Autonomic Drugs Flashcards
Muscarinic receptors in the lung
-M2 = Gαi = decreased cAMP, increase K+ channel opening
i. Inhibitory receptor controlling the release of Ach
ii. Asthma = activated eosinophils release major basic protein, which binds to M2 receptors and prevents binding of acetylcholine. Thus, the normal negative feedback control of acetylcholine release is lost, and acetylcholine release is increased. In conclusion, loss of function of inhibitory M2 muscarinic receptors on the airway parasympathetic nerves causes vagally mediated
bronchoconstriction and hyperresponsiveness following antigen challenge
-M3= Gαq = PLC activation = inc IP3/DAG = inc [Ca]i
i. Bronchial smooth muscle contraction
ii. Mucus gland activation
2. **net effect of cholinergic agonists will be bronchoconstriction and inc mucus secretion
Acetylcholine
- At minimal doses causes vasodilation and reflex tachycardia. At larger doses causes bradycardia, dec. AV nodal conduction celocity, and hypotension.
- Causes bronchoconstricion and inc. bronchial secretions
Bethanechol
- MOA-Activates muscarinic (M) receptors–>increases IP3 and DAG
- May cause bronchoconstriction and inc. bronchial secretions
- Oral, IM activity Poor lipid solubility: does not enter CNS
- Duration: 0.3–2 h
- Tox-All parasympathomimetic effects: cyclospasm, diarrhea, urinary urgency, plus vasodilation, reflex tachycardia, and sweating.
Pilocarpine
MOA-Activates muscarinic (M) receptors–>increases IP3 and DAG, may also activate EPSP via M receptors in ganglia
- May cause bronchoconstriction and inc. bronchial secretions
- Oral, IM activity
- Tox-Similar to bethanechol but may cause vasoconstriction via ganglionic effect
Muscarine
MOA-Activates muscarinic (M) receptors–>increases IP3 and DAG, may also activate EPSP via M receptors in ganglia
- May cause bronchoconstriction and inc. bronchial secretions
- No CNS effects
Nicotine
- MOA-Activates all nicotinic (N) receptors, opens Na+-K+ channels in ganglia and neuromuscular end plates
- Use-smoking cessation (also used as insecticide)
- High lipid solubility, absorbed by all routes
- Duration: 4–6 h
- Tox-Generalized ganglionic stimulation: hypertension, tachycardia, nausea, vomiting, diarrhea Major overdose: convulsions, paralysis, coma
Nicotinic ganglionic blockers
- hexamethonium, trimethaphan, mecamyline
- MOA-Selective block of Nn receptors
- Obsolete; was used for hypertension
- Oral, parenteral Block of all autonomic effects
- Trimethaphan: IV only, short-acting; was used for hypertensive emergencies and controlled hypotension
- mecamylamine: oral, enters CNS; investigational use for smoking cessation
- Tox: dec. arteriolar and venomotar tone–>hypotension. Also dec. contractility and moderate tachycardia
Echothiophate
- MOA-irreversibly binds AchE and slowly phosphorylates the active site of AchE very slowly=extremely stable
- Can undergo agin
- ->bronchoconstriction & inc. bronchial secretion
Physostigmine
- MOA-Inhibitor of cholinesterase, amplifier of endogenously released
- Use-Reversal of severe atropine poisoning (IV), occasionally used in acute glaucoma (topical)
- Lipid soluble, can be used topically in the eye
- Duration: 2–4 h
- Tox-Increased parasympathetic effects, especially nausea, vomiting, diarrhea, urinary urgency, CNS effects: seizures
Edrophonium
-MOA-Inhibitor of cholinesterase, amplifier of endogenously released ACh
-Use-Reversal of NM block by nondepolarizing
drugs
-used IV, Duration: 5–10 min
-Tox-Increased parasympathetic effects, especially nausea, vomiting, diarrhea, urinary urgency
Atropine, ipatropium, tiotropium, scopolamine
-MOA-Competitive pharmacologic antagonist at all
M receptors
-Uses-Useful in COPD where blockade of postganglionic parasypathetic M2 receptors can help to eliminate bronchodilation
-Lipid-soluble, Duration: 2–4 h, except in eye: ≥72 h
-Tox-All parasympatholytic effects plus sedation, delirium,
hyperthermia, flushing
-Ipratropium, tiotropium: inhaled for asthma, chronic obstructive pulmonary disease
-Scopolamine: anti-motion sickness via transdermal patch
Epinephrine
-MOA-α1, α2, β1, β2, β3 agonist
-Uses Anaphylaxis, hemostatic cardiac arrest
-Parenteral and topical only, does not enter CNS, Duration: short
-Tox-Hypertension, arrhythmia, stroke, myocardial
infarction, pulmonary edema
Norepinephrine
MOA-α1, α2, β1 agonist
-Uses-Shock, hypotension
-IV only Vasospasm
Tox-tissue necrosis, excessive blood pressure increase, arrhythmias, infarction
Albuterol, Terbutaline, Metaproterenol, Salmeterol
- MOA-β2 agonist
- Uses-Prompt onset for acute bronchospasm
- Inhalant via aerosol canister, Duration: 2–6 h
- Tox-Tachycardia, tremor
- Salmeterol-β2 agonists; slow onset, long action. Not useful in acute bronchospasm, used only with corticosteroids for prophylaxis of asthma
Tyramine
-MOA-Displaces stored catecholamines
-No clinical use but found in fermented foods
-Normally high first-pass effect, but in patients
taking MAO inhibitors it is absorbed
-Tox-Hypertension, arrhythmias, stroke, myocardial
infarction
Reserpine
- MOA-Drug that inhibits VMAT, transporter of dopamine and norepinephrine into transmitter vesicles of adrenergic nerves
- ->dec. cardiac ouput and dec. peripheral vascular resistance
- Tox-at high doses this can cause sedation, mental depression, parkinsonism symptoms, CI w/ depression
Guanadrel
- MOA-blocks reuptake of norepinephrine (NET) and depletes stores
- oral, long duration
- Tox-severe orthostatic hypotension
Ephedrine, psuedoephedrine
-MOA-Releases stored catecholamines, causes
nonselective sympathetic effects
-Use-Asthma (obsolete)
-Oral, Duration: 6–8 h
-Tox-Insomnia, tremor, anorexia, arrhythmias
-psuedoephedrine is just an enantiomer
Cocaine
-MOA-Blockade of Na+ channels slows, then prevents axon potential propagation, cocaine has intrinsic
sympathomimetic actions
-Rapid metabolism via plasma esterases, short half-lives
-Uses-Analgesia, topical
-Tox-CNS: excitation, seizures CV: vasodilation, hypotension, arrhythmias (bupivacaine)As above re CNS actions, cocaine vasoconstricts. When abused has caused hypertension and cardiac arrhythmias
Amphetamine
-Sympathomimetic drug that facilitates the release of catecholamines from adrenergic nerve endings
Prazosin, terazosin, tamsulosin
- MOA-Competitive antagonism at α1 receptors
- Uses-Nasal Decongestion, Hypertension, benign prostatic hyperplasia
- Oral, Duration: 8 h
- Tox-Orthostatic hypotension (especially first dose), but little reflex tachycardia
- terazosin: like prazosin; longer duration of action (12–24 h)
- Tamsulosin: like prazosin, approved only for benign prostatic hyperplasia
phenoxybenzamine
-MOA-alpha blocker-Irreversible (covalent) binding
to α receptors
-Uses-Pheochromocytoma, carcinoid, mastocytosis,
Raynaud’s phenomenon
-Oral, short half-life but long duration of action (24–48 h)
-Tox-Orthostatic hypotension, reflex tachycardia, gastrointestinal irritation
Phentolamine
-MOA-Competitive pharmacologic antagonism at α receptors
-Uses-Pheochromocytoma, antidote to overdose
of α agonists
-Oral, IV, short half-life, Duration: 2–4 h
-Tox-Orthostatic hypotension, reflex tachycardia
Labetalol
-MOA-Four isomers; 2 bind and block both α and β receptors, alpha1 selective, equally inhibits beta receptors
-Uses-Hypertension, hypertensive emergencies (IV)
-Oral and IV, Duration: 5 h
-Tox-Excessive β blockade: bronchospasm (can be fatal in asthmatics), atrioventricular block, heart failure, CNS
sedation, lethargy, sleep disturbances
Atenolol, Metoprolol, Esmolol
-Competitive block of β1 receptors
-Uses-Hypertension especially useful in HTN tx in asthmatics, angina, arrhythmias
-Oral, Duration: 6–9 h
-Tox-Excessive β blockade: bronchospasm (can be fatal in asthmatics), atrioventricular block, heart failure, CNS
sedation, lethargy, sleep disturbances
-Esmolol: IV agent for perioperative and thyroid storm arrhythmias, hypertensive emergency
-Metoprolol: like atenolol, oral, shown to reduce mortality in heart failure
Propanolol, Pindolol
-MOA-Competitive block of β receptors, local anesthetic
effect
-Uses-Angina, arrhythmias (treatment and prophylaxis),
hypertension, thyrotoxicosis, tremor, stage fright, migraine
-Oral and IV, Duration: 4–6 h. Ready entry into CNS
Excessive β blockade:
-Tox-C/I in asthma pts(bronchoconstriction) bronchospasm (can be fatal in asthmatics), atrioventricular block, heart failure, CNS sedation, lethargy, sleep disturbances
-Pindolol: partial agonist action; possibly safer in asthma
hexamethonium, trimethaphan, mecamyline
Nicotinic ganglionic blockers
