Exam 2 Drugs Flashcards
sypmathomimetic subclasses:
direct acting
indirect acting
midodrine
class: direct-acting (DA) sympathomimetic
receptor: alpha-1 agonist
indication: orthostatic hypotension
clonidine
class: DA sympathomimetic
receptor: CENTRAL alpha-2 agonist; considered a PARTIAL AGONIST
indication:
* HTN (off label: adjuvant drug for sedation)
* diarrhea
* hot flashes
* hemodynamic instability intraOP
* ADHD, Tourettes, withdrawal symptoms
* OFF LABEL: anxiety, PTSD, adjunct to anesthesia (prolongs anesthesia)
MOA:
CENTRAL Alpha-2-Rs:
* Rostro Ventrolateral Medulla (RVLM) stimulated > INHIBITION of sympathetic outflow leads to decreased vasoconstriction, HR, and contractility
* Nucleus of the Tractus Solitarius (NTS) stimulated > leads to INCREASED FIRING ON VAGUS NERVE (CN X) > leading to INCREASED PARASYMPATHETIC OUTFLOW leads to slower HR
* overall effects of decrased HR and decreased SV will decrease BP
SE:
* may see initial transient increase in BP prior to decrease in BP d/t peripheral alpha-2 stimulation via oral route prior to crossing BBB
* dry mouth
* also has effect to induce sedation
epinephrine
class: DA sympathomimetic
receptor: alpha + beta 1 + beta 2 agonist
indication: positive inotropic agent, positive chronotropic agent, dilation of skeletal muscles and bronchioles
norepi (NE)
class: DA sympathomimetic
receptor: alpha + beta 1 agonist
indication: hypotension
MOA: increase in SBP + DBP; vagal reflex overcomes chronotropic effects (does not stimulate HR as much)
isoproterenol
class: DA sympathomimetic
receptor: beta 1 + beta 2 agonist
indication: HTN
MOA:
* B1: will increase HR, CO, & contractility with a slight increase in SV; slight increase in pulse pressure but major effects will be to decrease DBP and a slight decrease in SBP
* B2: decrease vascular tone
dopamine
class: DA sympathomimetic
receptor: D + beta 1 agonist
indication: cardiac
MOA:
* decreases peripheral resistance at LOW DOSES (induces diuresis)
* mimics action of epinephrine at HIGH RATES OF INFUSION (increase in HR, increase in contractility, increase in peripheral resistance, could be arrythmogenic)
dobutamine (dobs)
class: DA sympathomimetic
receptor: beta 1 selective agonist
indication: cardiogenic shock, HF
MOA: positive inotropic/chronotropic effect
phenylephrine
class: DA sympathomimetic
receptor: pure alpha agonist
indication: decongestant, hypotension
midodrine
class: DA sympathomimetic
receptor: alpha-1 selective agonist
indication: postural/orthostatic hypotension
ephedrine
class: DA && INDIRECT ACTING sympathomimetic
receptor: alpha and beta agonist
indication: nasal decongestant (pseudoephedrine)
MOA: mimics epi (direct-acting); crosses the BBB
found in plants; can be used to make meth
dexmedetomidine
class: DA sympathomimetic
receptor: CENTRAL alpha-2-A selective agonist
indication: anxiolytic
MOA: induces anesthesia, analgesia, sympatholysis, sedation, anxiolysis, hypnosis, and increased congnition
amphetamines
class: INDIRECT-acting sympathomimetics
effects: mood elevator, appetite suppresant, increased attention
MOA: readily enter CNS
methamphetamines have a higher ratio of CNS to PNS actions
cocaine
class: indirect acting sympathomimetic
effects: amphetamine-like effects
MOA: inhibits dopamine reuptake into neurons in the “pleasure centers” of the brain
tyramine
class: indirect sympathomimetic
effects: releases stored catecholamines; metabolized by MAO
MAOIs (monoamine oxidase inhibitor) inhibit the breakdown of NTs and are often prescribed as antidepressants; MAOis may increase blood pressure after eating fermented foods
ex) cheese, chicken liver, sausage (fermented), red wine, yeast
phentolamine
class: reversible sympatholytic
receptor: competitive alpha-1, alpha-2 blocker
indication: HTN linked to pheochromocytoma, cardiac stimulant, ED (direct injection)
MOA:
* turns a pressor into a depressor
* if giving phentolamine BY ITSELF, very little effect
* if giving phentolamine AFTER pressor, will decrease some of the pressor agonists’ effects
* if giving phentolamine BEFORE pressor, GREATEST effect and decreases BP significantly
prazosin
class: reversible sympatholytic
receptor: alpha-1 selective blocker (low affinity for alpha-2)
indication: HTN, BPH
MOA: relaxes arterial and venous smooth muscle
labetalol
class: reversible sympatholytic
receptor: alpha & beta blocker
indication: HTN
phenoxybenzamine
class: IRREVERSIBLE sympatholytic
receptor: non-specific alpha antagonist & covalently bonds, blocks H1, ACh, and serotonin receptors
indication: HTN linked to
pheochromocytoma
MOA: inhihbits NE reuptake
-osin drug class
alpha-1 blockers
what is the drug Yohimbine?
an alpha-2 selective antagonist which has little use clinically
allegedly helps ED patients
propanolol
class: sympatholytic
receptor: non-specific beta blocker
indication: HTN
SE: bradycardia, rash, fever, CNS effects (sedation, sleep disturbances, depression), worsening of asthma (B2), hypoglyemia in diabetics (blocks glycogenolysis), must discontinue use gradually
metoprolol
class: sympatholytic
receptor: beta-1 blocker
indication: HTN (safer in COPD, asthma, and diabetic patients)
labetalol
class: sympatholytic
receptor: a1 **AND **b1, b2 blocker
indication: HTN, preeclampsia, pheochromocytoma
racemic mixture: 2 active forms and 2 inactive forms
esmolol
class: sympatholytic
receptor: beta-1 selective blocker
indication: tachycardia intraop, supraventricular arrythmia
other facts: ultra short acting, steady state infusion, terminated rapidly when discontinued, safer in critical care patients
ACh
class: DA parasympathomimetic// cholinomimetic
subclass: choline ester
indication: miosis (pupillary constriction)
insoluble in lipids
methacholine
class: DA parasympathomimetic // cholinomimetic
subclass: choline ester
indication: diagnostic drug for asthma
insoluble in lipids
carbachol
class: DA parasympathomimetic// cholinomimetic
subclass: choline ester
indication: to decrease IOP
insoluble in lipids; resistant to hydrolysis
bethanechol
class: DA parasympathomimetic// cholinomimetic
subclass: choline ester
indication: bladder dysfunction, reflux disease
insoluble in lipids; resistant to hydrolysis
muscarine
class: DA parasympathomimetic// cholinomimetic
subclass: alkaloid
effects: mimics parasympathetic nerve discharge (saliva, bowel motility, urination, etc.)
MOA: takes place at effector cells, not in ganglia
toxicity: exaggeration of all symptoms of muscarinic agonism (MYCETISM); can occur with high consumption of wild mushrooms
reversal for toxicity: ATROPINE 1-2mg IM
nicotine
class: DA parasympathomimetic// cholinomimetic
subclass: alkaloid
MOA: stimulates autonomic ganglia and skeletal muscle NMJ, not effector cells
release of dopamine, serotonin, GABA, and NE
SE: in larger doses – tremors, emesis, stimulates respiratory center, convulsions, fatal coma (OD ingestion), addiction
crosses BBB; lipid soluble
the antidote for nicotine OD is 2-PAM
arecoline
class: DA parasympathomimetic// cholinomimetic
subclass: alkaloid
stimulant; from betel nut
pilocarpine
class: DA parasympathomimetic// cholinomimetic
subclass: alkaloid
effects: N/V/D, salivation, sweating, bronchial constriction
edrophonium
class: INDIRECT-acting parasympathomimetic// cholinomimetic
subclass: simple alcohol
indication: diagonist drug for myasthenia gravis
onset: 5-15 mins
neostigmine
class: INDIRECT-acting parasympathomimetic// cholinomimetic
subclass: carbamate
indication: MG, surgical paralysis reversal agent
MOA: inhibits the effects of AChE
pyridostigmine
class: INDIRECT-acting parasympathomimetic// cholinomimetic
subclass: carbamate
indication: MG
MOA: inhibits the effects of AChE
echothiophate
class: INDIRECT-acting parasympathomimetic// cholinomimetic
subclass: organophosphate
indication: glaucoma
MOA: increases the drainage of intraocular fluid
atropine
class: parasympatholytic // anticholinergic
subclass: antimuscarinic
indication: organophosphate poisoning (with pralidoxime), bradycardia
- effects occur d/t racemix mixture
- competitively inhibits muscarinic responses to ACh
scopolamine
class: parasympatholytic // anticholinergic
subclass: antimuscarinic
indication: motion sickness, excessive salivation
tropicamide
class: parasympatholytic // anticholinergic
subclass: antimuscarinic
indication: mydriasis and cycloplegia (diagnostic drug)
ipratropium bromide
class: parasympatholytic // anticholinergic
subclass: antimuscarinic
indication: asthma
succinylcholine
class: parasympatholytic // anticholinergic
subclass: antinicotinic && choline ester
indication: DEPOLARIZING muscle relaxant
MOA:
* resembles ACh; it is considered a n-ACh-R AGONIST
* blocks n-ACh-R on motor end plate of skeletal muscle
* depolarization PERSISTS
* continuous end-plate depolarization causes muscle relaxation (prolonged depol = delayed repolarization of cell)
* this depolarizing agent causes a PHASE I BLOCK (depol w/ lack of repolarization) which will then lead to a phase II block
SE:
* fasciculations
* muscle pain (when drug is bound for too long)
* hyperK+
* MH
* apnea
curare derivatives (i.e. rocuronium)
class: parasympatholytic // anticholinergic
subclass: antinicotinic
indication: NON-depolarizing NMBA
**MOA: **
* competitive with ACh at n-ACh-Rs; acts as a COMPETITIVE ANTAGONIST
* does NOT depolarize motor end plate
* excessive [ ] = channel blockade
the reversal for ROCURONIUM & VECURONIUM is SUGGAMADEX
suggamadex
reversal agent for NON-DEPOLARIZING NMBAs: ROCURONIUM & VECURONIUM
a cyclic molecule that cycles around the non-depolarizing blocking agent to prevent binding at the receptor site
methyldopa
class: sympathoplegic
subclass: centrally acting alpha 2 agonist
indication: pregnancy induced HTN, (does NOT cross placental barrier); not first-line for normal HTN
MOA:
CENTRAL Alpha-2-Rs:
* Nucleus of the Tractus Solitarius (NTS) stimulated > leads to INCREASED FIRING ON VAGUS NERVE (CN X) > leading to INCREASED PARASYMPATHETIC OUTFLOW leads to slower HR
hydralazine
class: oral vasodilator
indication: HTN
MOA:
* induces NO production in endothelium to relax smooth muscle of arterioles
* reduces peripheral vascular resistance
* reduces MAP
pharmacokinetics: well abosrbed, rapid first pass metab, tachyphylaxis
SE: HA, nausea, sweating, flushing, worse in slow ACETYLATORS (phase II metabolism); symptoms resemble LUPUS
minoxidil
class: oral vasodilator
indication: HTN, hair growth (rogaine)
MOA:
* opens K+ channels in smooth muscles; stabilizes potential which will decrease likelihood to fire AP
* dilates arteries and arterioles
pharmacokinetics: well absorbed, typically rogaine
SE: HA, sweating, palpitations, tachycardia, angina, hypertrichosis (hair growth)
nitroprusside
class: vasodilator
indication: HT emergency, cardiac failure
MOA:
* relaxes vascular smooth muscle
* breaks down in blood to release NO
* NO > increased cGMP > vasodilation of arteries and veins
SE:
* rapidly lowers BP
* higher rates cause toxicity: CN accumulation will occur (met acidosis, arrhythmias, death – worse in renal insufficiency patients)
**sodium thiosulfate **facilitates metabolism of cyanide
fenoldopam
class: vasodilator
subclass: D1 agonist
indication: HTN emergencies, post-op HTN
MOA: peripheral arteriolar dilator; increases renal blood flow to promote diuresis
calcium channel blockers
class: CCBs - vasodilators
indication: HTN, anti-anginal, anti-arrhythmic
MOA: blocks mostly L-type Ca2+ channels in the heart and inhibits Ca2+ influx in arterial smooth muscle
ex) verapamil, diltiazem, dihydropyridines (-dipines, i.e. nicardipine)
**class IV **vaughn-williams classification for arrythmia drugs
ace inhibitors
class: anti-angiotensins
indication: HTN
MOA: inhibits the synthesis of angiotensin I to convert to angiotensin II by blocking the ACE enzyme
* decreaes PVR
* CO & HR are not significantly changed
* eliminated via kidneys
SE:
* severe hypotension
* teratogenic: contraindicated in pregnant women and especially those in their first trimester
* altereed sense of taste
* rashes
drug interactions:
* K+ supplements can lead to hyperK+
* NSAIDS block some effects
* DRY COUGH (d/t bradykinin build up; ACE converts bradykinin to its inactive metabolites, so inhibiting ACE would cause a build up of bradykinin
ex) -prils (i.e. captopril, lisinopril, enalapril)
ARBs
class: anti-angiotensin
indication: HTN
MOA:
* ARBs block ATII from binding to receptor sites at sites where vasoconstriction would occur, as well as on the adrenal cortex where aldosterone gets secreted; by blocking vasoconstriction as well as aldosterone secretion, the overall effect is decreased PVR and decreased sodium/water retention, lowering overall BP
ex) -sartans (i.e. losartan, valsartan)
no effect on bradykinin, since ACE is not being inhibited, therefore NO cough symptoms associated
bosentan (tracleer)
class: endothelin receptor antagonist
indication: PAHTN
MOA:
* blocks ET-1 from binding to ETa and ETb
* ET-1 is the active form of an endogenous product created in the lungs; normally ET-1 when bound to ETa receptors will cause vasoconstriction and increased cell proliferation
* when ET-1 is blocked from binding to ETa-Rs, there will be an increase in vasodilation in the pulmonary circulation as well as decreased cell proliferation to help with vascular remodeling
SE: HA, edema, rash, hepatotoxicity, teratogenic
nitroglycerin
class: vasodilator
indication: angina, HTN
MOA:
* NO release in vascular smooth muscle
* increases guanylyl cyclase
* increases cGMP
* cGMP will dephosphorylate myosin-LC-PO4 and will be left with myosin-LC
* this will cause relaxation in the vascular smooth muscle
SE: orthostatic hypotension, syncope, HA, reflex tachycardia, hemoglobin interactions (NO2- reacts with Hgb to form methemoglobin > can cause pseudocyanosis at extremely high levels, but will ALSO have a high affinity for CN in the case of CN poisoning)
mononitrate form: isosorbide dinitrate
digoxin
class: cardiac glycoside
indication: positive inotropic agent
MOA:
* blocks Na+/K+/ATPase pump
* leads to increased ICF [Na+] > lowers AP duration
* slows the NCX > increases ICF [Ca2+]
* increases more forcible contractility
SE:
* has a very low therapeutic index
* pro-arrythmogenic
* increases PR int & decreases QT int
* toxic doses = tachycardia, fibrillation, cardiac arrest
* hyperK+, hyperCa2+, and hypomg2+ can occur
milrinone
class: PDE3 inhibitor
indication: HF
MOA:
* PDE3 is an enzyme that inactivates cAMP/cGMP
* when PDE3 is inhibited, increases cAMP/cGMP
* more cAMP = more foricble contraction (positive inotropic effect)
* more cGMP = more vasodilation
* also increases/prolongs Ca2+ effects
levosimendan
class: calcium sensitizer
indication: positive inotropic agent; vasodilation
MOA:
* binds troponin
* stabilizes Ca2+ bound conformation
* opens K+ channels (vasodilation)
* not approved in US yet
class I antiarrythmics
sodium channel blockers
works on phase 0 of the cardiac cycle
class IA drugs (3)
- quinidine
- procainamide
- disopyramide
- these drugs prolong AP duration
- have an effective refractory period
- depresses PM rate
- lengthens QT int (2-8% Torsades de Pointes)
- depresses conduction and excitability, especially in depolarized tissue
class IB drug
- lidocaine
- shortens AP duration
- decreased ERP
- low toxicity; high efficacy
- acts exclusively on Na+ channel
- suppresses abnormal cardiac activity
- recovery from block between APs d/t rapid dissociation
- no effect on conduction
class IC drugs
- flecainide
- minimnal effects on APD
- slows dissociation; not enough sodium channels reset before next AP
- suppresses abnormal firing channels
- no effect on ERP (but sodium channels are still bklocked)
- some beta blocking properties
class II anti-arrythmics (2)
sympatholytics
(beta blockers)
- suppresses ventricular ectopic depolarization
- prevents infarction and sudden death in patients recovering from acute MI
- esmolol
- sotalol
works on phase 4 of the cardiac cycle
class III anti-arrythmics
K+ channel blockers
- prolongation of repolarization and refractoriness by increased AP duration
- amiodarone
+has all V-W class effects; only categorized in class II d/t the nature of the receptors it works on - dronedarone
these drugs work at phase 3 of the cardiac AP cycle
amiodarone
class: potassium channel blocker
v-w class: class III antiarrythmic
indications: VT/Vfib/Afib/Aflutter
MOA:
* lengthens APs well in tachycardias
* weak CCB
* non-competitive inhibitor of beta receptors
* inhibits normal automaticity
SE:
* dilation in peripheral vasculature
* can precipitate HF; fatal in pulm fibrosis patients
* [ ] in tissues; found in almost every organ
* VERY LONG HALF LIFE
class IV antiarrythmics
CCBs
- verapamil
MOA:
* blocks both activated/inactivated Ca2+ channels
* prolongs AV node conduction
* slows SA node
* useful in supRAventricular arrythmias
* (adenosine has become first line agent for SVT)
* can reduce ventricular rate in afib/flutters but rarely converts to NSR
these drugs work on phase 2 of the cardiac cycle
