehnidate shoot norepinephrine into CNS synapses stimulating CNS to treat ADHD
How do adrenergic receptor antagonists work?
- Competitive blockage of alpha and/or beta-adrenergic receptors
For what 3 issues are adrenergic receptor antagonists used for?
- Arrythmias
- Heart failure
- Hypertension
What are alpha-1-selective blockers used for?
- Block receptors in vscular smooth muscles of arterioles and veins, decreasing peripheral resistance and blood pressure over time
What is less observed with alpha-1-selective blockers as opposed to non-selective alpha-blockers?
- Tachycardia
What are 2 adverse effects of alpha-1-selective blockers?
- First-dose phenomenon: Marked postural hypotension and syncope observe 60 - 90 minutes after the first dose
- Water retention due to vasodilating effect
What is the effect of beta-adrenergic receptor blockers on the heart?
- Blocking of beta-1 receptors slows heart rate and reduces myocardial contratility
What is the effect of beta-adrenergic receptor blockers on the pulmonary system?
- No effect on normal individuals, but the blocking of beta-2 receptors in patients with asthma or COPD can lead to life threatening bronchoconstriction
What is the effect of beta-adrenergic receptor blockers on peripheral vascular resistance?
- Blockage of B-2 receptors in arteriolar smooth muscle decrease vasular resistance; beta-1 blockers can also reduce peripheral vascular resistance in hypertension patients over time
How do non-selective beta-blockers work?
Reversibly block beta-1 and beta-2 receptors with no selectivity towards either type
What are the therapeutic uses of beta-1-selective blockers?
- Hypertension
- CHF
- Angina and MI
What may occur in patients with AV conduction defects given beta-1-selective blockers?
- Life-threatening bradyarrhythmias
Why should long-term beta-1-selective blockers not be discontinued abruptly?
- Exacerabtes angina, and can bring on sudden heart attack
What effect can B2-selective blockers have on asthmatics?
- Worsen brochoconstriction
What type beta-selective-blockers produce lss broncho-constriction?
- B1 selective blockers or non-selective b-blockers with partial b2-agonism