ANS Drugs Flashcards
Vesamical
Inhibits the concentration of ACh in vesicles by vesicular ACh transporters (VAT)
Methyl Mercury
Inhibits ACh
Botulinum Toxin (BoTox)
Inhibits the Ca dependent release of ACh mediated SNAREs (soluble attachment protein receptors)
Hemicholinium
Inhibits the choline transporter (CHT) responsible for choline reuptake in the pre-synaptic cleft
Tyramine
Inhibits the reuptake of norepinephrine by the NE transporters (NETs)
*Serve as a ligand for NETs resulting in Ca release
Amphetamine
Inhibits the reuptake of norepinephrine by the NE transporters (NETs)
*Serve as a ligand for NETs resulting in Ca release
Cocaine
Non-competitive inhibitor of NETs through allosteric regulation
Tricyclic antidepressants
Non-competitive inhibitor of NETs through allosteric regulation
Non specific Cholinomimetics
Bethanochol (M1-M3>N)
Carbachol (M and N)
Methacholine (M and N)
Muscarinic Cholinomimetics
Muscarine (M only)
Pilocarpine (M»»N)
Nicotinic Cholinomimetics
Nicotine (N only)
Lobeline (N only)
Varenicline (partial Nn agonist)
Succinylcholine (Nm)
Indirect-acting Agonists (AChEIs)
Edrophonium Neostigmineo Physostigmine Echothiophate (organophosphate) Parathion (organophosphate) Malathion (organophosphate) Sarin (irreversible) Soman (irreversible) VX (irreversible) Pralidoxime (receptor regenerator)
Nootropics (Used to treat AD)
Tacrine
Donepezil
Rivastigmine
Galantamine
Other Cholinomimetic drugs
Cyclosporine
Cholinomimetic Drug Uses
Management of Glaucoma, GI and Bladder dysfunction, MG, mild Alzheimer’s disease, and surgery to produce muscle relaxation.
Bethanechol
Non-specific cholinomimetic
Uses: post-op Neurogenic Illeus (bowel obstruction from interruption of the ENS)/ urinary retention, Glaucoma (contraction of ciliary muscle, = miosis)
Toxicity: SLUDGEM & bronchospasm, esp. in asthmatics
No CNS
*Direct acting
MOA: full agonist at M1-M3, little effect on N
Effects: ^secretions, smooth muscle contract., vHR
Carbachol
Non-specific cholinomimetic
Uses: post-op Neurogenic Illeus (bowel obstruction from interruption of the ENS)/ urinary retention, Glaucoma (contraction of ciliary muscle, = miosis)
Toxicity: SLUDGEM & bronchospasm, esp. in asthmatics
No CNS
*Direct acting
MOA: full agonist at M1-M3, little effect on N
Effects: ^secretions, smooth muscle contract., vHR
Methacholine
Non-specific cholinomimetic
Uses: post-op Neurogenic Illeus (bowel obstruction from interruption of the ENS)/ urinary retention, Glaucoma (contraction of ciliary muscle, = miosis)
Toxicity: SLUDGEM & bronchospasm, esp. in asthmatics
No CNS
*Direct acting
MOA: full agonist at M1-M3, little effect on N
Effects: ^secretions, smooth muscle contract., vHR
Muscarine
Muscarinic cholinomimetics
Uses: Glaucoma/Sjogrens Syndrome
Effects: ^secretions, smooth muscle contract., vHR
Toxicity: SLUDGEM, bronchospasm (asthmatics)
Partial CNS (in large quantities)
MOA: direct acting agonist, full agonist at M1-M3, no N effect
Pilocarpine
Muscarinic cholinomimetics
Uses: Glaucoma (eye drops)/Sjogrens Syndrome
Effects: ^secretions, smooth muscle contract., vHR
Toxicity: SLUDGEM, bronchospasm (asthmatics)
Readily crosses CNS
MOA: direct acting agonist, full agonist at M1-M3, little N effect
Nicotine
Nicotinic Cholinomimetic
Uses: Smoking cessation
Toxicity: GI upset, nausea, ^BP, seizures
Yes CNS
Lobeline
Nicotinic Cholinomimetic
Uses: Smoking cessation (similar to nicotine)
Toxicity: GI upset, nausea, ^BP, seizures
Yes CNS
Varenicline
Nicotinic Cholinomimetic
Uses: Smoking cessation
Toxicity: GI upset, nausea, ^BP, seizures
Yes CNS
MOA: partial agonist at Nn receptors, reduces DA release in response to nicotine. Inhibits full nicotinic response, reduces withdrawal, and aids in sensation of continued nicotine intake.
Edrophonium
Indirect-acting agonist (AChEIs) Uses: MG diagnosis Toxicity: SLUDGEM No CNS MOA: bind to AChE, competitive reversible, increase ACh time in the synapse
Neostigmine
Indirect-acting agonist (AChEIs) Uses: MG diagnosis Toxicity: SLUDGEM No CNS MOA: process similar to ACh, carbamoylation slowly hydrate, produces signal blockade for hours.
Physostigmine
Indirect-acting agonist (AChEIs) Uses: MG diagnosis Toxicity: SLUDGEM Yes CNS MOA: process similar to ACh, carbamoylation slowly hydrate, produces signal blockade for hours.
Pyridostigmine
Indirect-acting agonist (AChEIs) Uses: MG diagnosis Toxicity: SLUDGEM No CNS MOA: process similar to ACh, carbamoylation slowly hydrate, produces signal blockade for hours.
Echothiophate, Parathion, Malathion
AChEI, organophosphates
MOA: phosphorylate the esteric site of AChE, irreversible inhibitors of AChE only removed upon aging process and receptor turn over.
Sarin, Soman, VX
AChEI, nerve gasses
MOA: phosphorylate the esteric site of AChE, irreversible inhibitors of AChE only removed upon aging process and receptor turn over.
Pralidoxime
considered AChEI
MOA: binds to the esteric site of AChE and regenerates it “rescue”
Tacrine
Nootropic
Use: Alzheimer’s (AD)
Toxicity: SLUDGEM
Yes CNS
Donepezil
Nootropic
Use: Alzheimer’s (AD)
Toxicity: SLUDGEM, sleep side effects, drug interactions, renal accumulation
Yes CNS
MOA: non-competitive, reversible inhibitor, long 1/2 life, greater selectivity for CNS AChE, low first pass metabolism, eliminated renally
Rivastigmine
Nootropic Use: Alzheimer's (AD) Toxicity: SLUDGEM Yes CNS MOA: psuedo-irreversible competitive inhibitor of ACh at active site, similar to physostigmine, longer duration of action.
Galantamine
Nootropic Use: Alzheimer's (AD) Toxicity: SLUDGEM Yes CNS MOA: Reversible, low potency, short 1/2 life, high metabolism, also non-competitive Nn agonist
Muscarinic Antagonists
Atropine M1-M5 no N Scopolamine M1-M5 >> Nn Ipratropium M1-M5 >> Nn Tiotropium Tropicamide Oxybutynin M3 Tolterodine M3 Darifenacin Solifenacin Fesoterodine Glycopyrrolate (Peripheral acting) Contraindicated in Glaucoma and Dementia
Neuro-Muscular Junction (NMJ) Blockers
D-tubocurarine Atracurium Pancuronium Rocuronium Succinylcholine
Ganglionic Blockers
Mecamylamine
Trimethaphan
Hexamethonium
NMJ Toxins
Alpha-Bungarotoxin
Alpha-Latrotoxin
Tick venom
Botulinum Toxin
Atropine
Cholinergic, Muscarinic Antagonist
Use: ACheI reversal (used as preoperative PANS inhibitor - reduce GI and bladder fxn, bronchial secretion and salivation) Originally used to treat PD
MOA: Surmountable antagonist (can be reversed by increasing ACh, usually with an AChEI) - traps ACh M receptor in inactive state blocking binding and signal transduction.
Effects: V sweating/salivation V GI activity,
Some CNS
Toxicity: antimuscarinic actions, CONTRAINDICATED: glaucoma, obstructive GI, urinary, and intestinal atony
Hot as a hare, blind as a stone, mad as a hatter, and dry to the bone (red as a beet)
Scopolamine
Cholinergic Muscarinic Antagonist
Use: motion sickness
MOA: Surmountable antagonist (can be reversed by increasing ACh, usually with an AChEI) - traps ACh M receptor in inactive state blocking binding and signal transduction (more Nn effects) Lipid soluble
Toxicity: antimuscarinic actions, CONTRAINDICATED: glaucoma, obstructive GI, urinary, and intestinal atony. Prolonged eye dialation!
Hot as a hare, blind as a stone, mad as a hatter, and dry to the bone (red as a beet)
Yes CNS
Ipratropium
Cholinergic Muscarinic Antagonist
Use: COPD/ asthma
MOA: Aerosal with beta-2 agonist, traps ACh M receptor in inactive state, block binding and signal transduction (Nn effects too)
Effects: blocks M3 receptors, reduce mucous production, increased bronchial caliber
No CNS
Toxicity: antimuscarinic actions, CONTRAINDICATED: glaucoma, obstructive GI, urinary, and intestinal atony
Hot as a hare, blind as a stone, mad as a hatter, and dry to the bone (red as a beet)
Tiotropium
Cholinergic Muscarinic Antagonist Uses: COPD/Asthma MOA: Aerosol No CNS Toxicity: HBMD
Tropicamide
Cholinergic Muscarinic Antagonist Use: Short acting eye dilation MOA: topical, Toxicity: cycloplegia No CNS
Oxybutynin
Cholinergic Muscarinic Antagonist Use: treat overactive bladder MOA: M3>>>, short acting No CNS Toxicity: HBMD - constipation and dry mouth
Tolterodine
Cholinergic Muscarinic Antagonist
Use: treatment of overactive bladder
MOA: M3»> more bladder selective, longer activing
No CNS
Toxicity: HBMD, GI hypomotility (constipation), dry mouth
Darifenacine
ACh M antagonist
Use: overactive bladder
No CNS
Solifenacin
ACh M antagonist
Use: overactive bladder
No CNS
Fesoterodine
ACh M Antagonist
Use: overactive bladder
No CNS
Glycopyrrolate
ACh M antagonist
Use: peripheral M blocker, can be used for overactive bladder, pre-op PANS control
No CNS
Toxicity: HBMD
D-tubocurarine
NMJ blocker (anti-ACh Use: not used clinically (Replaced by: atracurium, pancuronium, and rocuronium) - surgery/intubation MOA: Non-depolarizing blocker, competitive antagonist at NMJ with surmountable affinity for Nm receptor, at high doses, can = SANS/PANS effects Effect: dose-dependent NMJ blockade = weakness, eventually flaccid paralysis. blockade is surmountable No CNS Toxicity: high dose = respiratory compromise, stimulates release of histamine = hypotension, interacts with other muscle relaxants
Atracurium
NMJ blocker (Anti-ACh Use: Muscle relaxant/paralysis (replaced: d-tubocurarine) surgery/intubation MOA: Non-depolarizing blocker, competitive antagonist at NMJ with surmountable affinity for Nm receptor, at high doses, can = SANS/PANS effects Effect: dose-dependent NMJ blockade = weakness, eventually flaccid paralysis. blockade is surmountable No CNS Toxicity: high dose = respiratory compromise,
Pancuronium
NMJ blocker (Anti-ACh) STEROID Use: Muscle relaxant/paralysis (replaced: d-tubocurarine) surgery/intubation MOA: Non-depolarizing blocker, competitive antagonist at NMJ with surmountable affinity for Nm receptor, at high doses, can = SANS/PANS effects Effect: dose-dependent NMJ blockade = weakness, eventually flaccid paralysis. blockade is surmountable No CNS Toxicity: high dose = respiratory compromise,
Rocuronium
NMJ blocker (Anti-ACh) STEROID Use: Muscle relaxant/paralysis (replaced: d-tubocurarine) surgery/intubation MOA: Non-depolarizing blocker, competitive antagonist at NMJ with surmountable affinity for Nm receptor, at high doses, can = SANS/PANS effects Effect: dose-dependent NMJ blockade = weakness, eventually flaccid paralysis. blockade is surmountable No CNS Toxicity: high dose = respiratory compromise,
Succinylcholine
NMJ blocker (anti-ACh)
Use: surgery muscle relaxation/ tracheal tube placement
MOA: full and specific agonist at Nm receptors block NMJ by depolarization blockade. Phase1: occupies the receptor, continuous agonization preventing repolarization, NMJ is blocked. Phase2: eventually succinylcholine diffuses away from receptor, receptor remains activated making it unable to be activated for some time (even at high levels of ACh), eventually the receptor recovers and can be activated, restored fxn.
Effects: Muscle fasciculations, flaccid paralysis, slow recovery.
No CNS
Toxicity: hyperkalemia
Mecamylamine
Ganglionic Blocker
Use: Not used clinically, but could be used in hypertensive emergency, or in neurologic procedures to reduce CNS bleeding through peripheral pooling
Effects: Reduce overall PANS & SANS outflow (vasodialation, ^HR, vGI, vUrination, vSexual fxn, vSweating)
MOA: competitive agonists at Nn receptors, directly block receptor site.
Toxicity: Sedation, tremor, chorea (ANS absence)
Yes CNS
Trimethaphan
Ganglionic blocker
Use: hypertensive emergency or prevention of CNS bleeding in neurosurgical procedures
MOA: competitive agonist at Nn receptor, blocks receptor by binding directly to receptor site. SHORT ACTING *extremely water soluble, delivered IV only
Effects: overall loss of ANS function (PANS and SANS)
No CNS
Toxicity: ANS absence
Hexamethonium
Ganglionic blocker
Use: hypertensive emergency
MOA: competitive antagonists at Nn receptor, blocks primarily by steric hindrance of the ion channel.
Effects: overall ANS outflow reduced (PANS and SANS). vasodilation, ^HR, vGI, vUrination, vSexual fxn, vSweating
No CNS
Toxicity: Loss of ANS.
Alpha-1 Selective Agonists
Phenylephrine
Midodrine
Methoxamine
Alpha-2 Selective Agonists
Clonidine
Guanfacine
Methyldopa
Guanabenz
Beta non-selective Agonist
Isoproterenol
Beta-1 Selective Agonist
Dobutamine
Beta-2 Selective Agonists
Albuterol Terbutaline Metaproterenol Pirbuterol Salmeterol Formoterol
Non-specific Alpha Antagonists
Phenoxybenzamine
Phentolamine
Alpha-1 Selective Antagonists
Prazosin
Tamsulosin
Alpha-2 Selective Antagonists
Yohimbine
Non-Specific Beta Antagonists
Propranolol Nadolol Timolol Sotolol Pindolol Carvedilol
Selective Beta-1 Antagonists
Metoprolol
Atenolol
Esmolol
NE Depleting Agents
Guanethidine
Reserpine
Alpha-methyl-para-tyrosine
Indirect NE Agonists
Amphetamine Methamphetamine Ephedrine Pseudoephedrine Phenylpropanolamine Phenmetrazine Methylphenidate Modafinil Tyramine Cocaine Atomoxetine
Phenylephrine
Alpha-1 Selective Agonist *Prototypical drug Dog BP tracing
Uses: Decongestant, priapism, Reverse anesthetic hypotension, myadrisis, enhances alertness in cold medicines *Can be used in management of shock and hypotension with methoxamine
MOA: direct acting, competitive agonist at A1 receptor, specific A1 *Significant 1st pass metabolism
Effects: Smooth muscle contraction and other A1 effects (increased BP = decrease HR - baroreceptor)
Toxicity: Hypertension, seizures CI: closed angle glaucoma. Can be used in OAG because contracts papillary muscle = outflow of AH
Yes CNS
BP tracing: Vasoconstriction = ^TPR ^BP, baroreceptor reflex = decreased HR. No change in PP
Midodrine
A1 agonist (Prodrug) Use: prodrug to desglymidodrine, treats hypotension
Methoxamine
A1 Agonist
Use: treatment of hypotension, can be used in management of shock and hypotension
*Similar to phenylephrine
Clonidine
Alpha-2 Agonist *primary (prototypical)
Use: Management of hypertension (not common), Primarily in patients with high SANS activity as well as ADHD - used for sympatholytic effects
MOA: direct-acting, competitive agonist at A2 and is specific. Activated A2 receptors, inhibits NE release. leads to hypotension, but depends on ROA, oral = vSANS outflow, A2, vNE, =hypotension. IV/topical = mild vasoconstriction due to direct A2 receptor
Yes CNS
Toxicity: Orthostasis, tachycardia, sedation, headache, depression, appetite suppression, dizziness, fatigue
Guanfacine
Alpha-2 Agonist *primary (prototypical)
Use: Management of hypertension (not common), Primarily in patients with high SANS activity as well as ADHD - used for sympatholytic effects
MOA: direct-acting, competitive agonist at A2 and is specific. Activated A2 receptors, inhibits NE release. leads to hypotension, but depends on ROA, oral = vSANS outflow, A2, vNE, =hypotension. IV/topical = mild vasoconstriction due to direct A2 receptor
Yes CNS
Toxicity: Orthostasis, tachycardia, sedation, headache, depression, appetite suppression, dizziness, fatigue
Methyldopa
Alpha-2 Agonist *primary (prototypical)
Use: Management of hypertension (not common), Primarily in patients with high SANS activity as well as ADHD - used for sympatholytic effects
MOA: direct-acting, competitive agonist at A2 and is specific. Activated A2 receptors, inhibits NE release. leads to hypotension, but depends on ROA, oral = vSANS outflow, A2, vNE, =hypotension. IV/topical = mild vasoconstriction due to direct A2 receptor
Yes CNS
Toxicity: Orthostasis, tachycardia, sedation, headache, depression, appetite suppression, dizziness, fatigue
Guanabenz
Alpha-2 Agonist *primary (prototypical)
Use: Management of hypertension (not common), Primarily in patients with high SANS activity as well as ADHD - used for sympatholytic effects
MOA: direct-acting, competitive agonist at A2 and is specific. Activated A2 receptors, inhibits NE release. leads to hypotension, but depends on ROA, oral = vSANS outflow, A2, vNE, =hypotension. IV/topical = mild vasoconstriction due to direct A2 receptor
Yes CNS
Toxicity: Orthostasis, tachycardia, sedation, headache, depression, appetite suppression, dizziness, fatigue
Isoproterenol
Non-selective beta agonist *Dog BP tracing
Use: Asthma, Bradycardia, Heart block (causes cardiac issues - ^chronotrophy, ^inotrophy)
MOA: direct-acting, competitive B1, 2, and 3 agonist
Effects: Effects all Beta receptors, with little to no alpha effect
No CNS
Toxicity: Marked ^BP, vHR initially - then drop in BP and increased HR, palpitations, and arrythmias.
Tracing: non-specific B agonist = initial ^ systolic BP (B1), baroreceptor response = vSystolic BP, circulation to muscles = B2 effects cause vasodilation of large vessel pool in striated muscle, reducing TPR, dropping systolic/diastolic BP, PP increases, ^ HR. OVERALL: drop in systolic, large drop is diastolic, increased PP, reduced TPR, and ^HR.
Dobutamine
Selective Beta-1 Agonist
Use: Cardiac stress, Heart failure, Cardiogenic Shock
Effect: ^inotrophy
MOA: Selective B1, racemic mixture has some A1/2 effects
No CNS
Toxicity: Angina, Hypertension, Arrythmias
Albuterol
Selective Beta-2 Agonist
Use: rescue inhaler (acute asthma), some COPD
MOA: selective B2, direct-acting, agonist (R isomer)
Effects: No B1 cardiac effects, muscle vasodilation in pool, reduced TPR, reflex ^HR
Yes CNS (overdose)
Toxicity: Tremor/anxiety - when in CNS, Tachycardia, Arrythmias, Nervousness *chronic use = tolerance
Terbutaline
Selective Beta-2 Agonist
Use: rescue inhaler (acute asthma), some COPD
MOA: selective B2, direct-acting, agonist (R isomer)
Effects: No B1 cardiac effects, muscle vasodilation in pool, reduced TPR, reflex ^HR
Yes CNS (overdose)
Toxicity: Tremor/anxiety - when in CNS, Tachycardia, Arrythmias, Nervousness *chronic use = tolerance
Metaproterenol
Selective Beta-2 Agonist
Use: rescue inhaler (acute asthma), some COPD
MOA: selective B2, direct-acting, agonist (R isomer)
Effects: No B1 cardiac effects, muscle vasodilation in pool, reduced TPR, reflex ^HR
Yes CNS (overdose)
Toxicity: Tremor/anxiety - when in CNS, Tachycardia, Arrythmias, Nervousness *chronic use = tolerance
Pirbuterol
Selective Beta-2 Agonist
Use: rescue inhaler (acute asthma), some COPD
MOA: selective B2, direct-acting, agonist (R isomer)
Effects: No B1 cardiac effects, muscle vasodilation in pool, reduced TPR, reflex ^HR
Yes CNS (overdose)
Toxicity: Tremor/anxiety - when in CNS, Tachycardia, Arrythmias, Nervousness *chronic use = tolerance
Salmeterol
Selective Beta-2 Agonist
Use: longer lasting asthma management, most common in COPD, can be used in conjunction with Ipratropium (COPD)
MOA: selective B2, direct-acting, agonist (R isomer) long acting - 12 hours
Effects: No B1 cardiac effects, muscle vasodilation in pool, reduced TPR, reflex ^HR
Yes CNS (overdose)
Toxicity: Tremor/anxiety - when in CNS, Tachycardia, Arrythmias, Nervousness *chronic use = tolerance
Formoterol
Selective Beta-2 Agonist
Use: longer lasting asthma management, most common in COPD, can be used in conjunction with Ipratropium (COPD)
MOA: selective B2, direct-acting, agonist (R isomer) long acting - 12 hours
Effects: No B1 cardiac effects, muscle vasodilation in pool, reduced TPR, reflex ^HR
Yes CNS (overdose)
Toxicity: Tremor/anxiety - when in CNS, Tachycardia, Arrythmias, Nervousness *chronic use = tolerance
Amphetamine
Indirect acting adrenergic agonist
Use: anorexient, ADHD, less frequent treatment of narcolepsy
MOA: Competitive reuptake inhibitor, compete with neurotransmitter, carries transporter to cytosolic side of membrane, where mobile pool ligand can bind and be transported out of cell to synaptic pool. Ca-independent release! Does not involved vesicular pool. Also block monoamine oxidase (MAO)
Effects: Increase synaptic pool of NE=DA>5HT, resulting in non-specific effects at NE, DA, and 5HT receptors. ^HR and ^TPR. Improved attention, reaction time in fatigue, ^Motor activity, ^Anxiety, vAppetite, ^body temp, ^RR.
Yes CNS
Toxicity: dependence, vasoconstriction = ischemia and necrosis , hypothermia and metabolic acidosis Death from metabolic acidosis and hyperthermia usually do not decrease (ceiling effect) - at high dose Amphetamine builds up in mobile pool and competes for transporter with neurotransmitters, ends up being transported back out of cell preventing Ca-independent release
Methamphetamine
Indirect-acting adrenergic agonist
Similar to amphetamine
No clinical use
greater CNS effects
Readily pyrolysed (smoked), insufflated (snorted), or injected.
Toxicity: greater CNS effect, greater toxicity than amphetamine– still has ceiling effect.
*Biotransformed into amphetamine in liver
*Greater 5HT effect
Ephedrine
Indirect-acting adrenergic agonist
Effects: ^BP
Major component of Ma Huang
Pseudoephedrine
Indirect-acting adrenergic agonist
Use: decongestant, constricts nasal vessels = reduced congestion.
Effects: Constricts nasal vessels, alerting effect
*behind the counter due to ability to synthesize methamphetamine
Toxicity: insomnia, anxiety, hallucinations
Phenylpropanolamine
indirect-acting adrenergic agonist
Use: widely used as decongestant, and lesser extent appetite supressant
Effects: minor DA effects
Toxicity: increased BP, strokes, withdrawn from market
Phenmetrazine
Indirect-acting adrenergic agonist
*similar to amphetamine
Effects: less DA potency
Methylphenidate
Indirect-acting adrenergic agonist
Use: preferred drug from ADHD treatment
*less ANS effects
Modafinil
Indirect-acting adrenergic agonist
Amphetamine-like drug
Decreases GABA, increases Glu
Uses: treatment of narcolepsy
Tyramine
indirect-acting adrenergic agonist
Member of pressor amine family,
MOA: degraded my MAO in 1st pass metabolism. *Primarily an NE substrate, with little/no DA effect
Prevalent in aged foods–
Toxicity: hypertensive crisis when administered with MAOI
Methamphetamine
indirect-acting adrenergic agonist
Amphetamine-like drug
Effects: ^5HT effects,
*Pyrolysis (meth)
Cocaine
indirect-acting adrenergic agonist
MOA: inhibit NET and DAT without acting as a ligand for transport protein. DO NOT facilitate Ca-independent release of neurotransmitter.
*binds to allosteric regulatory site on re-uptake pumps (NET=DAT»SERT) produces non-competitive re-uptake inhibitory effect by altering structure of protein. = steric blockade of pump protein, inhibiting access of neurotransmitter to its binding site.
Effects: produces “Caine” properties. similar adrenergic effects to amphetamine - but cannot induce release itself. ^vasoconstriction, vBlood flow
Uses: rarely used, but occasionally for nasal procedures for “caine” properties.
Toxicity: perforated septa. high-dose=arrythmias, seizures (caine properties)
*Short-half life, cleared via liver
Phenoxybenzamine
Non-specific alpha antagonist
Use: pheochromocytoma (pre-surgical) *unsurmountable so resistant to NE and Epi surges.
MOA: Covalent binding to A1»A2 and is non-surmountable. Requires re-synthesis of receptors to reinstate fxn. long-acting, slow recovery
Effects: Blockade of SANS activity, in cases of elevated SANS activity. vBP, reduced headache and diaphoresis Toxicity: Little effect on BP when supine, but significant orthostatic hypotension when rising, and light-headedness when standing. HR and CO ^ to baroreceptor response to vBP, nasal stuffiness, inhibited ejaculation, sedation from CNS effects
Toxicity: Orthostasis, tachycardia, myocardial ischemia
Yes CNS
Phentolamine
Non-specific alpha antagonist
Use: pheochromocytoma (pre-surgical) *unsurmountable so resistant to NE and Epi surges.
MOA: Competitive inhibitor of A1 = A2, reversible
Effects: Greater A2 block = more cardiac effects. Blockade of SANS activity, in cases of elevated SANS activity. vBP, reduced headache and diaphoresis Toxicity: Little effect on BP when supine, but significant orthostatic hypotension when rising, and light-headedness when standing. HR and CO ^ to baroreceptor response to vBP, nasal stuffiness, inhibited ejaculation, less sedation.
Toxicity: Orthostasis, tachycardia, myocardial ischemia
Yes CNS
Alpha-methyl-para-tyrosine
NE Depleting agent
Use: hypertension (short-acting) *May also be used to treat pheochromocytoma (depletion of NE, but also effects DA neurons, etc.) *Short-acting, requires high maintinence.
MOA: Indirect acting antagonists, competitive inhibitor of tyrosine hydroxylase and enters CNS. Will block DA, NE, and Epi synthesis centrally and peripherally. Short acting
Yes CNS
Guanethidine
NE Depleting Agent
Use: Pheochromocytoma, Hypertension (overseas)
MOA: indirect acting agonist, potent substrate for NET (initially competitive re-uptake inhibitor) much more potent substrate for VMAT. Enters NE vesicles, displaces NE and acts as a false neurotransmitter (higher affinity for NET) *functional sympathectomy!
Toxicity: hypotension
NO CNS
Reserpine
NE Depleting Agent
Use: Hypertension *CNS depleting DA can be used to treat hyperkinetic movement for antipsychotic drugs, and manage Huntington’s
MOA: indirect acting antagonist, non-specific VMAT inhibitor that affects NE, 5HT, and DA = wide range effects and side effects, potent NE depletor *long-acting Inhibits the vesicular monoamine transporter of norepinephrine into vesicles within the neuron
Effects: functional sympathectomy, Very long duration (days), profound antihypertensive effects.
Toxicity: Hypotension, severe depletion of DA= parkinsonian-like feature, significant Depression
YES CNS
Prazosin
Selective Alpha-1 Antagonist Use: Hypertension MOA: profound vascular blocking Toxicity: Orthostatic hypotension ?CNS
Tamsulosin
Selective Alpha-1 Antagonist
Use: BPH
Toxicity: Orthostasis
?CNS
Yohimbine
Selective Alpha-2 Antagonist
Use: Erectile dysfunction, orthostatic hypotension
MOA: Competitive antagonist, bind to A2 autoreceptor, increase SANS activity during SANS activation, prevent negative feedback of NE. ^NE, Increased beta tone as well as A1 tone
Effects: ^NE release by preventing NE feedback at A2 receptors, can also ^ACh release by acting on the A2 receptors at those synapses.
Toxicity: Anxiety
Yes CNS
Propranolol
Non-specific beta antagonist *PROTOTYPICAL
Use: hypertension, angina, arrhythmias, migrane, glaucoma, tremor, *STAGE FREIGHT, sedation, PTSD(?)
MOA: partial agonist activity and local anesthetic actions *Significant 1st pass metabolism, dose-dependent, biotransformation become saturated at higher doses = varying bioavailability
Effects: reduces beta tone, reduces cardiac B1 effects, vInotropic and chronotropic effects. decreases heart work, relieves angina. vDromotrophy = regulation of arrhythmias. ^TPR due to loss of B2 vasodilation. *B1 = Reduces Renin release = reduced BP. B2 = skeletal muscle dilation, bronchiole relaxation, and glycogenolysis in liver. B3 = prevents lipolysis.
Toxicity: Bradycardia, CI: asthma (reduction in bronchiole tone). vivid dreams, fatigue, hypoglycemia, and increases VLDL. B2 block = reduce glucagon response to hypoglycemia, warning for T1D
Yes CNS
Nadolol
Non-specific beta antagonist
Use: hypertension, angina, arrhythmias, migrane, glaucoma, tremor, *STAGE FREIGHT, sedation, PTSD(?)
MOA: partial agonist activity *Significant 1st pass metabolism, dose-dependent, biotransformation become saturated at higher doses = varying bioavailability
Effects: reduces beta tone, reduces cardiac B1 effects, vInotropic and chronotropic effects. vIOP. decreases heart work, relieves angina. vDromotrophy = regulation of arrhythmias. ^TPR due to loss of B2 vasodilation. *B1 = Reduces Renin release = reduced BP. B2 = skeletal muscle dilation, bronchiole relaxation, and glycogenolysis in liver. B3 = prevents lipolysis.
Toxicity: Bradycardia, CI: asthma (reduction in bronchiole tone). vivid dreams, fatigue, hypoglycemia, and increases VLDL. B2 block = reduce glucagon response to hypoglycemia, warning for T1D
Yes CNS
Timolol
Non-specific beta antagonist
Use: hypertension, angina, arrhythmias, migrane, glaucoma, tremor, *STAGE FREIGHT, sedation, PTSD(?)
MOA: partial agonist activity *Significant 1st pass metabolism, dose-dependent, biotransformation become saturated at higher doses = varying bioavailability
Effects: reduces beta tone, reduces cardiac B1 effects, vInotropic and chronotropic effects. vIOP. decreases heart work, relieves angina. vDromotrophy = regulation of arrhythmias. ^TPR due to loss of B2 vasodilation. *B1 = Reduces Renin release = reduced BP. B2 = skeletal muscle dilation, bronchiole relaxation, and glycogenolysis in liver. B3 = prevents lipolysis.
Toxicity: Bradycardia, CI: asthma (reduction in bronchiole tone). vivid dreams, fatigue, hypoglycemia, and increases VLDL. B2 block = reduce glucagon response to hypoglycemia, warning for T1D
Yes CNS
Sotolol
non-specific beta antagonist
Use: CHF
Effects: reduction of heart work, and decreased arrhythmias, relief from angina. vInotropy and chronotropy and dromotropy. TPR^ due to loss of B2 vasodilation in capillary beds. Reduced renin release = vBP
Toxicity: reduced B2 = vBronchiole dilation, CI: asthma, also reduced glucagon response to hypoglycemia, !T1D
Pindolol
non-specific beta partial antagonist *PROTOTYPICAL
Use: CHF, heart disease
MOA: Mildly reduces beta tone, *surmountable when SANS is high. partial B antagonist, less hypotensive effects. limits NE, commonly used to *limit swings in NE, manage response (BP stabilization). need for increased SANS tone= blockade overcome by increased sympathomimetic activity (ISI). increased competition by NE or Epi surmounts effects of pindolol. *Main point: partial B agonist, competes with NE and Epi, does not fully block B (ISI), reduces renin release partial B1.
Effects: reduction of heart work, and decreased arrhythmias, relief from angina. vInotropy and chronotropy and dromotropy. TPR^ due to loss of B2 vasodilation in capillary beds. Reduced renin release = vBP
Toxicity: reduced B2 = vBronchiole dilation, CI: asthma, also reduced glucagon response to hypoglycemia, !T1D
Carvedilol
non-specific mixed antagonist *PROTOTYPICAL
Use: CHF
MOA: blocks both beta and alpha-1 receptors, blocking B1 = reduced cardiac work and BP. A1 blockade = reduced TPR (vasodilation).
Toxicity: SOB, lymphodema, exercise intolerance.
Metoprolol
Selective Beta-1 antagonist *PROTOTYPIC
Use: management of hypertension and cardiac issues.
MOA: no B2 effect– devoid of bronchiole effects (safe for asthmatics), safer in T1D too, no B2 glucagon effects.
Effects: no B2, vinotropy, chronotropy, and dromotropy, decreased cardiac work, and increase in TPR
Toxicity: safe for asthmatics, safe for T1D, safe for VLDL patients
Atenolol
Selective Beta-1 antagonist *PROTOTYPIC
Use: management of hypertension and cardiac issues.
MOA: no B2 effect– devoid of bronchiole effects (safe for asthmatics), safer in T1D too, no B2 glucagon effects.
Effects: no B2, vinotropy, chronotropy, and dromotropy, decreased cardiac work, and increase in TPR
Toxicity: safe for asthmatics, safe for T1D, safe for VLDL patients
Esmolol
selective beta-1 antagonist
Use: hypertension *mainly used in management of arrhythmias in ICU
MOA: short-acting, no B2 effects.
