Exam 2 Flashcards
A-B-C Blockers, Antidysrhythmics, Glycosides, Coagulation/Reversal, Opioids/Non-Opioid Analgesic
What are the agonist effects of postsynaptic Alpha 1 receptors?
- Increases intracellular Ca concentrations: contractions
- acts at smooth muscle (vascular, coronary arteries, skin, uterus, GI tract, splanchnic beds)
- positive inotropy (increased MAP, preload)
- vasoconstrictor (arteries & peripheral vasculature)
- enhances Na & H2O reabsorption in tubules
- GI tract relaxation
- contraction of GI & bladder sphincters
- bronchoconstriction
- mydriasis (pupil dilation) d/t radial muscle contraction
What are the agonist effects of presynaptic Alpha 2 receptors?
Inhibits release of NE -> dec. SVR, CO, Inotropy, & HR d/t a decrease in sympathetic outflow; affects the feedback mechanism of NE?
What are the agonist effects of postsynaptic Alpha 2 receptors?
- Vasoconstriction (arterial (coronary) & venous) are very dependent on extracellular calcium
- platelet aggregation
- promotes Na & H2O excretion by inhibiting ADH release
- inhibits insulin release (epi inhibits insulin release by interacting w/ these receptors in the pancreas)
- inhibits bowl motility
- hyperpolarization of CNS cells (analgesia, sedation, anxiolysis, hypnosis)
- stimulates growth hormone
How does increased sensitivity to alpha specific meds occur in patients w/ HF or a ischemic heart?
Increased # of alpha 1 R in heart-> increased sensitivity to alpha specific meds-> can contribute to positive inotropy or cause more ischemia d/t increased vascular resistance in smaller cardiac vessels
What would a selective pre-synaptic alpha-2 agonist do? Does such a drug exist?
Would enhance the negative feedback loop-> dec. NE release-> dec. peripheral vasodilation & SVR
What would a selective presynaptic alpha-2 antagonist do? Does such a drug exist?
Stop the negative feedback loop-> inc. BP yohymbin (prototype drug)
What happens if we block alpha-1 and alpha-2 post-synaptically, but not alpha-2 presynaptically?
Continued vasodilation because post R for NE are blocked & will only hit pre-synaptically -> negative feedback loop is stopped
What causes dexmedetomidine tachycardia & hypertension?
giving a bolus dose-> will have spillover effect & will affect the periphery-> HTN & tachycardia
What do alpha adrenergic receptor antagonists interfere with & where are the effects specifically seen?
Interfere w/ the ability of catecholamines or other sympathomimetics to provoke alpha responses. Effects specifically seen:
* Heart (Baroreceptor mediated reflex tachycardia)
* Peripheral vasculature (orthostatic hypotension; impotence)
* Insulin secretion (increases)
Explain how unopposed B-adrenergic receptor activity can result from an alpha blocker. Is this theoretical or actually possible with current alpha blocking drugs?
will only occur if you block pre-synaptic alpha 2-> no feedback mechanism to control NE release -> uncontrolled NE release & simultaneously blocking the post synaptic alpha R will cause NE to bind unopposed to Beta R
What are the two main MOA categories for alpha adrenergic receptor antagonists?
Bind w/ receptors competitively vs. non-competitively & selectively vs. non-non-selectively
Which alpha adrenergic receptor antagonists bind to receptors competitively? Non-competitively?
- Competitively- Phentolamine, Prazosin, & Yohimbine; Reversible
- Non-competitively- Phenoxybenzamine; covalently bind to produce an irreversible block
Which alpha adrenergic receptor antagonists bind selectively & at which receptor?
- Act only at alpha 1 receptors: Prazosin (Minipress), Terazosin (Hytrin), Doxazosin (Cardura), Tamsulosin (Flomax- high selectivity for 1a subtype- targets urinary smooth muscle contraction; different from the other drugs mentioned)
- Act only at presynaptic alpha-2 receptors: Yohimbine
Which alpha adrenergic receptor antagonists bind non-selectively & at which receptor?
Act at postsynaptic alpha 1 & presynaptic alpha 2 receptors: Phentolamine & Phenoxybenzamine
What is the relative receptor affinities for prazosin, terazosin, doxazosin, phenoxybenzamine, phentolamine, yohimbine, & tolazoline?
Prazosin,Terazosin,Doxazosin- A1»>A2
Phenoxygenzamine- A1>A2
Phentolamine- A1=A2
Yohimbine, Tolazoline-A2»A1
What applications can alpha adrenergic receptor antagonists be used in?
- Acute hypertensive crises (Dx and tx of pheochromocytoma- especially phentolamine & Autonomic hyperreflexia)
- Local infiltration for sympathomimetics accidently administered extravascularly
- Tx of peripheral vascular diseases
- BPH- relaxes smooth muscle
- Idiopathic orthostatic hypotension
What side effects are common w/ alpha adrenergic receptor antagonists?
- Orthostatic hypotension- except yohimbine
- Increased HR: baroreceptor mediated reflex tachycardia & exaggerated cardiac stimulation from NE occurs in the absence of -adrenergic blockers if presynaptic alpha-2 is involved
- Impotence- except yohimbine
What is the anesthetic concerns w/ alpha adrenergic receptor antagonists?
- Normal ANS responses to stress and IA may be blocked (may not get a normal physiological response of the vasodilation from IA if on an alpha blocker)
- Elevations of catecholamines will not cause a reflex increase SVR; SVR may decrease if vascular postsynaptic B2-receptors are left unopposed (vasodilation results)
- Preload w/ IV fluids to assure adequate central volume
- Careful titration of halogenated anesthetic drugs
- Cerebral and coronary vascular resistance not changed
Yohimbine- MOA, indications, & specifics
- MOA: A2 selective-> pre-synaptic inhibition of NE reuptake
- Indications: formerly widely used to tx erectile dysfunction, mostly for idiopathic orthostatic hypotension
- Not sold in US for financial reasons, may find it as a “nutritional” supplement
Phentolamine (Regitine)- MOA & routes of administration
- MOA: Non-selective (1 and 2 competitive antagonist (1 = 2 ) & includes antagonism of presynaptic 2); does hit the presynaptic A2 but mostly the postsynaptic A1 & A2
- Routes: IM or IV
Phentolamine (Regitine)- Indications (w/ doses)
Dx & tx of Pheochromocytoma
o Rapid onset (within 2 mins)
o Lasts up to 10-15mins after IV injection
o 30-70mcg/kg IVP
Tx of acute hypertensive emergencies (ex. from intraoperative manipulation of pheochromocytoma)
o Autonomic hyperreflexia: 5mg bolus
Local infiltration for extravascular agonists
o Tx epi, NE, Dopamine, or dobutamine that was administered extravascularly
o Dilute 2.5-5mg in 10ml 0.9 NS- s.c. infiltrate
Phentolamine (Regitine)- effects & their mechanisms
*DEC. B/P- Direct action on vascular smooth muscle d/t vasodilation from Alpha 1 blockade
- INC. HR and INC. CO from 2 sources:
o Baroreceptor mediated inc. in SNS activity
o Presynaptic Alpha 2 receptor blockade blocks feedback mechanism for NE release - Ocular- Miosis (pupil constriction) d/t radial fibers in iris being blocked
How is the old test for pheochromocytoma performed & how is it confirmed now
*Old test:
o Wait until BP is stabilized rapid injection of phentolamine (1 mg for children & 5mg for adults) BP recorded for 30 sec intervals for 1st 3 minutes & Q1min after for 7 minutes
o Positive response suggests Pheochromocytoma- Decrease of BP ≥ 35 mm systolic and ≥ 25 mm diastolic
*Now confirmed by urinary catecholamine and metabolite levels
What are the side effects of Phentolamine
- Tachycardia
- Cardiac dysrhythmias: INC. SNS activity = INC. rate of depolarization of ectopic cardiac pacemaker sites
- Angina pectoris: INC. in MvO2 due to INC. HR & CO
- Hypotension
- Hyperperistalsis, abdominal pain, diarrhea: Predominance of parasympathetic NS activity (blocked by atropine)- d/t alpha blockade
Phenoxybenzamine (Dibenzyline): Receptor selectivity & type of antagonist
Nonselective (blockade at A1 receptors > A2)
Noncompetitive antagonist (irreversible block)
- dependent on synthesis of new receptors
- usually 14-18 hours but can take days
Phenoxybenzamine (Dibenzyline): Dosing
Oral agent
- starting at 10 mg per day, then adjusted up as needed
- N: Long onset if taken orally ~ 1 h
Phenoxybenzamine (Dibenzyline): Indications
- Previously used for pre-op control of B/P in pts with pheochromocytoma (now replaced with phentolamine)
- Diseases with large component of cutaneous vasoconstriction such as Raynaud’s syndrome* most beneficial response.
- Micturition problems with neurogenic bladder and prostate obstruction
Phenoxybenzamine (Dibenzyline): Effects
*Orthostatic hypotension (esp. with preexisting hypertension or hypovolemia)
- may last for days
- Little change in B/P in supine, normovolemic patients in the absence of elevated SNS activity
- Decreased total peripheral resistance
*Reflex tachycardia
*Increased CO
*Cerebral & coronary vascular resistances are not changed
*Increases cutaneous blood flow; no effect on skeletal muscle blood flow
*Ocular
- Miosis (pupil constriction) - radial fibers in iris are blocked
* Possible CNS effects (sedation)
- N: sometimes from spillover and it’s hitting the central R?
- Nausea
Prazosin (Minipres) and others (doxazosin, terazosin): Selectivity & type of antagonist
- Selective for A1 receptors: peripheral vascular smooth muscle (both arterial and venous)
- A1 to A1 ratio 1,000:1
*Competitive antagonist
- A1 to A1 ratio 1,000:1
Prazosin (Minipres) and others (doxazosin, terazosin): Dosing & Indication
*Oral agent For chronic treatment of hypertension
- 6-15 mg/day divided doses
- Half life ~ 3hours
Prazosin (Minipres) and others (doxazosin, terazosin): CV & Respiratory effects
- Remember the -2 effect:
- Prazosin DOES NOT inhibit NE release
- Results in little change in HR and CO
- N: Does NOT hit presynaptic A2-> no inhibition of NE release
- Venodilation – decreased PVR & venous return
- Respiratory: May bronchodilate
Beta Receptors: Stimulation & causes of stimulation
- Stimulation is excitatory
- Increased HR, myocardial contractility
- Stimulation causes:
- Activation of adenylate cyclase:
- Increased conversion of ATP to cAMP
- which enhances Ca++ ion influx, increasing cytoplasmic Ca++ concentrations
- Increase in Ca++ enhances intensity of actin and myosin
- increased force of myocardial contractility
- N: Stimulation is excitatory: have an agonist hitting those sites- inc. HR & BP
- Increasing contractile forces- interaction w/ actin & myosin
- Increasing cytoplasmic Ca level
Beta 1 (postsynaptic): Response & Location of effects
*Respond to NE / Epi
* Myocardium - INC. contractility
* SA node and ventricular conduction
- INC. rate (chronotropic) & conduction velocity (dromotropic)
* Also in the kidneys and adipose tissue
Beta 2 (pre- & postsynaptic): Response & Location of effects
*Respond to Epinephrine
* Smooth muscle of blood vessels in skin, muscle, bronchial s.m., eye and mesentery
- Vasodilate & bronchodilate
- Eye: ciliary muscle relaxation (mydriasis)
- INC. aqueous humor production
- GI - decrease motility
ß-Adrenergic Receptor Antagonists: Location of effects & Chronic administration effects
- Interfere with ability of catecholamines or other sympathomimetics to provoke beta responses
- Effects seen on:
- Heart
- Smooth muscle of the airways (bronchodilate)
- Blood vessels (vasodilation)
- Most in this class have good absorption with oral administration
- Chronic administration is associated with an increase in the number of ß-adrenergic receptors
- up-regulation
ß-Adrenergic Receptor Antagonists: Structure activity relationships
- Derivatives of the beta-agonist drug isoproterenol
- Substituent on the benzene ring
- Determines whether the drug will act as an antagonist or agonist
- Levorotatory is more potent than dextrorotatory
- Because of first-pass metabolism, all drugs in this class have some limitations of bioavailability
- Propranolol most of all
ß-Adrenergic Receptor Antagonists: MOA/Classifications & Effect at very high doses
- Non-selective
- Selective
- Partial agonist - antagonist
- Pure antagonist
- At very high doses some have Local Anesthetic-like effect
- membrane stabilization
- Quinidine-like effect slows conduction
ß-Adrenergic Receptor Antagonists: Cardioselective agents & what receptor they act on
- Act at beta1 receptors
- Atenolol (Tenormin)
- Metoprolol (Lopressor)
- Esmolol (Brevibloc)
- Metabolized by RBC cytosol
- acebutolol (Sectral)
- betaxolol (Kerlone)
- bisoprolol (Zebeta)
- Nebivolol (Bystolic)- relatively new oral agent
N: Want cardioselectivity to prevent bronchospasm occurrence if Beta 2 is also hit
ß-Adrenergic Receptor Antagonists: Non-selective agents & what receptor they act on
- Act at beta1 & beta2 receptors
- propranolol (Inderal)
- timolol (Blocadren and Timoptic)
- nadolol (Corgard)
- carteolol (Cartrol)
- pindolol (Viskin)
- penbutolol (Levatol)
- sotalol (Betapace)
- K+ blocker (antidysrhythmic - Class II and III)
ß-Adrenergic Receptor Antagonists: Labetalol & Carvedilol
labetalol (Normodyne, Trandate)
- alpha:beta - iv = 1:7 / po = 1:3
- N: route determines ratio of R hit- giving IV -> beta R hit 7x more than alpha R
carvedilol (Coreg)
- One half alpha blocking effect than labetalol
- Antioxidant properties
- Ca2+ channel blocking properties at high doses
ß-Adrenergic Receptor Antagonists: MOA
Intrinsic Sympathomimetic Activity (ISA)
Partial antagonist (e.g. labetalol)
- Intrinsic sympathomimetic activity:
- They DEC. HR less: partial stimulation of B1
- Cause less direct myocardial depression and bradycardia than the pure antagonists
- May be better tolerated by those with LV dysfunction
- N: have less HR dec. than the pure antagonists
Pure antagonist
- Lack intrinsic sympathomimetic activity
- Can cause more cardiac depression and bradycardia
Common Dosing for Propanalol
IV: 0.5mg/kg (given 0.25-0.5mg Q5min)
Oral: 40-800mg/day
Common Dosing for Atenolol
IV: 5mg over 5 min
Oral: 25-50mg/day
Common Dosing for Esmolol
IV (bolus) 0.25-0.5mg/kg over 60 seconds
IV (infusion)
- loading dose: 500mcg/kg/min over 1-2 min
- maintenance: 50-300mcg/kg/min
Common Dosing for Metoprolol
IV: 2.5-5mg Q5min- up to 15 mg
Oral: 50 mg/day to start
ß-Adrenergic Receptor Antagonists: Applications
Treatment of essential hypertension
- Largely dependent on reduction in CO from decreased HR
- Advantage: absence of orthostatic hypotension & avoidance of Na+ & H20 retention
Management of angina pectoris
- Reduces angina from myocardial ischemia by a reduction in MvO2 from decreased HR & CO
Post MI
- Decreases mortality and re-infarction rates
Atherosclerosis
- Independent of effects on BP
- Possibly affinity of low-density lipoproteins for proteoglycans impedes cholesterol deposits in atherosclerotic lesions
- N: Improvements in atherosclerosis if BB is used for another purpose
CHF
- provides short term improvement but long-term adverse effects on cardiomyocytes:
- INC. calcium, hypertrophy, apoptosis (cell death)
Suppresses supraventricular/ventricular dysrhythmias
- Reduces SNS activity decrease in rate of depolarization of ectopic cardiac pacemakers
- N: Sometimes cross referenced as antidysrhythmic
Migraine prophylaxis
- inhibition of vasodilation & arteriolar spasm of pial vessels.
Prevention of excess SNS activity
- Perioperative for non-cardiac surgeries
- Direct laryngoscopy / intubation
- Pheochromocytoma / hyperthyroidism
- Hypertrophic obstructive cardiomyopathy
- Cyanotic episodes with Tetralogy of Fallot
Preoperative for hyperthyroid patients
- Advantage - rapid control of ANS hyperreactivity & elimination of need to administer iodine or antithyroid drugs
ß-Adrenergic Receptor Antagonists: SE & Precautions- What can occur w/ hypovolemic patients w/ compensatory tachycardia
profound hypotension
ß-Adrenergic Receptor Antagonists: SE & Precautions- How can it affect an A-V block
Accentuate pre-existing AV block
Principle contraindication is pre-exisiting AV block or cardiac failure not caused by tachycardia
ß-Adrenergic Receptor Antagonists: SE & Precautions- how can myocardial depression occur & what is the treatment
Excessive bradycardia &/or DEC. in CO
Tx of myocardial depression:
- Atropine- incremental doses of 70 µg/kg IV
- dobutamine – pure B1 agonist
- glucagon
- INC. intracellular cAMP
- 1-10 mg then 5 mg/hr
- calcium chloride- 250–1000 mg
- transvenous pacemaker
- N: Can be as gently as Glycopyrrolate
ß-Adrenergic Receptor Antagonists: SE & Precautions- May cross what layers & the effects of crossing over
May cross BBB-> fatigue, lethargy, mental depression, & memory loss
May cross placenta-> bradycardia, hypotension, & hypoglycemia in neonates
ß-Adrenergic Receptor Antagonists: SE & Precautions- what can occur from a reversal of NDMR w/ neostigmine
Severe bradycardia, in spite of prior administration of a normal dose of atropine
N: make sure to match anticholinergic dose to neostigmine dose during reversal
ß-Adrenergic Receptor Antagonists: Nonselective agents SE & Precautions
Can worsen rebound hypertension in patients that have had clonidine or alpha-methyldopa therapy withdrawn.
- Blocking both B1 & B2 leaves alpha1 unopposed which leads to -> vasoconstriction and HTN
- Question 6: WHAT DRUG WOULD BE A GOOD CHOICE TO TREAT THIS? Labetalol
Increase in airway resistance
- Bronchoconstriction caused by B2 blockade
Patients with peripheral vascular disease develop cold hands & feet
Patients on insulin or oral anti-hyperglycemic drugs are at risk of developing hypoglycemia
How do beta blockers alter carbohydrate metabolism?
- Gluconeogenesis normally occurs in response to epinephrine relsease
- If a pt develops low serum BG, epinephrine is released
- Glycogen stores converted to glucose
- Nonselective B blocker prevents this-> at risk for hypoglycemia which is further masked bc they don’t get tachycardic under anesthesia
ß-Adrenergic Receptor Antagonists: Interaction w/ Anesthesia
Inhalation agents can cause additive myocardial depression, although not excessive
Enflurane > halothane > iso > sevo > des
What is timolol used for and what are the anesthetic concerns?
Glaucoma- systemic absorption from eye drops -> added effects if you give another BB
Labetalol: MOA & Potency ratio
- Selective A1 antagonist & Nonselective B1 & B2 antagonist
- A to B blocking potency ratio:
- iv = 1:7
- po = 1:3
Labetalol: CV effects
- Decreases B/P by decreasing SVR
- decreased or unchanged P (reflex tachycardia triggered by vasodilation is attenuated by simultaneous beta blockade)
- CO is decreased or unchanged
Labetalol: Applications
- To attenuate increases in B/P & P that occur during & following surgery
- Pregnancy induced hypertension
Labetalol: Routes & Dosages
IV 0.1-0.25 mg/kg over 2 min.
- Maximum effect presents in 5-10 min.
- Additional doses may be injected q 10 min to max 300 mg
IV infusion .5-2 mg/min IV
PO 100-400 mg BID
Labetalol: Other specifics- advantage/most common SE
- Advantage is that you can convert from IV to PO forms of drug after the pt is stable
- All the precautions & risks relating to use of beta antagonists are also present for labetalol, although the incidence & severity are less
- Orthostatic hypotension: Most common side effect
- Usually combined with a diuretic (fluid retention)
ACC/AHA Perioperative B-Blockade Update Guidelines Recommendation
Full evaluation of each patient’s clinical and surgical risks
What are some clinical RF
- History of ischemic heart disease
- History of compensated or prior heart failure
- History of cerebrovascular disease
- Diabetes mellitus
- Renal insufficiency
Stratifications for patient risk factors & procedure risk factors
Patient Risk:
- Low Cardiac Patient risk
- Intermediate Cardiac Patient Risk
- CHD or High Cardiac Patient Risk
Surgical Risk
- Vascular (usually considered high risk)
- High-intermediate risk
- Low-risk
What are some procedure examples for each surgical risk stratification (Vascular, intermediate, low)
- Vascular: Aortic & other major vacular surgery; Peripheral vascular surgery
- Intermediate: Intraperitonal & intrathoracic surgery, carotid endarterectomy, Head/neck surgery, orthopedic, prostate
- low: endoscopic procedures, superficial procedures, cataract surgery, breast surgery, ambulatory surgery
Recommendations for perioperative beta-blocker therapy: Class 1
- B-blockers should be continued if on for angina, HTN, arrhythmias
- B-blockers should be given to patients having vascular surgery with a high cardiac risk
N: Consider using BB perioperatively or putting pt on one if they aren’t taking one already
Recommendations for perioperative beta-blocker therapy: Class II-a
- Beta blockers probably recommended for patients with CAD having vascular surgery
- Beta blockers probably recommended for patient with high cardiac risk and undergoing vascular surgery
- Treatment should be titrated to HR and BP
- Beta blockers are reasonable for patients with identified CAD or high cardiac risk (defined by the presence of more than 1 clinical risk factor) who are undergoing intermediate-risk surgery
- Treatment should be titrated to HR and BP
Recommendations for perioperative beta-blocker therapy: Class IIb
- The usefulness of beta blockers is uncertain for patients undergoing either intermediate risk procedures or vascular surgery in whom preoperative assessment identifies a single clinical risk factor in the absence of coronary artery disease.
- The usefulness of beta blockers is uncertain in patients undergoing vascular surgery with no clinical risk factors and who are not currently taking beta blockers
Recommendations for perioperative beta-blocker therapy: Class III
- Beta blockers should not be given to patients undergoing surgery who have absolute contraindications to beta blockade.
- Routine administration of high-dose beta blockers in the absence of dose titration is not useful and may be harmful to patients not currently taking beta blockers who are undergoing noncardiac surgery.
N: Absolute CI: pre-existing AV block
General Summary of ACC/AHA Guidelines
- Class I recommendations essentially unchanged
- Initiation of therapy in low-risk groups should be carefully considered
- Early initiation in advance of surgical interventions is strongly recommended
- In light of the POISE study Trial, routine administration (especially with fixed high-dose regimens) is not recommended.
- POISE = Perioperative Ischemic Evaluation Study
- Physiologic response-based dosing regimens are strongly recommended
- N: POISE trial: saw significant increase in stroke & death
- Beta blockade should be considered as part of risk reduction strategies in high-risk procedure/high risk patient settings
- Early initiation is probably beneficial (7-30 preoperatively)
- Longer acting agents may be better
- Caution in the presence of poor ventricular function
- Patients on outpatient beta-blockade should have that therapy continued
Calcium Channel Blockers: MOA
- Selectively interfere with inward Ca2+ ion movement (influx)
- Myocardial cells - DEC. contractility
- Conduction system – DEC. formation & propagation of impulse
- Vascular smooth muscle – DEC. coronary & vascular tone
- N: Affect influx of Ca -> dec. coronary & systemic vascular resistance?
Calcium Channel Blockers: Whrere are voltage-gated Ca ion channels present in
- Skeletal
- Mesenteric
- Neurons
- Cardiac and vascular smooth muscle cell membranes
- Two types: L and T
What are the 2 types of calcium currents
L-type (ICa-L) & T-type (ICa-T)
Describe L-type calcium current
- Large and long lasting
- Dominant
- Provides sustained inward current – plateau (phase 2)
- N: Phase 2 of action potential
- Has 5 subunits
- alpha1
- Forms central part of channel
- Provides main pathway for calcium to enter cells
- Site where blockers act
- N: Alpha 1 forms central part of L-type channel; main site where ca entry blockers work
- alpha2
- beta
- gamma
- delta
- alpha1
Describe T-type calcium current
- Transient
- Atrial, Purkinje and nodal cells
What are the 3 classes of Calcium Channel Blockers
Phenylalkylamines, 1-4-Dihydropridines, & Benzothiazepines
Describe Phenylalkylamines: MOA, agents, selectivity
- Bind to intracellular L-type channel alpha1
- Physically occlude channel
- Selective for a-v node
- Verapamil
- N: more selective for a-v nodal region
Describe 1,4-Dihydropridines: MOA, agents, selectivity
- Extracellular modulations of L-type channel
- Selective for arteriolar beds
- nifedipine, nicardipine, nimodipine, isradipine, felodipine, amlodipine
- N: change shape of channel?
Describe Benzothiazepines: MOA, agents, selectivity
- Act on channel alpha1
- Mechanism is unknown
- Selective for a-v node
- diltiazem
CCB: Pharmacologic effects
DEC. intracellular Ca causes:
- Decreased myocardial contractility (negative inotropic)
- Decreased HR (negative chronotropism)
- DEC. rate of depolarization of SA node
- Slowed conductance of the AV node (negative dromotropism)
- Coronary, peripheral and pulmonary vasculature vasodilation (DEC. BP and SVR)
CBB: Applications (mention the specific agents)
- Essential HTN
- SVT
- verapamil (75-150 ug/kg IV over 3-5 min), but not nifedipine, is effective
- diltiazem (0.1 mg/kg) slows heart rate in patients with atrial fibrillation who develop supraventricular tachydysrhythmias
- Exercise-induced angina pectoris
- Myocardial protection (ex. global myocardial ischemia associated w/ cardiopulmonary bypass)
- Raynaud’s
-Maternal / fetal tachydysrhythmias and premature labor- Verapamil with caution: uterine blood flow & and fetal AV conduction
