Cardiovascular Drugs Flashcards
What is an arrythmia?
Alteration in normal impulse pathway b/c of:
- Alteration in pacemaker (SA node)→Ectopic focus is source of rhythm start (Standard reason)
- Alteration in transmission pathway
Single ectopic beat not an issue
Ppl can have arrythmias under GA
What is ventricular fibrillation
Life threatening unsynchronized contraction of muscle fibers
Leads to decreased CO and clots can form in heart
Ventricular arrythmias are the major cause of sudden cardiac death
Cardiac AP
-90mV resting potential
- Na influx→Rapid depolarization
- Ca influx→Plateau (prob. responsible for contraction of heart)
- K efflux→Repolarization
In most cases how do we treat arrythmias
No tx unless life threatening
Drugs can cause arrythmias
Types of non-drug tx for arrythmias
Note that non-drug tx is preferable
- Pacemaker
- Implantation
- Very complex
- Cardioversion
- Global depol. of heart
- Sends e- shocks to heart through electrodes on chest
- Automatic defibrillator
- Senses when rhythm is out of balance and gives global depol.
- Ablation
- Surgical removal of ectopic focus
Class I drugs for arrythmias
Characteristics and names
Na channel blockers
Local anesthetics→decreased rate of depol.
These drugs can cause arrythmias
These have a greater effect on ectopic foci vs AV node foci
1a drugs: “Double Quarter Pounder”
- Disopyramide
- Quinidine
- Procainamide
1b drugs: “Lettuce+Mayo”
- Lidocaine
- Mexiletine
Quinidine
Tx: All arrythmias (Class Ia)
Mech: Na channel blocker
- Depresses all mm fxn
SE:
- Anti-cholinergic effects (antivagal effects)
- Quinidine will direclty slow the heart, but it may indirectly speed up HR by suppressing the vagus nerve
- Vagal innervation slows HR
- May lead to arrythmias
- GI
- Nausea and vomiting
- Anorexia
- CNS
- Tinnitus
- Alterted color vision
With _Qu_inidine you feel _qu_easy and need _qu_iet (tinnitus)
Procainamide
Tx: All arrythmias (Class Ia)
- Also LA
Mech: Na channel blocker
- Like quinidine but does not get into CNS
SE:
- Lupus like syndrome in slow acetylators
Disopyramide
Tx: Arrythmias (Class Ia)
Mech: Na channel blocker
SE:
- Even stronger antivagal effects (than quinidine)
- Antimuscarinic effects (opposite of DUMBBELS)
- Wouldn’t use w/ glaucoma pts
Our mnemonic was Double Quarter Pounder
_D_isopyramide has double the antivagal effects as quinidine
Lidocaine
Tx: arrythmias (Class Ib)
*also LA
Mech: Na channel blocker
Route: Given IV
Kinetics: First pass effect
Toxicity: Low
Clinical use:
- Emergency tx of ventricular arrythmias
- Tx of ventricular tachycardia
SE:
- Less likely to cause arrythmias but can enter CNS
- Tremors
- Seizures
Mexiletine
Tx: arrythmias (Class Ib)
Mech: Na channel blocker
Clinical use:
- Emergency tx of ventricular arrythmias
- Tx of ventricular tachycardia
Like lidocaine but can be given orally
Class II drugs for arrythmias
Names and characteristics
Beta1 receptor blockers in heart
“olol” drugs
Used to treat excessive symp. stimulation–slows HR
Drugs:
- Esmolol
- Propranolol
- Metoprolol
Propranolol
Tx: arrythmias (Class II)
Mech: B1 blocker
Nonspecific B blocker
Decreases pacemaker firing rate
SE:
- Bradycardia
- Hypotension
- B2 effects-asthma
Metoprolol
Tx: arrythmias (Class II)
Mech: B1 blocker
Specific B1 blocker
SE:
- Bradycardia
- Hypotension
Esmolol
Tx: arrythmias (Class II)
Mech: B1 blocker
Specific B1 blocker
More rapid onset of action
SE:
- Bradycardia
- Hypotension
Class III drugs for arrythmias
*Names *
K+ channel blockers
“-arone”s +sotalol
Drugs: “A Diet Soda”
- Amiodarone
- Dronedarone
- Sotalol
Sotalol
Tx: arrytmhias (Class III)
Mech: K+ channel blocker
Also a beta blocker
Amiodarone
Tx: arrytmhias (Class III)
DOC for cardiac arrest–most effective anti-arrythmic
Mech: K+ channel blocker
Acts like all 4 classes of anti-arrythmic
SE:
- Potentially fatal pulmonary fibrosis
- Replaces lung tissue w/ fiber composites
- Liver damage
- Corneal deposits-optic neuritis
- Deposits in skin-blue/gray skin coloration
- GI upset
*Iodine responsible for some deposits
Dronedarone
Tx: arrytmhias (Class III)
Mech: K+ channel blocker
Analog of amiodarone
Fewer SE-less efficacious
Class IV drugs for arrythmias
Ca channel blockers→Increase refractory period
Tx: all arrythmias EXCEPT ventricular arrythmias
Most of the “ipine”s
Drugs: “Very Nifty Dildos”–put dont put that dildo in your ventricle (all arrythmias except ventricular)
Verapamil
Nifedepine
Diltiazem
Verapamil
Tx: Arrythmias except vent. arrythmias (class IV)
Mech: Ca channel blockers
Increase refractory period
Diltiazem
Tx: Arrythmias except vent. arrythmias (class IV)
Mech: Ca channel blockers
Increase refractory period
Nifedipine
Tx: Arrythmias except vent. arrythmias (class IV)
Mech: Ca channel blockers
Increase refractory period
Adenosine
Tx:
- Arrythmias (Other class)
- Adenosine for Atrial Tachycardia
Mech:
- Binds to adenosine receptor
- Decreases firing rate of AV node
- Coronary vasodilator
Kinetics-Very short T1/2=10sec
Angina definition and general tx methods
Not enough BF to heart
Causes chest pain (m becomes anoxic)
We usually have chest pain after we work out b/c we need more O2
But if at rest it is unstable angina
Tx by increasing BF or decreasing O2 demand
Tx:
- Behavioral
- Diet
- Exercise
- Creates collateral circulation (more blood vessels) in heart
- Stop smoking
- Drugs
Glyceryl Trinitrate (nitroglycerin) (GTN)
Tx: Angina
Mech:
GTN→NO→Act. guanylate cyclase→cGMP→vasodilation
Rapidly dilates all blood vessels, including coronary art.
Route: Given sublingually–1st pass effect
Effects last 30-60min
Rapid tolerance so cannot take continuously
SE:
- Hypotension
- Skin flushing
- Headache-opening blood vessels in brain, feel pulsing
*Nitroglycerin is unstable and explosive in some conditions
Isosorbide dinitrate
Tx: Angina
Slow release nitrate formulation
Can be given orally
Slow enough that effects occur before 1st pass metabolism
Other agents to treat angina
Agents that decrease heart work
- B blockers-“olol”
- Ca channel blockers- often “ipines”
What is and what causes congestive heart failure
Heart m doesn’t contract strongly enough→Rest of body lacks BF
- Tissues become anoxiated
- Heart enlarges
- Blood backs up in lungs→Pulmonary congestion→ decreased ability to breath
- Kidney not well perfused
- Not getting enough O2
- Retention of Na fluid-leads to peripheral edema
Congestive-lot of fluid accumulation, pitting edema
Most common cause of hospitalization of ppl over 60
Cause=cardiac damage
Compensation is what kills pt– Don’t want fluid retention w/ increased HR
How does our body adapt to CHF
In short, body thinks we are losing blood, but we are only losing O2
1) Apparent loss of blood b/c tissues underperfused
- Release of E, NE, and Angiotension II
- Lead to increase BP→Increase HR, vasoconstriction (peripheral)
2) Increase in BV
- Make more blood
- Angiotensin II causes increase in Na retention and aldosterone secretion→Na/K exchanger increase
3) Enlargement of heart
* Due to increase force of contraction
Initially this is okay but continued degradation of heart m→heart failure
Tx of cardiac insufficiency
General scheme not drug names
Increase cardiac m contractility
Via inotropic agents to increase amount of Ca in heart m
Digoxin
Tx: CHF
Class: Cardiac glycoside
- Naturally occuring (foxglove and milk weed)
- Produced as protection for plant
Route: orally
Kinetics: long T1/2
Mech:
- When m stimulated, small influx of Ca→causes release of Ca into cell from SR→contraction
- In order for m to relax after contraction, Ca must be removed (Na and Ca pumped out, K pumped in)
- Digoxin inhibits NaK-ATPase
- Na remains high in cell→prevents loss of Ca
- High conc of Na inhibits the Na-Ca exchanger
- Net result: Ca remains high
- High Ca→greater contractility
Effects:
- Increases duration of contractile response
- Stimulates vagus n
- Anti-arrythmic effects
SE:
- Cardiac arrythmias
- CNS effects
- Yellow-green tinting of vision
- Hallucinations
- Activation of chemoreceptor trigger zone→severe nausea
- Effects enhanced in hypokalemia
- Bind K site
- If less K outside of cell, more effective (less competition for K site)
Digoxin poisoning treated w/ anti-digoxin anti-bodies
Dobutamine
Tx: CHF
Class: Inotropic agents
Mech: Beta1 agonist
Effects: Increase force of contraction
Current best tx of CHF
Ace inhibitors→Decrease BP and fluid retention
Beta blockers→decrease HR
Vasodilators→Decrease BP
Diuretics too?
“-afils”
Sildenafil
Vardenafil
Tadalafil
Avanafil
Tx: ED
Mech:
- Inhibits type 5 cGMP phosphodiesterase
- Nitrates→NO→cGMP→smooth m relax
- cGMP degraded to 5’GMP via type 5 cGMP phosphodiesterase
- Relaxes arteries in corpus cavernosum→increase BF
SE:
- Slight drop in BP
- Do not use w/ alpha 1 blockers or nitrates
- Too much drop in BP
- Stroke
- MI (may be due to activity)
- Visual disturbances
- Impaired blue/green color discrimination
- NAION-some potential for damage to retina induced by cGMP PDE inhibitors
Metabolism: P450
Alprostadil
Tx: ED
Injectable prostaglandin (PGE1) leads to vasodilation when injected directly into penis
- Think: Alprosta_dil_*
- Prost=prostaglandin*
- Dil=dilation*
