PNS and Cardio Flashcards
Acetylcholine (miochol)
Muscarinic agonist
- hydrolyzed fast by AchE
Charged, don’t penetrate BBB, don’t penetrate tissue easily
Uses:
- cataract extraction - used to constrict circular muscle/stretch iris, good cuz hydrolyzed rapidly
Contraindications:
- asthma, hyperthyroidism, coronary insuffficiency, peptic ulcer, mechanical obstruction in GI or urinary tract, peritonitis
Parasympathetic overstimulation: SLUDGE
Carbamylcholine
Muscarinic agonist
- resistant to hydrolysis by AchE
- more nicotinic than muscarinic
- improves aqueous outflow in glaucoma, constricts pupil
Potent in GI, bladder and eye
Charged, don’t penetrate BBB, don’t penetrate tissue easily
Contraindications:
- asthma, hyperthyroidism, coronary insuffficiency, peptic ulcer, mechanical obstruction in GI or urinary tract, peritonitis
Parasympathetic overstimulation: SLUDGE
Acetyl-B-methylcholine
Muscarinic agonist
- slowly hydrolyzed by AchE
Potent in heart
Charged, don’t penetrate BBB, don’t penetrate tissue easily
Contraindications:
- asthma, hyperthyroidism, coronary insuffficiency, peptic ulcer, mechanical obstruction in GI or urinary tract, peritonitis
Parasympathetic overstimulation: SLUDGE
Bethanechol
Muscarinic agonist
- resistant to hydrolysis by AchE
- muscarinic selective
Potent in GI, bladder and eye
Charged, don’t penetrate BBB, don’t penetrate tissue easily
Uses:
- post-op ileus, congenital megacolon, GERD - increases tone of GI and sphincter, don’t use for inflammatory or microbial causes
- urinary retention problems - inject into detrusor, helps pee
Contraindications:
- asthma, hyperthyroidism, coronary insuffficiency, peptic ulcer, mechanical obstruction in GI or urinary tract, peritonitis
Parasympathetic overstimulation: SLUDGE
Pilocarpine
Muscarinic agonist
Not charged, used for local applications, penetrates tissue
Apply topically
Uses:
- for increased intraocular pressure/narrow angle glaucoma - constricts sphinter pupillae, stretches iris to allow for drainage of aqueous humor
- xerostomia - induces salivation
Contraindications:
- asthma, hyperthyroidism, coronary insuffficiency, peptic ulcer, mechanical obstruction in GI or urinary tract, peritonitis
Parasympathetic overstimulation: SLUDGE
Atropine
Muscarinic antagonist
- non-selective
Penetrates tissue but not as fast as scopolamine (uncharged, can get into CNS)
Uses:
- prevent vagal reflexes induced by surgical manipulation of visceral organs
- pre-anesthesia - inhibit salivation and respiratory tract secretions
- block response triggered in parasymp system from reversal of neuromuscular blockade, can penetrate CNS cuz not charged
- ophthalmology: mydriasis
- treat anticholinesterase poisoning by organophosphates (given with oxime)
- blocks slow IPSP (muscarinic antagonists)
- blocks slow EPSP (muscarinic antagonists)
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Scopolamine
Muscarinic antagonist
- non-selective
Rapidly penetrates tissue
Uses:
- tranquilize and produce amnesia following surgery
- if gets in/used in eye: mydriasis
- anti-emetic, motion sickness
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
- more potent than anti-histamines for motion sickness (patch behind ear)
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Pirenzepine
Muscarinic antagonist - M1 selective Doesn't penetrate BBB well Uses: - peptic ulcers Contraindications - inflammatory conditions or infections, narrow angle glaucoma, cardiac arrhythmia, chronic lung disease Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Tropicamide
Muscarinic antagonist
- non-selective
Uses:
- ophthalmology: dilate pupil, rapid onset and shortest duration (2-3hrs) - cycloplegia and mydriasis
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
Side effects:
- cycloplegia and mydriasis
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Glycopyrrolate
Muscarinic antagonist
- non-selective
Doesn’t cross BBB or penetrate tissue well
Uses:
- prevent vagal reflexes induced by surgical manipulation of visceral organs (IV)
- pre-anesthesia - used to dry up salivary glands and respiratory tract for trach tube
- counteract muscarinic activation that occurs due to recovery from anesthesia, block M3 in GI (neostigmine given to overcome neuromuscular blockade)
- inject into GI, used for intestinal hypermotility and diarrhea
- see dry mouth and cycloplegia
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Cyclopentolate
Muscarinic antagonist
Uses:
- ophthalmology: dilate pupil, longer lasting than tropicamide (6hrs) - cycloplegia and mydriasis
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
Side effects:
- cycloplegia and mydriasis
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Tiotropium
Muscarinic antagonist
- M3 in lung selective
Uses:
- used as aerosol in lung
- chronic bronchitis and emphysema
Can use in chronic lung disease, does not effect viscosity
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Tolterodine
Muscarinic antagonist
- M3 in detrusor selective
Uses:
- overactive bladder
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Darifencin
Muscarinic antagonist
- M3 in detrusor selective
Uses:
- overactive bladder
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia, chronic lung disease
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Ipratropium
Muscarinic antagonist
- non-selective
Uses:
- potency in lung for bronchial smooth muscle - relaxes it
- cold remedy OTC, chronic rhinitis/hay fever
- chronic bronchitis and emphysema
Can use in chronic lung disease, does not effect viscosity
Can dilate pupil if get into/touch eye
Contraindications:
- narrow angle glaucoma, cardiac arrhythmia
Symptoms opposite of SLUDGE; tachy; cutaneous vasodilation
Dimenhydrinate
Antihistamine
- cross reacts to block muscarinic receptors
- chronic rhinitis/hay fever
- motion sickness
Diphenhydramine
Antihistamine
- cross reacts to block muscarinic receptors
- chronic rhinitis/hay fever
- motion sickness
Meclinzine
Antihistamine
- cross reacts to block muscarinic receptors
- chronic rhinitis/hay fever
- motion sickness
Muscarine
Leads to cholinergic symptoms/SLUDGE (salivation, lacrimation, perspiration)
- poisoning from Amanita muscaria, Inocybe, and Clitocybe mushrooms
- treat with atropine
Pralidoxime
Oxime (2-PAM)
- displaces anticholinesterases
- treat anticholinesterase poisoning by organophosphates (given with atropine)
Edrophonium
Quaternary amine
- reversible acetylcholinesterase inhibitor (shortest lasting, seconds)
Contraindications:
- don’t use for inflammatory condition, bronchial asthma, peptic ulcer, coronary insufficiency, hyperthroidism
SLUDGE side effects
Carbamate
Reversible acetylcholinesterase inhibitor (longer lasting, hours)
Contraindications:
- don’t use for inflammatory condition, bronchial asthma, peptic ulcer, coronary insufficiency, hyperthroidism
SLUDGE side effects
Organophosphate
Irreversible (very long lasting) acetylcholinesterase inhibitor
- form stable covalent bond to serine group oc AchE
- pesticides usually
SLUDGE side effects
Physostigmine
Carbamate
- Reversible acetylcholinesterase inhibitor
- penetrates BBB and tissue, not charged
Uses:
- glaucoma, penetrates cornea (applied locally), constrict circular muscle and increase aqueous humour outflow (used with pilocarpine)
- poisoning by anti-muscarinic or anti-nicotinic
Contraindications:
- don’t use for inflammatory condition, bronchial asthma, peptic ulcer, coronary insufficiency, hyperthroidism
SLUDGE side effects
Neostigmine
Carbamate
- Reversible acetylcholinesterase inhibitor
- doesn’t penetrate tissue, charged
Uses:
- paralytic ileus and atony of urinary bladder (used in conjuction with cholinomimetic bethanechol), injected into bladder
- used for MG with an antimuscarinic (glycopyrrolate/atropine)
- recovery of neuromuscular block following surgery (if nondepolaring blocker), plus an antimuscarinic
- poisoning by anti-muscarinic or anti-nicotinic
Contraindications:
- don’t use with peritonitis, inflammatory obstruction, bronchial asthma, peptic ulcer, coronary insufficiency, hyperthroidism
SLUDGE side effects
Pyridostigmine
Carbamate
- reversible acetylcholinesterase inhibitor
- charged, doesn’t penetrate tissue
Uses:
- used for MG with an antimuscarinic (glycopyrrolate/atropine)
- poisoning by anti-muscarinic or anti-nicotinic
- prophylaxis for nerve agent exposure - can also give galantamine (or human BuChE)
Contraindications:
- don’t use for inflammatory condition, bronchial asthma, peptic ulcer, coronary insufficiency, hyperthroidism
SLUDGE side effects
Malathion
Anticholinesterase - organophosphate pesticide - low toxicity to man/birds - inactivated by carboxylesterase in mammals and birds SLUDGE side effects
Diazanon
Anticholinesterase
- organophosphate pesticide
- household use for cockroaches
SLUDGE side effects
Carbaryl
(Sevin) Anticholinesterase - carbamate pesticide - used in gardens SLUDGE side effects
Soman/Tabun
Anticholinesterase
- organophosphate nerve agent
- chemical warfare agent
SLUDGE side effects
Sarin
Anticholinesterase
- organophosphate nerve agent
- chemical warfare agent
SLUDGE side effects
VX
Anticholinesterase - organophosphate nerve agent - chemical warfare agent Smallest lethal dose SLUDGE side effects
Aminoglycosides and Tetracycline
Kanamycin, Neomycin, Streptomycin
- block Ca transport, reduces free Ca in presynaptic terminal
- need less neuromuscular blocker if on these cuz less Ach released
Botulinum toxin
Interferes with snare proteins, prevents vesicle release
- Botulin toxin A - cleaves SNAP 25
- Botuliln toxin B - cleaves synaptobrevin/VAMP
Uses:
- ophthalmology - strabismus, blepharospasm
- hyperhydrosis
- cervical dystonia - torticollis
- cosmetic
Hemicholinium
Blocks choline re-uptake
Succinylcholine
Depolarizing nicotinic antagonist, neuromuscular blocker
- hydrolyzed by butyryrlcholine esterase
- inactivation of Na channel produces the block
Fast onset, short acting
- used for intubation
Toxicity:
- arrest all muscles, including those of respiration
- stimulates histamine release, induces malignant hyperthermia (if RyR mutation), give dantroline
- can increase intraocular pressure
- infants need more
- hypothermia need less
- hypokalemia need more
- hyperkalemia need less
- bronchiogenic/small cell carcinoma need less
Contraindications:
- burn and truma
d-Tubocurarine
Non-depolarizing nicotinic antagonist, neuromuscular blocker
Toxicity:
- arrest all muscles, including those of respiration
- increases histamine release, causes ganglionic blockade
Physiological factors
- hypokalemia enhances effect
- hyperkalemia attenuates effect
- infants need less
- hypothermia need more
- MG needs less
- bronchiogenic/small cell carcinoma need less
Pancuronium
Non-depolarizing nicotinic antagonist, neuromuscular blocker
- longest lasting
Toxicity:
- arrest all muscles, including those of respiration
Vecuronium
Non-depolarizing nicotinic antagonist, neuromuscular blocker
- metabolism decreased in liver disease
Toxicity:
- arrest all muscles, including those of respiration
Cisatracurium
Non-depolarizing nicotinic antagonist, neuromuscular blocker
- not hydrolyzed enzymatically (Hoffman elimination), use in liver disease
Toxicity:
- arrest all muscles, including those of respiration
Rocuronium
Non-depolarizing nicotinic antagonist, neuromuscular blocker
- fastest onset, shortest lasting
- metabolism decreased in liver disease
Toxicity:
- arrest all muscles, including those of respiration
Hexamethonium
Nicotinic antagonist/ganglionic blocker
- blocks fast EPSP
Mecamylamine
Ganglionic blocking agent
Trimethaphan
Ganglionic blocking agent
Carbachol
Cholinergic/muscarinic agonist
- doesn’t penetrate as well as pilocarpine
Used to reduce intraocular pressure by stretching iris and opening drainage canal
Acetyl-B-methylcholine
Muscarinic agonist
- hydrolyzed by acetylcholinesterase
Neuromuscular blocking agents
Uses: - miuscle relaxants - intubation and surgery - muscle paralysis (botox) - orthopedic procedures - electroconvulsive therapy - treatment for poisoning with black widow spider venom and tetanus Drugs: - d-Tubocurarine - Pancuronium - Vecuronium - Cisatracurium - Rocuronium - Succinylcholine - Botulinum toxin - Hemicholinium - Aminoglycosides/tetracycline (block Ca transporter)
Muscarinic agonists
Ach Carbamylcholine Acetyl-B-methylcholine Bethanechol Pilocarpine Muscarine
Muscarinic antagonists
Atropine Scopolamine Pirenzepine Tropicamide Glycopyrrolate Cyclopentolate Tiotropium Ipratropium Tolterodine Darifencin Systemic side effects: - mad as a hatter, dry as bone, blind as a bat, red as a beet - dry skin/mouth, flushed face, fever, urinary retention, constipation, tachy, irrability
Antihistamines
Dimenhydrinate
Diphenydramine
Meclinzine
Anticholinesterases
Carbamates: - Physostigmine, Neostigmine, Pyridostigmine, Carbaryl (insecticide) Edrophonium - quaternary amine Organophosphates - malathion, diazanon, sarin, VX, tabun
Neuromucular blockers
Aminoglycosides - kanamycin, neomycin, streptomycin Tetracycline Botulinum toxin Hemicholinium Non-depolarizing - dTC, pancuronium, vecuronium, cisatracurium, rocuronium Depolarizing - succinylcholine
Ganglionic blockers
Mecamylamine
Trimethaphan
Hexamethonium
Catecholamines
Sympathomimetic amines, direct acting adrenergic agonists Norepinephrine Epinephrine Isoproterenol Dopamine Dobutamine
Alpha-agonists
Sympathomimetic, direct acting adrenergic agonists Non-catecholamines Phenylephrine - alpha 1 Clonidine - alpha 2 Brimonidine - alpha 2
Beta-agonists
Sympathomimetic, direct acting adrenergic agonists Non-catecholamines Beta 2 - albuterol - salmeterol - formoterol - ritodrine Beta 3 - mirabegron
NE releasers
Sympathomimetic, indirect acting Non-catecholamines Tyramine Amphetamine Ephedrine
Sympathomimetic-like drugs
Cocaine - NET inhibitor, increases synaptic NE
PDE inhibitors
- caffeine
- theophylline (asthma uses)
Reserpine
Sympatholytic - inhibits VMAT2, depletes NE in vesicles (and other monoamines) - crosses BBB and placenta Slow recovery on withdrawal Inactivates NE releasers Adrenoceptor up-regulation Higher doses - sedatives, tranquilizer Lower doses - anti-hypertensive - peripheral sympatholytic Adverse CNS effects - increased risk of clinical depression - potentiation of CNS depressants - exacerbation of parkinsonism - lowered seizure threshold
Adrenergic receptor agonist effects
Alpha 1 agonists
- vascular, iris and GU smooth muscle contraction
- viscous secretions from salivary and localized sweat glands (palms)
- K release from liver
Alpha 2 agonists
- vascular smooth muscle contraction
- decreased insulin release from pancreatic beta cells
- platelet aggregation
- decreases NE release from nerve terminals
Beta 1 agonists
- increase HR, contractile force and conduction velocity
- increase renin release from JG cells
Beta 2 agonists (NE weak)
- vascular, respiratory and uterine smooth muscle relaxation
- tremors in skeletal muscle
- increased glucose in skeletal muscle and increased K uptake
- increase glucose in liver
- decrease mast cell degranulation
Beta 3 agonists (EPI weak)
- relaxes urinary bladder
- thermogenic and lipolysis in adipose tissue
Prazosin
Alpha 1 antagonist - short half-life - vasodilation Uses: - primary hypertension (3rd/4th line) - no increase in NE release - vasodilation in peripheral vascular disease vasospasms - Raynaud's - relaxation of urinary tract smooth muscle in BPH Adverse events - orthostatic hypotension seen - nasal congestion - dry mouth - intraoperative floppy iris syndrome - retrograde ejaculation - delayed ejaculation - priapism
Yohimbine
Alpha 2 antagonist
- potentiates contraction of vascular smooth muscle cuz increases NE release
NE
Alpha 1 and 2, Beta 1 and 3 agonist - vasoconstrictor, increases MAP, increase in HR but vagal reflex decreases it Uses: - hypotension - mucosal congestion - local anesthesia (to keep it local) Adverse effects: - increased O2 demand in heart - cardiac arrhythmias - decreased organ/tissue perfusion - necrosis at infusion site - dose/concentration variable on route of administration
EPI
Alpha 1 and 2, Beta 1 and 2 agonist - vasodilator, this predominates at low doses; looks like NE at higher doses - increases CO and HR Uses: - cardiac arrest - anaphylactic shock - hypotension - mucosal congestion - local anesthesia (to keep it local) - lowers intraocular pressure via increased outflow - short term decongestant in eye - long term inflammatory in eye - mydriasis Adverse effects: - increased O2 demand in heart - cardiac arrhythmias - decreased organ/tissue perfusion - necrosis at infusion site - dose/concentration variable on route of administration - physiologic tremer via B2 receptor Metabolic effects: - B1 and B3 in adipose tissue - FFAs - B2 in muscle - increase glucose - B2 in liver - increase glucose - a2 in Beta cells - block insulin secretion - a1 in liver - K release, uptake into skeletal muscle via Na/K pump due to B2
ISO
Beta 1, 2 and 3 agonist
- vasodilator, MAP decreases, increases CO and HR
- relaxes bronchial/tracheal smooth muscle
Dopamine
Beta 1 at high doses, D1 (renal and GI vascular beds)
Uses:
- acute heart failure and circulatory shock
Dobutamine
Beta 1 selective Uses: - acute heart failure and circulatory shock - selectively increases CO Inotrope - increases CO - not much HR increase - reduces preload - decreases TPR
Lavamisole
MAO/COMT inhibitor
Can lead to neutropenia when cut in cocaine
Clenbuterol
Beta 2 agonist - promotes growth of muscle in livestock - skeletal muscle hypertrophy Adverse cardiovascular effects: - cardiac hypertrophy - beta 2 agonists illegal in athletes
Ritodrine
Beta 2 agonist - tocolytic - relaxes myometrium, inhibits contractions - used to delay preterm labor Adverse effects: - tachycardia - fetus/mom - hyperglycemia - fetus/mom - hypokalemia - fetus/mom - tremor - desensitization/tolerance - pulmonary edema in mom
Ergotamine
Alpha 1 adrenergic partial agonist
- used to abort migraines, take when experiencing the aura
- vasoconstrictor
- can lead to ergotism: vasospasm, painful extremities, peripheral gangrene
5HT 2B agonist - valvular disease
Ergonovine
Alpha 1 adrenergic partial agonist
- used to contract post-partum uterus to prevent hemorrhage
- oxytocic
Phenylephrine
Alpha 1 agonist
- decongestant, vasopressor, mydriatic
Clonidine
Alpha 2 agonist - inhibits NE release, sympatholytic - at high concentration, alpha 1 receptor agonist leading to smooth muscle contraction - at lower doses, CNS effects - renal excretion, short half-life Uses: - opiate withdrawal - anesthetic (analgesic sparing) - stimulates growth hormone release - Anti-hypertensive, but not commonly used for this Adverse events - drowsiness, somnolence - dry mouth - withdrawal excess symp outflow - exacerbation of HTN and myocardial ischemia Must taper down the dose
Brimonidine
Alpha 2 agonist
- sympatholytic
- lowers intraocular pressure
Albuterol
Beta 2 agonist
- short acting symptomatic relief for asthma
- inhaled
- bronchodilation and decrease mast cell degranulation
Adverse pro-inflammatory effects via B-arrestin
Salmeterol
Beta 2 agonist
- long acting slower onset, prophylactic for asthma, used with corticosteroid
- synergism with corticosteroid: phosphorylation of glucocorticoid receptor, glucocorticoids up-regulate B2AR expression, LABAs reverse glucocorticoid insensitivity
- inhaled
- bronchodilation and decrease mast cell degranulation
Adverse pro-inflammatory effects via B-arrestin
Formoterol
Beta 2 agonist
- long duration faster onset
- bronchodilation and decrease mast cell degranulation
Adverse pro-inflammatory effects via B-arrestin
Mirabegron
Beta 3 agonist
- for overactive bladder, mediates relaxation in bladder wall
- tolerance not observed
- not inhibited by beta blockers
- not useful in management of obesity
Tyramine
NE releaser
Aged/fermented foods (cheese and wine)
Oxidized by MAO - doesn’t get into circulation
- interactions with MAO-I leadng to hypertensive crisis
Ephedrine
NE releaser, weak B2 agonist
- psycostimulant and appetite suppressant
- decongestant, vasopressor/constrictor, stress urinary incontinence
Amphetamine
NE releaser
- psychostimulant, narcolepsy and ADD
5HT 2B agonist - valvular disease
Cocaine
Blocks NE uptake via NET
Increases symp output and decreases Na transport (local anesthetic)
- increase BP and HR, coronary artery spasm, can leaad to ischemia, infarction and arrythmia
- dilated cardiomyopathy, myocarditis, accelerated atherosclerosis, contraction band necrosis
- persistent hyperthermia
- neutropenia
Indacaterol and olodaterol
Beta 2 agonists
Ultra long acting
- only for COPD, not asthma
Adrenergic receptor antagonist effects
Alpha 1 blocker - vasodilation, decreased BP - relaxation of radial muscle, miosis - relaxation of genitourinary muscle - decreased viscous salivation Uses: - hypertension, catecholamine secreting tumors, peripheral vascular disease, iris radial relaxation, urethral sphincter relaxation (for prostatic hyperplasia), vas deferens relaxation, corpus cavernosum relaxation (for erectile dysfunction), ureters/urinary tract relaxation (for renal calculi), decreases viscous salivation (causes dry mouth) Adverse events: - orthostatic hypotension, nasal congestion, priapism, delayed ejaculation, retrograde ejaculation, IFIS Alpha 2 blocker - increase NE release - increase insulin secretion Uses: - orthostatic hypotension - but increases HR - increases GI motility Adverse events: - increase HR, diarrhea, dyspepsia Alpha 1 and 2 blocker - alpha 1 block effects, beta effects (increase HR, force, contractility, smooth muscle relaxation)
Phenoxybenzamine
Alpha 1 and 2 antagonist - irreversible antagonist - long acting - vascular smooth muscle relaxation Uses: - management of catecholamine secreting tumors before and during surgical resection, alpha block before beta block Adverse events: - orthostatic hypotension - nasal congestion - dry mouth - intraoperative floppy iris syndrome - retrograde ejaculation - delayed ejaculation - priapism
Phentolamine
Alpha 1 and 2 antagonist - competitive antagonist - short acting - vascular smooth muscle relaxation Uses: - management of catecholamine secreting tumors before and during surgical resection, alpha block before beta block - intracavernosal injection/oral for erectile dysfunction Adverse events: - orthostatic hypotension - nasal congestion - dry mouth - intraoperative floppy iris syndrome - retrograde ejaculation - delayed ejaculation - priapism
Terazosin
Alpha 1 antagonist - long half-life - vasodilation Uses: - primary hypertension (3rd/4th line) - no increase in NE release - vasodilation in peripheral vascular disease vasospasms - Raynaud's - relaxation of urinary tract smooth muscle in BPH, improves bladder emptying Adverse events: - orthostatic hypotension still seen - nasal congestion - dry mouth - intraoperative floppy iris syndrome - retrograde ejaculation - delayed ejaculation - priapism
Tamsulosin
Alpha 1 A antagonist
- relaxant of urinary tract smooth muscle, improves bladder emptying
- less vasodilator activity, less effect on BP
- use in older male for BPH treatment if you don’t want to cause orthostatic hypotension
Adverse events
- especially causes intraoperative floppy iris syndrome
- orthostatic hypotension
- nasal congestion
- dry mouth
- retrograde ejaculation
- delayed ejaculation
- priapism
Beta adrenergic receptor antagonists
Effect
- negative inotropic and chronotropic, decreases automaticity and conduction velocity
Use
- MI, dysrythmias, post-infarction, hyperthyroidism, primary HTN, heart failure
Indications
- angina of effort, decreases cardiac O2 consumption
- postinfarction, lowers mortality
- cardiac arrhythmias
- systolic heart failure, decreases morbidity and mortality
- primary hypertension, decreases BP
- hyperthyroidism - decreases HR, tremor and anxiety
- migraine headache prophylaxis
- glaucoma - decreases aqueous secretion and intraocular pressure
- decreases tremors
Adverse events:
- decreased peak exercise capacity
- bradycardia
- AV conduction block
- acute exacerbation of heart failure
- peripheral vasoconstriction
- withdrawal beta-supersensitivity - trigger infarction
- bronchoconstriction
- mast cell destabilization
- blunted subjective signs of hypoglycemia
- delayed recovery from hypoglycemia
- exercise induced hyperkalemia
- hypertensive crisis in adrenergic excess
Beta blockers
Non-selective - propanolol - timolol - pindolol B1 selective - atenolol - esmolol - metoprolol Non-selective w/vasodilator - carvedilol - labetalol - betaxolol - beta 1 selective Acute effect is drop in CO, increase in TPR (unless partial agonist pindolol) - decrease in HR and contractilty Chronic use leads to fall in BP Anti-hypertensive, anti-arrhythmatic (rate control), relieve angina symptoms
Propanolol
Beta 1 and 2 blocker
- high lipid solubility, liver metabolism
Timolol
Beta 1 and 2 blocker
- lowers intraocular pressure
- eye drop
Pindolol
Beta 1 and 2 blocker
- partial agonist
- low lipid solubility
- if pt has AV block, can use this
Atenolol
Beta 1 blocker
- low lipid solubility - renally excreted
- longer halflife than propanool
Esmolol
Beta 1 blocker
- short half-life
Metoprolol
Beta 1 blocker
- moderate lipid solubility
CHF use for HFrEF:
- decrease contractility
- negative chronotropy - reduced SA node activity, slowed atrial and AV conduction, increase AV refractory period
- improve survival, improve LVEF, decrease sudden death events
Carvedilol
Non-selective beta blocker with vasodilator activity
- long half-life
- vasodilates
- moderate lipid solubility
- used for heart failure, improves cardiomyocyte survival through beta-arrestin signaling
CHF use for HFrEF:
- decrease contractility
- negative chronotropy - reduced SA node activity, slowed atrial and AV conduction, increase AV refractory period
- improve survival, improve LVEF, decrease sudden death events
Labetalol
Non-selective beta blocker with vasodilator activity
- alpha 1 and beta blocker
- low lipid solubility
- used for hypertension in pregnancy
- vasodilator
Betaxolol
Beta 1 selective
- long half-life
- Ca entry block
- decrease production of aqueous, reduce intraocular pressure in glaucoma
- cardioselective
Side effects:
- bradycardia, worsen heart block, lowers BP, CNS depression
Dipiprazole
Alpha blocker
- eye drops for ophthalmology
- reverse dilation
Homatropine
Cholinergic antagonist
- mydriasis for ophthalmology
Glaucoma treatment
Beta antagonist - decrease aqueous production - timolol - beta 1 and 2 - betaxalol - beta 1 Alpha agonist - decrease aqueous production - brimonidine - alpha 2 - apraclonidine - alpha 2 Cholinergic agonist - constricts pupil - pilocarpine - cabamylcholine Prostaglandin analogues - most used
Apraclonidine
Alpha 2 agonist
- decrease aqueous production
- weak alpha 1 agonist - diagnosis of Horner’s syndrome
Alpha blockers
Alpha 1 selective antagonists
- prazosin, terazosin, tamsulosin
Alpha 1 and 2 antagonists
- phenoxybenzamine, phentolamine
Anti-hypertensive drugs: sympatholytics
Beta blockers Combined alpha and beta blockers Alpha 1 blockers Central alpha 2 agonists - methyldopa - clonidine Adrenergic neuron blockers/depleters - reserpine - metyrosine Drugs: - reserpine - methyldopa - clonidine - moxonidine - metyrosine
Anti-hypertensive drugs: Calcium Channel Blockers
Dihydropyridines
- Nifedipine
- Amlodipine
Nondihydropyridines
- Verapamil
- Diltiazem
Arteriovasodilators - relax VSM
Dilate coronary arteries - useful in coronary vasospasms
Variably cardiodepressant - nonDHPs more than DHPs due to frequency (closed) binding vs voltage (inactivated) binding
- decrease HR, automaticity, conduction velocity, reduced contractility
No retention of Na/water - DHPs natriuretic
First line antihypertensives
Other uses:
- tocolytic preterm
- manage vertigo
- neuroprotective
Adverse events:
- DHPs - hypotension, headache, reflex symp activation, swollen ankles
- nonDHPs - LV dysfunction, AV block, avoid with beta blockers, GI effects
Anti-hypertensive drugs: RAS inhibitors
ACE inhibitors - captopril - enalapril(at) - lisinopril Angiotensin II receptor blockers - losartan - valsartan Renin inhibitors - aliskiren Mineralocorticoid receptor antagonists - spironolactone - eplerenone
Anti-hypertensive drugs: Diuretics
Thiazide type
Loop diuretics
K sparing diuretics (MRAs)
Anti-hypertensive drugs
Diuretics Sympatholytics Calcium Channel Blockers RAS inhibitors Direct vasodilators
Parenteral antihypertensives
Nitroprusside - nitrovasodilator Nitroglycerin - nitrovasodilator Nicardipine - CCB, DHP Clevidpine - DHP, short acting Fenoldopam - D1 agonist, short half-life Enalaprilat - ACE-I Hydralazine - Direct vasodilator Labetalol - Alpha/Beta blocker Esmolol - Beta blocker, short acting Phentolamine - Alpha blocker
Hydralazine
Direct vasodilator, arteriolar Afterload reducer - anti-hypertensive, 3rd/4th line Not used on own due to psuedotolerance (inc. CO/HR, Na+H2O retention), give sympatholytic and diuretic Beneficial for: - weak pump and poor organ perfusion - can use for eclampsia - IV Can cause lupus like syndrome
Minoxidil
Direct vasodilator, arteriolar - KATP channel opener selective for VSM Afterload reducer - anti-hypertensive, 3rd/4th line Not used on own due to pseudotolerane (inc. CO/HR, Na+H2O retention), give sympatholytic and diuretic Beneficial for: - weak pump and poor organ perfusion Can cause hypertrichosis
Diazoxide
KATP channel opener, mimics MgADP
- for hyperinsulinemic hypoglycemia and sulfonylurea overdose
- decreases insulin release
Adenosine
Arteriovasodilator
Antiarrhythmic - decreases HR and AV conduction
Pharmacologic stress test
Ischemic pre/post conditioning
Bronchoconstriction
Anti-inflammatory
Opens KATP channels through binding adensoine receptor
Sulfonylureas
KATP channel inhibitor
- oral glucose lowering agent
- increase insulin release from pancreatic B cells
Inhibit ischemic pre/post conditioning
Methyldopa
Anti-hypertensives - alpha 2 receptor agonist, brainstem - decrease symp outflow Prodrug - metabolized to methylDA then methylNE First line antihypertensive in pregnancy
Metyrosine
Inhibitor of NE synthesis - competitively inhibits tyrosine hydroxylase
Uses:
- Catecholamine secreting tumors
Diltiazem
Anti-hypertensive and cardiodepressant nonDHP - less effective than verapamil on reducing cardiac contractility Adverse effects - LV dysfunction, AV block, constipation - don't combine with BB
Verapamil
Anti-hypertensive and cardiodepressant nonDHP - heart effects more than vasodilation Adverse effects - LV dysfunction, AV block, constipation - don't combine with BB
Nifedipine
Anti-hypertensive, mostly vasodilation DHP Adverse events: - hypotension, flushing, headache - reflex symp activation - swollen ankles
Amlodipine
First line anti-hypertensive - long acting DHP Adverse events: - hypotension, flushing, headache - swollen ankles
ACE-inhibitors
Anti-hypertensive
Also inhibit bradykinin inactivation, increase levels of bradykinin
- also increases prostaglandins
- angioedema, dry cough
Drugs:
- captopril - sulfhydryl, rash, neutropenia, nephropathy, dysgeusia, short half-life, renal excretion
- enalapril - prodrug, longer half-life, renal excretion
- fosinopril - prodrug, longer half-life, renal and bile excretion
- lisinopril
Subject to escape in heart failure (see increase in Ang II from other mechanisms); add MARs
May lead to hyperK; watch when used with MARs (and BBs)
Uses:
- antihypertensive
- regression of LVH, increased survival in HF
- inhibition of vascular hyperplasia
- renal fnx okay in DM
Adverse events:
- dizziness, hypotension
- hyperK
- risk of renal failure in renal artery stenosis
- teratogenic
Spironolactone
Mineralocorticoid receptor antagonists
Eplerenone
Mineralocorticoid receptor antagonist
ARBs
Block AT1 receptor Disadvantageous in CAD Drugs: - losartan - valsartan Uses: - antihypertensive - regression of LVH (not as good as ACE-I) - good for CHF - inhibition of vascular hyperplasia - renal fnx okay in DM Adverse events: - dizziness, hypotension - hyperK - risk of renal failure in renal artery stenosis - teratogenic
Nesiritide
B type natriuretic peptide
- modestly improves shortness of breath 6 to 24hr post-treatment in severe, acute heart failure but does not alter 30 day outcomes
Sacubitril-valsartan
Angiotensin receptor neprilysin inhibitor ARNI
Neprilysin inhibitor - sacubitril
ARB - valsartan
Reduce risk of death and hospitalizations for heart failure
- see higher levels of BNP but lower levels of NT pro-BNP
Anti-arrhythmic drugs
Na channel blockers - quinidine - lidocaine - flecainide - procainamide - propafenone Beta blockers - propranolol - esmolol - beta 1 - metoprolol - beta 1 - atenolol - beta 1 K channel blocker - amiodarone - sotalol - ibutilide - dofetilide - dronedarone CCB - verapamil - diltiazem Adenosine Digoxin
Class I antiarrhythmics
Fast Na channel blockers
- decrease Na current, decrease rate of rise of phase 0 AP
- reduce exicitability of non-nodal tissues
Class IA antiarrhythmics
Quinidine
Procainamide - used acutely, NAPA is an active metabolite K channel blocker
Disopyramide
Action:
- depress Na current and rate of rise of AP moderately
- increase AP duration, block K channels, increase refractoriness
- prolong ventricular effective refractory period
Metabolism and effects:
- hepatic metabolism
- procainamide renal excretion
- high incidence of torsade
- nauseau
- quinidine - diarrhea, antagonist at M2 receptor
Class IB antiarrhythmics
Lidocaine
Action:
- depress Na current and rate of rise of AP
- decrease duration of AP
Crosses BBB - cognitive effects, seizures
Class IC antiarrhythmics
Flecainide Propafenone Action: - depress Na current and rate of rise of AP strongly - does not affect AP duration
Class II antiarrhythmics
Beta blockers
- propranlol, metoprolol, esmolol, atenolol, carvedilol, labetalol
- propranlol crosses BBB - nightmares and sedation
- metoprolol crosses BBB
Action:
- reduce excitability and decrease conduction velocity in AV node
Class III antiarrhythmics
K channel blockers
Amiodarone
- iodine, long half-life, hepatically metabolized, can affect thyroid, pulmonary fibrosis, blue skin, neuropathy, hepatotoxicity, corneal deposits, but rarely torsades
Sotalol
- not metabolized, renally excreted, high incidence of torsades
Ibutilide
Dofetilide
Dronedarone
Action:
- prolong duration of AP without altering rate of rise or resting potential - increase refractory period
- tend to produce long QT and torsade
Uses:
- more effective for A flutter than class IC
Class IV antiarrhythmics
L type Calcium channel blockers
Verapamil
Diltiazem
Action:
- block slow, non-activating Ca current
- slow conduction, increase refractoriness in AV node
- main affect on slow AP fibers like SA and AV node
Digoxin
Shortens refractory periods, enhances excitability
Renally excreted, long half-life
Quinidine increases plasma digoxin levels
Serous adverse effects
- cognitive and vision, crosses BBB
Ca Channel Blockers
DHPs - nifedipine, amlodipine Non-DHPs - diltiazem, verapamil As antihypertensives: - first line - dilate coronary arteries, useful in coronary vasospasm - no retention of salt and water CYP3A4 metabolism - drug drug interactions
Renin inhibitors
Aliskiren - antihypertensive Adverse events: - dizziness, hypotension - hyperK - risk of renal failure in renal artery stenosis - teratogenic
Nitrates
Used for angina - relieves symptoms - non-endothelium dependent - vasodilation - veins and arteries, coronary arteries - decreases preload and afterload - increases O2 supply and subendocardial flow Adverse events: - headache - hypotension
Fibrinolytics
Uses:
- ischemic symptoms for more than 30mins with ST elevation, within 10 hrs
- not used for nonSTEMIs and unstable angina
Lipid drugs
Statins - HMG-CoA reductase inhibitors - lovastatin - pravastatin - atorvastatin Bile acid binding resin - cholestyramine - colesevelam Chosterol absorption inhibitor - ezetimibe PCSK9 inhibitor - alirocumab - evolocumab Fibrates - gemfibrozil - fenofibrate Nicotinic acid - Niacin - vit B3
Statins
Inhibit HMG CoA reductase, no mevalonate production from HMG CoA - reduce LDL levels - cause increase in LDL R production - also reduce isoprenylation of proteins CYP450 metabolism 1st gen - simvastatin, pravastatin 2nd gen - atorvastatin, rosuvastatin Pravastatin - not CYP450 Rosuvastatin - only 10% metabolized Adverse events: - hepatitis - myositis, muscle pain, rhabdomyolysis (results in renal failure) - diabetes - teratogenic - polyneuropathy - drug interactions Get serum aminotransferase and creatinine baseline
Bile acid binding resins
Block bile acid uptake by enterocytes - increases bile acid synthesis from cholesterol - incremental lowering of LDL with statin combination Adverse events - GI distress - adsorb vitamins and drugs like statins - increase TGs in hyperTG Drugs - cholestyramine - colesevelam
Ezetimibe
Block intestinal uptake of cholesterol and plant sterols via NPC1L1
Treats sitosterolemia
Lowers LDL
- reduced CHD events, no reduction in all cause mortality
Eliminated in feces
Fibrates
Act on PPAR-a, nuclear receptor for FFAs
- increase oxidation of FFAs in liver, reduced TG synthesis
- increase ApoA-I and ABCA1 expression
- increase LPL expression and decrease ApoC-III expression - increase TG hydrolysis
Increase HDL
Decrease TG
Decrease LDL if high, increase it if low
Renal excretion, enterohepatic cycling
Decline in CV events, not in all caues mortality
Drugs:
- gemfibrozil
- fenofibrate
Nicotinic acid
Give high doses cuz rapidly metabolized Acts on GPCR, activates Gi - inhibits breakdown of TGs in adipose - decrease ApoA-I breakdown - increase PGs via beta-arrestin signaling Increase HDL Decrease TG Adverse events: - cutaneous vasodilation and burning sensation on upper body and face - hyperglycemia - GI distress - hepatotoxicity
PCSK9 inhibitors
PCSK9 promotes degradation of LDL receptors via binding
- the drug prevents this
PCSK9 is upregulated by statins - limits statin max effectiveness
- increase number of LDL receptors, more LDL endocytosed
- reduce LDL when added to statins
- reduce Lp(a)
Drugs:
- alirocumab
- evolocumab
Anti-platelet agents
Act on platelet activation, aggregation and thrombus formation Thromboxane inhibitor - Aspirin - salicylate ADP receptor antagonist - Clopidogrel - Prasugrel - Ticagrelor GPIIb/IIIa inhibitors - Abciximab - Eptifibatide - Tirofiban PAR-1 antagonist - Vorapaxar
Anti-thrombotic agents
Rivaroxaban Apixaban Low molecular weight heparin Unfractionated heparin Bivalirudin Dabigatran
Aspirin
Anti-platelet
Dose dependent inactivation of cyclooxygenase via acetylation of prostaglandin G/H synthase
- no TXA2 production, reduces vasoconstriction and platelet aggregation
- acetylation is permanent/irreversible
Indications:
- primary prevention - stable angina, known coronary disease and maybe asymptomatic high risk ppl
- secondary prevention - prior TIA/strok, post MI, post CABG, post stent, post peripheral vascular surgery
Adverse events:
- Allergy/sensitivity - asthma, nasal polyps
- GI intolerance
- GI bleeding
- Aspirin resistance
Dipyridamole
Inhibits platelet cAMP PDE, inhibits TXA2 formation
- can use if aspirin allergy
Adverse events:
- dizziness, GI distress, rash, headache
Clopidogrel
P2Y12 inhibitor
- ADP receptor antagonist, no expression of GPIIb/IIIa
- thienopyridine
Prodrug:
- 2 pass metabolism by CYP2C19
Used after cardiac stent deployment for in-stent thrombosis
Reduce risk of recurrent ischemia in NSTEMI/STEMI if medically managed
Dose dependent platelet aggregation inhibition
Dose dependent onset of action, more faster
Indications:
- reduced MI/stroke/vascular death in pts with recent MI, CVA, PVD
- reduce thrombus in stent
- reduce morbidity/mortality post PCI
Dual antiplatelet therapy with aspirin
Adverse events:
- rash
- GI upset
- bleeding
Prasugrel
P2Y12 inhibitor
- ADP receptor antagonist, no expression of GPIIb/IIIa
- thienopyridine
Prodrug:
- activated by CYP3A4/2B6
Used after cardiac stent deployment for in-stent thrombosis
Reduce risk of recurrent ischemia in NSTEMI/STEMI if medically managed
Less effective in renal disease; okay in liver disease
Compared to clopidogrel more reduction in CV death/MI/stroke, and more bleeding seen
Vs clodipogrel:
- no advantage in 75yo or over, under 60kg
- worse in pt with stroke history
Indication:
- pt who goes to cath lab for ACS
Ticagrelor
P2Y12 inhibitor
ADP receptor antagonist
Used after cardiac stent deployment for in-stent thrombosis
Survival benefit - reduces cardiovascular death risk
BID - downside
Ticlopidine
ADP receptor antagonist Used in cerebrovascular disease Active drug Adverse events: - hematologic - neutropenia, thrombocytopenia - diarrhea - rash
Abciximab
Inhibits GPIIb/IIIa - most potent antiplatelets Irreversible IV Use: - periangioplasty, STEMI pts not treated with antiplatelet agents prior to PCI - or large burden of thrombi in STEMI pts Adverse events: - bleeding at cath site
Tirofiban
Inhibits GPIIb/IIIa
- most potent antiplatelets
IV
Eptifibatide
Inhibits GPIIb/IIIa - most potent antiplatelets IV, short half-life Uses: - unstable angina/nonSTEMI pts getting PCI Adverse events: - bleeding at cath site - thrombocytopenia - monitor platelet count 2,4,24hrs
Anticoagulants
Factor Xa inhbitors - unfractionated heparin IV/SQ - low molecular weight heparin - enoxaparin SQ - rivaroxaban PO - apixaban PO Vit K antagonists - warfarin PO Direct Thrombin inhibitors - bivalirudin IV - dabigatran PO
Heparin
Anticoagulant With cofactor antithrombin inhibits thrombin - antithrombin binds pentapeptide sequence, thrombin binds through 13 saccharides - inactivates thrombin - inactivates factor Xa As dose increases, clearance decreases - higher risk of bleeding at higher doses Shorter half-life in PE Longer half-life in renal disease Monitor PTT Uses: - ACS - DVT/PE prevention and treatment - cerebrovascular disease Adverse events: - bleeding - HIT, HITT - chronic use: osteoporosis, hyperaldosteronism, hyperK Safe in pregnancy
Argatroban
Anticoagulant
Direct thrombin inhibitor - treat thrombosis in HIT/HITT
Low molecular weight heparin
Anticoagulant Enoxaprin Greater relative activity against factor Xa - inhibits this - still binds antithrombin through pentapeptide sequence Advantages - more predictable anticoagulant response - better bioavailability at lose doses - dose independent clearance mechanism - longer half-life Adverse events: - bleeding - thrombocytopenia - less than UFH - local irritation Safe in pregnancy
Rivaroxaban
Anticoagulant
Factor Xa inihbitor
Indications:
- non-valvular A fib pts for reduction of stroke and systemic embolism
- DVT prophylaxis in hip/knee replacement
- DVT/PE prophylaxis and treatment
For A fib, must give with meal
- Avoid in pts with low CrCl
For DVT/PE tx, must give with meal
For DVT prophylaxis, no food needed, lower dose
Lower bleeding risk than warfarin in pts with A fib
Adverse events:
- bleeding
CYP3A4
Apixaban
Anticoagulant Factor Xa inhibitor Indications: - non-valvular A fib pts for reduction of stroke and systemic embolism - DVT prophylaxis in hip/knee replacement - DVT/PE prophylaxis and treatment For prophylaxis, lower dose Older, thinner, renal disease lower dose Lower bleeding risk than warfarin in pts with A fib Adverse events: - bleeding CYP3A4
Warfarin
Coumadin Anticoagulant Binds vitamin K epoxide reductase - VKOR normally regenerates reduced vit K - inhibits formation of factors 2,7,9,10 99% bound to plasma proteins - if give aspirin, increase serum warfarin concentration Indications - DVT/PE tx and prophylaxis - prosthetic heart valves - stroke prevention in A fib/flutter - CAD to prevent recurrent infarction, and CVA prevention (prefer antiplatelets) - peripheral artery disease Adverse events: - life threatening bleeding - give vit K - skin necrosis - contraindicated in pregnancy
Dabigatran
Anticoagulant Direct thrombin inhibitor - oral, BID - INR not helpful, use PTT - faster action than warfarin - prodrug - inhibits free and clot-bound thrombin - renal elimination - lower CrCl, lower dose Adverse events: - GI effects - rifampin interactions No different from warfarin in bleeding risk
Bivalirudin
Anticoagulant
Direct thrombin inhibitor
- IV
- can use in HIT
- inactivates soluble and fibrin bound thrombin
- renal clearance - lower dose in renal failure cuz risk of bleeding
Uses:
- pts with ACS undergoing PCI, with or without GPIIb/IIIa inhibitors
- pts with/at risk of HIT/HITT undergoing PCI
- less bleeding than heparin in PCI, but use P2Y12 more now
Adverse events:
- bleeding
Measure activated clotting times
Fibrinolytics
Streptokinase tPA TNK-tPA r-PA Dissolve clots Indications - ACS for STEMI if can't get to cath lab Uses: - large venous thromboembolism - STEMI, in combo with antiplatelets and anticoags - stroke - within 3 hrs - IR Adverse events: - bleeding Contraindications - surgery within 10 days, trauma - serious GI bleed within 3 months - DBP over 110 - active bleeding, hemorrhagic disorder - cerebrovascular accident - aortic dissection - acute pericarditis
Streptokinase
Activates plasmin, digests fibrinogen - loading dose given cuz antigenic - monitor thrombin time Adverse events: - fever - allergic skin rxn - anaphylaxis - headache, muscle aches
tPA
Serine protease
- activates plasminogen in presence of fibrin
Uses:
- unclot cath in interventional radiology
- treatment of choice in pts with major PE
- useful in stroke within 3hr of symptom onset
3 pronged administration route
rPA
2 bolus
TNK-tPA
Tenecteplase
- single dose
- lower plasma clearance rate, longer half-life
- greater fibrin specificity
NOS inhibitors
Endogenous methylated products of argnine
- L-NMMA
- tilarginine
- ADMA
Elevated ADMA levels predict CV morbidity
Nitroprusside
NO donor
- IV, short half-life
- used in HTN emergencies
Actions:
- relaxes veins, coronary arteries and resistance vessels (non-selective vasodilator)
Release NO non-enzymatically
Creates thiocyanate - toxin that accumulates
Organic nitrates
Nitroglycerin - glyceryl trinitrate Isosorbide dinitrate Isosorbide mononitrate Lipid soluble Relax venous, coronary artery, biliary, esophageal smooth muscle - little effect on resistance vessels Release NO enzymatically Tolerance can occur Main effect is venodilation, decreases preload, decreases wall tension which decreases O2 demand and increases O2 supply Uses: - relief, prophylaxis for angina - increased exercise tolerance - reduce pulmonary congestion in acute HF - relieve coronary spasms Hydralazine-isosorbide dinitrate is an anti-oxidant, reduces morbidity/mortality in HF Adverse effects - headache - goes away over time - orthostatic hypotension - tolerance: 8-12 hr nitrate free every 24 hr Get rid of tolerance with anti-oxidants
Nitroglycerin
Short half-life and duration
- weakly active metabolites
Sublingual - fastest onset, shortest durtation, no tolerance
Buccal - fast onset, short duration
Transdermal/IV - longer onset, last 24hrs, tolerance
Isosorbide dinitrate/mononitrate
Longer half-life than GTN - metabolites more active and last longer also Dinitrate - sublingual and oral - longer duration than GTN - oral can develop tolerance Mononitrate - oral - longest duration and onset - can develop tolerance
Sildenafil
PDE 5 inhibitor, blocks cGMP inactivation
- maintains smooth muscle relaxation/dilation
- amplifies erectile response to arousal
- do not combine with nitrovasodilators
Also used in pulmonary HTN
Riociguat
Soluble GC stimulator
- treat pulmonary HTN
Milrinone
Enoximone is another one Phosphodiesterase type 3 inhibitor - increases levels of cAMP CHF use for HFrEF - enhanced inotropy - enhanced lusitropy - positive chronotropy/increase HR - AV conduction velocity increased - also increases automaticity and arrhythmogenicity
Bisoprolol
Beta 1 selective antagonist
CHF use for HFrEF:
- decrease contractility
- negative chronotropy - reduced SA node activity, slowed atrial and AV conduction, increase AV refractory period
- improve survival, improve LVEF, decrease sudden death events
Digitalis
Cardiac glycoside
- inhibits Na/K ATPase, results in Na/Ca exchanger pumping in Ca
CHF use for HFrEF
- inotrope
- improved carotid baroreflex sensitivity - decreased symp tone
Used for A fib and A flutter
- increased cholinergic receptor sensitivity - increased vagal tone
Toxicity:
- excessively HR slowing due to SN or AV block
- arrhythmias due to increased automaticity
- worse in hypoK
- abdominal cramping, vomiting
- yellow/green halos in vision
- confusion
