Exam 3 Drug MOA Flashcards
Spironolactone
and
Eplerenone
Aldosterone Antagonist—> Acts on the RAAS system; ↓ Na+ reabsorption, ↑ Na+, Cl+, H2O excretion; ↓ K+ excretion ↓ decreases myocardial fibrosis
Eplerenone more selective for aldosterone antagonist
Captopril
and
Enalapril
Blocks the conversion of Ang I to Ang II;
↓ preload and afterload; Protects heart against adverse remodeling
Captopril is active drug w/ renal excretion
Enalapril is prodrug hydrolyzed in liver, renal and fecal excretion
Candesartan
and
Valsartan
Blocks Ang II binding to the AT1 receptor
On arteries —> ↓ vasoconstriction & therefore ↓ AFTERload
On adrenals —> ↓ aldosterone secretion, ↓ Na+ reabsorption —> ↓ PREload
Protects against adverse myocardial remodeling
Valsartan has lower bioavailability
Sacubitril/Valsartan (Entresto)
ARNI—> Blocks neprilysin & AT1 to enhance ARB effect
Decreases: BP, sympathetic tone, aldosterone seretion, fibrosis, hypertrophy
Increases: naturesis and diuresis
Carvedilol
ARB--> beta (non-specific) and alpha1 Beta effect--> at juxtaglomerular cells ↓ renin secretion, angiotension ii and vasoconstriction --> ↓ AFTERload; ↓ NA+ reabsorption and PREload; at CNS ↓ BP; at SA node ↓ HR; at myocardium ↓ contractility; at AV node ↓ conduction velocity *Blocks adverse remodeling* Alpha1 block contributes to vasoconstriction
Ivabradine
Inhibits I(f) channel to ↓ SA node rate
Isosorbide Dinitrate
releases NO–> increases cGMP–> ↓ MLC–> vasodilation of veins (↓ preload) > arteries (↓ afterload)
Hydralazine
MOA unknown but results in dilated arterioles–> ↓ AFTERload
Milrinone
↑ cAMP in heart leads to ↑Ca2+–> ↑contractility–> ↑CO
↑cAMP in artery –> ↑vasodilation–> ↓ AFTERload
Digoxin
Inhibits Na+/K+ ATPase which then has effect on Na+/Ca2+ exchanger
results in: Na+ is stuck outside the cell, Ca2+ stuck inside cell, decreased K+ inside cell
1) ↑ myocardium contractility dt increased Ca inside cell
2) ↑ risk of arrhythmias dt decreased K+
3) ↑ vagal tone and ↓ HR and conduction velocity
4) improved CO
Metoprolol
Same effects as Carvedilol except sustained-release and *Beta-1 specific Rate control Give this to asthma and COPD patients over carvedilol
Epinephrine
released from adrenal medulla; not very selective
at low doses prefers beta > alpha
at high doses strong preference for Alpha1 and Betas
At Beta 1–> vasodilation, ↑ HR and contractility
At Alpha 1–> vasoconstriction and leads to reflex decrease in HR
Norepinephrine
Postganglionic sympathetic neuron binds to alpha and beta receptors;
At presynaptic alpha2 receptors for feedback inhibition of NE release
At Alpha 1–> ↑ BP
At Beta1 that activates Gs–> ↑ Ca2+ into heart and ↑ rate and contractility
Isoproterenol
Selective Beta agonist to stimulate heart,
↓ BP
relaxes Bronchi
Dopamine
CNS transmitter
↓ BP in renal and mesenteric bends at low dose by beta activation; ↑ BP at high doses by Alpha activation
↑ HR by Beta 1 stimulation
Dobutamine
at low doses acts at Beta 1 and some Beta2; at high doses acts at Beta 1 and some Beta 2 and Alpha1
At Beta 1–> ↑ contractility without affecting rate
↑ BP at high doses via Alpha1
Phenylephrine
CNS penetration; Alpha 1 stimulator–> ↑ BP
Ephedrine
CNS penetration; Alpha 1 stimulator–> ↑ BP
weak Beta agonist
Terbutaline
Beta 2 selective; opens airways, inhibits allergic response in anaphylactic shock, relaxes pregnant uterus
Albuterol
Beta 2 selective; opens airways, inhibits allergic response in anaphylactic shock, relaxes pregnant uterus
Amphetamine
Substrate for NET and kicks out NE leading to increased synaptic NE via Facilitated Exchange Diffusion
CNS penetration
Methylphenidate
CNS stimulant that increases NE in front of the brain
Phenoxybenzamine
Irreversible selective Alpha 1 blocker
Phentolamine
Non-selective alpha Antagonist; Blocks NE from alpha receptor; ↓ BP resulting in reflex tachycardia
Propranolol
Non-selective beta Blocker; Blocks NE–> ↓ HR and CO; ↓ conduction velocity, oxygen demand
Atenolol
Selective B1 blocker
Esmolol
Selective B1 blocker with short half life
Timolol
Non-selective Beta blocker used to decrease aqueous humor production for glaucoma
Prazosin
Reversible selective Alpha 1 blocker –> ↓ BP resulting in reflex tachy
Clonidine
Acts directly at Alpha 2 (agonist)
Methyldopa
must be metabolized to alpha-methyl-NE to become alpha 2 agonist
Fiber
Slows cholesterol and bile acid absorption and facilitates excretion
Increases GI motility
Omega-3 Fatty Acids
↑ TG clearance, ↓ Lipogenesis, ↑ beta-oxidation, ↓ VLDL
Anti-inflammatory
Atorvastatin
Inhibits HMG CoA Reductase–> ↓cholesterol synthesis–> ↑ synthesis of hepatic LDL receptors –> ↑ LDL and VLDL remnant clearance
metabolized by CYP3A4
Pravastatin
Inhibits HMG CoA Reductase–> ↓cholesterol synthesis–> ↑ synthesis of hepatic LDL receptors –> ↑ LDL and VLDL remnant clearance
metabolized by sulfation and is NOT P450 dependent
Ezetimibe
Blocks absorption of cholesterol from intestinal track by inhibiting Niemann-Pick C1-like 1–> ↓ delivery of intestinal cholesterol to liver which ↓ choelsterol in chylomicrons/remnants
all leads to ↑ LDL receptors and ↑ LDL clearance
Ezetimibe
Blocks absorption of cholesterol from intestinal track by inhibiting Niemann-Pick C1-like 1–> ↓ delivery of intestinal cholesterol to liver which ↓ choelsterol in chylomicrons/remnants
all leads to ↑ LDL receptors and ↑ LDL clearance
Cholestyramine
Binds bild, metabolites of cholesterol–> prevents reabsorption and promotes excretion–> ↑ conversion of cholesterol into bile acids –> ↑ LDL receptors and LDL clearance
Niacin
Poorly understood mechanism
inhibits lipase in adipose tissue and ↓ free fatty acids transport–> ↓ VLDL synthesis–> ↓ LDL production
↓ TG synthesis
↓ HDL catabolism –> ↑HDL levels
Gemfibrozil
PPAR-alpha receptor agonist–> ↓ TGs
Cholestyramine
Binds bild, metabolites of cholesterol–> prevents reabsorption and promotes excretion–> ↑ conversion of cholesterol into bile acids –> ↑ LDL receptors and LDL clearance
Niacin
Poorly understood mechanism
inhibits lipase in adipose tissue and ↓ free fatty acids transport–> ↓ VLDL synthesis–> ↓ LDL production
↓ TG synthesis
↓ HDL catabolism –> ↑HDL levels
Gemfibrozil
PPAR-alpha receptor agonist–> ↓ TGs
Evolocumab
Inhibit PCSK9 in order to upregulate the LDL receptor –> increase LDL clearance
Lidocaine
and Mexiletine
Class 1B, Just VT,
Blocks Na+ channels (primarily in depol cells) –> ↑ ERP
increase K+ out–> ↓ AP duration
Flecainide
Class 1C, VT>SVT, rhythm control, Na+
Quinidine
Class 1A, VT>SVT, rhythm control, long QT
Procainamide
and
Disopyramide
Class 1A, VT>SVT, rhythm control, long QT
Lidocaine
and Mexiletine
Class 1B, Just VT,
Blocks Na+ channels (primarily in depol cells) –> ↑ ERP
increase K+ out–> ↓ AP duration
Flecainide
Class 1C, VT>SVT
rhythm control
Blocks Na+ channels–> ↑ refractory period
Quinidine
Class 1A, VT>SVT
rhythm control
Blocks Na+ channels, Blocks TEA-type K+ channel–> ↑ refractory period
Procainamide
and
Disopyramide
Class 1A, VT>SVT
rhythm control
Blocks Na+ channels, Blocks TEA-type K+ channel–> ↑ refractory period
Amiodarone
Class III, VT & SVT, rhythm control Blocks K+ efflux, ↑ AP duration Blocks Na+ channels, ↑ refractory period Blocks Ca2+ channels Blocks beta receptors
Sotalol
and
Ibutalide
Class III, VT & SVT,
rhythm control
Blocks K+ efflux, ↑ AP duration
Verapamil
and
Diltiazem
Class IV, SVT only (fibrillation and flutter), rate control
Ca2+ channel blocker, slows SA and AV node conduction. ↓automaticity
Metoprolol
Class II, SVT only, rate control
Beta blocker–> ↓ AV node conduction, ↓excitability, ↓ SA node rate, ↓contractility
Digozin
used for SVT only
rate control
Inhibits Na+/K+ ATPase–> ↓ resting potential, ↓ conduction velocity
indirect: ↑ vagal activity–> ↑ refractory period, ↓ conduction in AV node
Adenosine
Increases K+ eflux–> hyperpolarizes–> ↓ Ca2+–> ↓ AV node conduction, ↓ SA pacemaker, ↓automaticity
Ethanol
CNS depressant, enhances GABA binding to GABA-A
Inhibits glutamate binding to NMDA
facilitates release of endogenous opiods in VTA
Benzodiazepines
CNS depressant, enhances GABA binding to GABA-A
Barbiturates
CNS depressant, GABA binding and directly activate GABA-A
Opioids
Activation of mu opioid receptor reward pathway
Nicotine
Activation of nicotinic acetylcholine receptors in reward pathway
Cannabinoids (THC)
Activation of cannabinoid receptors in reward pathway
Stimulants (cocaine, amphetamine, methamphetamine)
Amphetamine and Methamphetamine enhance synaptic release of DA
Cocaine blocks reuptake of DA
LSD and psilocybin
Act as agonists at DA receptors- weak effects in reward pathway
MDMA or ecstasy
Induce DA release; act as agonists at DA receptors- weak effects
Dissociatives (PCP, ketamine)
Inhibit NMDA receptors in reward pathway
Disulfiram
Inhibits acetaldehyde dehydrogenase, leading to accumulation of acetaldehyde upon alcohol consumption. Acetylaldehyde causes facial flushing, nausea, headache, vomiting, hypotension
Acamprosate, Topiramate
Anti-craving mechanism unknown; known to increase activity of GABA-A receptors and inhibit glutamatergic NMDA receptor activity
Naloxone (Narcan)
Inhibits mu opioid receptors in ventral tegmental (VTA) of brain; short acting antagonist
Naltrexone
Inhibits mu opioid receptors in VTA of brain; long acting antagonist
Methadone
High efficacy agonist at mu opioid and receptor
suppresses symptoms of craving and withdrawal
produces plasma opioid levels that remain stable over time
LAAM
High efficacy agonist at mu opioid and receptor
suppresses symptoms of craving and withdrawal
produces plasma opioid levels that remain stable over time
Buprenorphine
Partial agonist at mu opioid receptor and antagonist at kappa opioid receptor
Nicotine replacement therapy
different kinetics from smoking; slower absorption and longer nicotine plasma levels, therefore less rewarding, alleviates craving and less frequent withdrawal symptoms
Bupropion
Antidepressant; unknown MOA; non-competitive antogonist of nicotinic acetylcholine receptors in reward pathway; weak inhibitor of DA, NE and 5HT reuptake in reward pathway
Varenicline
Partial agonist at alpha4beta2 nicotinic acetylcholine receptors (nAChRs) in ventral tegmental area (VTA) and nucleus accumbens region of brain
Inhibits nicotine full agonist activation at nAChRs
Diphenhydramine
H1 Antihistamine; Competitive antagonist to histamine’s effects on smooth muscles
“inverse agonist”; penetrate the BBB
Diphenhydramine (Benadryl)
H1 Antihistamine; Competitive antagonist to histamine’s effects on smooth muscles
“inverse agonist”; penetrate the BBB
Dimenhydrinate (Dramamine)
H1 Antihistamine
Competitive antagonist to histamine’s effects on smooth muscles
“inverse agonist”, Penetrate the BBB
Loratadine (Claritin)
Second Generation H1 Antihistamine; Competitive antagonist to histamine’s effects on smooth muscles
“inverse agonist; Little BBB
Cetirizine (zyrtec)
Second Generation H1 Antihistamine; Competitive antagonist to histamine’s effects on smooth muscles
“inverse agonist; Little BBB
Fexofenadine (Allegra)
Second Generation H1 Antihistamine; Competitive antagonist to histamine’s effects on smooth muscles
“inverse agonist; Little BBB
