Term
|
Definition
Only NT in parasympathetic, first NT in sympathetic
Muscarninc and nicotinic receptors
acetyl CoA + choline via choline acetyltransferase -> acetylcholine
Hydrophilic-> poorly absorbed, poorly distributed to CNS; rapidly hydrolyzed
Effects: DUMBELSS |
|
|
Term
|
Definition
Muscarinic cholinergic receptor agonist
Effects: miosis; vasodialation, slowing of HR (at higher levels of receptor activation); bronchial constriction, increased respiratory secretion; increased GI motility and secretion, sphincter relaxation=> DUMBELSS
High resistance to hydrolysis
Use: post-op urinary retention or paralytic ileus
Oral or parenteral; does not enter CNS
Toxicity: parasympathomimetic effects, bronchospasm in asthmatics |
|
|
Term
|
Definition
AchE inhibitor; carbamate ester
MOA: forms covalent bond w/ AchE that is resistant to hydrolysis; excess activation of muscarinic and nicotinic Ach receptors by excess Ach in synapse-> parasympathetic affects predominate=> DUMBELSS
Hydrolysis can occur but at a slow rate (30min-6hr)
Well absorbed but in general carbamates are not
Use: glaucoma; antimuscarinic drug intoxication |
|
|
Term
|
Definition
AchE inhibitor; Organophosphate insecticide
MOA: Prevents breakdown of acetylcholine; phosphorylates the active site of AchE and forms a bond that is extremely stable; excess activation of muscarinic and nicotinic Ach receptors by excess Ach in synapse-> parasympathetic effects predominate=> DUMBELSS
Hydrolyzes at an extremely slow rate (100s of hours)
Can undergo aging where there is strengthening of the AchE-phosphorus bond
Relatively safe for humans because it is metabolized into an inactive product
Very well absorbed
Prodrug that is activated in animals and plants |
|
|
Term
|
Definition
AchE inhibitor; Organophosphate "nerve gas"
MOA: Prevents breakdown of acetylcholine; phosphorylates the active site of AchE and forms a bond that is extremely stable; excess activation of muscarinic and nicotinic Ach receptors by excess Ach in synapse-> parasympathetic effects predominate=> DUMBELSS
Hydrolyzes at an extremely slow rate (100s of hours)
Can undergo aging where there is strengthening of the AchE-phosphorus bond-> w/in 10mins |
|
|
Term
|
Definition
Nicotinic cholinergic receptor agonist
Ionotropic receptor- increased Na+ influx and depolarization
Nn receptor: PNS, SNS, ganglion cells
Nm receptor: neuromuscular junction
Activate both the sympathetic and parasympathetic nervous systems, but the net effect depends on the organ and the predominant tone
Highly lipophilic-> penetrates BBB, well absorbed across skin
Toxicity: increased GI activity; increased BP; continued agonist occupancy is associated w/ desensitization (depolarization blockade)-> flaccid paralysis/respiratory arrest
Can also be used as a pesticide |
|
|
Term
|
Definition
Muscarinic cholinergic receptor agonist
Metabotropic receptor
Effects: miosis; vasodilation, slowing of HR (at higher levels of receptor activation); bronchial constriction, increased respiratory secretion; increased GI motility and secretion, sphincter relaxation=> DUMBELSS
Occurs through actions on effector cells |
|
|
Term
|
Definition
Antimuscarinic
Treatment: partial AV block (b/c parasympathetic control over AV node is significant); bradyarrhythmia
Muscarinic receptor antagonist- competitive antagonist
MOA: reversible blockade of Ach receptors
Effects: eye dilation (mydriasis); cycloplegia (loss of accommodation); tachydcardia; bronchodilation; dry mouth; reduced GI motility; reduced urination; reduced sweating
Use: cholinergic poisoning; eye examination
Given IV, topically (drops)-> well absorbed from conjunctival and gut membranes
Toxicity: increased intraocular pressure in closed angle glaucoma; dry mouth, flushed skin; agitation; delirium; hyperthermia-> dry as a bone, blind as a bat, red as a beet, mad as a hatter |
|
|
Term
|
Definition
Muscarinic receptor antagonist
Effects: eye dilation (mydriasis); tachydcardia; bronchodilation; dry mouth; reduced GI motility
Use: vertigo; nausea
Given IM or transdermal
Faster onset of action than Atropine but shorter duration of effect and crosses CNS more readily -> well absorbed from gut and conjunctival membranes; can also cross skin
Toxicity: tachycardia, blurred vision, delirium, xerostomia (dry mouth), drowsiness, amnesia, hallucinations, coma |
|
|
Term
|
Definition
Antimuscarinic
MOA: competitive, nonselective antagonist for muscarinic receptors
Treatment: asthma/COPD-> reduces bronchospasm
Given via aerosol
Toxicity: xerostomia (dry mouth), cough |
|
|
Term
|
Definition
Ganglion blocker
MOA: block the action of Ach at sympathetic and parasympathetic nicotinic receptors; blockade by occupying sites in/on nicotinic ion channel but not the actual cholinoceptor
Use: HTN
Effects: cycloplegia/loss of accommodation; decreased BP (decreased arteriolar and venomotor tone)-> orthostatic hypotension; decreased GI motility/secretion-> constipation; urinary retention; sexual dysfunction (erection and ejaculation); reduced sweating |
|
|
Term
|
Definition
Ganglion blocker
MOA: block the action of Ach at sympathetic and parasympathetic nicotinic receptors; blocks the nicotinic receptor, not the pore
Use: hypertensive emergency, dissecting aortic aneurysm, reduce surgical bleeding, ECT
Short acting; given IV infusion (inactive orally)
Effects: cycloplegia/loss of accommodation; decreased BP (decreased arteriolar and venomotor tone)-> orthostatic hypotension; decreased GI motility/secretion-> constipation; urinary retention; sexual dysfunction (erection and ejaculation); reduced sweating |
|
|
Term
|
Definition
Mixed α/β agonist; α1=α2; β1=β2
Vasoconstriction and cardiac stimulant (increase HR)
Rise in systolic BP-> α and β1
Rise in diastolic BP is less than systolic b/c of β2 agonism
Use: complete heart block or cardiac arrest-> redistributes blood flow during CPR to coronaries and brain; hemostasis; reducing diffusion of local anesthetics; asthma; anaphylaxis (EpiPen) |
|
|
Term
|
Definition
Mixed α/β agonist; α1=α2; β1>>β2
Increased PVR, total BP, and contractility
Compensatory baroreflex overcomes positive chronotropic effects-> decrease in HR
Use: acute hypotension |
|
|
Term
|
Definition
Alpha agonist; α1 > α2
Increased BP (increased vascular tone), decreased HR (vagal reflex)
Not a catechol derivative so not inactivated by COMT-> longer duration of action
Use: mydriasis, decongestant, raise BP (orthostatic hypotension)
Given oral, nasal, parenteral, and opthalmic |
|
|
Term
|
Definition
Alpha agonist; α1 > α2
Increased BP (increased vascular tone), decreased HR (vagal reflex)
Use: hypotensive states |
|
|
Term
|
Definition
Beta agonist; β1>β2
Increase CO by increased contractility w/ less reflex tachycardia
Given as racemic mixture-> + isomer=β1 agonist and α1 antagonist; - isomer=α1 agonist
Use: cardiogenic shock and acute heart failure; pharmacologic stress test
Given IV; duration a few minutes
Toxicity: angina/arrhythmia in pts w/ CAD |
|
|
Term
|
Definition
Beta agonist; β1=β2
Decreased BP (decreased vascular tone), increased HR and contractility-> increase in CO
Treatment: bradyarrhythmia; asthma
Given IV |
|
|
Term
Terbutaline
Albuterol
Salmeterol |
|
Definition
Beta agonist; β2>>β1
Treatment: asthma, premature labor (uterine relaxation) |
|
|
Term
|
Definition
Antihypertensive- racemic mixture of 4 isomers
MOA: reversible adrenergic antagonist (β≥α1>α2) w/ partial agonist and local anesthetic activity
Decreases BP w/ limited HR increase
Use: HTN emergencies; phoechromocytoma
Half-life 5hrs; given oral or parenteral
Toxicity: less tachycardia than other α1 blockers |
|
|
Term
|
Definition
Antihypertensive- racemic mixture
MOA: adrenergic antagonist (β≥α1>α2)
Use: chronic heart failure- reduces mortality
Moderate lipid solubility; half-life 7-10hrs; extensive liver metabolism (CYP2D6); given orally
Attenuates ROS-initiated lipid peroxidation and inhibits vascular sm musc mitogenesis-> beneficial in CHF
Toxicity: fatigue |
|
|
Term
|
Definition
Antihypertensive
MOA: reversible α1 adrenergic receptor antagonist; allows NE to exert neg feedback on its own release (via α2)
α1 in arterioles and venules-> lowers BP by reducing vascular pressure
Usu used in combo w/ β-blocker and diuretic; may also raise HDL levels
Primarily used in men w/ HTN and prostatic hyperplasia (reduces bladder obstruction symptoms)
Half-life 3-4hrs; extensively metabolized; given orally
Toxicity: retention of salt and water; dizziness, palpitations, headache, lassitude, positive test for antinuclear factor (no rheumatic symptoms) |
|
|
Term
|
Definition
Antihypertensive
MOA: reversible α1 adrenergic receptor antagonist; allows NE to exert neg feedback on its own release (via α2)
α1 in arterioles and venules-> lowers BP by reducing vascular pressure
Usu used in combo w/ β-blocker and diuretic
Primarily used in men w/ HTN and prostatic hyperplasia (reduces bladder obstruction symptoms)
Half-life 12hrs; little 1st past metabolism (given once daily)
Toxicity: retention of salt and water; orthostatic hypotension w/ 1st dose; dizziness, palpitations, headache, lassitude, positive test for antinuclear factor (no rheumatic symptoms) |
|
|
Term
|
Definition
MOA: irreversible α-adrenoceptor antagonist (α1>α2); inhibits reuptake of NE; blocks H1, Ach, and 5-HT receptors
Attenuation of catecholamine induced vasoconstriction; reduces BP when symp tone is high; increased CO (reflex/α2 blockade)
Use: diagnosis and treatment of pheochromocytoma
Long duration (14-48hrs); given orally
Toxicity: orthostatic hypotension, tachycardia, MI; nasal stuffiness; inhibits ejaculation, fatigue, sedation, nausea |
|
|
Term
|
Definition
MOA: reversible α-adrenoceptor competitive antagonist (α1=α2); minor inhibition of 5-HT receptor and agonism of M, H1, and H2 receptors
Decreased PVR (α1) and increased cardiac stimulation (α2/baroreflex)
Use: diagnosis and treatment of pheochromocytoma; combined w/ propranolol to treat clonidine withdrawal syndrome; erectile dysfunction
Given IV and oral; half-life 45mins
Toxicity: severe tachycardia, arrhythmia, MI |
|
|
Term
|
Definition
Antihypertensive; Antiarrhythmic- Class 2
Treatment: prevention of recurrent infarction and sudden death after acute MI; suppression of ventricular ectopic depolarization (less effective than Na+ channel blockers); HTN; angina; migraine; hyperthyroidism; tremor
MOA: nonselective β-adrenergic receptor antagonist; local anesthetic action
Anti-ischemic effects-> decrease in CO (decreased HR); inhibits renin production (β1)
Half-life 3-5hrs; given orally (sustained release prep available) or parenterally; highly lipid soluble
Toxicity: bradycardia; asthma; fatigue; vivid dreams; cold hands; withdrawal from β-receptor upregulation-> nervousness, tachycardia, angina, increase BP, MI
Contraindications: bradycardia, cardiac conduction disease, asthma, peripheral vascular insufficiency, diabetes |
|
|
Term
|
Definition
Antihypertensive
Use: HTN, angina; arrhythmia; migraine
MOA: β-adrenergic receptor partial agonist, but greater agonist for β2-> intrinsic sympathomimetic effect; local anesthetic action
Lower BP by reducing PVR; moderate decrease in HR; beneficial for pts w/ bradyarrhythmias or PVD
Moderate lipid solubility; half-life 3-4hrs; given orally
May potentiate actions of antidepressants
Toxicity: fatigue, cold hands, vivid dreams |
|
|
Term
|
Definition
Antihypertensive; Antiarrhythmic- Class 2
Treatment: prevention of recurrent infarction and sudden death after acute MI; suppression of ventricular ectopic depolarization (less effective than Na+ channel blocker); angina; HTN; migraine
MOA: cardioselective β-adrenergic receptor antagonist (β1>>>β2) w/ local anesthetic action
Anti-ischemic effects-> lower HR/BP; reduce renin
Metabolized by CYP2D6, high 1st pass metabolism; half-life 3-7hrs; moderate lipid solubility
Sustained release version effective in HTN + heart failure
Toxicity: bradycardia, fatigue, vivid dreams, cold hands |
|
|
Term
|
Definition
Antihypertensive
Treatment: angina; HTN; arrhythmia
MOA: cardioselevtive β-adrenergic receptor antagonist (β1>>>β2)
Lowers HR/BP and renin
Half-life 6-9hr; not extensively metabolized; given once daily
Reduction in dosage required in moderate renal insufficiency
Toxicity: bradycardia, fatigue, vivid dreams, cold hands |
|
|
Term
|
Definition
Antihypertensive
MOA: selective β1 adrenergic receptor antagonist (β1>>>β2)
Rapidly metabolized via hydrolysis by RBC esterases; half-life 9-10mins
Given constant IV infusion for intra and postop HTN, hypertensive emergencies w/ tachycardia, supraventricular arrhythmias, and MI
Toxicity: bradycardia, hypotension |
|
|
Term
|
Definition
L-arginine --NOS--> L-citrulline + NO
NOS requires O2 and NADPH
Enzyme bound cofactors: heme, BH4, FAD |
|
|
Term
| L-NMMA (Nω-monomethyl-L-arginine) |
|
Definition
Nitric Oxide Synthase Inhibitor- nonselective
MOA: competitive inhibitor; binds arginine binding site in NOS
Treatment: hypotension |
|
|
Term
|
Definition
| MOA: inhibits 5-phosphodiesterase-> prolonged cGMP elevation = vasodilation |
|
|
Term
|
Definition
NO Scavenger
MOA: NO is inactivated by superoxide; superoxide dismutase scavenges superoxide anion, protecting NO
Enhances NO potency, prolongs its duration |
|
|
Term
|
Definition
Soluble guanylyl cyclase inhibitor
MOA: NO activates soluble guanylyl cyclase to convert GTP->cGMP which activates PKG, an inhibitor of VSMC Ca2+ release and contraction; methylene blue inhibits guanylyl cyclase
Treatment: hypotension |
|
|
Term
|
Definition
Antihypertensive
MOA: ACE Inhibitor- inhibits conversion of angiotensin I to II and inhibits inactivation of bradykinin (a vasodilator)-> decrease PVR
Reduction of dosage required in moderate renal insufficiency; safe for use in ischemic heart disease and chronic kidney disease
Half-life 2.2hrs; renal elimination
Toxicity: neutropenia/proteinuria; hypotension after initial dose in hypovolemic pts; acute renal failure; hyperkalemia; dry cough, angioedema; teratogenic, altered sense of taste; allergic skin reaction; drug fever
Contraindication: pregnancy
DI: K+ or K+ sparing diuretics-> hyperkalemia; NSAIDs-> block bradykinin vasodilation |
|
|
Term
|
Definition
Antihypertensive
MOA: prodrug ACE Inhibitor; active metabolite enalaprilat (available for IV use)-> decrease PVR
Reduction of dosage required in moderate renal insufficiency; safe for use in ischemic heart disease and chronic kidney disease
Half-life 11hrs; renal elimination
Toxicity: hypotension after initial dose in hypovolemic pts; acute renal failure; hyperkalemia; dry cough, angioedema; teratogenic, altered sense of taste; allergic skin reaction; drug fever
Contraindication: pregnancy
DI: K+ or K+ sparing diuretics-> hyperkalemia; NSAIDs-> block bradykinin vasodilation |
|
|
Term
|
Definition
Antihypertensive
MOA: prodrug ACE Inhibitor-> decrease PVR
Reduction of dosage required in moderate renal insufficiency; safe for use in ischemic heart disease and chronic kidney disease
Half-life 12 hrs; renal elimination
Toxicity: hypotension after initial dose in hypovolemic pts; acute renal failure; hyperkalemia; dry cough, angioedema; teratogenic, altered sense of taste; allergic skin reaction; drug fever
Contraindication: pregnancy
DI: K+ or K+ sparing diuretics-> hyperkalemia; NSAIDs-> block bradykinin vasodilation |
|
|
Term
|
Definition
Antihypertensive
MOA: prodrug ACE Inhibitor- long acting-> decrease PVR
Reduction of dosage required in moderate renal insufficiency; safe for use in ischemic heart disease and chronic kidney disease
Renal elimination
Toxicity: hypotension after initial dose in hypovolemic pts; acute renal failure; hyperkalemia; dry cough, angioedema; teratogenic, altered sense of taste; allergic skin reaction; drug fever
Contraindication: pregnancy
DI: K+ or K+ sparing diuretics-> hyperkalemia; NSAIDs-> block bradykinin vasodilation |
|
|
Term
LOSARTAN
VALSARTAN
CANDESARTAN |
|
Definition
Antihypertensive
MOA: angiotensin II type 1 receptor (AT1) antagonist
Half-life 1-2hrs (active metabolite is 3-4hrs)
Toxicity: hypotension; acute renal failure; hyperkalemia; teratogenic
Contraindication: pregnancy |
|
|
Term
|
Definition
Antihypertensive
MOA: renin inhibitor
Decreases baseline renin and the rise caused by other antihypertensives |
|
|
Term
|
Definition
Antihypertensive
β-adrenergic receptor antagonist (β1=β2) |
|
|
Term
|
Definition
Antihypertensive
MOA: nonselective β-adrenergic receptor antagonist
Little metabolism, excreted in urine
Given once daily
Reduction of dosage required in moderate renal insufficiency |
|
|
Term
|
Definition
Antihypertensive- dihydropyridine
Treatment: angina, HTN
MOA: Ca2+ channel blocker
More selective as vasodilators-> low cardiac depressant effects
Half-life 35hrs |
|
|
Term
|
Definition
Antihypertensive- dihydropyridine
Treatment: HTN, Raynaud's phenomenon
MOA: Ca2+ channel blocker
More selective as vasodilators-> low cardiac depressant effects |
|
|
Term
|
Definition
Antihypertensive- dihydropyridine
Treatment: angina, HTN
MOA: Ca2+ channel blocker
More selective as vasodilators-> low cardiac depressant effects |
|
|
Term
|
Definition
Antihypertensive- dihydropyridine
Treatment: HTN, angina, Raynaud's phenomenon
MOA: Ca2+ channel blocker; binds α1 subunit of L-type channel on inner side of membrane; binds open/inactivated channels more effectively; reduces frequency of opening
More selective as vasodilators-> low cardiac depressant effects; more selective for arterioles than veins (no orthostatic hypotension)
Oral short acting form- hypertensive emergency; half-life 2-4hrs
Toxicity: increased risk of MI/mortality in short acting form; cardiac depression, flushing, dizziness, nausea, constipation, peripheral edema |
|
|
Term
|
Definition
Antihypertensive- dihydropyridine
MOA: Ca2+ channel blocker
IV |
|
|
Term
|
Definition
Antihypertensive; Antianginal; Antiarrhythmic- Class 4
Treatment: supraventricular tachycardia; reduce ventricular rate in atrial flutter and fibrillation; HTN
MOA: activated and inactivated L-type Ca2+ channel blocker-> effect is more marked in tissues that fire frequently, that are less completely polarized at rest, and where activation depends solely on Ca2+ (SA/AV nodes)
Effects: AV nodal conduction time and refractory period are prolonged; slows SA node by direct action but hypotensive actions may result in small increase in rate; can suppress afterdepolarizations; decreased HR and CO
Oral or IV; low oral bioavailabilty bc metabolized by liver; half-life 4-6hrs
Toxicity: peripheral vasodilation; hypotension and ventricular fibrillation in pts w/ ventricular tachycardia; AV block w/ large doses or in pts w/ AV nodal disease; constipation, lassitude, nervousness, peripheral edema
Drug Interactions: β-blockers/digoxin-> additive effect at AV node; displaces digoxin from tissue
Contradictions: ventricular tachycardia |
|
|
Term
|
Definition
Antihypertensive
MOA: centrally acting sympathoplegic-> partial α2 agonist (> α1); binds imidazoline receptor
Reduces symp and increases parasymp tone-> bradycardia and decreased BP (decreased PVR and renal resistance w/ relaxation of capacitance vessels); sensitizes brain stem vasomotor centers to inhibition by baroreflexes
Lipid soluble-> rapidly crosses BBB; half-life 8-12hrs
Oral 2X/day; transdermal path (7days)-> skin rxns
Reduction of dosage required in moderate renal insufficiency
Toxicity: dry mouth, sedation; withdrawal-> nervousness, tachycardia, sweating, headache, hypertensive crisis
Contraindications: depression; TCA-> block antiHTN effects |
|
|
Term
|
Definition
Antihypertensive
Treatment: HTN, esp during pregnancy
MOA: centrally acting sympatholplegic- converted to α-methyldopamine and α-methylnorepinephrine; α-methylNE stimulate central α-adrenoceptors (α2 > α1)
Reduces PVR and renal vascular resistance
Onset = 4-6hrs; half-life 2hrs
Toxicity: orthostatic hypotension (V depleted pts); sedation, lassitude, impaired concentration; nightmares; vertigo; EPS; lactation (increased prolactin); positive Coombs test; rarely hemolytic anemia, hepatitis, and drug fever |
|
|
Term
|
Definition
Antihypertensive-> Diuretic
Treatment: mild to moderate HTN w/ normal renal/cardiac function
MOA: blocks Na/Cl transporter in distal convoluted tubule-> increased fluid loss
Half-life 12hrs
Toxicity: hypokalemia, Mg2+ depletion, impaired glucose tolerance, increased serum lipid, increase uric acid (gout) |
|
|
Term
|
Definition
Antihypertensive-> Diuretic
Treatment: severe HTN; heart failure
MOA: blocks Na/K/2Cl transporter-> acts on the loop of Henle to promote Na/water removal
BP response continues to increase w/ increased dose
Toxicity: hypokalemia, Mg2+ depletion, impaired glucose tolerance, increased serum lipid, increase uric acid (gout) |
|
|
Term
|
Definition
Antihypertensive-> Diuretic- steroid
MOA: aldosterone receptor antagonist-> reduced Na/water retention = reduce venous pressure/preload
Favorable effect on heart function in people w/ heart failure
Oral; duration 24-72hrs
Toxicity: gynecomastia, hyperkalemia
DI: ACE inhibitor/angiotensin receptor blocker-> hyperkalemia |
|
|
Term
|
Definition
Antihypertensive-> Adrenergic Neuron Blocker
Now rarely used
MOA: uptake into symp nerves by NET and replaces NE stores
Too polar to enter CNS-> no central SE
Half-life 5days (120hrs); maximal effect in 1-2wks
May require reduction of dosage in moderate renal insufficiency
Toxicity: orthostatic and exercise hypotension; delayed/retrograde ejaculation; diarrhea
DI: TCAs/sympathomimetics (cocaine, amphetamine)-> block uptake and cause hypertension
Contraindications: pheochromocytoma-> hypertensive crisis |
|
|
Term
|
Definition
Antihypertensive
Guanethidine-like drug available in USA |
|
|
Term
|
Definition
Antihypertensive-> Adrenergic Neuron Blocker
Now rarely used
MOA: irreversibly blocks VMAT, depleting stores of NE, DA, and serotonin in central and peripheral neurons and adrenal medulla
Decreased CO and PVR
Rapidly crosses BBB; half-life 24-48hrs
Toxicity: diarrhea, GI cramps, increases gastric acid secretion; sedation, lassitude, nightmares, depression, EPS/Parkinsonism
Contraindications: depression |
|
|
Term
|
Definition
Antihypertensive-> Vasodilator
Complex of iron, cyanide, and nitrous groups
Treatment: hypertensive emergencies and severe heart failure
MOA: release of NO activates guanylyl cyclase-> increases intracellular cGMP to relax arterioles and venules-> decrease PVR and venous return
Given parenterally (IV infusion)
Rapidly metabolized by RBC w/ release of cyanide-> metabolized by mito. rhodanase to thiocyanate-> renal elimination
Effects disappear w/in 1-10mins
Sensitive to light, so keep covered
Toxicity: cyanide-> metabolic acidosis, arrhythmia, hypotension, death; thiocyanate-> weakness, disorientation, psychosis, muscle spasms, convulsions, hypothyroidism, methemoglobinemia
May give sodium thiosulfate or hydroxocobalamin for cyanide metabolism |
|
|
Term
|
Definition
Antihypertensive-> Vasodilator
Treatment: long term, outpatient for severe HTN; heart failure
MOA: release of NO to dilate arterioles-> decrease PVR; reduces damaging remodeling of heart
In combo w/ nitrate effective in HTN+heart failure, esp in Af. Am. pts
Given orally, well absorbed, high metabolism by acetylation; half-life 1.5-3hrs
Toxicity: headache, nausea, anorexia, palpitations, sweating, flushing; angina/ischemic arrhythmia in pts w/ ischemic heart disease; lupus syndrome at higher doses-> arthralgia, myalgia, skin rash, fever; peripheral neuropathy and drug fever uncommonly |
|
|
Term
|
Definition
Antihypertensive-> Vasodilator
Treatment: hypertensive emergencies
MOA: opens K+ channels to hyperpolarize arteriole sm muscle to prevent contraction
Highly bound to albumin and vascular tissue
Lower doses in renal failure (reduced protein binding-> hypotension)
Given parenterally; long acting (4-12hrs); half-life 24hrs
Toxicity: hypotension (stroke, MI); reflex sympathetic response (angina, ischemia, cardiac failure); hyperglycemia-> inhibits insulin release (used to treat hypoglycemia); salt and water retention
DI: β-blocker-> exaggerated hypotensive effects (prevents reflex tachycardia)
Contraindications: ischemic heart disease |
|
|
Term
|
Definition
Antihypertensive-> Vasodilator
Treatment: long term, outpatient for HTN
MOA: opens K+ channels to hyperpolarize arteriole sm muscle to prevent contraction-> decrease PVR
High Na+ and fluid retention w/ reflex sympathetic stimulation-> must be given w/ diuretic and β-blocker
Given orally; half-life 4hrs
Toxicity: tachycardia, palpitations, angina, edema, headache, sweating, hypertrichosis (used in Rogaine) |
|
|
Term
|
Definition
Vasodilator
Treatment: angina
MOA: denitrated by glutathione S-transferase-> nitrite ion released an converted to NO; or metabolized to NO by mitochondrial aldehyde reductase in venous smooth muscle; activation of soluble guanylyl cyclase by NO converts GTP to cGMP which leads to dephosphorylation of myosin light chain-> relaxation
Marked venous relaxation = decreased preload; reflex tachycardia; decreased platelet aggregation
Usu given as sublingual tablet; can also be given transdermal, parenteral, buccal, or oral (high dose); available in long-acting forms
High first-pass metabolism (sublingual avoids this); effect 15-30mins; half-life 2-8mins; renal excretion
Toxicity: orthostatic hypotension, syncope, reacts w/ Hb to produce methemoglobin; tachycardia; tachyphylaxis/tolerance; carcinogenic?
Contraindications: increased intracranial pressure |
|
|
Term
|
Definition
Vasodilator
Treatment: angina; heart failure
MOA: converted to NO; activation of soluble guanylyl cyclase converts GTP to cGMP which leads to dephosphorylation of myosin light chain-> relaxation; reduces damaging remodeling of heart
Marked venous relaxation = decreased preload; reflex tachycardia; decreased platelet aggregation
Given orally or sublingual
High first-pass metabolism (sublingual avoids this); effect 15-60mins; half-life 2-8mins; renal excretion
Toxicity: orthostatic hypotension, syncope, reacts w/ Hb to produce methemoglobin; tachycardia; tachyphylaxis/tolerance; carcinogenic?
Contraindications: increased intracranial pressure |
|
|
Term
|
Definition
Treatment: prophylaxis of angina
MOA: reduces contractility via blockade of a late Na+ current that facilitates Ca2+ entry via the Na-Ca exchanger
Oral w/ 6-8hr duration; metabolized by CYP3A
Toxicity: QT prolongation, nausea, constipation, dizziness, headache |
|
|
Term
|
Definition
β-adrenergic receptor and D-receptor agonist
Increases renal blood flow; higher doses increase cardiac force and BP
Treatment: decompensated heart failure; shock
Given IV; duration a few minutes
Toxicity: arrhythmia |
|
|
Term
|
Definition
Cardiac glycoside
MOA: inhibits Na/K-ATPase, increased intracellular Na+ = decreased Na/Ca exchange = increased intracellular Ca2+-> increased contractility
Increased parasympathetic effects-> decrease HR
Treatment: heart failure; atrial fibrillation
Oral or parenteral; widely distributed to tissue, and 2/3 excreted unchanged in kidneys; half-life 36-40hrs
Toxicity: arrhythmia; anorexia, nausea, vomiting, diarrhea; disorientation, hallucinations, visual disturbances; gynecomastia
Interactions: K+-> inhibit each others binding to Na/K-ATPase (hyperkalemia reduces enzyme inhibition); Ca2+-> hypercalcemia increases risk of arrhythmia; Mg2+-> opposite of Ca2+
Contraindication: Wolff-Parkinson-White Syndrome |
|
|
Term
|
Definition
Cardiac glycoside
MOA: inhibits Na/K-ATPase, increased intracellular Na+ = decreased Na/Ca exchanger = increased intracellular Ca2+-> increased contractility
Increased parasympathetic effects-> decrease HR
Treatment: heart failure; atrial fibrillation
Longer acting version of Digoxin; unlike Digoxin, eliminated by liver-> used for pts w/ renal dysfunction
Toxicity: arrhythmia; anorexia, nausea, vomiting, diarrhea; disorientation, hallucinations, visual disturbances; gynecomastia |
|
|
Term
| Digibind (aka Digoxin immune fab) |
|
Definition
Antibodies directed against cardiac glycosides
Reversing severe glycoside intoxication |
|
|
Term
|
Definition
Phosphodiesterase-3 Inhibitor
MOA: prevents inactivation of cAMP by phosphodiesterase-3-> increase in contractility and vasodilation
Treatment: heart failure
Parenterally; half-life 3-6hrs; renal excretion
Toxicity: arrhythmia; may cause bone marrow/liver toxicity |
|
|
Term
| Amrinone (aka Inamrinone) |
|
Definition
Phosphodiesterase-3 Inhibitor
MOA: prevents inactivation of cAMP by phosphodiesterase-3-> increase in contractility and vasodilation
Treatment: heart failure
Parenterally; half-life 3-6hrs; renal excretion
Toxicity: arrhythmia; nausea/vomiting; thrombocytopenia; hepatotoxicty |
|
|
Term
|
Definition
Vasodilator
MOA: synthetic form of BNP; increases cGMP = reduced vasculature tone and causes diuresis
Treatment: decompensated heart failure
Given IV; half-life 18mins
Toxicity: hypotension; renal damage; death |
|
|
Term
|
Definition
Na+ channel blockade
Class 1A- prolong action potential duration (APD); dissociate w/ intermediate kinetics (all Class 1A are also Class 3)
Class 1B- shorten APD; dissociate w/ rapid kinetics
Class 1C- minimal effect on APD; dissociate w/ slow kinetics |
|
|
Term
|
Definition
| Sympatholytic- reduce β-adrenergic activity |
|
|
Term
|
Definition
| Prolong action potential duration- block rapid delayed rectifier K+ channels (IKR) |
|
|
Term
|
Definition
| Block cardiac Ca2+ current- slows conduction in SA/AV nodes |
|
|
Term
|
Definition
Antiarrhythmic- Class 1A
Treatment: atrial < ventricular arrhythmia (2nd/3rd choice)
MOA: blocks Na+ channels in depolarized cells > nondepolarized; nonspecific K+ channel blockade; direct depressant on SA and AV nodes (anticholinergic)
IV, IM, oral (well absorbed)
Hepatic metabolism via acetylation and renal clearance; metabolite = NAPA-> class 3 activity=> may cause torsade de pointes; less likely to develop SLE in pts that have high NAPA production
Half-life- 3-4hrs; longer for NAPA
Ganglion blockade reduces peripheral vascular resistance-> hypotension (esp w/ rapid infusion or L ventricular dysfunction)
Toxicity: excessive AP prolongation, QT prolongation, torsade de pointes arrhythmia/syncope, excessive slowing conduction, new arrhthymias; nausea/diarrhea; rash; fever; hepatitis; agranulocytosis (rare); w/ long term therapy-> syndrome resembling SLE (arthraligia, arthritis, pleuritis, pericarditis, parenchymal pulmonary disease; renal lupus (rare); increased antinuclear Ab (nearly all)) |
|
|
Term
|
Definition
Antiarrhytmic- Class 1A
Treatment: ventricular > supraventricular arrhythmia (rarely used)
MOA: blocks Na+ channels in depolarized cells > nondepolarized; nonspecific K+ channel blockade; anticholinergic and α-receptor blocking
Readily absorbed from GI; hepatic metabolism; half-life 6hrs
Toxicity: excessive QT prolongation, torsade de pointes; excessive Na+ channel blockade w/ slowed conduction throughout heart; diarrhea/nausea/vomiting; cinchondism (headache, dizziness, and tinnitus); rarely thrombocytopenia, hepatitis, angioneurotic edema, and fever
Drug Interactions: hyperkalemia, displaces high protein bound drugs-> digoxin |
|
|
Term
|
Definition
Antiarrhythmic- Class 1A
Treatment: ventricular arrhythmia (not 1st line)
MOA: blocks Na+ channels in depolarized cells > nondepolarized; nonspecific K+ channel blockade;
Large antimuscarinic effects-> must use a combo drug that slows AV conduction when treating atrial flutter or fibrillation
Oral use; renal excretion; half-life 7-8hrs
Toxicity: excessive QT prolongation, torsade de pointes; excessive Na+ channel blockade w/ slowed conduction throughout heart; urinary retention (esp in males w/ prostatic hyperplasia), dry mouth, blurred vision, constipation, worsening of glaucoma
Contraindications: pts w/ heart failure |
|
|
Term
|
Definition
Antiarrhytmic- Class 1B
Treatment: termination of ventricular tachycardia and prevention of ventricular fibrillation in the setting of acute ischemia
MOA: blocks activated and inactivated Na+ channels in depolarized cells > nondepolarized
Given IV-> extensive 1st pass hepatic metabolism when given orally (only 3% appears in plasma); half-life 1-2hrs
Pts w/ MI may require higher concentration-> increased α1-acid glycoprotein binds drug
Heart failure- V of distribution/total body clearance decrease-> decrease loading and maintenance dose
Liver disease- reduced plasma clearance, increased V of distribution, increased half-life-> decrease maintenance dose, normal loading dose
Toxicity: hypotension in large doses w/ preexisting heart failure; parasthesias, tremor, nausea, lightheadedness, hearing disturbances, slurred speech, convulsions
Drug Interactions: those that decrease liver blood flow reduce drug clearance |
|
|
Term
|
Definition
Antiarrhythmic- Class 1B
Orally active congener of LIDOCAINE
Treatment: ventricular arrhythmia; chronic pain relief (due to diabetic neuropathy and nerves injury)
MOA: blocks activated and inactivated Na+ channels in depolarized cells > nondepolarized
Half-life- 8-20hrs
Dose related SE: tremor, blurred vision, lethargy, nausea |
|
|
Term
|
Definition
Antiarrhythmic- Class 1C
Treatment: pts w/ normal hearts w/ supraventricular arrhythmia
MOA: blockade of Na+ and K+ channels; does not prolong AP or QT interval
Well absorbed; half-life 20 hrs; hepatic metabolism w/ renal clearance
Highly effective in suppressing premature ventricular contractions, but may exacerbate arrhythmia in pts w/ ventricular tachyarrhythmia or MI/ventricular ectopy |
|
|
Term
|
Definition
Antiarrhythmic- Class 1C
Treatment: supraventricular arrhythmia
MOA: blocks Na+ channels; weak β-adrenergic blockade
Hepatic metabolism; half-life 5-7hrs
SE: metallic taste, constipation, arrhythmia exacerbation |
|
|
Term
|
Definition
Antiarrhythmic- Class 1C
Treatment: ventricular arrhythmia (no longer in use)
MOA: potent Na+ channel blocker w/o prolonged action potential duration; slight Ca2+ channel and β-adrenergic blockade |
|
|
Term
|
Definition
Antiarrhythmic- Class 2 and Class 3
Racemic mixture
Treatment: ventricular arrhythmia and maintenance of sinus rhythm in atrial fibrillation; supraventricular and ventricular arrhythmia in pediatric pts
MOA: nonselective β-blocker (L-isomer); prolongs action potential (D and L-isomers)
Oral bioavailability 100%; renal excretion unchanged; half-life 7-12hrs
Anti-ischemic effects
Toxicity: torsade de pointes; pts w/ heart failure may experience further L ventricular functioning; depression
Interactions: decreases threshold for cardiac defibrillation |
|
|
Term
|
Definition
Antiarrhythmic- Class 3 (w/ Class 1, 2, and 4 actions also)
Treatment: approved for ventricular arrhythmias; effective for supraventricular arrhythmia (atrial fibrillation)
MOA: prolongs AP duration and QT interval by blocking rapid K+ current channels; blocks Na+ channels; weak adrenergic and Ca2+ blocking actions
CYP3A4 hepatic metabolism w/ active metabolites; half-life of 50% of the drug is 3-10days w/ the rest at several weeks ( > 80days)-> effects maintained 1-3months post discontinuation
Toxicity: peripheral vasodilation; bradycardia/heart block in pts w/ nodal disease; accumulates in heart, lungs (pulmonary fibrosis), liver (hepatitis), skin (photodermatitis, discoloration), and tears; corneal microdeposits; halos in peripheral visual fields; hypo/hyperthyroidism; blocks peripheral conversion of T4 to T3; potential source of inorganic I-
Drug Interactions: cimetidine decreases metabolism; rifampin increases metabolism; inhibits other cytochrome P450 substrates; increases the pacing and defibrillation threshold in pts w/ ICD |
|
|
Term
|
Definition
Antihypertensive; Antiarrhythmic- Class 4
Treatment: supraventricular arrhythmia and rate control in atrial fibrillation; HTN
MOA: Ca2+ channel blocker
IV SE: hypotension, bradyarrhythmia
Half-life 4-8hrs
Contraindication: ventricular tachycardia
Drug Interactions: β-blockers/digoxin-> additive effect at AV node |
|
|
Term
|
Definition
Antiarrhythmic
First choice treatment of supraventricular tachycardia-> returns to sinus rhythm
MOA: activation of K+ channels and blocks Ca2+ channels (indirectly)
Toxicity: flushing, shortness of breath, chest burning, high grade AV block (short lived), atrial fibrillation, headache, hypotension, nausea, paresthesias
Half-life in blood <10sec; short duration of action
Drug Interactions: theophylline/caffeine-> adenosine receptor blockers; dipyradamole-> adenosine uptake inhibitor |
|
|
Term
|
Definition
Bile Acid-Binding Resin
MOA: bind bile acids in intestine and prevent their reabsorption-> excretion is increased resulting in increase in cholesterol to bile salt conversion in liver via 7α-hydroxylase; decreased FXR receptor activation by bile salts-> decreased LDL/IDL and increase in TG but improved glucose metabolism in diabetics
Used in pts w/ Primary Hypercholesterolemia, relieving pruritus in pts w/ cholestasis and bile salt accumulation, digitalis toxicity (binds digitalis)
Insoluble in water; not itself absorbed
Available in granular preparations, mixed w/ juice or water and taken w/ meals
Toxicity: constipation/bloating (relieved by fiber or psyllium seed); heartburn, diarrhea; hypoprothrombinemia (malabsorption of Vit K); decreased folic acid uptake
Contraindications: diverticulitis
DI: digitalis/thiazides/warfarin/thyroxine/pravastatin/folic acid/aspirin/Vit C-> impairs the absorption of these drugs (drugs should be given 1hr before or 2hrs after resins) |
|
|
Term
|
Definition
Fibric Acid Derivative
MOA: PPAR-α agonist (transcription factor)-> up-regulate LPL, apoA-I and apoA-II and down-regulate apoCIII (inhibitor of lipolysis)=> increase in FA oxidation in liver/striated musc; overall decrease in VLDL w/ modest increase in HDL; LDLs may decrease (most) or increase (in hyperlipidemia)
Used in Hypertriglyceridemia and Dysbetalipoproteinemia
Hydrolyzed completely in intestines-excreted in urine > feces; half-life 20hrs
Toxicity: rashes, GI symptoms, myopathy, arrhythmia, hypokalemia, increased aminotransferases/alkaline phosphatases; decreased WBC/hematocrit; rhabdomyolysis (increased when given w/ reductase inhibitors); gallstones
DI: increases effects of anticoagulants
Contraindications: hepatic or renal dysfunction; used w/ caution in women, obese persons, and Native Americans |
|
|
Term
|
Definition
Fibric Acid Derivative
MOA: PPAR-α agonist (transcription factor)-> up-regulate LPL, apoA-I and apoA-II and down-regulate apoCIII (inhibitor of lipolysis)=> increase in FA oxidation in liver/striated musc; overall decrease in VLDL w/ modest increase in HDL; LDLs may decrease (most) or increase (in hyperlipidemia)
Used in Hypertriglyceridemia and Dysbetalipoproteinemia
Absorbed from intestine- increased when taken w/ food; tightly protein bound-> readily crosses placenta
Half-life 1.5hrs; eliminated through kidneys > liver
Toxicity: rashes, GI symptoms, myopathy, arrhythmia, hypokalemia, increased aminotransferases/alkaline phosphatases; decreased WBC/hematocrit; rhabdomyolysis (increased when given w/ reductase inhibitors); gallstones
DI: increases effects of anticoagulants
Contraindications: hepatic or renal dysfunction; used w/ caution in women, obese persons, and Native Americans |
|
|
Term
| Niacin (aka Nicotinic Acid, Vitamin B3) |
|
Definition
Converted to amide then incorporated into niacinamide adenine dinucleotide (NAD)
MOA: decreased apoAI catabolism and inhibits VLDL secretion-> decreased LDL production; increased clearance of VLDL by LPL; inhibits adipose tissue lipase-> reducing VLDL production by decreased flux of FFA to liver
Only drug that decreases Lp(a) and most effective drug at increasing HDL
Excretion of sterols in stool increases acutely
Excreted in urine unmodified or as metabolites
Normalizes LDL in Hypercholesterolemia in combo w/ resin or reductase inhibitors; useful in Severe Mixed Lipemia in combo w/ omega-3 and in Hyperlipidemia and Dysbetalipoproteinemia
Toxicity: cutaneous vasodilation and sesation of warmth-> decreased w/ aspirin or ibuprofen and lessens w/in a few days; pruritus, rashes, dry skin/mucous membranes; acanthosis nigricans; nausea/GI discomfort-> less w/ antacids not containing aluminum; elevated aminotransferases; hepatotoxicity; decreased carbohydrate tolerance; hyperuricemia (gout); arrhythmia; toxic amblyopia (blurred vision); teratogenic
Contraindications: acanthosis nigricans-> insulin resistance; severe peptic disease
DI: may enhance antihypertensive drug effects |
|
|
Term
|
Definition
Sterol Absorption Inhibitor
MOA: inhibits NPC1L1 transport protein-> decreased absorption of cholesterol and phytosterols=> reduction of LDL
Absorbed in intestines, excreted in feces; half-life 22hrs
DI: increased when given w/ fibrates and decreased w/ cholestyramine; synergistic w/ reductase inhibitors
Toxicity: reversible impaired hepatic function; myositis |
|
|
Term
| STATINS aka REDUCTASE INHIBITORS |
|
Definition
MOA: competitive inhibitors of HMG-CoA reductase; partial inhibition-> increases high-affinity LDL receptor = decreased LDL in plasma; also modest decrease in TG and small increase in HDL
High 1st pass metabolism; most excreted in bile, some in urine
Causes reduced prenylation of Rho (vascular changes) and Rab (decreased Aβ in neurons)
Should not be given to women who are pregnant, lactating, or likely to become pregnant; only used in children w/ Familial Hypercholesterolemia or Familial Combined Hyperlipidemia
Lower doses given w/ hepatic parenchymal disease, Asians, elderly; temporarily discontinue w/ serious illness, surgery, or trauma
Toxicity: elevated serum aminotransferase [(esp w/ liver disease/alcohol abuse)-> hepatic toxicity, malaise, anorexia, exaggerated decrease in LDL=> must stop use immediately]; elevated CK [(esp w/ heavy physical activity)-> discomfort, sk musc weakness, myoglobinuria, renal injury, myopathy]; rarely hypersensitivity rxns |
|
|
Term
|
Definition
MOA: HMG CoA Reductase Inhibitor
Active congener; contains F-
Half-life 14hrs; catabolized by CYP3A4
Absorption helped by food; elevated levels w/ grapefruit juice intake >1L
DI: fibrates/antibiotics-> decreased metabolism; amiodarone/verapamil-> increased risk of myopathy; phenytoin/barbiturates-> increase metabolism |
|
|
Term
|
Definition
MOA: HMG CoA Reductase Inhibitor
Active congener; contains F-
Half-life 19hrs; catabolized by CYP2C9
Absorption helped by food
DI: amiodarone-> decrease metabolism |
|
|
Term
|
Definition
MOA: HMG CoA Reductase Inhibitor
Inactive prodrug, activated in GI tract
Half-life 1-3hrs; catabolized by CYP3A4
Given at night when majority of cholesterol synthesis occurs; absorption helped by food; elevated levels w/ grapefruit juice intake >1L
DI: fibrates/antibiotics-> decreased metabolism; amiodarone/verapamil-> increased risk of myopathy; phenytoin/barbiturates-> increase metabolism |
|
|
Term
|
Definition
MOA: HMG CoA Reductase Inhibitor
Active form
Half-life 1-3hrs; dose response curve levels off in the upper dosage range; catabolism mediated by sulfation rxns
Given at night when majority of cholesterol synthesis occurs
Lowest incidence of myalgias among statins |
|
|
Term
|
Definition
Antiplatelet
MOA: irreversibly acetylates and inactives COX1, reducing TXA2 synthesis (TXA2 = vasconstriction, pro-clotting)
Low dose therapy for primary prophylaxis of MI; administered immediately on MI presentation and continued indefinitely |
|
|
Term
|
Definition
MOA: non-selective β-blocker with additional weak α-blocking properties and some intrinsic sympathomimetic activity
It was under review by the FDA in the US for the treatment of heart failure |
|
|
Term
|
Definition
HMW parenteral anticoagulant-> effective against venous thrombosis, pulmonary embolism, angina, myocardial infarction
Continuous IV infusion
MOA: indirect thrombin inhibition by inducing antithrombin III-> inhibits thrombin, IXa, Xa
Is not consumed during reaction-> higher the dose, higher the 1/2 life
Must watch PTT-> a double the normal PTT = therapeutic
SE: HIT, bleeding
Contraindications: HIT, hemophilia, hypersensitvity, hemorrhage, sever hypertension, recent surgery of eye, brain, spinal cord |
|
|
Term
|
Definition
Opioid
Treatment: chronic, severe pain; acute pulmonary edema
MOA: μ-receptor agonist; histamine releasing effect
In acute pulmonary edema: reduces anxiety and acts as a venous dilator to facilitate pooling of blood peripherally
Decreases respiratory and heart rate
Given oral, parenteral, rectal
SE: nausea, vomiting, pruritus, sphincter of Oddi spasm; disruption of sleep patterns
Contraindications: renal failure (metabolite build up) |
|
|
Term
|
Definition
Fibrinolytic; not an enzyme itself
MOA: forms complex w/ plasminogen that catalyzes conversion to plasmin
Indications: peripheral arterial and venous thrombi |
|
|
Term
| t-PA (tissue-plasminogen activator) |
|
Definition
Fibrinolytic
MOA: preferentially activates plasminogen bound to fibrin-> confines fibrinolysis to thrombus, but can lyse all thrombi
Used to dissolve clot in acute coronary syndromes |
|
|
