11-Drugs affecting the ANS Flashcards
What are the receptors of the somatic nervous system? Which neurotransmitter is associated with these receptors?
Nicotinic Cholinergic Receptors. Acetylcholine.
Which drugs are used to block the somatic nervous? What is the effect of these drugs?
Neuromuscular Blocking Agents. Induce paralysis of skeletal muscle.
When are NMBAs (Neuromuscular blocking agents) used? What is an example of an NMBA?
Specifically used in the context of surgery, endotracheal intubation or mechanical ventilation (to keep muscles from contracting so we can cut open).
Vecuronium (Norcuron) is an NMBA.
What is the antagonist to Vecuronium (an NMBA)? What is its mechanism of action?
Acetylcholinesterase inhibitors (neostigmine). Inhibits the activity of acetylcholinesterase which metabolizes acetylcholine. Ach levels will rise and compete actively against Vecuronium.
True or False. Neuromuscular blocking agents have an affect on the autonomic nervous system.
False. They bind to nicotinic-cholinergic receptors of the somatic nervous system, a different subtype than the ones found in the ANS.
Which receptors are associated with the sympathetic division of the ANS? What neurotransmitter is associated?
Adrenergic receptors (alpha and beta). Norepinephrine.
Which receptors are associated with the parasympathetic division of the ANS? What neurotransmitter is associated?
Muscarinic cholinergic receptors . Acetylcholine.
True or False: Nicotinic Cholinergic receptors are only found in the parasympathetic division?
False. Nicotinic Cholinergic receptors are found in sympathetic and parasympathetic postganglionic neurons.
Which organs and glands do not receive input from both branches of the ANS? Which input do they receive?
The arterioles. They only receive sympathetic input.
True or False: sympathetic and parasympathetic input to organs is of equal strength.
False. One system will always predominate (typically the parasympathetic with bursts of sympathetic tone).
Nicotininc cholinergic receptor antagonists (Autonomic Nervous System):
- mechanism of action
- outcome
- inhibits both the smaller sympathetic input and the predominant parasympathetic input
- results in a net sympathetic effect
What would the effect of a nicotinic cholinergic receptor antagonist be on the heart?
The heart receives both sympathetic and parasympathetic input. The parasympathetic input predominates and slows the intrinsic rhythm. If a nicotinic cholinergic receptor antagonist is used, then the predominant parasympathetic input will be blocked, resulting in a net sympathetic effect. Therefore tachycardia will result.
Why do we not longer use drugs that target nicotinic cholinergic receptors?
They result in a messy dose response curve because we are all a little different in which system predominates. The target is not as specific.
Which receptors are found in the target tissues of the sympathetic division vs. the parasympathetic division.
Sympathetic - Adrenergic receptor
Parasympathetic - Muscarinic cholinergic receptor
What are two other names for cholinergic drugs class?
Muscarinic agonists and parasympathomimetics.
What effects do cholinergic drugs have?
stimulate smooth muscle (lungs, GI), stimulate gland secretions, decrease heart rate and force of contraction, constrict the pupil
What are two other names for anticholinergic drug class?
Muscarinic antagonists and parasympatholytics.
What effects do anticholinergic drugs have?
Opposite of cholinergics - Suppression of smooth muscle (lungs and GI), suppression of oral secretions, increased heart rate and force of contractions, pupil dilation.
Direct acting cholinergic drugs vs. Indirect acting cholinergic drugs.
Direct acting cholinergic drugs bind to muscarinic cholinergic receptors whereas indirect acting inhibit acetylcholinesterase which causes an increase in acetylcholine. Ach levels rise systemically which means that it binds to receptors in the SNS as well as ANS.
Clinical use of direct acting cholinergic drugs (Bethanechol).
- Bethanechol stimulates smooth muscle contraction via M3 receptors couple to Gq proteins.
- It is used to treat postoperative ileus and bladder atony
- drugs used in surgery can have negative effects on the gut and bladder and sometimes people require a kickstart with bethanechol
Clinical use of indirect acting cholinergic drugs.
Myasthenia graivs and Alzheimer’s disease (Ach is important to memory at the level of the hippocampus) - Because these drugs affect autonomic gnaglia, muscarinic receptors, skeletal muscle and cholinergic receptors in the CNS, we only use them when we don’t have anything else.
Which drug class are insecticides? What are the two types of insecticides and how do they differ?
Indirect acting cholinergic drugs.
Carbamate insecticides reversibly bind and the effects are often reverse 2-8 hours post exposure.
Organophosphate insecticides irreversibly bind and recovery requires synthesis of new enzymes (1-2 weeks).
What can insecticides induce?
Cholinergic crisis.
Explain a cholinergic crisis.
Nicotinic effects: muscle fasiculations and fatigue
Muscarinic effects (pro-parasympathetic): salivation, lacrimation, urination, diarrhea, dyspnea, bradycardia, sweating, pin-prick pupils
This pro-parasympathetic state happens early on and very quickly.
Effects of muscarinic antagonists.
Inhibition of parasympathetic input to target organs, inducing similar effects to sympathetic nervous system activation.
What is the antidote for high levels of acetylcholine?
Atropine
Atropine:
- mechanism of action
- solubility
- effects
- clinical use
- inhibits Ach binding at muscarinic receptors
- highly lipid soluble
- increased heart rate, bronchodilation, decreased GI motility, pupil dilation, decreased gland secretion
- mydriatic (to dilate pupils - optometrists), treatment of carbamate insecticide poisoning, increaseing HR in shock patients, suppressing gastric and oral secretions in surgery patients
What are some clinical uses of anticholinergic drugs?
Motion Sickness - Scopolamine
Bronchodilation: asthma & COPD - Ipratropium
Urinary urgency & incontinence - Oxybutynin & Tolterodine
What are some clinical uses of anticholinergic drugs?
Motion Sickness - Scopolamine
Bronchodilation: asthma & COPD - Ipratropium
Urinary urgency & incontinence - Oxybutynin & Tolterodine
What is another name for adrenergic agonists?
Sympathomimetics
What is another name for adrenergic antagonists?
Sympatholytics
What effects do adrenergic agonists have on the following receptors?
- Alpha 1 receptors
- Beta 1 receptors
- Beta 2 receptors
- constrict smooth muscle (blood vessels, uterus) and dilate pupils
- increase heart rate and force of contraction, increase release of renin
- inhibit smooth muscle (bronchioles, uterus)
What effects do adrenergic antagonists have on the following receptors?
- Alpha 1 receptor
- Beta 1 receptor
- Beta 2 receptor
- relax smooth muscle (blood vessels, uterus) and constrict pupils
- decrease heart rate and force of contraction, inhibit release of renin
- activate smooth muscle contraction (bronchioles, uterus)
True or False: There are no indirect acting drugs in the sympathetic division.
true
When are adrenergic drugs generally used? What are the adverse effects associated with?
Significant effects for cardiovascular and respiratory diseases.
Adverse effects are associated with over-stimulation of the sympathetic nervous system (tachycardia, hypertension…).
Which drug class would be used to treat anaphylaxis, shock or heart failure? What would the therapeutic effects be? What is an example of this type of drug?
Beta 1 receptor agonist. This would increase heart rate, contractility and cardiac output.
E.g. epinephrine
Which drug class would be used to treat acute asthmatic bronchoconstriction? What would the therapeutic effects be? What is an example of this type of drug?
Beta 2 receptor agonist. Induces relaxation of bronchial smooth muscle.
E.g. salbutamol
Which drug class would be used to treat hypotension and nasal congestion? What would the therapeutic effects be? What is an example of this type of drug?
Alpha 1 receptor agonist. Induces vasoconstriction.
E.g. Phenylephrine
Which drug class treats preterm labour? What would the therapeutic effects be? What is an example of this type of drug?
Beta 2 receptor agonists. Induces relaxation of uterine smooth muscle.
E.g. terbutaline, ritodrine
When are adrenergic antagonists generally used? What adverse effects are they associated with?
They have significant effects for hypertension. Adverse effects are associated with inhibition of the sympathetic nervous system (bradycardia, hypotension, etc.).
What are the most widely prescribed class of autonomic drug?
Adrenergic antagonists.
How do alpha-adrenergic antagonists decrease blood pressure?
Relax vascular smooth muscle.
How do beta-adrenergic antagonists decrease blood pressure.
Decrease the heart rate and force of contraction of the heart and reduce the production of renin.
Why do we generally choose beta- adrenergic antagonists over alpha-adrenergic antagonist?
Alpha adrenergic antagonists cause so much vasodilation that people get orthostatic hypotension.
Which Beta-adrenergic antagonists are cardio-selective. Why do we generally choose these drugs for treatment?
Beta 1 receptor antagonists are cardio-selective. We use these because they don’t pose the risk of bronchoconstriction (specifically in patients with history of asthma or COPD).
