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Pharm 2 exam 1
Exam 1 of pharm 2
218
Pharmacology
Graduate
01/24/2011
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Term
Class I Anti-Arrhythmics

Site of action/mechanism of action
 Definition
*Membrane Stabilizing Drug
*Na+ Channel Blockers

NB: The more use of a cell, the more the drug will bind
Term
Quinidine

Site of action/ MOA
 Definition
 Class IA: Membrane Stabilizing Drug
 Na+ Channel Blockers
 This slows the repolarization of Phase 0 and ↓the slope of phase 4
Term
Quinidine

effect
 Definition
 Binds to activated Na+ channels which pvts. Na+ influx; This slows the repolarization of Phase 0 and ↓the slope of phase 4; ↑ ERP
 Use Dependent Block: Tissues that are frequently depolarizing will be selectively suppressed over tissues that depolarize at a normal frequency
 Blocks Na+ & K+ channels
 Has anti-muscarinic & α-blocking action (will act on AV Node and not block it, so must use another drug to block AV Node conduction)
Term
Quinidine

Clinical use
 Definition
Clinical Uses:
 Atrial fibrillation
 Ventricular tachycardia
Term
Quinidine

side effects
 Definition
 GIT: Diarrhea, N/V
 *Cinchorism (tinnitus, ringing in the ears, dizziness)
 Thrombocytopenia
 *Ppt torsade de pointes by prolonging QT interval (Resistant to treatment)
 Many drug-drug interactions (b/c inhibitor of CYP450 system)
 Can cause digoxin toxicity (n/v, visual disturbances, cardiac abnormalities): It ↑plasma concentration of digoxin by displacing it from tissue binding sites and↓ its renal & biliary clrnce
Term
Procainamide

Site of action/MOA
 Definition
 Class IA: Membrane Stabilizing Drug
Term
Procainamide

effect and clinical use
 Definition
 Less antimuscarinic action than Quinidine
 ↑ ERP

Clinical Uses:
 Suppression and treatment of Ventricular Tachycardias
Term
Procainamide

side effects
 Definition
 *SLE-like syndrome consisting of arthralgia and arthritis butterfly rash, inflammation on cheeks especially in slow acetylators (this is actually d/t the drug itself, NOT from the metabolites)
Term
Disopyramide

mechanism of action / site of actin
 Definition
 Class IA: Membrane Stabilizing Drug
Term
Disopyramide

effect and clinical use
 Definition
 Very prominent *antimuscarinic
 Avoid using this drug in heart failure
 Excreted in urine unchanged

Clinical Uses:
 Only approved for ventricular arrhythmia (Not first line)
Term
Disopyramide

Side effects
 Definition
 Dry mouth, urinary retention, constipation, ppt of glaucoma d/t anti-cholinergic effects
Term
Lidocaine

site of action / moa
 Definition
 Class IB: Membrane Stabilizing Drug
 Decrease the duration of the AP by shortening Phase 3
 Does NOT slow conduction
Term
Lidocaine

Effect/Clinical Uses
 Definition
 Lidocaine blocks both open and inactivated channels w/a preference for partially depolarized cells in ischemic areas
 ↓ ERP
 High first pass metabolism – NOT given orally
 Works within seconds, but has a short duration


Clinical Uses:
 Only Effective against rapid ventricular arrhythmias and ventricular ectopics (does not work in atrial arrhythmias)
 *Lidocaine works wells in ischemic heart tissue b/c most cells are inactivated or depolarized
Term
Lidocaine

side effects
 Definition
 Neurological: *Drowsiness, *Nystagmus, *Seizures, Numbness, slurred speech
Term
Phenytoin

site of action/moa
 Definition
 Class IB: Membrane Stabilizing Drug
Term
Phenytoin

effect/clinical use
 Definition
 Prolongs the inactivated state
 ↓ ERP

Clinical Uses:
 *Helps w/ digoxin induced arrhythmia (DOC)
Term
Phenytoin

side effect
 Definition
 Nystagmus, Ataxia
 Gingival hyperplasia
 Serious BM & dermatologic reactions can occur
Term
Flecainide

site of action/ moa
 Definition
 Class IC: Membrane Stabilizing Drug
 Potent Na+ channel blocker
Term
Flecainide

effect and clinical use
 Definition
 Negative inotropic effect
 Has little effect on the duration of AP, rather, they↓ automaticity by ↑ threshold potential & thus slowing conduction velocity

Clinical Uses:
 Indicated for life threatening atrial fibrillation and refractory ventricular arrhythmias
Term
Flecainide

side effects
 Definition
 High Pro-arrhythmic Potential - Can cause↓ motility when used
Term
Propafenone

site of action/ moa
 Definition
 Class IC: Membrane Stabilizing Drug
 Potent Na+ channel blocker
Term
Propafenone

effect and side effects
 Definition
 Negative inotropic effect
 Has little effect on the duration of AP, rather, they↓ automaticity by ↑ threshold potential & thus slowing conduction velocity

SIDE EFFECTS
 High Pro-arrhythmic Potential - Can cause↓ motility when used
Term
Class II Anti Arrhythmics
 Definition
 Beta blockers
 Prevents beta receptor activation, which would normally ↑cAMP


 Most efficacious anti-arrhythmics (decrease motility, safe, effective)
Term
Propanolol, Metoprolol

Site of action/ moa
 Definition
 β- blocker
 ↓ SA & AV Nodal Activity
Term
Propanolol, Metoprolol

effect and clinical use
 Definition
 Diminish Phase 4 depolarization -↓ automaticity (↓HR)
 Prolong/Block AV Conduction

Clinical Uses:
 Used in post-MI prophylaxis and SVTs
Term
Esmolol, Acebutolol

random
 Definition
NB: Use Esmolol in Acute SVT’s
Term
Esmolol, Acebutolol

site of action/ MOA
 Definition
 β- blocker
 ↓ SA & AV Nodal Activity
Term
Esmolol, Acebutolol

effect and clinical use
 Definition
Clinical Uses:
 Used in post-MI prophylaxis and SVTs
Term
Sotalol

Site of action/ moa
 Definition
 β- blocker
 ↓ SA & AV Nodal Activity
Term
sotalol

Effect / clinical use
 Definition
 Diminish Phase 4 depolarization -↓ automaticity (↓HR)
 Prolong/Block AV Conduction

Clinical Uses:
 Can be used in life-threatening ventricular arrhythmias
Term
Class III Anti-Arrhythmics
 Definition
 K+ Channel Blockers
 Agents widening APD
Term
Amiodarone

site of action/ moa
 Definition
 K+ Channel Blockers
 Agents widening APD
Term
Amiodarone

effect / clinical use
 Definition
 Can block K+ Channel to prevent K+ movement during Phase 3
 Prolongs repolarization
 Also blocks inactivated Na+ channels
 Inhibits Ca+ channels
 Widening the AP duration
 Takes a long time to manifest action


Clinical Uses:
 Effective in Ventricular Tachycardia & Ventricular fibrillation
 All effective in Atrial fibrillation

Need to monitor LFTs, PFTs, TFTs
Term
Amiodarone

side effects
 Definition
 *Pulmonary fibrosis (SOB, ↓ Pulmonary function)
 *Skin pigmentation (blue discoloration d/t Iodine accum.)
 Corneal deposits & blindness
 Hepatotoxic – hepatocellular necrosis
 Can induce *hypothyrpidism (hair loss, weight gain) or hyperthyroidism (similar to TSH)
Term
Bretylium

site of action/ moa
 Definition
 K+ Channel Blockers
 Agents widening APD
Term
Bretylium

effect/ clinical use
 Definition
 Prolongs ventricular AP & ERP
 Also blocks NE release


Clinical Uses:
 Ventricular fibrillation after lidocaine has failed
Term
Sotalol

site of action/ effect/ clinical use
 Definition
 K+ Channel Blockers
 Agents widening APD


 ↓ Automaticity, slows AV Node and prolongs AV refractory period


Clinical Uses:
 Ventricular arrhythmia
Term
Ibuilide

site of action and clinical use
 Definition
 K+ Channel Blockers
 Agents widening APD

Clinical Uses:
 *Converts Atrial Flutter and fibrillation to a Normal Sinus Rhythm
Term
Class IV Anti-Arrhythmics
 Definition
 Calcium Channel Blockers
 Block “L type” Calcium channels &↓both SA node automaticity & AV nodal conduction
 They↓ rate of Phase 4 spontaneous depolarization & thus ↑the ERP
Term
Verapamil

site of action/ moa
 Definition
 Calcium Channel Blocker (important in Phase 0 of automatic cell)
Term
Verapamil

effect and clinical use
 Definition
 ↓Conduction thru the AV node and shorten the plateau of the cardiac potential
 ↓The contractility of the heart, so inappropriate in heart failure

Clinical Uses:
 First line for SVT (Atrial Flutter & Fibrillation)
Term
Verapamil

side effects
 Definition
SE:
 Bradycardia (AV Heart Block)
 Hypotension, dizziness
 Gingival Hyperplasia
 Constipation

Contraindications:
 Ventricular arrhythmias b/s it will cause the heart to stop (If unsure if the rhythm is SVT or Ventricular arrhythmia – Give Adenosine)
 CHF
Term
Diltiazam

site of action and moa
 Definition
 Calcium Channel Blocker (important in Phase 0 of automatic cell)
Term
Diltiazam

effect/ clinical use
 Definition
 ↓Conduction thru the AV node and shorten the plateau of the cardiac potential
 ↓The contractility of the heart, so inappropriate in heart failure


Clinical Uses:
 First line for SVT (Atrial Flutter & Fibrillation)
Term
Adenosine

site of action / moa
 Definition
 Activates the K+ channel in the AV Node causing hyperpolarization (NO AP) & ↓ automaticity (**shortens ERP & AP duration)
 Reduces Ca++ currents (esp. in SA & AV Nodes)
Term
Adenosine

effect and clinical use
 Definition
 AV Conduction is slowed (Causes a transient heart block*)
 Short t ½ life ~10seconds
 Shortened ERP & AP duration
 Causes endothelial dependent smooth muscle relaxation(inside BV)


Clinical Uses:
 DOC for SVT (terminates in seconds [palpitations])
Term
Adenosine

Side effects
 Definition
 Bronchospams d/t histamine release
o Chest burning
o SOB
o Flushing
Term
Digoxin

site of action/ moa
 Definition
 Inhibits the Na/K ATPase pump in myocardial cell membrane
Term
Digoxin

effect and clincal use
 Definition
 ↑ vagal activity via its central action on the CNS, thus ↓conduction thru the AV Node (↑ERP)
 Slows heart down (↓AV & SA node conduction)
 Has a narrow Therapeutic Index

Clinical Uses:
 Can be used in SVT & Atrial fibrillation
 Has a small role in CHF w/A-fib
Term
Digoxin

side effects
 Definition
 Digoxin induced arrhythmias (Esp. A-tachycardia)
• Tx. with Phenytoin or Lidocaine or Mg+
• Hyperkalemia
• Could lead to AV
 *Blurry vision with color changes
Term
Magnesium

site of action/ moa
 Definition
 Weakly blocks Ca++, Na+ & K+ channels

Clinical Uses:
 Used post-operatively
 Used IV to tx. HTN Crisis
Term
Magnesium

effect/ clinical use
 Definition
 Thought to stabilize cardiac cell membranes

Clinical Uses:
 Used in torsades pointes (Resistant polymorphic tachycardia which often does NOT respond to normal treatment)
 Used in Digoxin induced arrhythmias
 Tx. Pre-Eclampsia or Eclampsia
Term
ACE Inhibitors

name them
 Definition
Captopril
Lisinopril
Enalapril
Ramipril
Benzapril
Fosinopril
Term
ACE Inhibitors

site of action/ MOA

Captopril
Lisinopril
Enalapril
Ramipril
Benzapril
Fosinopril
 Definition
 Inhibit ACE, the enzyme that converts Angiotensin I to Angiotensin II
Term
ACE Inhibitors

Effects

Captopril
Lisinopril
Enalapril
Ramipril
Benzapril
Fosinopril
 Definition
 ↓In arterial resistance by inhibiting vasoconstriction (afterload)
 ↓In Venous Tension (preload, ↓Blood volume )
 ↓In Aldosterone secretion
 ↓ breakdown of Bradykinin (build up of bradykinin causes a *dry, persistent, irritating cough
Term
ACE Inhibitors

clinical use

Captopril
Lisinopril
Enalapril
Ramipril
Benzapril
Fosinopril
 Definition
Clinical Uses:
 CHF (anti-remodeling effect)
 HTN (frontline drug)
 LVHF – Overlaps w/ CHF
 DOC in Pvt. of nephropathy in DM
Term
ACE Inhibitors

side effects

Captopril
Lisinopril
Enalapril
Ramipril
Benzapril
Fosinopril
 Definition
Dry, persistent, Irritating Cough
 Hypotenstion
 Hyperkalemia (blocks Aldosterone synthesis)
 Rash and taste disturbance w/ Captopril
 *Angioedema - Edema of larynx & upper resp tract d/t accumulation of bradykinin)

 NB: NSAIDS block action of Bradykinin

Contraindications:
 Pregnancy
 Bilateral renal artery stenosis (ACE can still be used with unilateral RAS)
Term
ARB
(at subtype 1)

name them and what is their site of action
 Definition
Losartan
Erbesartan
Candesartan


 Competitive antagonist of Angiotensin II at receptor
 No inhibition of ACE or breakdown of bradykinin
Term
ARB
(at subtype 1)

Effect and clinical use

Losartan
Erbesartan
Candesartan
 Definition
 Similar to ACE inhibitors, but does NOT produce the dry, persistent, irritating cough

Clinical Uses:
 HTN
 CHF
Term
Renin Inhibitor
Aliskiren

this is it what it does
 Definition
 Block renin and you block the formation of Angiotensin I
Term
Beta Blockers

what are the anti-hypertensive ones
 Definition
Atenolol, Propanolol
Term
Beta Blockers
site of action/moa

Atenolol, Propanolol
 Definition
 Β-adrenergic receptor Antagonist
 Also blocks rennin secretion
Term
Beta Blockers

effect

Atenolol, Propanolol
 Definition
 ↓CO (blockade of cardiac β1 Receptors)
 *Inhibition of Renin release (blockade of β1 Receptors on Juxtaglomerular cells)
 Inhibition of NE release from pre-synaptic adrenergic terminals (blockade of presynaptic beta receptors)
 Reduction of central adrenergic tone
Term
Beta Blockers
Clinical use/ side effects
Atenolol, Propanolol
 Definition
Clinical Uses:
 DOC for HTN young adult (esp. if there is a history of migraines)


Contraindications: PVD, Bronchial asthma, Acute heart failure, Diabetes
Term
calcium channel blockers for hypertention, what are they?
 Definition
Verapamil
Diltiazem
Nifedipine
Amlodipine
Nimodipine
Term
CCB

Site of action/ moa

Verapamil
Diltiazem
Nifedipine
Amlodipine
Nimodipine
 Definition
 CCB cause relaxation by ↓the intracellular availability of calcium
 Inhibit the influx of Ca++ into cardiac & smooth muscle cells by blocking voltage-dependent “L-type” Ca++ channels, thereby ↓smooth muscle & cardiac contractility
 The degree of blockade is proportional to degree of stimulation/use of these Ca++ channels
Term
CCB

Effect

Verapamil
Diltiazem
Nifedipine
Amlodipine
Nimodipine
 Definition
 Relaxes mainly arteries*
 Extravascular smooth muscles – bronchial, biliary and intestinal also relax (will not exacerbate bronchial asthma)
 *Negative Chronotropy (Heart Rate)
 Negative Inotropy (Contractility)
 Negative dromotropy (Conduction Velocity)
Term
CCB

clinical use

Verapamil
Diltiazem
Nifedipine
Amlodipine
Nimodipine
 Definition
Clinical Uses:
 Angina
 Arrhythmia
 *HTN
 SAH (Nimodipine; dilation of cerebral BV)
 Nifedipine (Vasospastic Angina)
Term
Alpha2 Receptor Agonist

what are they?
 Definition
Clonidine
Methyldopa
Term
Alpha2 Receptor Agonist

Site of action/ moa

Clonidine
Methyldopa
 Definition
 Reduces sympathetic outflow from CNS by acting on brain stem (inhibits NE release)
 ↓SNS outflow results in ↓PVR and in some ↓CO
Term
Alpha2 Receptor Agonist

clinical use

Clonidine
Methyldopa
 Definition
Clinical Uses:
 HTN
 Methyldopa is DOC for treatment of HTN in pregnancy
 Clonidine can control Opioid withdrawal syndrome (which induces SNS response)
 Clonidine also has a role in anesthesia
Term
Alpha2 Receptor Agonist

Side effects

Clonidine
Methyldopa
 Definition
 Clonidine can cause *HTN Crisis, when the drug is abruptly withdrawn leading to tachycardia, sweating, nausea, tremor, apprehension and may be life-threatening
 Methyldopa could cause +Coomb’s Test and Hemolytic Anemia
Term
Hydralazine

site of action / moa
 Definition
 Direct arteriolar vasodilator
 Release of NO causes the vasodilation of arteries (↓PVR)
Term
Hydralazine

clinical use
 Definition
Clinical Uses:
 HTN that is NOT first controlled by frontline antiHTNs
 Can be used to treat HTN in pregnancies (2nd DOC)
 HTN emergencies
Term
Hydralazine

side effects
 Definition
 Reflex tachycardia (SNS activation)
 Fluid retention
 Throbbing headache
 Palpitations
 *SLE-like syndrome in slow acetylators or on prolonged use at a higher dose (Myalgia, arthralgia, inflammation, butterfly rash)
 Ppt. of Angina, Myocardial infarction
 NE release from nerve endings can ↑ Myocardial contractility
Term
Minoxidil
(Rogaine)

site of action/moa and effect
 Definition
 Arteriolar vasodilation – K+ channel activator
 Open K+ channel which results in hyperpolarization & relaxation of smooth muscles

 Arteriolar vasodilation
Term
Minoxidil
(Rogaine)


clinical uses and side effects
 Definition
Clinical Uses:
 Used to treat HTN patients with renal failure

 Chronic therapy can produce *excess growth of hair on face, back and arms
 HA, Edema, Flushing
Term
Diazoxide

site of action and effect
 Definition
 Prevents arterial smooth muscle contraction by opening K+ channels & stabilizing the membrane potential

 Causes activation of ATP-sensitive potassium channels, leading to hyperpolarization of arteriolar smooth muscle, relaxation & dilation
Term
Diazoxide

clinical use and side effect
 Definition
Clinical Uses:
 Used to treat HTN
 Used in HTN emergencies



 *Hyperglycemia (inhibits insulin secretion)
 Hypotension
Term
Sodium Nitroprusside

site of action / moa
 Definition
 Releases NO which ↑cGMP concentration resulting in ↓ in intracellular Ca++ ions & consequent relaxation of vascular smooth muscles *(Arterial & venous)
Term
Sodium Nitroprusside

first drug in HTN crisis
 Definition
 Order of drugs used in HTN Crisis:
1. Sodium Nitroprusside
2. NTG
3. Diazoxide
4. Esmolol
Term
Sodium Nitroprusside

Clinical use and side effect
 Definition
Clinical Uses:
 Used in HTN emergencies


Cyanide poisoning d/t cyanide production during metabolism
Term
Fendoldopam

site of action, effect, clinical use
 Definition
 Selective peripheral Dopamine D1 receptor weak partial agonist

 Anti-HTN used post-operatively
Term
Nitrates

site of action/moa
 Definition
 Nitrates relax vascular smooth muscle thru conversion into Nitric Oxide (NO) & subsequent *elevation of intracellular cGMP
 The ↑activity of cGMP ultimately leads to dephosphorylation of myosin light chains and smooth muscle relaxations
Term
Nitrates

effects
 Definition
 Systemic Vasculature
-Vasodilation (venous > arterial)
-↓venous pressure
-↓arterial pressure
 Cardiac effects
-↓Preload & afterload (↓wall stress)
-↓O2 demand (better perfusion)
 Coronary effects
-prevents vasospasm
-vasodilation (epicardial vessels)
-Improved subendocardial perfusion
-Increased O2 delivery
 Improves the collateral circulation & improves perfusion to ischemic areas
Term
Nitrates

pharmacokinetics
 Definition
Short Acting: SL* –GTN, Nitroglycerine, Isosorbide dinitrate
-Long Acting: Oral – Isosorbide dinitrate, Nitroglycerine
-Organic Nitrates are lipid soluble
-Extensive first pass metab. Occurs in the liver
-Nitrates are denitrated by glutathione reductase
-Denitrated metabolites are less active but longer acting (mononitrates are preferred in prophylaxis rather than treatment)
Term
Nitrates

clinical use
 Definition
Clinical Uses:
 Angina*main use
 CHF & LVHF
 Cyanide poisoning^
 *Sodium Nitroprusside is a DOC for Emergency HTN (it directly releases NO & produces vasodilation
Term
Nitrates

side effects
 Definition
Hypotension (which can induce reflex tachycardia- so, also use a beta blocker))
 Throbbing headache (d/t meningeal artery dilation)
 *Methemoglobinemia (cyanosis)-does not carry O2 (Must try to reduce it w/Methylene Blue)
 *Tolerance – activation of SNS & volume expansion (fluid retention); (Must have “nitrate-free” periods w/ long term use-at least 8 hrs every 10days)

Contraindications:
 Taken with drugs like sildenafil citrate (Viagra); a PDE inhibitor also↑ cGMP, so could get excessive hypotension- leading to reflux tachy and an ↑load on the heart which could ppt an MI
Term
Beta Blockers
Atenolol
Metoprolol
Propanolol

site of action for angina
 Definition
 Bind to β-adrenergic receptor
 Reduce the myocardial oxygen demand by ↓heart rate (improving diastole blood flow to the myocardium)
Term
Beta Blockers
Atenolol
Metoprolol
Propanolol

Cardiac effects
 Definition
 Cardiac effects
-↓Contractility ( - Inotropy)
-↓Relaxation rate
(- Lusitrophy)
-↓Heart Rate (- chronotropy)
-↓Conduction velocity
(- dromotrophy)
 Vascular effects
-smooth muscle contraction (mild vasoconstriction)
Term
Beta Blockers
Atenolol
Metoprolol
Propanolol

Pharmokinetics
 Definition
 Reduce the work of the heart
 Reduce the heart’s response to exercise
Term
Beta Blockers
Atenolol
Metoprolol
Propanolol

clinical use
 Definition
Clinical Uses:
 Classic Angina
 Could use w/nitrates b/c it will counteract the reflux tachycardia induced by nitrates
Term
Beta Blockers
Atenolol
Metoprolol
Propanolol


side effects
 Definition
 Feeling of coldness in the extremities (peripheral blood flow ↓ b/c CO↓)
 Elevated Triglycerides

Contraindications:
 Variant Angina, Asthma (Bronchoconstriction), Diabetes (can inhibit hypoglycemia induced tachycardia-blocks the warning sign), PVD, AV block (Bradycardia)
Term
Calcium Channel Blockers
Nifedipine
Diltiazem
Verapamil

site of action/ moa in angina
 Definition
 CCB cause relaxation by ↓the intracellular availability of calcium
 Inhibit the influx of Ca++ into cardiac & smooth muscle cells by blocking voltage-dependent “L-type” Ca++ channels, thereby ↓smooth muscle & cardiac contractility
Term
Calcium Channel Blockers
Nifedipine
Diltiazem
Verapamil

effects
 Definition
 Relaxes mainly arteries
 Extravascular smooth muscles – bronchial, biliary and intestinal also relax (will not exacerbate bronchial asthma)
Term
Calcium Channel Blockers Nifedipine Diltiazem Verapamil

pharmokinetics
 Definition
[image]
Term
Calcium Channel Blockers
Nifedipine
Diltiazem
Verapamil

clincal use
 Definition
Clinical Uses:
 *DOC for Prinzmetal’s Angina
 Smooth muscle relaxation
 Negative Chronotropy (Heart Rate)
 Negative Inotropy (Contractility)
 Negative dromotropy
 Also used for Stable Angina, HTN, LVHF, Migraine, SVT, Raynaud’s Syndrome
Term
Calcium Channel Blockers
Nifedipine
Diltiazem
Verapamil


other jazz, angina
 Definition
 NB: “L-type” Calcium channels are found in smooth muscles, SANode, AVNode
Term
K+ Channel Blockers
Nicorandil
Cromakalin

angina site of action/effect
 Definition
 Causes a hyperpolarization ( so that cell will not fire) and causes a vessel relaxation

 Smooth muscle relaxation of vascular and visceral tissue
 Could also relax bronchial smooth muscle
Term
K+ Channel Blockers
Nicorandil
Cromakalin

clincal use
 Definition
Clinical Uses:
 Treat Angina Pectoris
Term
Trimetazidine (Vastarel)

site of action, effect, clinical use
 Definition
 Cardioprotective anti-ischemic agent

 An anti-ischemic agent that improves myocardial utilization thru inhibition of fatty acid metabolism (promotes the heart to use glucose for energy which uses O2 more efficienctly)


Clinical Uses:
 Treat Angina Pectoris
Term
Angina pectoris

Three types:
 Definition
printzmetal’s/Variant Angina (Vasospasm)
 Only for a split second (Tx: Vasodilator)
• Chronic, Classic, Stable Angina (fixed Stenosis)
 Less blood flow can produce angina on exertion – usually d/t an atheromatous lesion
• Unstable Angina (Thrombus)
 “Pre-MI”- Can occur at rest (suddenly)
Term
ACE Inhibitors
Captopril
Lisinopril
Enalapril
Ramipril
Quinapril

site of action
 Definition
 Inhibit the conversion of Angiotensin I to Angiotensin II
 Block the degradation of Bradykinin (helps to ↓ BP)
Term
ACE Inhibitors
Captopril
Lisinopril
Enalapril
Ramipril
Quinapril

effect
 Definition
 Improve mortality, morbidity, exercise tolerance, left ventricular ejection fraction
 ↓PVR by vasodilation (afterload)
 Minimize Na+ and water reabsorption by ↓Aldosterone levels
 ↓Cardiac & vascular remodeling
 ↓Venous tension (preload)
Term
ACE Inhibitors
Captopril
Lisinopril
Enalapril
Ramipril
Quinapril

clinical use
 Definition
Clinical Uses:
 CHF (first choice; anti-remodeling effect)
 HTN (frontline drug)
 LVHF – Overlaps w/ CHF
 DOC in Pvt. of nephropathy in DM
Term
ACE Inhibitors
Captopril
Lisinopril
Enalapril
Ramipril
Quinapril

side effects
 Definition
 Dry, persistent, irritating cough (d/t Bradykinin)
 Hyperkalemia
 Angioedema
 Fetal toxicity

Contraindications:
 Pregnancy
 Bilateral Renal Stenosis
Term
ARB
Losartan
Irbesartan
Candesartan
site of action
 Definition
 Block ATII at its receptor site, thus inhibiting both vasoconstriction and aldosterone-secreting effects of ATII
 Do not affect the Bradykinin system
Term
ARB
Losartan
Irbesartan
Candesartan

clinical use and side effect
 Definition
Clinical Uses:
 HTN (mild to moderate)
 CHF

se:

 Headache
 Hyperkalemia
 Hypotension
Term
Isosorbide dinitrate
Hydralazine

site of action and effect
 Definition
(vasodilators)
MOA
 Isorbide dinitrate works as a venous dilator at low dose
 Hydralazine works on arterial side


effect

 Isorbide dinitrate ↓Preload & ↓Cardiac workload therefore ↓O2 demand
 Hydralazine ↓PVR therefore ↓BP
Term
Isosorbide dinitrate
Hydralazine

clincal use and side effects
 Definition
(Vasodilators)

Clinical Uses:
 Used especially in patients who cannot tolerate ACE Inhibitors


SE:

 Tolerance is a big issue w/Nitrates (need a “nitrate free” period)
 Hydralazine can cause reflex tachycardia and fluid retention can follow, so use Beta blockers to block reflex
 Hydralazine also produces an SLE-like syndrome (myalgia, arthralgia, inflammation, butterfly rash)
Term
Amlodipine
Prazosin

site of action, effect, clincal use
 Definition
(vasodilator)
site of action: Amlodipine is a CCB
 Prazosin is an α-1 Receptor blocker

effect:
 ↓Preload & ↓Afterload
 Amlodipine does not cause reflex tachycardia

clinical use:
 CHF
 HTN
Term
Diuretics use in chf
 Definition
 Useful in ↓the symptoms of fluid overload by ↓ECF Volume or ↓the venous pressure (↓ Preload)
 ↓Preload by minimizing Na+ & water retention
 May also ↓ afterload by↓ plasma volume
Term
Loop Diuretics
Furosemide

use and side effect
 Definition
Clinical Uses:
 Most effective and most commonly used diuretic in CHF
 DOC for tx. of Pulmonary Edema

 Hypokalemia (can trigger arrhythmias)
Term
Thiazide Diuretics

use and side effects
 Definition
Clinical Uses:
 Effective for long-term mild cases of CHF


 Hypokalemia (can trigger arrhythmias)
Term
Potassium-sparing Diuretics
Amiloride
Spironolactone

Site of action and effect
 Definition
MOA:
 Spironolactone is an aldosterone antagonist

 Amiloride is a direct Na+ channel inhibitor


Effect: Reduces the effects of potassium losing diuretics, prevents K+ loss (↓Preload & ↓O2 demand on the heart)
 Prevents water retention, endothelial dysfunction and myocardial fibrosis
 Improves the overall survival rate of CHF patients (so do ACE Inhibitors)
Term
Potassium-sparing Diuretics
Amiloride
Spironolactone

clinical use
 Definition
Clinical Uses:
 Often used with other diuretics in CHF to increase diuresis and prevent K+ loss
Term
Beta blockers
Carvedilol
Metoprolol

mechanism of action/ effect
 Definition
MOA: Acts primarily by inhibiting the SNS
 ↑Beta receptor sensitivity (up regulation); Tries to retain Beta receptors


Effect: Although Beta blockers may seem paradoxical, clinical trials have shown that mortality is ↓; they seem to prevent adverse SE of chronic SNS output and ↓ remodeling
Term
Beta blockers
Carvedilol
Metoprolol

Clinical use and side effects
 Definition
Clinical Uses:
 Tx of arrhythmic
 Anti-oxidant
 Tx of HTN
 Tx for mild to moderate CHF
 Should only be used in a hemodynamically stable patient


SE: Bradycardia

 NB: Never use in acute heart failure b/c will decrease contractility of the heart
Term
Digoxin

Site of Action
 Definition
 Inhibition of Na/K ATPase pump, which↑ intracellular Na+
 The ↑ in intracellular Na+ ↓ the electrochemical gradient that drives the extrusion of IC Ca++ by Na/Ca exchange
 The resulting accumulation of IC Ca++ is stored in the sarcoplasmic reticulum & when released causes ↑ myocardial contractility
Term
Digoxin

Effect
 Definition
 Restores vagal tone & abolishes sympathetic over activity
 Reduced Na/Ca gradient slows Ca++ removal and Ca++ accumulates intracellularly
 Positive Inotropic effect (contractility)
 Can ↑ the refractoriness of AV Node thus ↓ the ventricular response to atrial rate (Can block AV Node, so can use in SVT or Atrial fibrillation)
 Narrow Therapeutic Index
Term
Digoxin

Clincal use
 Definition
Clinical Uses:
 Tx. of SVT
 First line drug in tx. of CHF patients who are in Atrial-fibrillation (Digoxin slows the conduction velocity and↑ the refractory period at the AV Node)



Treatment of Digoxin toxicity:
-Higher than normal dose of K+
-Lidocaine to treat the arrhythmia
-Digoxin antibody (Digibind) is used specifically to treat life-threatening digoxin overdose
Term
Digoxin

Side effects
 Definition
 N/V/D, Headache
 Gynecomastia
 *Visual disturbances (blue vision or yellow-green halos)
 Psychosis
 Bradycardia
 *Ventricular bigamy (coupled beats)
 AV block (could also see prolonged PR Interval, shortened QT Interval & inverted t wave)
 Digoxin toxicity is enhanced by hypokalemia (Digoxin normally competes w/ K+ ions for the same binding site in Na/K ATPase)
 Quinidine, Amiodarone, Verapamil can ↑ the plasma concentration of digoxin by inhibiting its excretion (works by displacing tissue binding sites and depressing renal digoxin clearance)
 Hyperkalemia


Contraindications:
 Bradycardia
 Ventricular fibrillation
Term
Cardiac Inotropes
Milrinone
Dobutamine


Site of action
 Definition
 Milrinone is a PDE III Inhibitor which leads to ↑ levels of cAMP and Intracellular Ca++, which results in↑ contractility
 Dobutamine is a β-1 agonists which ↑contractility and cardiac output
Term
Cardiac Inotropes
Milrinone
Dobutamine
 Definition
Effect:
 Milrinone is a vasodilator and causes positive inotropy (Contractility)
 Dobutamine ↑contractility & Cardiac Output
Term
Cardiac Inotropes
Milrinone
Dobutamine

clinical use
 Definition
Clinical Uses:
 Only used in Acute Heart Failure
Term
 Causes of Heart failure
 Definition
CAD, HTN, Diabetes, Mitral valve disease and chronic alcohol
Term
 Three major approaches to treat CHF:
 Definition
• Improve myocardial contractility
• ↓Preload (which↓ O2 demand)
• ↓Afterload (CO = HR *SV); which will↓ PVR
Term
 Compensatory mechanisms occurring in heart failure:
 Definition
• ↑ SNS Tone, which results in tachycardia and greater PVR
• ↓Renal blood flow, which stimulates aldosterone and ↑salt & water retention
• Myocardial hypertrophy (d/t AngiotensinII)
Term
CHF drug summary
 Definition
 ACE Inhibitors are cornerstone in the treatment of CHF
 Beta blockers are used in selected patients (mild/moderate heart failure at a low dose)
 Diuretics and digoxin are other drugs useful in CHF selective patients
Term
Furosemide (Lasix)

site of action
 Definition
 Called High Ceiling loop diuretic b/c they have the highest efficacy of all diuretics
 Inhibits the Na+/K+/2Cl Co-transporter in the Thick Ascending LOH
Term
Furosemide (Lasix®)

effect
 Definition
 *Major action is on the thick ascending loop of Henle
 Minor action on PCT – weak carbonic anhydrase activity
 Increases Calcium excretion (↑Ca++ content in the urine
Term
Furosemide (Lasix®)

clinical use
 Definition
Clinical Uses:
 Useful in Pulmonary Edema (*IV use can cause rapid ↑ in systemic venous capacitance and ↓left ventricular filling pressure
 Systemic Edema
 CHF
 Forced diuresis
 HTN
 Hypercalcemia
Term
Furosemide (Lasix®)

side effects
 Definition
 *Mild alkalosis at high doses (b/c of hypokalemia)
 Hyperglycemia (Could ppt DM)
 Hyperuricemia
 Hypocalcemia (NOT used in post-menopausal women)
 Hypomagnesemia
 Ototoxicity occurs more frequently with IV administration
 Volume depletion
 Interstitial nephritis (loop diuretics are sulfonamide derivatives)
Term
Bumetanide

site of action / effect
 Definition
MOA:
High Ceiling loop diuretic
 Inhibits the Na+/K+/2Cl Co-transporter in the Thick Ascending LOH


Effect:

 40X more potent than Furosemide
 *Major action is on the thick ascending loop of Henle
 Minor action on PCT – weak carbonic anhydrase activity
 Increases Calcium excretion (↑Ca++ content in the urine)
Term
Bumetanide

Clincal use
 Definition
Clinical Uses:
 Edema
 Acute Pulmonary Edema
 Forced diuresis
 HTN
 CHF
 Hypercalcemia
Term
Bumetanide

Side effects
 Definition
 *Mild alkalosis at high doses (b/c of hypokalemia)
 Hyperglycemia (Could ppt DM)
 Hyperuricemia
 Hypocalcemia (NOT used in post-menopausal women)
 Hypomagnesemia
 Ototoxicity occurs more frequently with IV administration
 Volume depletion
 Interstitial nephritis (loop diuretics are sulfonamide derivatives)


(all the same as fureosemide)
Term
Ethacrynic Acid

site of action
 Definition
 High Ceiling loop diuretic
 Inhibits the Na+/K+/2Cl Co-transporter in the Thick Ascending LOH
Term
Ethacrynic Acid

effect
 Definition
 Similar to Furosemide

 *Major action is on the thick ascending loop of Henle
 Minor action on PCT – weak carbonic anhydrase activity
 Increases Calcium excretion (↑Ca++ content in the urine)
Term
Ethacrynic Acid

clinical use
 Definition
Clinical Uses:
 Edema
 Acute Pulmonary Edema
 Forced diuresis
 HTN
 CHF
 Hypercalcemia
Term
Ethacrynic Acid

Side effects
 Definition
 Irritant orally
 Diarrhea
 *Toxic & can cause hearing loss
 Hepatotoxicity
Term
Thaizides

Site of action
 Definition
(Hydro-chlorothiazide; Metazolone
Indapamide)

 Inhibit Na+/Cl- Symporter in the Early Distal Tubule
 Secondary Action is CA inhibitor in proximal convoluted tubule
Term
Thaizides: Hydro-chlorothiazide; Metazolone
Indapamide

Effect
 Definition
 More Na is presented to the distal nephron, so more of Na+ is exchanged w/K+ and H+ which results in ↑urinary K+ & H+ excretion
 ↑ the reabsorption of Calcium, so Thiazides retain Calcium (↑Serum Ca2+ levels) comparatively to Furosemide
 ↑BS and Uric Acid levels
 Moderate efficacy as 90% of Na+ is reabsorbed before it reaches the DCT
Term
Thaizides: Hydro-chlorothiazide; Metazolone
Indapamide


Clinical uses
 Definition
Clinical Uses:
 Metalozone & Indapamide are useful even in moderate renal failure (not severe RF)
 Edema
 HTN & CHF
 Nephrogenic diabetes insipidus (non-lithium induced)-
 Tx. of Ca++containing renal stones
Term
Thaizides: Hydro-chlorothiazide; Metazolone
Indapamide

Side effects
 Definition
SE:
 Hypokalemia **Most Common
 Hearing loss
 Hyperuricemia, hyperglycemia
 Hypercalcemia

 NB: Thiazides have the ability to produce a slightly hyperosmolar urine and thus diminish polyuria, so it is useful in treating Nephrogenic diabetes insipidus (Thiazides ↓distal tubular Na+ reabsorption, which↑ UO, which ↓EC Volume, leading to ↑PCT Na+ and water reabsorption and ↓distal delivery of Na+ and water resulting in ↓ UO)---DO NOT use Thiazides in LI-DI b/c will result in excessive reabsorption of lithium from PCT
Term
Acetazolamide

site of action
 Definition
 Weak Diuretic
 Carbonic anhydrase inhibitor, therefore Na+ and HCO3 are NOT reabsorbed- it inhibits the exchange of Na+ for H+ in PCT (Carbonic acid ionizes into HCO3 & H+, thus helps in the transport of CO2 and H+ secretion)
 The CA enzyme is present in the renal tubular cells, gastric mucosa, pancreas, ciliary body, & RBC
Term
Acetazolamide

Effect
 Definition
 Net effect is inhibition of HCO3 reabsorption in PCT
 H+ secretion is inhibited
 The urine produced is rich in bicarbonate – alkaline urine results and depletes body of HCO3, producing *Acidosis*
NB: there is a ↓reabsorption of K+, Na+ & Water b/c no osmotic gradient; ↓Reabsorption of Cl- b/c not reabsorbing water; Reabsorption of glucose does not change
Term
Acetazolamide

clincal uses
 Definition
Clinical Uses:
 Glaucoma (Lowers IOT d/t ↓ production of aqueous fluid)
 To Alkalinize urine (helps w/ excretion of acidic things)
 Epilepsy (↑levels of CO2 [acidosis]b/c no CA enzyme and ↓ of pH, which raises the seizure threshold)
 Acute Mountain Sickness
 Also ↓gastric acid and bicarbonate secretion
Term
Acetazolamide

side effect
 Definition
 Acidosis (d/t loss of HCO3)
 *Hypokalemia (d/t ↑excretion of K+ & ↑ flow rate)
 *Paresthesia
 Hypochloremia
 Renal Calculus (b/c the alkalinization of the urine can cause the ppt of calcium salts)

Contraindications:
 Liver Disease – b/c these diuretics interfere with elimination of ammonia
Term
Spironolactone

site of action
 Definition
 Weak Diuretic
 Aldosterone Antagonist; binds to aldosterone receptor sites and prevents formation of mediator proteins
 Works in late DCT or Collecting duct
Term
Spironolactone

Effect
 Definition
 Its action is dependent on Aldosterone
 Counteracts the K+ loss d/t thiazides & loop diuretics
 When combined w/another diuretic, it makes it stronger
 K+ Sparing Diuretic
Term
Spironolactone

clinical uses
 Definition
Clinical Uses:
 Useful in cirrhotic, nephritic, and refractory edema
 ↓Mortality in heart failure
Term
Spironolactone

Side Effects
 Definition
SE
 *Gynecomastia (b/c blocks androgen receptors;↓Testosterone, ↑Estrogen)
 Menstrual irregularities
 Impotence
 Hyperkalemia

NB: Aldosterone normally stimulates Na+ Reabsorption & K+ Secretion by↑ activity & expression of proteins at Apical border, also ↑ protein synthesis of K+ leak channels
Term
Amiloride, Triamterene

site of action / effect
 Definition
 Inhibits Na+ channels of the principal cells in the late DCT or collecting duct


effect:
 Works independent of aldosterone
 Often used in conjunction with other diuretics
 Amiloride is 10X more potent than Triamterene
 ↓Calcium & Magnesium excretion
Term
Amiloride, Triamterene

clinical uses
 Definition
Clinical Uses:
 *If used as an aerosol, Amiloride can cause symptomatic improvement in CF by ↑fluidity of respiratory secretions
 *Amiloride is preferred in lithium induced nephrogenic diabetes insipidus (Blocks the entry of lithium into renal cells)
 Can be used in hypoaldosteronism & Addison’s Disease (b/c it directly blocks the Na+ channels)
Term
Amiloride, Triamterene

Side effect
 Definition
 Hyperkalemia occurs when used w/ACE inhibitors
 Metabolic Acidosis (d/t intracellular shift of H+ Ions)
 Triamterene can cause leg cramps & form renal stones
Term
Mannitol

Site of action/ effect
 Definition
 Primary Action is to ↑Urinary Volume
 Not Metabolized & freely filtered in the glomerulus
 Expands ECF and ↑GFR
 Not effective in excreting sodium
Term
Mannitol

clinical uses/ side effects
 Definition
Clinical Uses:
 Maintains GFR & urine flow in renal failure
 *Reduces ICT & IOC by its osmotic activity


Side Effects:

 If given orally it will cause SEVERE diarrhea
 Hypovolemia
 Hypernatremia
 Pulmonary Edema (b/c it rapidly enters the ECF and pulls water out of the cells)
Term
High Efficacy Diuretics:
 Definition
 Inhibitors of Na+/K+/2Cl Cotransporter
 Furosemide, Bumetanide, Ethacrynic acid
Term
Medium Efficacy Diuretics
 Definition
 Inhibitors of Na-Cl Cotransport
 Hydrochlorothiazide, Chlorothalidone, Metolazone, Indapamide (the last two can be used in Renal Failure)
Term
Weak or adjuvant Diuretics
 Definition
 Carbonic Anhydrase Inhibitors: Acetazolamide
 Potassium sparing diuretics: Spironolactone
 Inhibitors of Renal endothelial Na+ Channel: Triamterene, Amiloride
 Osmotic diuretics: Mannitol, Glycerol
Term
Drugs enhancing action of Vasopressin
 Definition
(Retains water) (Want to do this in Central Diabetes insipidus)
 NSAIDS
 Carbamazepine
 Chlorpropamide
Term
Drugs inhibiting action of Vasopressin:
 Definition
(Want to do this when there is too much ADH- SIADH)
 *Demeclocycline – Exclusively for SIADH
 Lithium
 Conivaptin – V2 Antagonist
Term
Treatment of Central Diabetes Insipidus:
 Definition
Desmopression, Chlorpropamide, Carbamazepine
Term
Treatment of Nephrogenic Diabetes Insipidus:
 Definition
Adequate intake of Water, Amiloride (for Li+ induced), Thaiazides (for non-Li+), Indomethacin
Term
Inhalation Agents generally, anesthetics

MOA
 Definition
 Much of the MOA is speculation & is not completely clear, but the most accepted theory is that: The GABAA receptors play a role
 All anesthetics have the common property of ↑ the threshold of AP and inhibiting the rapid ↑ in membrane permeability to Na+ ions
Term
Inhalation Agents anestitics

B:G (λ) & O:G&MAC
 Definition
High O:G Coefficient gives Higher potency (lower MAC)

High B:G Coefficient gives Higher Solubility and Slower Induction and Recovery
Term
Inhalation Agents

Effects/Advantage
 Definition
 CNS: Depresses different regions variably. Cortex & brainstem (ARAS)affected first. Analgesia d/t effects on spinal cord
 ANS: Desflurane and NO2 can ↑ sympathetic discharge. Halothane↓ sympathetic activity Body temp is ↓ by all
 Respiration: All anesthetics produce a dose-dependent depression of RR. They ↓ tidal volume and ↑ventilation rate. They ↓ sensitivity of Resp. center to CO2
 CV: All currently used agents ↓ BP in a concen.-dependent manner. Most inhalation agents depress force of myocardial contraction
 Hepatic & Renal: ↓ Hepatic & Renal blood flow & GFR; ↓P-450 enzymes; metabolites of anesthetics are usually more toxic than parent compound
Term
Inhalation Agents

Toxicities & Side Effects
 Definition
Side Effects:
 Nausea & vomiting (action on CTZ);
 Malignant hyperthermia in genetically susceptible (Tx: Dantrolene which interferes w/release of Ca++ and Cools them down)
 Seizures (w/enflurane) – depends on CO2 partial pressure
Term
Diethyl ether

MOA/ B;G, O;G, MAC/ Effects advantages/ disadvantages
 Definition
 First general anesthetic discovered, no longer used d/t flammability

B:G = 12
O:G = 65
MAC = 1.9%

 Respirations fails before heart (can revive in case of overdose)

 Irritating to respiratory membranes
 Causes a lot of Nausea & Vomiting
Term
MOA/ B;G/ advantages uses/ disadvantages/ side effects
 Definition
 Colorless, Odorless, Laughing Gas
 Good analgesic (high analgesic index)
 Used in combo w/other agents to speed onset
 Perfusion Limited Agent

B:G = 0.47
MAC = 108%

advantages: Fast onset b/c perfusion limited (Low λ); Not Metabolized

Disadvantages:
 Not potent enough for surgical anesthesia
 Can ↑ SNS discharge


Side effects:
 Can cause Megaloblastic Anemia if there is a >6hr exposure
 Diffusion hypoxia* can occur
Term
Halothane

MOA/ B:G jazz/ Advantage, uses/ Disadvantages
 Definition
 *MOST Cardio-depressant, so DO NOT use on a patient with HTN/CHF
 Very Potent

B:G = 2.3
O:G = 224
MAC = 0.78%
 Used in Children
 Not irritating to airway, so can induce with it
 Can ↓ SNS discharge
Term
Halothane

disadvantage

side effects
 Definition
 Increase sensitivity of myocardium to catecholamines leading to arrhythmias
 Depresses the CV System more than other agents
 Has prolonged induction and recovery
 *Hepatotoxic

An immune rxn to trifluoroacetylated proteins leads to fulminant halothane-induced hepatic necrosis
Term
Enflurane

moa/b:g/ advantages
 Definition
 Very potent modern anesthetic
 Ventilation-limited agent
 Medium Rate of Onset and Recovery


B:G = 1.9
MAC = 1.7%


 Only 8% is metabolized to a fluoride ion (not enough to cause renal problems)
Term
Enflurane

disadvantages
 Definition
 *In the presence of hypocapnia it can cause seizures (Most commonly seen on induction & recovery)
 Not good for children; it causes breath holding d/t irritating effect on
inhalation
 Can form Fluoride Ion, but usually the concentration is too low to cause a problem
 Cardiac depressant and peripheral vasodilation leading to ↓ in BP (like Halothane, but less so)~ Can produce cardiac arrhythmias
Term
Isoflurane

Moa/ B:G/ advantages/disadvantages
 Definition
 Used for maintenance of anesthesia after induction d/t pungent odor
 Ventilated limited agent
 Medium rate of Onset and Recovery, but faster than halothane

B:G = 1.4
MAC = 1.4%

 No seizures w/hypocapnia
 <2% metabolized, so metabolites DO NOT cause viscerotoxicity (98% eliminated in the AIR unchanged)


 Causes airway irritation (like enflurane)
Term
Desflurane

Moa/ B:G/ advantages/disadvantages
 Definition
 Widely used for outpatient surgery d/t rapid onset and recovery
 Perfusion Limited Agent
 Less potent than halothane

B:G = 0.42
MAC = 6%

 Rapid recovery
 <0.5% metabolized, so low viscerotoxicity


 Extremely irritating to the airway, so only used for maintenance
 Can produce laryngospams & bronchospams
Term
Sevoflurane


Moa/ B:G/ advantages/disadvantages
 Definition
 The Newest Anesthetic
 Can be used for outpatient surgery d/t fast recovery
 Perfusion limited Agent

B:G = 0.69
MAC = 2%


 3% metabolized in liver, can yield a free fluoride ion, but not enough to be harmful
 Not irritating to airway, so can be used in children for induction
 Fast onset and recovery
 Has Bronchodilator effects


 *Reacts with CO2 absorbents (i.e.soda lime, supposed to remove CO2) with an exothermic reaction that can burn patient’s airways
Term
Barbiturates

MOA
 Definition
*Thiopental, Thioamylal
Methohexital


  MOA: Binds to GABA A gated Chloride channel and ↑ duration of open time
 Thiopental is MOST commonly used for anesthesia in short procedures; Action is terminated by redistribution from brain to viscera & muscle
 Redistribution: if give a single Bolus injection will recover w/in a few minutes b/c viscera & muscle pull it out of the brain
Term
Barbiturates

metabolism/ negatives/ Side Effects
 Definition
*Thiopental, Thioamylal
Methohexital


 Metabolism plays a role in determining duration of drug & t½ is “content-dependent” (i.e. B/c it could accumulate in fat & muscle; t½ depends on duration of anesthesia b/c during long surgeries more anesthesia will accumulate in Fat) t½ =12.1hr.

 No antagonist available for overdose

Toxicity: Severe depression of medullary center in medulla; Induces porphyria in genetically susceptible individuals
NB: It decreases cerebral blood flow and O2 consumption by the brain; so *it should be used on a patient with cerebral edema

NB: Thiopental can be used to treat status epilepticus
Term
Benzodiazepines

MOA
 Definition
Midazolam
Diazepam
Lorazepam

 Midazolam (Versed) is MOST commonly used (Endoscopy)
 *Slower onset than other IV anesthetics
 Use more commonly for deep sedation in outpatient endoscopy procedures
 Used as a pre-anesthetic to produce amnesia, which calms the patient
Term
Benzodiazepines

metabolism/ side effects
 Definition
*Midazolam
Diazepam
Lorazepam

 Action initially terminated by redistribution, which is followed by metabolism by P450 enzymes
 Half-life = 2-4hr
 Has an antagonist available- Flumazenil for reversing OD


 May cause severe post-op respiratory distress
Term
Propofol *Diprivan

mechanism of action
 Definition
 Enhances action of GABA??
 Very Fast onset, very popular
 Duration shorter than for Thiopental
Term
Propofol

side effects metabolism and jazz
 Definition
 Has an *antiemetic effect; prevents post-op N/V
 Action terminated by redistribution & metabolism
 Metabolized in the liver by glucuronidation & sulfation. Total body clearance is > hepatic blood flow, suggesting extrahepatic metabolism
 Half-life = 1.8hr

 Insoluble in water; so must be suspended in an emulsion & bacteria can grow in the emulsion
 No antagonist available
 Can even be a cardiac depressant and cause seizures on induction and recovery

Toxicity: Causes pain at injection site, *depresses respiration, vasodilation, may cause*seizures, bacteremia
Term
Etomidate

MOA/ effects
 Definition
 Enhances GABA??
 IV anesthetic used in patients with limited *cardiovascular reserve
 Used for induction in patients at risk for hypotension


 Produces little or NO CV or Respiratory depression compared to other IV agents
 No ↓ in CO or HR
Term
Etomidate

side effects andjazz
 Definition
 Can inhibit adrenal steroid synthesis (i.e. ↓Cortisol level); Tends to occur with chronic use, BUT can occur with single use and can ↓ the patient’s stress response

Toxicity: Pain at injection site, myoclonus, postoperative N/V
Term
Ketamaine

MOA
 Definition
 Blocks NMDA glutamate Receptors
 *Dissociative Anesthetic – Produces catatonia, amnesia, analgesia, with or without loss of consciousness
 Profound analgesia
Term
Ketamaine
 Definition
 Produces cardiovascular stimulation via sympathetic nervous system (Release of Catecholamines); SO can be used in pts w/hypotension
 Less depression of respiration than other general anesthetics
 Can cause bronchodilation (okay to use for asthmatics)
 Action terminated by redistribution, but is also metabolized
Term
ketamine bad jazz
 Definition
Toxicity: Can ↑ICP & Cerebral blood flow, Can cause *post-op disorientation, sensory illusions and vivid dreams (psychic phenomena)
Term
The 4 Stages of Anesthesia:
 Definition
1. Stage 1 – Analgesia
• Reduced sensation of pain; patient is still conscious and talks

2. Stage 2 – Excitement
• Delirium and combative behavior ensue
• Increased BP & Respiration

3. Stage 3 – Surgical Anesthesia

• Patient is unconscious and regular RR; Muscle relaxation and decreased vasomotor response to painful stimuli

4. Stage 4 – Medullary Paralysis
• Decreased Respiratory drive; vasomotor output diminishes
• Death may ensure quickly
Term
Adjuncts to General Anesthesia:
 Definition
Benzodiazepines – Produce Anxiolytic Effects, Amnestic effects

Analgesics – Opioids for pain & to enhance sedation

Anticholinergics – Reduce respiratory secretions

Neuromuscular Blocker – Paralyze skeletal m. during intubation
Term
Diffusion hypoxia –
 Definition
NO2 equilibrates FAST with blood and ↑ pp FAST; NO2 comes out of blood rapidly & into the alveoli & replaces O2 and patient becomes hypoxic; so to prevent this, MUST switch to 100% O2
Term
Anesthesia involves: (Usually all reversible)
 Definition
Anesthesia involves: (Usually all reversible)
Term
Intravenous Anesthetics

Generals
 Definition
Highly Lipid Soluble (so get into brain rapidly)

-Depends on redistribution and metabolism for termination

Concentration of agents is driving force for mvt. across membranes
Term
Inhalation Anesthetics
 Definition
• Controllability of blood and brain level of anesthesia (min to min basis)

• Depends on pulmonary process for onset and termination

• Partial pressure of agent is driving force for mvt. across membranes
o Higher pp for gases that want to come out of the liquid
• Little or NO metabolism
• Low therapeutic Index, steep Dose response (DR)-curve, no antagonist
Term
Cholchicine

MOA/ Effect
 Definition
 *Selective inhibitor of microtubule assembly and inhibits cell division (inhibits Mitosis)
 Also ↓leukocyte migration & phagocytosis
 ↓ free radical formation

 Traditional & effective treatment, if used early in the attack
Term
Cholchicine

clinical use and side effect
 Definition
Clinical Uses:
 Treatment of Acute Gout
 Can be used in low does as a prophylactic therapy for chronic gout, to inhibit future attacks


 Diarrhea
 Can cause severe damage to the kidney and liver
 Overdose is fatal
Term
Probenecid *

mechanism of action and effect
 Definition
 Uricosuric drug that competes with uric acid for reabsorption in the PCT of kidney
 Also can inhibit the secretion of penicillin & MTX

 Uricosuric drug that competes with uric acid for reabsorption in the PCT of kidney
 Also can inhibit the secretion of penicillin & MTX
Term
Probenecid *

clincal uses and side effect
 Definition
Clinical Uses:
 Prevention of recurrent Gout attacks

 Increase urate stones d/t probenecid can be prevented by making urine alkaline with sodium bicarbonate
 Probenecid can precipitate acute gout during their early phase and can be avoided by simultaneous administration of colchicines or NSAIDS
 Probenecid should be withheld for 1-2 weeks after an acute attack
 Contraindicated in renal failure patients
Term
Allopurinol *

MOA and Effect
 Definition
 Irreversible inhibitors of xanthine oxidase, an enzyme that converts hypoxanthine to xanthine & xanthine to uric acid
 It ↑ the concentration of the more soluble hypoxanthine and xanthine and the ↓ concentration of uric acid



 Results in excretion of hypoxanthine
 Should be withheld for 1-2 weeks after an acute attack of gouty arthritis
 Effective in patients with renal failure and in overproduction of uric acid
Term
Allopurinol *

Clincal use and side effect
 Definition
Clinical Uses:
 Prevention of recurrent Gout attacks
 Used as an adjunct in cancer chemotherapy to slow formation of uric acid by purines


 *Inhibits the metabolism of mercaptopurine (6MP) and azathoprine that depend on xanthine oxidase
 Serious Toxicity includes: hypersensitivity reactions like skin rashes and toxic epidermal necrolysis and BM suppression (Steven-Johnson like syndrome)
Term
Sulfinpyrazone

everything
 Definition
 Increase Uric Acid Excretion

 Uricosuric drug; More potent than probenecid

 Its hematological toxicity has limited its widespread use
Term
Losartan
 Definition
 Increase Uric Acid Excretion

 Modest uricosuric effect
Term
 Uric acid is a relatively insoluble compound that is the end products of purine metabolism

 Urate crystals tend to crystallize in colder and acidic conditions
 Definition
 Neutrophils ingesting urate crystals secrete inflammatory mediators that lower the local pH and lead to further urate precipitation
Term
Prevention of Recurrent attacks
 Definition
• Serum uric acid levels <5mg/dL will prevent recurrent gouty arthritis & eliminate tophaceous deposits
• Prophylaxis Treatment: Probenecid, allopurinol and cholchicine
Term
Acute Gout Attack treatment
 Definition
NSAIDS, 3rd choice cholchicine, Glucocoticoids

 Aspirin is NOT used b/c it can inhibit urate excretion at low doses and can increase the risk of renal caliculi at high doses
Term
Acetyl Salicyclic acid (Aspirin)

MOA and clinical use
 Definition
 Irreversibly acetylates and thus inactivates COX-1 & COX-2 Enzymes
 Different effects occur at different doses

Clinical Uses:
 Antipyretic at mod. dose
 Analgesic at mod. dose
 Anti-inflammatory actions at high dose
 Anti-platelet to prevent MI at low dose
 Chronic use helps to prevent colon cancer
 *Methyl salicylate is used externally for the relief of musculoskeletal pain
Term
Acetyl Salicyclic acid (Aspirin)

Effect
 Definition
 Anti-platelet effect: If you use aspirin @ a low dose it only blocks TXA2 (COX-1) & blocks platelet aggregation; platelets do NOT have a nucleus so they cannot synthesize a new enzyme; it will not block COX-2 (PGI2) b/c endothelial cells have a nucleus so they can re-synthesize the enzymes
 Aspirin inhibits the synthesis of protective mucous in stomach and stimulates gastric acid secretion
 Inhibit the synthesis of PGE2 and PGI2 in the kidney responsible for maintaining renal blood flow
 At low doses, it can ↓the uric acid excretion; at high doses, uric acid reabsorption is blocked resulting in ↑uric acid excretion
 At low doses, aspirin follows – first order kinetics
 At high doses, aspirin follows zero order kinetics
Term
Acetyl Salicyclic acid (Aspirin)

side effect
 Definition
 *Epigastric distress, ulceration and hemorrhage, dyspepsia
 Long term use is associated with *papillary necrosis & interstitial nephritis
 Prolonged bleeding time
 Can ppt gout at low doses and can cause urate crystals in the kidney at high doses
 At high doses, aspirin can cause mild uncoupling of oxidative phosphorylation, which leads to elevated CO2 hyperventilation & respiratory alkalosis; at toxic levels, central respiratory paralysis and acidosis occurs
 Hypersensitivity – exaggerated bronchial asthma (blocks synthesis of PG and all pathways get pushed toward leukotriene production)
 *Hypersensitivity to nasal polyps
 Reye’s syndrome is associated w/fatal hepatitis and cerebral edema during the viral infection in children
 Mild salicylate intoxication is called salicylism characterized by n/v, hyperventilation, tinnitus & vertigo
 *Severe salicylism is characterized by hallucinations, restlessness, convulsions, and acidosis (Treatment: want to minimize drug absorption-gastric lavage and maximize elimination- alkalize with Sodium bicarbonate)


NB: *Misoprostol, PGE-1 analog is used in the treatment of gastric ulcers produced by NSAIDS
Term
Proprionic Acid Derivatives: Ibuprofen, Ketoprofen, Naproxen

MOA, effect
 Definition
 Reversibly inhibit and inactivate COX-1 & COX-2 enzymes

 Has less intense gastric irritant effects
 All are well absorbed orally and bound to plasma protein
 *Oxaprozin has the longest half life and can be used once daily
Term
Proprionic Acid Derivatives: Ibuprofen, Ketoprofen, Naproxen

clinical use
 Definition
Clinical Uses:
 Used in the treatment of Rheumatoid arthritis and osteoarthritis

Ibuprofen
Closing patent ductus arteriosus in preterm infants
Term
Acetic Acid Derivatives: Indomethacin, Etodolac, Sulindac

MOA, clincal use, side effects
 Definition
 Reversibly inhibit and inactivate COX-1 & COX-2 enzymes

Clinical Uses:
 Indomethacin is mainly used in the treatment of *acute gouty arthritis and ankylosing spondylitis
 Indomethacin also used to help close a PDA (it blocks the PG which help keep it open)

 Indomethacin is associated with serious hematological toxicity (BM suppression leading to agranulocytosis)

NB: Do not use NSAIDS in pregnant women because it might close the PDA in the intrauterine fetus
Term
Oxicam derivatives
Piroxicam, Meloxicam


everything
 Definition
 Reversibly inhibit and inactivate COX-1 & COX-2 enzymes
 *Meloxicam is relatively COX-2 selective at the therapeutic dose

 Long half life; so can be used once a day

Clinical Uses:
 Rheumatoid Arthritis
 Osteoarthritis
 Ankylosing spondylitis
Term
Ketorolac

everything
 Definition
 Reversibly inhibit and inactivate COX-1 & COX-2 enzymes

Clinical Uses:
 Can be administered IM or IV in post-operative pain;
 Excellent Analgesic
 Allergic conjunctivitis
Term
Diflunisal

everything
 Definition
 Has NO anti-pyretic action as it does not enter the CNS
 Causes fewer gastrointestinal side effects than aspirin

Clinical Uses:
 Analgesic
 Anti-inflammatory
Term
Celexoxib, Valdecoxib

everything
 Definition
 Reversibly inhibit COX-2 Selectively

 Potent anti-inflammatory, anti-pyretic & analgesic effect
 Fewer GI side effects and lower risk of gastric ulcers
 NO significant effect on platelets

Clinical Uses:
 Osteoarthritis
 Rheumatoid arthritis


 May cause Hypertension
 Renal Toxicity
 When COX-2 is blocked, prostacyclin may also be suppressed, allowing platelets to stick together and blood vessels to constrict, which can lead to myocardial infarctions and strokes
Term
Acetaminophen

MOA and Effect
 Definition
nhibits PG synthesis via inhibition of COX in the CNS (not in the periphery)-anti-pyretic effect (it is inactivated by peroxides in the inflamed tissues)
 Peripherally block generation of pain impulses – analgesic effect


 Patients who have hemophilia or peptic ulcer disease tolerate Acetaminophen better than other NSAIDS
 Does not have effect on platelet function or clotting time
 Major Pathway: The majority of the drug is metabolized via CYP450 to produce a non-toxic metabolite and undergoes glucuronide/sulfate conjugation in the liver and excreted in the urine
 Minor Pathway: Produces a highly reactive intermediate that normally conjugates with glutathione (endogenous anti-oxidant) and is excreted in the urine
Term
Acetaminophen

clinical use and side effects
 Definition
Clinical Uses:
 Anti-pyretic
 Analgesic

 Weak anti-inflammatory effect
 Chronic alcoholics have a lot of CYP450 enzymes, so may produce more toxic metabolites
 At toxic levels of acetaminophen, the liver supply of glutathione is depleted as it is limited, causing the reactive intermediate to react with sulfhydryl groups of hepatic proteins and cause hepatic toxicity & necrosis; Renal tubular necrosis may also occur (Treat this overdose w/Acetylcysteine which has a sulhydryl group similar to glutathione and therefore acts as a substitute to bind any free toxic metabolites)
Term
Function of Prostaglandins:
 Definition
 Activation of the inflammatory response (self protective phenomena of vascular changes [vasodilation] and cellular changes [Neutrophils] with the aim being to remove the injurious agent
 Inhibit gastric acid secretion & increase secretion of protective mucus lining; also helps with perfusion of gastric mucosa
 Involved in the induction & maintenance of labor
 Help to maintain of the blood flow to kidney
 TXA2 causes vasoconstriction and aggregation of platelets
 PGI2 causes vasodilatation and anti-platelet action
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