Cardiovascular Drugs Flashcards
(245 cards)
1
Q
What are the components that make up chylomicrons?
A
Triglycerides (free FAs + glycerol)
Cholesterol
2
Q
VLDL formation and metabolism
A
- synthesis of VLDL by liver
- conains triglycerides and cholesterol esters
- assembled in ER
- Hydrolyzed by LPL
- HDL is cleaved off
3
Q
Uses of LDL
A
Hormone production
BIle acid production
Cell membrane synthesis
4
Q
What results from high circulating LDL?
A
Form foam cells
(accumulate intracellular cholesterol)
Formation of athermatous plaques
5
Q
Where are HDLs synthesized? What are their components? Why are they beneficial?
A
Liver and Intestines
phospholipid and apolipoproteins
Benefit: removal of excess cholesterol from cells = anti-atherogenic!
6
Q
Optimal levels of:
- Cholesterol
- LDL
- HDL
- Triglycerides
A
- Cholesterol: <200
- LDL: <100
- Goal: <160 unless there are other risk factors
- Risk factors: CHD, diabetes, Vascular disease
- HDL: >60
- Triglycerides: <150
7
Q
What is metabolic syndrome?
A
- Abdominal obesity (precipitating factor)
- Atherogenic Dyslipidemia (lipids the wrong way)
- Small LDL, low HDL, High Tg
- HTN
- Insulin Resistance
- Prothrombotic/Proimflammatory state
**All can be fixed by weight loss
8
Q
Some causes of Secondary Dyslipidemia
A
- Diabetes
- Hypothyroidism
- Obstructive Liver Disease
- Chronic Renal Failure
- Drugs (progestins, anabolic steroids, corticosteroids)
9
Q
What are the effects of taking fish oil?
A
- Increase cell membrane fluidity
- may help prevent hardening of arteries
- Alter receptor responses
- Antiarrythmic
- Decrease Triglycerides
10
Q
Dose recommendations for Fish Oil
- For Primary Prevention
- For Secondary Prevention (previous CV event)
- For Hypertriglyceridemia
A
- For Primary Prevention
- 500mg/day
- For Secondary Prevention (previous CV event)
- 1g/d
- For Hypertriglyceridemia
- 4g/d
11
Q
What is the mechanism of action of statins?
A
- Competitive inhibitors of HG CoA reductase (rate-limiting step in Cholesterol synthesis
- reduced cholesterol in the liver
- Increased LDL receptor formation and cycling (bring LDL and cholesterol into cell)
Final result:
- Decrease LDLs
- Raise HDLs
- Decrease Triglycerides
- decrease in VLDL synthesis
12
Q
Change in lipid profile with use of statins
A
- Decrease:
- Total cholesterol
- LDL
- Triglycerides (TGs)
- Apo-B
- Increase:
- HDL
13
Q
Side effects of Statins
A
- Hepatic
- increased aminotransferases
- Myalgia
- May have Increased serum creatine kinase
- could also be related to trauma or hypothyroidism
- May have Increased serum creatine kinase
- Proteinuria
14
Q
What is the Mechanism of Action of Fibrates?
A
- decrease cholesterolgenesis, hepatic lipogenesis, secretion of VLDL
- increase LPL activity
- Decrease LDL
- increased oxidation of TG-derived FA
- decrease TGs
15
Q
What is the mechanism of action of Niacin (Nicotinic Acid)?
A
- Decreased FFA from adipose to liver
- Decreased VLDL synthesis
- Decreased LDL synthesis
- Increased HDL
16
Q
What is the mechanism of action of bile acid sequestrants? What side effect is present?
A
Mechanism of action:
- Bind bile acid in the intestine and prevent reabsorption
- Livers need to produce more (use cholesterol)
- Decreased cholesterol in the body
Side effect: bloating
17
Q
Neuromuscular blockers
- Function
- Act on what receptor?
A
Function:
- Paralysis (sequence below)
- mm of fine movement
- limbs
- trunk
- intercostals
- Diaphragm
- No analgesic properties
Receptor: Nicotinic ACh receptor
18
Q
Excretion mechanisms of non-depolarizing neuromuscular blockers
A
- Renal (Primary)
- Liver
- Hofmann Elimination
- spontaneous breakdown
- Plasma (plasma esterases)
Recovery can be accelerated by cholinesterase inhibitor
19
Q
How to accelerate recovery from paralysis with any non-depolarzing neuromuscular blocker
A
Recovery can be accelerated by cholinesterase inhibitor
20
Q
Drugs enhancing curare-type Neuromuscular blockade
A
- Aminoglycoside antibiotics
- Calcium channel blockers
- Inhalation anaesthetics
21
Q
Succinylcholine
- Type of drug and structure
- What is the initial response to administration?
A
- Depolarizing neuromuscular blocker (anesthetic muscle relaxant)
- Structure: looks like 2 ACh
- cholinesterases terminate function
- What is the initial response to administration?
- Wave of fasciculation (achy feeling later)
22
Q
Side effects and contraindications of Succinylcholine (depolarizing neuromucular blockade)
A
Side effects:
- Myalgia (due to fasciculation)
- Potasium release from skeletal muscle
- hyperkalemia => arrythmias
- Prolonged paralysis (with atypical pseudocholinesterase)
- Malignant hyperthermia
Contraindications
- extensive burns/soft tissue damage
- Paraplegics
- Spinal chord injury
- DMD in children
23
Q
Treatment of malignant hyperthermia
A
- ***Dantrolene
- Hyperventilation
- Cooling
24
Q
What is the mechanism of action of local anesthetics?
A
Block “fast” voltage-gated sodium channels in nerves to reversibly block conduction
25
Which nerve types are blocked by local anesthetic?
* Small fibers: A-delta and C fibers
* unmyelinated
* Function: pain, temp, touch
* Bigger ( A-alpha, a-beta, motor) = less sensitive
Autonomic \> Pain fibers \> Sensory fibers \> Motor fibers
26
Two types of linkage present in local anesthetic molecules
1. Ester link
2. Amide link
27
Metabolism of Amide and Ester-type local anesthetics
Amide
* Broken down in liver
* P450 (problem with hepatic disease)
Ester
* hydrolysis
* Not in liver
* Plasma cholinesterases
Drugs within both groups vary in duration
28
What is the result of the use of epinephrine (a vasoconstrictor) with (after) a local anesthetic?
Vasoconstrictor will
1. Decrease absorption/redistribution
2. Prolong duration of anesthesia
3. Reduce risk of systemic toxicity
29
What intrinsic qualities of local anesthetics affect their duration of action?
1. Protein binding
2. Hydrophobicity
* more lipid soluble, more potent
30
Bupivacaine
* Use
* Primary site of action
* Risk
* Use
* Anesthetic for long-duration surgeries
* Low dose for obstetrics
* Primary site of action
* spinal nerve roots
* Risk
* Cardiotoxicity
31
Etidocaine
* Use
* Primary site of action
* Use
* muscle relaxant during surgery (motor block)
* Primary site of action
* spinal nerve roots
32
With spinal anesthesia, a sympathetic block may occur. What are common results of a sympathetic block?
* Vasodilation: results in
* blood pooling
* Reduced CO
* Treatment:
* fluids
* vasoconstrictors
33
What is the function of Benzocaine?
Topical anesthetic
34
What is the function of a eutectic mixture of lidocaine and prilocaine?
anesthetic action to 5mm after topical administration
Eutectic = low melting point
35
What are some side effects of local anestetics?
1. CNS
* Simulation
* Depression
2. Heart: Depression
* Decreased conduction
* Decreased force of contraction
* Decreased excitability
3. Vascular
* Vasodilation =\> decreased BP
36
Contraindications of anesthetic amides? Of anesthetic esters?
Amides: hepatic disease
Esters: low esterase activity
37
What are the components of the anesthetic state?
1. Amnesia
2. Sedation (decreased arousal)
3. Hypnosis (unconsciousnenss)
4. Immobility
38
First anesthesia and date of discovery
Ether, 1842
39
What is Minimum Alveolar Concentration (MAC)? How is it measured? What are its limitations?
* Concentration of gas in alveoli that results in a lack of pain response in 50% of subjects
* Measure concentration of expired air (at equilibrium)
* Limitations:
* 50% still respond to pain
* may not lose consciousness
\*\*\***Want to give dose \>MAC**\*\*\*
High MAC = less potent, quick time to action
Low MAC = more potent
40
What is the Mechanism of Action of General Anesthetics?
1. **increase GABA** receptor activity
2. **increase** activity of **potassium** channels
3. **Decrease** activity of **ACh** receptors
4. **Decrease** activity of **glutamate** receptors
41
What are the function and contraindications Barbiturates?
General anesthetic
Con: Porphyria
Clearance (rapid, but continued infusion helps)
42
Propofol
* Function
* characteristics:
* analgesia
* clearance
* Function: General anesthetic
* Poor analgesia, poor respiratory depression
* High degree of clearance (rapid recovery)
43
Etomidate
* Function
* Used in which special population? Why?
* Toxicity effect on adrenals
* Function:
* General anesthetic
* Cardiostable =\> use in patients at risk of hypotension
* Toxicity
* causes suppression of adrenocortical stress response
44
Ketamine
* Function
* Side effects
* Use in special populations
* Toxicity effects
* Function
* General IV anesthetic
* Side effects
* increased BP (increased cerebral blood flow)
* Bronchodilator
* Use in special populations
* At risk for Hypotension
* Bronchospasm
* Toxicity effects
* emergence delirium
45
Cause and Treatment for malignant hyperthermia
* Cause:
* hypermetabolism
* Treatment:
* dantrolene
46
Clinical problems of IV anesthetics
1. Respiratory depression
* low response to CO2 or hypoxia
2. CV depression
3. Muscular rigidity (Opioids)
47
Which General anesthetics are used in patients at risk of hypotension?
Etomidate
Ketamine
48
Which general anesthetic is used in patients at risk for bronchospasm?
Ketamine
49
Which general anesthetic is associated with emergence delirium?
Ketamine
50
Which general anesthetic is used to increase cerebral blood flow?
Ketamine
51
Inhalation anesthetics are what molecule type?
Halogenated hydrocarbons
52
What is Henry's Law? What are its implications?
Concentrations of drug in liquid = partial pressure of gas x solubility
The amount of gas which is soluble does not contribute to partial pressure and does not enter other tissues
53
What is the effect of the blood/gas partition coefficient on induction and duration of anesthetic?
* Partition coefficient measures solubility
* Higher = longer time to induction
* Higher = longer duration of action
54
What is the blood/gas coefficient of NO? What is it's potency?
Low coefficient
Not potent (short effect) but quick effect
55
What is the blood/gas coefficient of Halothane? What is it's potency?
High coefficient
Potent, but takes time for effect
56
Halothane
* Blood/gas co-efficient
* Toxicity
* High coefficient: potent but takes time for action
* Toxicity:
* Liver tox: hepatitis and hepatic necrosis
* Malignant hyperthermia
57
Cause and Treatment of malignant hyperthermia
Cause: hypermetabolism
Treatment: dantrolene
58
Desflurane
* Important side effect
* MAC
* inhaled anesthetic
* Strong airway irritant
* MAC = 6%
* not soluble
* Faster effect
* Shorter duration (not potent)
59
Sevoflurane
* MAC
* Inhaled anesthetic
* Not an airway irritant
* MAC = 2%
* more potent than desflurane
60
NO
* Function
* MAC
* Inhalant anesthetic
* MAC = 105%
* quick induction
* short action
61
Effect of blood-gas coefficient on induction time
Proportional
* Low = short induction time
* High = long "
62
Effect of MAC on Potency
Inversely proportional
* Low MAC = Strong potency
* High MAC = Weak potency
63
Effect of oil-gas coefficient on Potency
Measures lipid solubility
Proportional
* High coefficient = strong potency (high lipid solubility)
* Low coefficient = low potency
64
What is the mechanism of action of ACE inhibitors?
1. inhibit Angiotensin I to AII
* Reduce Na+ and water retention
* Decrease afterload and wall tension
* Inhibit cardiac remodeling
2. Inhibit degradation of bradykinin
* Prostaglandin synthesis
* Vasodilation =\> Decreased BP
* Increase renal blood flow
## Footnote
**\*\*\*Decreased TPR and effective circulating volume\*\*\***
65
Where are ACE Inhibitors metabolized? What are the exceptions?
* Kidneys
* Exceptions: Kidneys and liver
* Fosinopril
* Spirapril
66
What is the effect of ACE inhibitors in patients with elevated plasma renin activity? How is their treatment modified?
* Effect:
* hyper-responsive to induced hypotension
* Initial dose should be reduced
* At-risk patients:
* CHF, Na depletion
67
What are the therapeutic uses of ACE Inhibitors?
1. Hypertension
* especially in diabetic patients b/c are renal protective
2. CHF
* counteract ventricular remodeling
3. L Ventricular Systolic Dysfunction
* even w/o overt symptoms
4. Acute MI
* especially in diabetic and hypertensive patients
5. Chronic Renal Failure
* associated with T1DM
* Captopril and Lisinopril
68
How do ACE Inhibitors counteract hypertension?
1. Decreased TPR
2. Increase Na+/water excretion at lower BP
3. Increased arterial compliance
69
What drugs are used in Hypertension with Diabetes?
ACE Inhibitors
70
What drugs are used in MI with either hypertension or diabetics?
ACE Inhibitors
71
Which drugs are used to delay/prevent Chronic Renal Failure with Diabetes type I?
Captopril
Lisinopril
(ACE Inhibitors)
72
What is the MOA of renal protective effect in ACE Inhibitors?
* Decrease BP and resistance =\> Decreased glomerular pressure
* Decreased damage to GBM
73
What are the adverse effects associated with ACE Inhibitors?
1. Teratogen (fetal hypotension)
2. Acute renal failure
* In diseases with decreased renal perfusion
* CHF, bilateral renal stenosis, volume depletion (BP dependent on RAAS)
3. Cough
4. Angioedema
* first-dose effect
5. Hypotension
* first-dose effect
6. Hyperkalemia
* In patients with renal insufficiency or who are taking drugs that promote K uptake
74
What is the MOA in ARBs?
* Angiotensin II antagonists
* selective competitive for AT1 receptors
* Decrease TPR
* Decrease effective circulating volume (increase Na+ and H20 excretion)
* Inhibition is insurmountabile
* blockade even with missed dose
75
What are the therapeutic uses of ARBs?
1. High renin forms of hypertension
2. Renoprotective in Type II Diabetes
76
What are the adverse effects of ARBs?
1. Teratogen
2. Hypotension/Acute Renal Failure
* In patients whose BP is dependent on RAAS
3. Hyperkalemia
* In renal disease or taking drugs that promote K+ retention
77
What are the differences between ACE inhibitors and ARBs?
_ARBs:_
* reduce activation of AT1 receptors more effectively
* Do not affect Bradykinin levels
* No cough
* No angioedema
_ACE Inhibitors:_
* Increased levels of Bradykinin
* Cough
* Angioedema
* Increased Ac-SDKP
* Promotes toxic anemia
_Both:_
* Other side effects are the same
* Affect RAAS
78
Aliskiren
* MOA
* Indications
* Contraindications
* MOA
* Direct renin inhibitor
* Indications
* Hypertension
* Contraindications
* Diabetes
* Renal Impairment
* Use with ACE inhibitors or ARBs
79
What is diuretic braking?
* Renal compensatory mechanisms that bring Na+ excretion in balance with intake
* Activate SNS
* Activate RAAS
* Decreased arterial BP (decreased pressure natriuresis)
* Hypertrophy of renal epithelial cells
* \*\*Important in the use of **DIURETICS**
80
What is the MOA of Carbonic Anhydrase Inhibitors (CAIs)?
* **Inhibit membrane and cytosolic Carbonic Anhydrase**
* **excrete carbonic acid, Na+, and Cl-**
* **Proximal tubule**
* Increased phosphate excretion
* Decreased acid reabsorption in collecting duct
* Renal effects
* Increased afferent arteriolar resistance
* Reduced Renal blood flow
* Reduced GFR
* Inhibition of CA in eye
* decreased aqueous humor formation
81
Location of CAI action in the kidney
Proximal tubule
82
Indications of CAIs
1. Glaucoma
* Due to decreased aqueous humor and intraocular pressure
2. Altitude sickness
3. Correct metabolic alkalosis
* Increased HCO3- secretion
* Inhibit reuptake of weak organic bases
83
Adverse effects of CAIs
Sulfonamide derivatives:
1. allergic rxn in patients hypersensitive to sulfonamides
2. **Bone marrow depression**
3. Renal lesions
4. Skin toxicity
5. **Metabolic / Respiratory Acidosis**
6. **Renal calculi**
7. Direct renal ammonia into circulation
84
Contraindications of CAIs
1. Hepatic cirrhosis
* directs ammonia into circulation
2. Hyperchloremic acidosis
3. COPD
* worsens respiratory acidosis
85
What is the MOA of Osmotic Diuretics?
* Reduce the vertical osmotic gradient in the Loop of Henle
* Results in reduced water reabsorption in the collecting ducts
* Increased excretion of nearly all electrolytes
* Renal:
* Increased RBF (dilate afferent arteriole)
* Total GFR unchanged
86
What are the therapeutic uses of Osmotic Diuretics?
1. Acute Renal Failure
* attenuate decreased GFR
2. **Reduce cerebral Edema**
3. Reduce IOP
4. Dialysis disequilibrium syndrome
* Hypotension and CNS effects
87
Contraindications and Adverse effects of Osmotic Diuretics
1. Pulmonary edema
* In CHF or pulmonary congestion
2. Hyponatremia
3. Hypernatremia and dehydration
* con: aneuric patients from severe renal disease
Contraindications;
1. Patients with active cranial bleeding
2. CHF/Pulmonary congestion
3. Aneuric patients with severe renal disease
88
What is the MOA of Loop Diuretics?
\*\*\*Inhibit the **Na-K-2Cl symporter** in the **thick ascending** limb of the loop of henle\*\*\*
* Large effect on Na excretion
* 25% normally reabsorbed here
* Reduce vertical medullary osmotic gradient
* Decreased water reabsorption in collecting duct
* Furosemide increases venous capacitance (distensibility)
* reduces pulmonary edema before diuresis begins
89
What is the elimination half-life of Loop diuretics? How does this affect treatment?
Short elimination half-life
Cannot be used for long-term therapy
90
What are the therapeutic uses of Loop Diuretics?
Conditions with edema:
1. Pulmonary edema (diuresis and increased venous capacitance)
2. CHF congestion
3. Nephrotic syndrome
4. Liver cirrhosis (ascites)
5. Hyponatremia (used with hypertonic saline)
91
What are the adverse effects of Loop diuretics?
1. Ototoxicity
2. Fats go wrong way (LDL, cholesterol and TG up; HDL down)
3. Hyperglycemia
4. Hyperuricemia (leads to gout)
92
What are the contraindications of Loop diuretics?
1. Postmenopausal osteopenic women
* Calcium loss
2. Hypersensitivity to sulfonamides
93
What is the mechanism of action of Thiazinde Diuretics?
\*\*\*Inhibit Na/Cl symport in distal convoluted tubule\*\*\*
* Increased excretion of K+, Acid, Uric acid (but not with chronic use)
* Decreased excretion of Ca2+, increased reabs. of Ca2+
94
What are the therapeutic applications of Thiazide diuretics?
1. Hypertension (First-line agent)
* Dose for anti-hypertensive effect is lower than for diuretic effect
2. Nephrogenic diabetes insipidus (decreased urine volume)
3. Calcium nephrolithiasis (stones)
4. Osteoporosis
95
What are the adverse effects of Thiazide Diuretics?
* Hypokalemia
* Hyperglycemia
* Increased lipid profile
* ED
* sulfonamide hypersensitivity
96
What effect results from combined use of thiazide diuretics and Quinidine?
* Quinidine: prolonged QT
* Thiazide diuretics: hypokalemia
* Result:
* Early after-depolarizations
* Torsades de Pointes
* Ventricular fibrillation
97
What is the MOA of Amiloride?
\*\*\*Blocks epithelial Na+ channels in distal tuble and collecting duct\*\*\*
* Because uptake of sodium usually causes excretion of K+, blockage of this channel is K-sparing
98
What are the therapeutic applications of Amiloride?
Used in conjuction with more effective diuretics to reduce K+ excretion and prevent hypokalemia
* Edema
* Hypertension
99
What are the contraindications for Amiloride?
* Hyperkalemia
* Renal failure
* K+ supplements
* NSAIDs
100
What is the MOA of Aldosterone Antangonist-Diuretics?
* Decrease Na+ reuptake
* Increase K+ reuptake/retention
Spironolactone: competitive antagonist of androgen receptors
* Testosterone converted to estradiol
101
What are the therapeutic applications of Aldosterone - antagonist Diuretics?
1. Diuretic of choice with hepatic cirrhosis
2. Coadministration with other diuretics for K+ sparing
3. Primary Hyperaldosteronism
4. CHF
102
Which diuretic is used in hepatic cirrhosis?
Aldosterone-antagonist diuretics:
Spironolactone
Eplerenone
103
What are the adverse effects common to all aldosterone-receptor antagonists? Those to spirolactone alone?
All:
* Hyperkalemia
* Peptic Ulcers
Spirolactone: (converts testosterone to estradiol)
* Gynecomastia
* Impotence
* Menstrual irregularities
* Breast cancer
104
Nesiritide
* MOA
* Indications
* Side effects
* MOA
* Structure: synthetic B-type natriuretic peptide
* decreased TVR
* Increased SV
* decreased pulm. congestion
* Indications
* Short-term management of decompensated HF
* Side effects
* Hypotension
* Increased risk renal dysfunction
105
What are the effects of B1 receptors?
1. + inotrope
2. + chronotrope
3. Increased CO
4. Increased Systolic BP
5. Increased O2 consumption of heart
\*\*B = fight or flight; B1 = heart effects of fight or flight
106
What are the effects of B2 receptors?
1. Vasodilation
* Decreased TPR
* Decreased diastolic BP
* Increased blood to mm
2. Glucose mobilization
3. Bronchodilation
\*\*\*B2 = non-cardiac effects of fight or flight
107
What are the effects of alpha-1 receptors?
1. Vasoconstriction
* Increased vascular resistance
* Increased BP (Systolic and Diastolic)
108
What are the indications for alpha-1-selective agonists?
1. Orthostatic hypotension
2. Hypotension in shock
3. Locally as congestants
Function: vasoconstriction
* increased TPR
* increase/maintain BP
109
Phenylephrine and Pseudoephrine
* MOA
* Indications
* Side effects
* MOA:
* selective alpha-1 agonists
* Indications
* Rhinitis (acts as nasal decongestant)
* Side effects
* rebound nasal vasodilation and congestion
110
Mephentermine
* MOA
* Indications
* Side effects
* MOA
* alpha-1 agonist
* release of NE
* Causes increased BP, (+) ino, (+) chronotrope
* Indications
* Hypotension from spinal anesthesia
* Side effects
* CNS stimulation
* Very high BP
* arrythmias
111
Metaraminol
* MOA
* Indications
* Side effects
* MOA
* alpha-1 agonist
* release of NE
* Causes increased BP, (+) ino, (+) chronotrope
* Indications
* Hypotension from spinal anesthesia
* Side effects
* CNS stimulation
* Very high BP
* arrythmias
112
What drugs are used to treat hypotension associated with spinal anesthesia? What is their MOA?
Mephentermine
Metaraminol
MOA: (+) ino, (+) chrono, increased BP
113
Midodrine
* MOA
* Indications
* Side effects
* MOA
* alpha-1 agonist
* Indications
* Conditions with autonomic insufficiency and postural hypotension
* Side effects
* CNS stimulation
114
What drug is used for conditions with autonomic insufficiency and postural hypotension?
Midodrine
alpha-1 agonist
115
Norepinephrine
* MOA
* Indications
* MOA
* Alpha and beta-1 agonist
* a = vasoconstriction =\> Increased TPR =\> increased BP
* b = increased contractility (no effect on CO)
* Indications
* Severe hypotension and shock
116
Epinephrine
* MOA
* Indications
* MOA
* low dose: beta agonist
* increased HR and contractility
* Increase CO, systolic BP
* Bronchodilation
* High dose: alpha agonist
* vasoconstriction
* Indications
* Asthma
* Anaphylaxis
* Locally decrease blood flow to extend local anesthetic effect
117
Dopamine
* MOA
* Indications
* MOA
* Low dose: D1 and beta1 agonists
* increased HR, CO (beta effects)
* increased renal perfusion (D1 effect)
* renal and splanchnic flow
* Indications
* Hypotension and shock
* treats decreased CO and renal function
* Acute Heart Failure if BP is low
118
What is the MOA of alpha-2 receptor agonists?
stimulate receptors in CV control centers in the CNS to reduce sympathetic nerve outflow and BP
119
Metaproterenol
* MOA
* Indications
* MOA
* beta-2 agonist
* Indications
* Long-term treatment COPD and asthma
120
Terbutaline
* MOA
* Indications
* MOA
* beta-2 agonist
* Indications
* asthma and COPD
121
Albuterol
* MOA
* Indications
* MOA
* beta-2 agonist
* Indications
* asthma (symptomatic relief)
122
Salmeterol
* MOA
* Indications
* Side effects
* MOA
* beta-2 agonist
* Indications
* long acting
* treat COPD
* Side effects
* increased HR
* Hyperglycemia
123
Formoterol
* MOA
* Indications
* MOA
* beta-2 agonist
* long-acting
* Indications
* Asthma
* exercise-induced bronchospasm
* COPD
124
What is the suffix for beta-2 agonists?
- terol
- terenol
Isoproterenol is a non-selective beta agonist (1 and 2)
125
Isoproterenol
* MOA
* Indications
* Side effects
* MOA
* non-selective beta agonist
* Indications
* Bronchodilator
* Torsades de pointes
* Side effects
* Hypotension
* Arrhythmia
126
Which drug is indicated to reduce local blood flow in surgery to increase length of effectiveness of local anesthetics?
Epinephrine
127
Which drugs are indicated for use as a nasal decongestant?
Phenylephrine
Pseudoephrine
(alpha-1 agonists)
128
What drug group is indicated for treatment of asthma?
beta-2 agonists
- terol
- terenol
129
What are the effects of alpha-2 receptors?
Decrease sympathetic outflow
Decreased: HR, BP
130
Phenoxybenzamine
* MOA
* Indications
* Side effects
* MOA
* non-selective alpha receptor blocker
* Irreversible
* Indications
* Treatment of Pheochromocytoma
* Side effects
* Orthostatic hypotension w/ reflex tachycardia/arrhythmia (alpha-2-blockade)
* Inhibit ejaculation
131
Phentolamine
* MOA
* Indications
* Side effects
* MOA
* non-selective alpha antagonist
* competitive, reversible
* Stimulates GI smooth mm and secretion
* Indications
* diagnose Pheochromocytoma
* Relieve pseudo-obstruction on bowel
* Treat hypertensive crisis associated with MAOIs and tyramine
* ED
* Side effects
* Orthostatic hyptotension w/reflex tachycardia and arrythmia
* Inhibition of ejaculation
* exacerbates peptic ulcer
132
What drug is used to treat pheochromocytoma?
Phenoxybenzamine
non-selective alpha receptor antagonist
133
What drug is used to diagnose pheochromocytoma and relieve pseudo-obstruction of bowel in this disease?
Phentolamine
non-selective alpha receptor antagonist
134
Prazosin
* MOA
* Indications
* Side effects
* MOA
* selective alpha-1-receptor antagonist
* Indications
* Hypertension (monotherapy)
* CHF
* Side effects
* Postural hypotension and syncopy
* first-dose effect
135
Suffix of selective alpha-1-blockers
-osin
like the ocean
Prazosin
Tamsulosin
etc.
136
Tamsulosin
* MOA
* Indications
* Side effects
* MOA
* selective alpha-1-blocker (alpha-1A)
* Indications
* Benign prostatic hypertrophy
* without HTN
* Side effects
* impaired ejaculation
Very little effect on BP, so less likely to cause orthostatic hypotension
137
Terazosin and Doxazosin\
* MOA
* Indications
* Side effects
* MOA
* selective alpha-1-blockers
* induce prostatic apoptosis
* Indications
* benign prostatic hyperplasia
* associated w/HTN
* Side effects
* First dose syncopy and orthostatic hypotension
138
What drug is used to treat Benign Prostatic Hyperplasia (BPH) without associated HTN?
Tamsulosin
139
What drug is used to treat Benign Prostatic Hyperplasia (BPH) with associated HTN?
Terazosin or Doxazosin
140
What are the indications for beta blockers?
1. hypertension
2. ischemic heart disease (angina, prophylactic)
3. Acute MI
4. CHF
5. Arrhythmia
141
What is the suffix associated with beta-blockers?
-olol
beta fish giving **lol**ipop to heart
142
What are the effects of non-selective beta-blockers?
* CV
* Respiratory
* Metabolic
* CV:
* decrease CO
* Decrease HR
* Decreased BP in patients w/HTN but not normal patients
* Decrease conduction
* increase AV node refractory period
* can cause heart block
* decreased work capacity during exercise
* Respiratory
* Bronchoconstriction
* Con: COPD and asthma
* Metabolic
* Decrease insulin sensitivity
* delay recovery from hypoglycemia
* blunt effects of hypoglycemia
* CON: diabetes (I)
* Lipids in wrong direction
143
What are the therapeutic applications of Propranolol?
HTN
Angina (prophylactic)
144
What are the side effects associated with Propranolol?
1. Bronchoconstriction
2. Arrhythmias
* decreased HR
* CHF
* (-) AV conduction
3. Hypotension
4. fasting gypoglycemia
145
From which beta-blocker must patients be weened? Why?
Propranolol
* Effects of Long-term use
* Receptor upregulation
* Hypersensitivity
* Effects of abrupt discontinuation
* exacerbate Angina
* increased risk of death
146
What are the contraindications associated with Propanolol?
1. Heart Block
* decreased conduction
2. Asthma/COPD
* bronchoconstriction
3. Diabetes
* insulin insensitivity
147
Esmolol
* MOA
* Indications
* MOA
* selective beta-1-antagonist
* decrease HR and contractility
* Extremely short-acting
* Indications
* emergency beta-block (pre-op where expect large increase in SNS activity)
* arrhythmia
* HTN
* MI
148
Cavedilol
* MOA
* Indications
* MOA
* alpha-1 and beta-receptor blocker
* decreased HR and contractility (B1)
* Bronchoconstriction (B2)
* Decrease BP (A1)
* Increase NO
* Ca2+ blocker
* Antioxidant (protective, decreased apoptosis)
* inhibit RAAS (decrease Na/H2O retention)
* Indications
* CHF
* anti-remodeling effect (decreased stress =\> decreased ventricular size)
149
What are the symptoms of beta-blocker overdose? What is the treatment?
* cardiodepression
* Hypotension
* bradycardia
* prolonged AV conduction
* widened QRS
* Treatment
* atropine (bradycardia), isoproterenol (hypotension)
150
What does a depressed/elevated S-T segment on an ECG signal?
Angina
151
What is the difference between typical and variant angina?
Typical:
* Induced by exercise, eating, or emotional stress (active)
* Cause: atherosclerotic coronary artery disease
Variant:
* Occurs any time (even at rest)
* Cause: coronary artery vasospasm w/coronary thrombosis
152
How much time can elapse in ischemic injury before irreversible damage occurs?
15 minutes
early irreversible: 1 hour
Late irreversible: 1 day
Note: irreversible has Ca2+ influx, stimulates lysosomal enzymes to destroy cell
153
What is the MOA of Nitroglycerin?
* Reacts with thiol =\> nitrosothiol (CV1, p4-5)
* Release NO
* Stimulate guanylate cyclase (Increased cGMP)
* deactivation of myosin light chain
* **Smooth mm relaxation**
* preferentially in veins
* decreased: Oxygen demand
* preload
* afterload
* ventricular size
* wall stress
* Decreased ventricular pressure facilitates blood flow into endocardium
154
What is the therapeutic application of Nitroglycerin?
Acute angina/Prophylaxis
| (peak effect in 3 minutes)
155
What are the side effects of nitroglycerin?
1. Angina
* reach point where flow proportional to pressure (vessels @ max dilation)
* increased dose =\> decreased BP and flow to heart =\> ischemia =\> angina
2. Headache
* cerebral aa. dilation
3. Orthostatic hypotension
* from preferred venodilation
4. Syncopy
* decreased arterial pressure
5. Rapid onset of tolerance
* reflex activation of SNS and RAAS
* Thiol depletion/ROS production (inactivates NO)
156
What are the contraindications of Nitroglycerin?
1. PDE5 inhibitors
* treat ED
* potentiate vasodilatory effect
2. alpha-1-receptor blockers
157
Ranolazine
* MOA
* Indications
* MOA
* limits Na+ and Ca2+ influx into cardiac cells
* prevents overload
* decreases diastolic wall tension
* Myocardium less stiff
* increased filling
* increased diastolic function
* Increased exercise capacitance
* Indication:
* Angina
158
Nicorandil
* MOA
* Indications
* MOA
* Dilates arteries and veins
* reduce O2 demand of heart
* Indications
* Angina
(nitroglycerin effect)
159
Perhexiline
* MOA
* Indication
* MOA
* shift heart from FA to glucose metabolism
* decreases O2 demand
* Indications
* Angina
160
Trimetazine
* MOA
* Indications
* MOA
* shift heart from FA to glucose metabolism
* decreases O2 demand
* Indications
* Angina
161
What diseases are commonly associated with ED?
1. HTN
2. Diabetes
3. Hypercholesterolemia
162
What is the MOA of PDE5 inhibitors? What important drug interaction should be prevented?
MOA
* Inhibit GMP-specific phosphodiesterases
* Increase cGMP (which is normally stimulated by increased NO)
* Amplify actions of NO on vascular tissue =\> increased vasodilation
Drug interaction:
* Nitroglycerin: extreme reduction in BP
* alpha-1-receptor antagonists: same
163
Which channel subtypes are inhibited by Ca2+ channel blockers?
L-Type
Mostly in CV tissue
164
What are the indications for Ca-channel blockers?
Major
1. MI
2. HTN
* DHPs if hypertensive crisis
3. Cardiac Arrythmia
* Not DHPs
* Verapamil best, or diltiazem
Minor
1. Cardioprotection
2. Migraine
3. Esophageal spasm
165
Nifedipine
* MOA
* Indications
* Side effects
* Contraindications
* MOA
* Calcium channel blocker (1,4 DHP)
* inhibits recovery of channel
* lipid-soluble
* (-) cNMP phosphodiesterase, so vessels stay dilated
* baroreceptor reflex occurs
* Indications
* Hypertensive crisis
* Side effects
* Hypotension
* Peripheral Edema
* Headache
* Contraindications
* heart failure or conduction abnormalities
166
What is the MOA of Nifedipine?
* class = 1,4-DHP
* Ca-channel blocker
* inhibits recovery of channel
* lipid-soluble
* (-) cNMP phosphodiesterase, so vessels stay dilated
* baroreceptor reflex occurs
167
What are the therapeutic applications for Nifedipine?
Hypertensive crisis
168
What are the side effects of Nifedipine?
Headache
Hypotension
Peripheral edema
169
Verapamil
* MOA
* Indications
* Side effects
* Contraindications
* MOA
* Ca-channel blocker
* inhibits recovery
* Hydrophilic, so action depends on frequency of receptor opening
* Indications:
* HTN
* Arrhythmias
* A-Fib
* re-entry tachycardia thru AV node
* supraventricular tachycardia
* Side effects
* Bradycardia
* Heart Block
* Hypotension
* Peripheral edema
* Contraindications
* SA or AV conduction abnormalities
170
Diltiazem
* MOA
* Indications
* Side effects
* Contraindications
* MOA
* Ca-channel blocker
* inhibits recovery
* Hydrophilic, so action depends on frequency of receptor opening
* Indications:
* HTN
* Arrhythmias
* A-Fib
* re-entry tachycardia thru AV node
* supraventricular tachycardia
* Side effects
* Bradycardia
* Heart Block
* Contraindications
* SA or AV conduction abnormalities
171
What is the MOA of Verapamil? What is its indication?
* MOA
* Ca-channel blocker
* inhibits recovery
* Hydrophilic, so action depends on frequency of receptor opening
* Indications: Arrhythmias
* supraventricular tachycardia
* re-entry tachycardia thru AV node
* A-Fib
172
What are the side effects of Verapamil? What are its contraindications?
* Side effects
* Bradycardia
* Heart Block
* Hypotension
* Peripheral edema
* Contraindications
* SA or AV conduction abnormalities
173
What is the MOA of Diltiazem? What are its indications?
* MOA
* Ca-channel blocker
* inhibits recovery
* Hydrophilic, so action depends on frequency of receptor opening
* Indications: Arrhythmias
* supraventricular tachycardia
* re-entry tachycardia thru AV node
* A-Fib
174
What are the side effects of Diltiazem? What are its contraindications?
* Side effects: VERY MILD
* Some Bradycardia
* Some cardiodepression
* Contraindications
* SA or AV conduction abnormalities
175
Bepridil
* MOA
* Indications
* Side effects
* Contraindications
* MOA
* Ca-channel blocker
* Indications
* Angina
* Side effects
* prolonged AP (prolonged QT)
* May cause Torsade de pointes in susceptible individuals
* Contraindications
* Arrhythmia
* Prolonged QT
176
What are the physiological causes of increased vascular pressure in hypertension?
1. Smooth muscle hypertrophy and hyperplasia
2. enhanced sensitivity to constrictor stimuli
3. reduced sensitivity to dilator stimuli
177
What are the 5 first-line agents for treatment of HTN?
1. Thiazide diuretics (used first)
2. ACE inhibitors
3. Calcium Channel Blockers
4. beta-blockers
5. alpha-1-blockers
178
What drug reduces the risk of stroke in HTN patients?
Thiazide diuretics (chlorothiazide, chlorthalidone)
179
What is believed to be the long-term effect of thiazide diuretics that results in decreased BP?
Decreased peripheral vascular resistance
180
Which drugs are used for hyptertensive patients with MI, Myocardial ischemia, or Heart Failure?
beta-blockers
181
What is the most likely mechanism of beta-blockers leading to decreased BP?
decreased plasma renin activity
182
Which drugs are used for diabetic patients with HTN?
ACE inhibitors
Exert renal-protective effect
183
Which drug has a side effect of hypertrichosis? What is its vascular indication?
Minoxidil
Hypertensive emergency
184
Minoxidil
* MOA
* Indications
* Side effects
* MOA
* opens K channels, depolarizing cells
* vasc. smooth muscle dilates
* Indications
* hypertensive emergency
* Side effects
* hypertrichosis
185
Hydralazine
* MOA
* Indications
* Side effects
* MOA
* K channel activation
* NO production
* arteries \> veins (little orthostatic hypotension)
* Indications
* Hypertension (short-term)
* use with beta-blockers and diuretics (see SE's)
* CHF
* with isosorbide dinitrite
* Side effects
* reflex SNS activation and fluid retention
* **Drug-induced Lupus**
186
What drug can cause Lupus?
Hydralazine
187
Nitroprusside
* MOA
* Indications
* MOA
* directly produces NO
* stimulates cGMP-mediated vasodilation
* Indications
* Hypertensive emergencies
188
Fenoldopam
* MOA
* Indications
* Side effects
* Contraindications
* MOA
* D1 receptor agonist
* dilates arteries
* Indications
* Hypertensive crisis
* Side effects
* Increased HR
* Headache
* **increased intraocular pressure**
* Contraindications
* Glaucoma
189
Alpha-methyltyrosine
* MOA
* Indications
* MOA
* false substrate for tyrosine hydroxylase
* inhibits NE synthesis and decreases BP
* Indications
* HTN in pheochromocytoma
190
Methyldopa
* MOA
* Indications
* MOA
* alpha-2-agonist
* converted to methyl-NE in the brain
* causes vasomotor centers to decrease NE production
* decreased vasoconstriction
* Indications
* HTN
191
Drugs that treat Pheochromocytoma
1. Phenoxybenzamine
* chronic treatment
* surgical resection
2. Phentolamine
* diagnosis
* treat pseudo-obstruction of bowel
3. Alpha-methyl-tyrosine
* HTN
192
What drug is used to treat HTN in patients with benign prostatic hyperplasia (BPH)?
Terazosin
Doxazosin
193
Guanethidine and Guanadrel
* MOA
* Indications
* Side effects
* MOA
* Deplete NE stores from sympathetic nerve terminals
* Results in a massive release at first
* Indications
* HTN, rarely used
* Side effects
* Hypertensive Crisis w/first dose
194
Reserpine
* MOA
* Indications
* Side effects
* MOA
* Blocks the VMAT transporter (no NE into vesicles)
* Depletes terminal of NE stores
* Indications
* HTN
* Side effects
* May have hypertensive crisis
* psychotic disorders
* mimic paranoid schizophrenia
195
Tamsulosin
* MOA
* Indications
* MOA
* alpha-1A-agonist
* relaxes muscles in bladder neck and prostate
* Indications
* HTN with BPH
* BPH (urinary tract symptoms)
196
Why are guanethidine and guanadrel not currently used as anti-HTN?
They cause a large release of NE from nerve terminals, resulting in hypertensive crisis
197
Which drug can cause side effects mimicking paranoid schizophrenia?
Reserpine
198
What drug is used for HTN patients with angina?
beta-blocker
199
What drug is used for HTN patients with MI?
beta-blocker
Thiazide diuretics
200
What drug is used for HTN patients with CHF?
beta blocker
thiazide diuretics
201
What drug is used for HTN patients with a high stroke risk?
Thiazide diuretics
202
What drug is used for HTN patients with kidney disease?
thiazide diuretics
203
What drug is used for HTN patients with diabetes?
thiazide diuretics
204
What drug is used for HTN patients with asthma?
ACE inhibitors
ARBs
205
What drug is used for HTN patients with Migraines?
beta-blocker (Propanolol)
206
What drug is used for pregnant HTN patients?
Methyldopa
207
What drug is used for HTN patients with Atrial fibrillation?
Verapamil
Diltiazem
beta-blocker
208
What drug is used for HTN patients with supraventricular tachycardia?
Verapamil
Diltiazem
beta-blocker
209
What drug is used for HTN patients with osteoporosis?
Thiazide diuretics
210
What drug is used for HTN patients with renal calculi?
thiazide diuretics
211
What drug is used for HTN patients with glaucoma?
beta-blockers
212
What is the effect of using Diuretics with ACE inhibitors?
antihypertensive
controls K levels
Controls excessive reflex AII effects
213
What is the effect of using Diuretics with hydralazine?
Prevent fluid retention from hydralazine
214
What is the effect of using Diuretics with beta-blockers?
beta-blocker controls reflex activation of CV and RAAS from diuretic
215
What is the effect of using Diuretics with beta-blockers and Ca-channel blockers?
refractory HTN
216
What are the causes of cardiac remodeling in CHF? What drugs can be used to reduce this effect?
* Causes:
* SNS stimulation
* RAAS
* Drugs:
* Beta-blockers
* ACE inhibitors
217
What are the effects of vasodilator therapy on the failing heart?
* Venodilation: reduced preload
* decreased pulmonary congestion
* Little effect on SV
* Arteriodilation: Decreased afterload
* increase SV
* Together:
* increase perfusion
* relieve pulm congestion
* Reduce ventricular chamber size
218
Which venodilators are used in the treatment of CHF?
1. Hydralazine with isorbide dinitrite
2. ACE inhibitors
219
What are the effects of beta-blockers in CHF?
* reduce arrhythmia
* reduce water retention (RAAS inhibition)
* Reduce myocyte apoptosis
* reduced cardiac remodeling
220
What is the MOA of digitalis?
1. (+) INO
* increases intracellular Ca2+
* Increases contractile strength
2. Increased ventricular performance
* Increased CO
3. Automaticity = increase rate of Vm rise in phase 4
* create ectopic foci/DAD/arrhythmia
4. Inactivate SA node at high dose
* create ectopic foci
5. Increase vagal and decrease SNS to heart
* decreased nodal conduction
* Block SA node =\> **heart block!**
221
What are the side effects of Digitalis?
arrhythmia
Heart Block
222
What drug is contraindicated for use with digitalis?
Quinidine
increases digitalis plasma concentration
223
What is used to treat digitalis overdose?
Fab Fragments
224
What is the therapeutic application of digitalis?
CHF
225
What drugs are indicated when ventricular remodeling is present even if the patient is asymptomatic?
ACE inhibitors
Beta-blockers
226
What drugs are indicated in acute heart failure when SBP is over 90?
1. Furosemide (loop diuretic)
* relieves congestion only
2. Nitroprusside
* increased perfusion and relieves congestion
227
What drugs are indicated in acute heart failure if SBP \<90?
1. Levisomendan
* Ca2+ sensitizers
2. Amrinone
* increase cAMP
* (+) INO
3. Dobutamine
* Beta-1-agonist
* stimulates the heart
4. Dopamine
* (+) INO
* Peripheral constrictor
* renal dilator for increased perfusion
228
What are the actions of thrombin in the clotting cascade?
* Forms and stabilizes the fibrin clot
* Reactivates the coagulation cascade
* Triggers platelet activation
229
What cleaves fibrin?
Plasmin
230
Expression of what receptor is the final common pathway to platelet aggregation?
* GP IIb-IIIa
* Binds fibrinogin and platelets stick together
* Binds vWF
231
What activates platelets to express GP IIb-IIIa and initiate aggregation?
1. thrombin receptor
2. ADP
3. TXA2
232
Aspirin
* MOA
* Time to peak action
* MOA:
* perminant inactivation of COX 1 and 2
* inhibits TXA2 synthesis
* Inhibits platelet aggregation
* Time to peak action: 30-40 minutes
233
Mechanisms of anti-platelet agents
1. Inhibit TXA2
2. GP IIb/IIIa antagonist
3. ADP receptor inhibitor
4. PAR-1 receptor inhibitor
234
What is the effect of ADP receptor inhibitors?
anti-platelet aggregation
235
What is the pathology of NSTE acute coronary syndrome?
* Not completely occlusive
* site of plaque rupture
* Expose GPIIb-IIIa
* Platelets cross-link
No ST elevation on ECG
236
What is the pathology of STE MI?
* Caused by complete occlusion
* Stabilization of platelet aggregation by fibrin
ST elevation on ECG
237
Unfractioned Heparin
* MOA
* Limitations
* MOA:
* Binds anti-thrombin III
* inactivates Factors IIa, Xa, IXa, XIIa
* Limitations:
* Neutralized by platelet factor 4 (PF4)
* Requires continuous anticoagulant monitoring
238
What is the benefit of Low Molecular Weight Heparin over Unfractionated Heparin?
Easier administration
More predictable response, so no monitoring needed
239
Warfarin (Coumadin)
* MOA
* How does Vit K affect warfarin activity?
* Limitations
* MOA: Anti-thrombin
* inhibits Vitamin K Oxide Reductase
* Inhibits factors II, VII, IX, and X as well as proteins C and S (can't be carboxylated)
* Affects extrinsic pathway
* Measured by Prothrombin time!!!
* Dependent by Vit K levels in the body
* works best with low Vit K
* High Vit K = need higher dose
* Limitations
* Narrow Therapeutic Range
240
What does CHADS2 score measure? What are the factors considered? How does that score affect medication regimine?
* measures stroke risk in A Fib patients
* CHADS2
* Congestive heart failure
* Hypertension
* Age \>75
* Diabetes
* Stroke or TIA (worth 2 points)
* Meds:
* Score = 0 = aspirin
* Score = 1 = aspirin or warfarin
* Score \>1 = warfarin
241
Which coagulation pathway does warfarin affect? How is the effect measured?
Extrinsic pathway
Prothrombin Time (PT)
242
What is the advantages of Direct Thrombin Inhibitors?
* Affects only one factor
* Independent of anti-thrombin III
243
What is the effect of Factor Xa inhibitors on thrombin activity, thrombin generation, and platelet function?
* No inhibition of thrombin activity
* Inhibits thrombin generation
* No effect on platelet function (unlike heparin)
244
What is the effect of tPA?
fibrinolytic
activates plasmin
245
Clotting cascade
