PNS and Cardio Flashcards
(183 cards)
1
Q
Acetylcholine (miochol)
A
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
2
Q
Carbamylcholine
A
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
3
Q
Acetyl-B-methylcholine
A
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
4
Q
Bethanechol
A
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
5
Q
Pilocarpine
A
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
6
Q
Atropine
A
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
7
Q
Scopolamine
A
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
8
Q
Pirenzepine
A
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
9
Q
Tropicamide
A
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
10
Q
Glycopyrrolate
A
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
11
Q
Cyclopentolate
A
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
12
Q
Tiotropium
A
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
13
Q
Tolterodine
A
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
14
Q
Darifencin
A
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
15
Q
Ipratropium
A
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
16
Q
Dimenhydrinate
A
Antihistamine
- cross reacts to block muscarinic receptors
- chronic rhinitis/hay fever
- motion sickness
17
Q
Diphenhydramine
A
Antihistamine
- cross reacts to block muscarinic receptors
- chronic rhinitis/hay fever
- motion sickness
18
Q
Meclinzine
A
Antihistamine
- cross reacts to block muscarinic receptors
- chronic rhinitis/hay fever
- motion sickness
19
Q
Muscarine
A
Leads to cholinergic symptoms/SLUDGE (salivation, lacrimation, perspiration)
- poisoning from Amanita muscaria, Inocybe, and Clitocybe mushrooms
- treat with atropine
20
Q
Pralidoxime
A
Oxime (2-PAM)
- displaces anticholinesterases
- treat anticholinesterase poisoning by organophosphates (given with atropine)
21
Q
Edrophonium
A
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
22
Q
Carbamate
A
Reversible acetylcholinesterase inhibitor (longer lasting, hours)
Contraindications:
- don’t use for inflammatory condition, bronchial asthma, peptic ulcer, coronary insufficiency, hyperthroidism
SLUDGE side effects
23
Q
Organophosphate
A
Irreversible (very long lasting) acetylcholinesterase inhibitor
- form stable covalent bond to serine group oc AchE
- pesticides usually
SLUDGE side effects
24
Q
Physostigmine
A
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
25
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
26
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
27
Malathion
```
Anticholinesterase
- organophosphate pesticide
- low toxicity to man/birds
- inactivated by carboxylesterase in mammals and birds
SLUDGE side effects
```
28
Diazanon
Anticholinesterase
- organophosphate pesticide
- household use for cockroaches
SLUDGE side effects
29
Carbaryl
```
(Sevin)
Anticholinesterase
- carbamate pesticide
- used in gardens
SLUDGE side effects
```
30
Soman/Tabun
Anticholinesterase
- organophosphate nerve agent
- chemical warfare agent
SLUDGE side effects
31
Sarin
Anticholinesterase
- organophosphate nerve agent
- chemical warfare agent
SLUDGE side effects
32
VX
```
Anticholinesterase
- organophosphate nerve agent
- chemical warfare agent
Smallest lethal dose
SLUDGE side effects
```
33
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
34
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
35
Hemicholinium
Blocks choline re-uptake
36
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
37
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
38
Pancuronium
Non-depolarizing nicotinic antagonist, neuromuscular blocker
- longest lasting
Toxicity:
- arrest all muscles, including those of respiration
39
Vecuronium
Non-depolarizing nicotinic antagonist, neuromuscular blocker
- metabolism decreased in liver disease
Toxicity:
- arrest all muscles, including those of respiration
40
Cisatracurium
Non-depolarizing nicotinic antagonist, neuromuscular blocker
- not hydrolyzed enzymatically (Hoffman elimination), use in liver disease
Toxicity:
- arrest all muscles, including those of respiration
41
Rocuronium
Non-depolarizing nicotinic antagonist, neuromuscular blocker
- fastest onset, shortest lasting
- metabolism decreased in liver disease
Toxicity:
- arrest all muscles, including those of respiration
42
Hexamethonium
Nicotinic antagonist/ganglionic blocker
| - blocks fast EPSP
43
Mecamylamine
Ganglionic blocking agent
44
Trimethaphan
Ganglionic blocking agent
45
Carbachol
Cholinergic/muscarinic agonist
- doesn't penetrate as well as pilocarpine
Used to reduce intraocular pressure by stretching iris and opening drainage canal
46
Acetyl-B-methylcholine
Muscarinic agonist
| - hydrolyzed by acetylcholinesterase
47
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)
```
48
Muscarinic agonists
```
Ach
Carbamylcholine
Acetyl-B-methylcholine
Bethanechol
Pilocarpine
Muscarine
```
49
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
```
50
Antihistamines
Dimenhydrinate
Diphenydramine
Meclinzine
51
Anticholinesterases
```
Carbamates:
- Physostigmine, Neostigmine, Pyridostigmine, Carbaryl (insecticide)
Edrophonium - quaternary amine
Organophosphates
- malathion, diazanon, sarin, VX, tabun
```
52
Neuromucular blockers
```
Aminoglycosides
- kanamycin, neomycin, streptomycin
Tetracycline
Botulinum toxin
Hemicholinium
Non-depolarizing
- dTC, pancuronium, vecuronium, cisatracurium, rocuronium
Depolarizing
- succinylcholine
```
53
Ganglionic blockers
Mecamylamine
Trimethaphan
Hexamethonium
54
Catecholamines
```
Sympathomimetic amines, direct acting adrenergic agonists
Norepinephrine
Epinephrine
Isoproterenol
Dopamine
Dobutamine
```
55
Alpha-agonists
```
Sympathomimetic, direct acting adrenergic agonists
Non-catecholamines
Phenylephrine - alpha 1
Clonidine - alpha 2
Brimonidine - alpha 2
```
56
Beta-agonists
```
Sympathomimetic, direct acting adrenergic agonists
Non-catecholamines
Beta 2
- albuterol
- salmeterol
- formoterol
- ritodrine
Beta 3
- mirabegron
```
57
NE releasers
```
Sympathomimetic, indirect acting
Non-catecholamines
Tyramine
Amphetamine
Ephedrine
```
58
Sympathomimetic-like drugs
Cocaine - NET inhibitor, increases synaptic NE
PDE inhibitors
- caffeine
- theophylline (asthma uses)
59
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
```
60
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
61
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
```
62
Yohimbine
Alpha 2 antagonist
| - potentiates contraction of vascular smooth muscle cuz increases NE release
63
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
```
64
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
```
65
ISO
Beta 1, 2 and 3 agonist
- vasodilator, MAP decreases, increases CO and HR
- relaxes bronchial/tracheal smooth muscle
66
Dopamine
Beta 1 at high doses, D1 (renal and GI vascular beds)
Uses:
- acute heart failure and circulatory shock
67
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
```
68
Lavamisole
MAO/COMT inhibitor
| Can lead to neutropenia when cut in cocaine
69
Clenbuterol
```
Beta 2 agonist
- promotes growth of muscle in livestock
- skeletal muscle hypertrophy
Adverse cardiovascular effects:
- cardiac hypertrophy
- beta 2 agonists illegal in athletes
```
70
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
```
71
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
72
Ergonovine
Alpha 1 adrenergic partial agonist
- used to contract post-partum uterus to prevent hemorrhage
- oxytocic
73
Phenylephrine
Alpha 1 agonist
| - decongestant, vasopressor, mydriatic
74
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
```
75
Brimonidine
Alpha 2 agonist
- sympatholytic
- lowers intraocular pressure
76
Albuterol
Beta 2 agonist
- short acting symptomatic relief for asthma
- inhaled
- bronchodilation and decrease mast cell degranulation
Adverse pro-inflammatory effects via B-arrestin
77
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
78
Formoterol
Beta 2 agonist
- long duration faster onset
- bronchodilation and decrease mast cell degranulation
Adverse pro-inflammatory effects via B-arrestin
79
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
80
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
81
Ephedrine
NE releaser, weak B2 agonist
- psycostimulant and appetite suppressant
- decongestant, vasopressor/constrictor, stress urinary incontinence
82
Amphetamine
NE releaser
- psychostimulant, narcolepsy and ADD
5HT 2B agonist - valvular disease
83
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
84
Indacaterol and olodaterol
Beta 2 agonists
Ultra long acting
- only for COPD, not asthma
85
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)
```
86
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
```
87
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
```
88
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
```
89
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
90
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
91
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
```
92
Propanolol
Beta 1 and 2 blocker
| - high lipid solubility, liver metabolism
93
Timolol
Beta 1 and 2 blocker
- lowers intraocular pressure
- eye drop
94
Pindolol
Beta 1 and 2 blocker
- partial agonist
- low lipid solubility
- if pt has AV block, can use this
95
Atenolol
Beta 1 blocker
- low lipid solubility - renally excreted
- longer halflife than propanool
96
Esmolol
Beta 1 blocker
| - short half-life
97
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
98
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
99
Labetalol
Non-selective beta blocker with vasodilator activity
- alpha 1 and beta blocker
- low lipid solubility
- used for hypertension in pregnancy
- vasodilator
100
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
101
Dipiprazole
Alpha blocker
- eye drops for ophthalmology
- reverse dilation
102
Homatropine
Cholinergic antagonist
| - mydriasis for ophthalmology
103
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
```
104
Apraclonidine
Alpha 2 agonist
- decrease aqueous production
- weak alpha 1 agonist - diagnosis of Horner's syndrome
105
Alpha blockers
Alpha 1 selective antagonists
- prazosin, terazosin, tamsulosin
Alpha 1 and 2 antagonists
- phenoxybenzamine, phentolamine
106
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
```
107
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
108
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
```
109
Anti-hypertensive drugs: Diuretics
Thiazide type
Loop diuretics
K sparing diuretics (MRAs)
110
Anti-hypertensive drugs
```
Diuretics
Sympatholytics
Calcium Channel Blockers
RAS inhibitors
Direct vasodilators
```
111
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
```
112
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
```
113
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
```
114
Diazoxide
KATP channel opener, mimics MgADP
- for hyperinsulinemic hypoglycemia and sulfonylurea overdose
- decreases insulin release
115
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
116
Sulfonylureas
KATP channel inhibitor
- oral glucose lowering agent
- increase insulin release from pancreatic B cells
Inhibit ischemic pre/post conditioning
117
Methyldopa
```
Anti-hypertensives
- alpha 2 receptor agonist, brainstem
- decrease symp outflow
Prodrug - metabolized to methylDA then methylNE
First line antihypertensive in pregnancy
```
118
Metyrosine
Inhibitor of NE synthesis - competitively inhibits tyrosine hydroxylase
Uses:
- Catecholamine secreting tumors
119
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
```
120
Verapamil
```
Anti-hypertensive and cardiodepressant
nonDHP
- heart effects more than vasodilation
Adverse effects
- LV dysfunction, AV block, constipation
- don't combine with BB
```
121
Nifedipine
```
Anti-hypertensive, mostly vasodilation
DHP
Adverse events:
- hypotension, flushing, headache
- reflex symp activation
- swollen ankles
```
122
Amlodipine
```
First line anti-hypertensive
- long acting DHP
Adverse events:
- hypotension, flushing, headache
- swollen ankles
```
123
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
124
Spironolactone
Mineralocorticoid receptor antagonists
125
Eplerenone
Mineralocorticoid receptor antagonist
126
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
```
127
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
128
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
129
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
```
130
Class I antiarrhythmics
Fast Na channel blockers
- decrease Na current, decrease rate of rise of phase 0 AP
- reduce exicitability of non-nodal tissues
131
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
132
Class IB antiarrhythmics
Lidocaine
Action:
- depress Na current and rate of rise of AP
- decrease duration of AP
Crosses BBB - cognitive effects, seizures
133
Class IC antiarrhythmics
```
Flecainide
Propafenone
Action:
- depress Na current and rate of rise of AP strongly
- does not affect AP duration
```
134
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
135
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
136
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
137
Digoxin
Shortens refractory periods, enhances excitability
Renally excreted, long half-life
Quinidine increases plasma digoxin levels
Serous adverse effects
- cognitive and vision, crosses BBB
138
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
```
139
Renin inhibitors
```
Aliskiren
- antihypertensive
Adverse events:
- dizziness, hypotension
- hyperK
- risk of renal failure in renal artery stenosis
- teratogenic
```
140
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
```
141
Fibrinolytics
Uses:
- ischemic symptoms for more than 30mins with ST elevation, within 10 hrs
- not used for nonSTEMIs and unstable angina
142
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
```
143
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
```
144
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
```
145
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
146
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
147
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
```
148
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
149
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
```
150
Anti-thrombotic agents
```
Rivaroxaban
Apixaban
Low molecular weight heparin
Unfractionated heparin
Bivalirudin
Dabigatran
```
151
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
152
Dipyridamole
Inhibits platelet cAMP PDE, inhibits TXA2 formation
- can use if aspirin allergy
Adverse events:
- dizziness, GI distress, rash, headache
153
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
154
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
155
Ticagrelor
P2Y12 inhibitor
ADP receptor antagonist
Used after cardiac stent deployment for in-stent thrombosis
Survival benefit - reduces cardiovascular death risk
BID - downside
156
Ticlopidine
```
ADP receptor antagonist
Used in cerebrovascular disease
Active drug
Adverse events:
- hematologic - neutropenia, thrombocytopenia
- diarrhea
- rash
```
157
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
```
158
Tirofiban
Inhibits GPIIb/IIIa
- most potent antiplatelets
IV
159
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
```
160
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
```
161
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
```
162
Argatroban
Anticoagulant
| Direct thrombin inhibitor - treat thrombosis in HIT/HITT
163
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
```
164
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
165
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
```
166
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
```
167
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
```
168
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
169
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
```
170
Streptokinase
```
Activates plasmin, digests fibrinogen
- loading dose given cuz antigenic
- monitor thrombin time
Adverse events:
- fever
- allergic skin rxn
- anaphylaxis
- headache, muscle aches
```
171
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
172
rPA
2 bolus
173
TNK-tPA
Tenecteplase
- single dose
- lower plasma clearance rate, longer half-life
- greater fibrin specificity
174
NOS inhibitors
Endogenous methylated products of argnine
- L-NMMA
- tilarginine
- ADMA
Elevated ADMA levels predict CV morbidity
175
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
176
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
```
177
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
178
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
```
179
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
180
Riociguat
Soluble GC stimulator
| - treat pulmonary HTN
181
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
```
182
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
183
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
