Pharm - conceptual Flashcards
1st line therapy for STABLE angina
Beta blockers!
decrease HR & contractile force, increase efficiency
- esp. B1 blockers –> increase coronary perfusion
* only helpful as prophylaxis, not for acute episode.
purpose of anti-anginal drugs
= to treat/manage symptoms, increase exertional capacity;
NOT proven to reduce mortality or MI.
ie: beta blockers, nitrates, Ca2+ channel blockers
adverse effects of beta blockers
all: mask hyperglycemia/worsen glycemic control;
also fatigue, depression, impotence
B1 –> heart failure, bradycardia, AV block
B2 –> bronchospasm, Reynauld’s, periph. vascular disease
mech of action of nitrates
- Decrease cardiac work (relax smooth muscle –> venous/vasodilation) => decrease preload (#1) and afterload,
- Increase O2 to heart (vasodilate, decrease preload)
- Decrease platelet aggregation
= for acute angina symptoms, does NOT decrease mortality.
common side effects of organic nitrates
reflex tachycardia, flushing, syncope;
headache, dizziness, postural hypOtension.
* effects = dose related (proportional to size of dose)
** do NOT take w/in 24 hrs of PDE-5 inhibitors (ie: sildenafil/viagra) –> severe hypotension **
Mechanism of action of Ca2+ channels blockers (“VOCC”)
- L-type blockers: (oral, liver metabolism)
- relax arteriolar sm muscle cells –> vasodilation
- block myocytes, SA & AV node tissues –> reduced inotropic effect.
(= 3rd line agents, BUT great for asthmatics!)
Adverse effects of VOCCs (Ca2+ channel blockers)
- do NOT take w. beta blockers! => severe/compounded bradycardia.
Also: headache, nausea, flushing.
List of MI-prevention drugs (for angina pts)
(to prevent adverse outcomes)
Primary (#1): aspirin, statins
Secondary: beta blockers (post-MI), or ACE Inhibitors (if DMII or LV dysfunction)
Combo therapy strategy for asthma/COPD
use 2 different classes of drugs to manage different parts of disease:
- bronchodilators = symptom management (acute Sx Tx)
- anti-inflammatories = prevent lung damage (“controller” Tx)
Contraction mechanism in Asthma
- blocked w/ meds for Sx management*
1. CysLT Rs and M3 ACh Rs = activated (by PNS) - -> signal cascade
2. increase intracellular Ca2+
3. => smooth muscle contraction
Relaxation mechanism in asthma
- stimulated by drugs to manage symptoms *
1. Beta-2 Rs activated by circulating catecholamines
2. increase cAMP –> activate PDE
3. relax bronchial smooth muscle
classes of bronchodilators used for asthma
- Beta-adrenoceptor agonists (increase relaxation)
- Beta-2 = most potent bronchodilators
- CysLT R antagonists (inhibit contraction)
- also anti-inflammatory
drugs used as anti-inflammatories for asthma
–>decrease inflammation = limit damage to lungs, NOT for Sxs
#1. glucocorticoids - highly effective
2. cromones - weak, poorly understood
3. anti-IgE antibodies - if specific allergic trigger
drug treatment for COPD
- can’t reverse damage, so no need for anti-inflammatories
#1. bronchodilators - esp. anticholinergics, …or beta agonists
2. PDE-5 inhibitors - for combo Tx, decrease chronic inflammation
strategy for combinatorial therapy for asthma
1st (mild): inhaled corticosteroid (“ICS”) for exacerbations
*try increasing dose of ICS before add meds;
2nd (moderate): ICS + daily oral long-acting beta agonist (“LABA”)
*can use LOW dose of ICS when add LABA
3rd (severe): high dose ICS + LABA + oral corticosteriod
types & potencies of inhaled glucocorticosteroids (ICS)
1. Fluticasone (highest potency)
2. Budesonide (~high potency
3. Beclomethasone (lower potency)
4. Flunisolide (low potency)
5. Prednisone = oral)
most effective approach to treating CHF
block AngII and aldosterone, (& NE) => decrease: - fluid retention (decrease afterload) - tissue remodeling - neurohormonal/reflex compensation
inotropic agent
substance that increases cardiac contractility (inotropic effect)
2 main mechanisms of ACE Inhibitors
by blocking ACE activity:
1. block AngI –> AngII
2. increase bradykinin levels (=> increase endogenous NO, prostacyclins –> vasodilation and anti-proliferative effects)
==> increase survival.
Major effects of ACE Inhibitors and ARBs
- vasodilation –> decrease TPR and afterload, increase CO; decrease PCWP and preload (a little);
- diuresis & natriuresis
* 3. NO direct change to HR or contractility
* ** no tolerance dvpt! ***
list of ARBs
(= Angiotensin I Receptor Blockers)
“-sartan”
Losartan, valsartan, irbesartan, telmisartan.
orthostatic hypotension = SE for…
any drugs that dilate veins.
- only venous: organic nitrates
- mixed a/v: nitroprusside, PDE-Is, ACEIs, ARBs, nesirtide
Hemodynamic effects of Nitrates/NO donors
- arteriolar dilation: decrease afterload
- coronary vasodilation: increase cardiac perfusion
- venodilation: decrease preload & pulmonary congestion
Clinical uses for nitrates
1: chronic/acute CHF…w/ MI, pulmonary edema
Also:
pulmonary congestion, orthopnea, paroxysmal nocturnal dyspnea
Contraindications/Risks w/ nitrates
Contraindications:
mitral stenosis, increased ICP (intracranial P), anemia
SE: tolerance, headache, syncope,
Function of diuretics
(ie: thiazides/Loop diuretics)
decrease Na+ retention –> decrease plasma volume;
=> decrease preload & congestion, usually no effect on CO.
Used short term for CHF w/ pulmonary congestion
(decrease morbidity/mortality, increase exercise capacity)
Concerns about diuretics
- can activate neurohormonal systems –> stimulate NE & AngII
- Hypokalemia (may dangerously alter electrolyte levels)
- -> do NOT use w/ Digoxin!
- may develop diuretic resistance
risk of electrolyte changes w/ diuretics
With all diuretics (thiazides AND Loop): decrease Na+, K+
–> metabolic alkalosis
only w/ Loop diuretics: decrease Mg2+, Ca2+
Concerns about aldosterone antagonists (diuretics)
- hyperkalemia (esp. if use w/ ACE Inh. or ARB)
- gynecomastia (just Spironolactone bc steroidal structure)
Why use Beta-adrenergic R antagonists (“BARX”) for CHF?
- antiHTN, anti-anginal, anti-arrhythmic
- decrease neurohormonal activation
- decrease sudden death & hypokalemia
- anti-proliferative & decrease myocyte apoptosis
Inotropic drugs
For end-stage CHF, no effect on survival (may Increase mortality)!
- cardiac glycosides (digoxin)
- Beta adrenergic R agonists (dobutamine)
- PDE-3 Inhibitors (inamrinone)
Hemodynamic effects of Digoxin
- increase CO & renal f(x)
- increase LV ejection fraction & decrease LV End-diastolic P
- increase exercise tolerance
- increase renal BF and natriuresis
neurohormonal effects of digoxin
- increase vagal tone
- decrease cardiac and peripheral SNS activity
- decrease Renin/AngII/Ald activity
- normalizes arterial baroRs
Digoxin Toxicity
- very narrow therapeutic range! renal clearance…
- ventricular/supraventricular arrhythmias
- SA node/AV node blocks
- GI: nausea, vomiting, diarrhea; NS: depression, paresthesia,
- blurry vision/color changes, hyperestrogenism…
factors influencing Digoxin toxicity
Toxicity Increased by:
- hypOkalemia (Dig binds to K+)
- Hypothyroidism - renal failure
- drugs that decrease clearance
Toxicity Decreased by: - hyperthyroidism - in infants
classes of anti-arrhythmic drugs
class I: Na channel blockers (delay depolarization) class II: Beta blockers (slow HR... - via pacemaker potential, plateau, & repol. phases) class III: K+ channel blockers (delay repolarization) class IV: Ca channel blockers (prolong plateau & repol. phases)
Na+ channel blocking drugs (6)
(used as anti-arrhythmics) 1A: (prolong AP) Disopyramide, Procainamide, Quinidine 1B: (shorten AP) Lidocaine 1C: Flecainide, Propafenome (delay AP peak, no change in duration)
K+ blocking drugs (4)
(used as anti-arrhythmics)
Amiodarone, Drondearone, Bretylium, Sotalol
Ca2+ channel blocking drugs (2)
(used as anti-arrhythmics)
Diltiazem & Verapamil
Mech of action for Class 1 anti-arrhythmic drugs
Block voltage-dep. Na+ channels –> delay depolarization.
* higher affinity for active channels, so selectively target damaged regions of heart.
Use: V-fib., sustained ventricular tachycardia
SE: CNS effects & long-term = pro-arrhythmic
Use of beta blockers for arrhythmias
Mech: block B1 receptors @ SA & AV nodes -> prolong recovery time.
Use: atrial flutter, A-fib, AV nodal reentry
use w/ Ca channel blockers for A-fib.
Why? prevent transmission of rapid atrial beats through AV node
Mech for Class III anti-arrhythmic drugs
Mech: K+ channel blockers, prolong repolarization
Use: V-fib., long-term for ventricular tachycardia
SE: bradycardia, prolonged QT interval/torsades de pointe, long term pro-arrhythmic
Drug classes best used for supraventricular arrhythmias
Class II and IV
II - beta blockers (propanolol)
IV - verapamil/diltiazem
Drug classes best used for ventricular arrhythmias
Classes I and III
I - Lidocaine
(also Disopryramide, Procainamide, Quinidine; Flecainide)
III - Sotalol, *digoxin
(also Amiodarone, Bretylium, Dronedarone)
3 parts to medical management of atrial fibrillation
- Anti-thrombotics (to decrease risk of stroke)
- Ventricular rate control (beta or Ca2+ channel blockers)
- Control any other co-existing heart problems
- optional: anti-arrhythmics, cardioversion
Why use anti-thrombotics for A-fib treatment?
= only treatment shown to decrease mortality w/ A-fib.
* anti-platelet drugs (ie: warfarin) = more effective than anti-coag. (ie: Aspirin)
Use of cardiac glycosides in A-fib
(ie: digoxin) Can be ventricular rate control and CHF,
BUT: only work at rest, so okay for elderly if inactive.
* narrow therapeutic range!
Drug-drug interactions for Warfarin:
– DEcrease effect
- P450 Inducers: barbiturates, rifampin, carbemazine, phentoin.
- Alter GI absorption: cholestyramine
- Alter binding: excess K+ consumption, hypothyroidism
Drug-drug interactions for warfarin:
– INcrease effect
- Decrease metabolism: cimetidine, trimethoprim
- Alter plasma: high albumin, aspirin
- Hypokalemia: acute intoxication, some antibiotics
- Coag. factor deficit: hepatic dysfunction, hyperthyroidism
antidotes to warfarin overdose
#1: fresh frozen plasma (IV, immediate) 2. vitamin K (oral/IV, has lag time)
