LAST DECK OF PHARM 1 Flashcards
1
Q
Patient with volume overload, who needs progressively higher doses of loop diuretics, usually has:
A
Loop Resistance
Tx with Chlorothiazide or Metolazone
Metolazone works at GFR <20ml/min
Retains efficacy at supa low GFRs!
Work on collecting duct:
- Amiolioride (K)
- Triamterne (K)
- Spirnolactone (Ald)
2
Q
How do you fix Loop Resistance?
A
- If on oral, use parenteral/IV.
- Increase dose (limited).
- Utilize continuous infusion loop diuretics.
- Use a different loop, or add a thiazide diuretic.
3
Q
Causes of Loop Resistance
A
- High sodium intake.
- Reduced number of working nephrons from ATN.
- Heavy proteinuria.
- Renal compensation - water and salt reabsorbed at DCT.
4
Q
What electrolytes are not as easily removed in Renal Replacement Therapy?
A
RRT - hemodialysis pulls off excess electrolytes to restore a normal balance.
Phosphorous and Magnesium
-High levels in trauma, rhabdomyolysis, tumor lysis syndrome
5
Q
Why do you avoid calcium when doing RRT on a trauma patient, rhabdomyolysis patient, or tumor lysis syndrome?
A
High levels of phosphorous in blood.
Calcium and phosphorous can precipitate in the blood when at high conc. and form crystals causing further injury.
6
Q
Why do RRT patients develop hypocalcemia?
A
To keep blood from clotting, they use citrate anticoag., which binds to calcium in blood.
Prevents calcium from activating clotting factors. When put back into patients, prevents their blood from clotting.
7
Q
Kidney failure
Stages?
Causes?
Risks?
Patho? :)
A
CKD caused by diabetes, HTN, GN.
Stage 1 >90 Stage 2 60-89 Stage 3 30-59 Stage 4 15-29 Stage 5 <15 = Kidney Failure
Risks include DM, HTN, smoking, obesity, proteinuria.
Pathophys of CKD:
Progressive neuropathy leads to loss of nephron mass, glomerular capillary HTN, and proteinuria.
8
Q
Renal Osteodystrophy
A
Renal osteodystrophy is a bone disease that occurs when your kidneys fail to maintain proper levels of calcium and phosphorus in the blood.
It’s common in people with kidney disease and affects most dialysis patients.
- Decreased renal fxc
- Increased phosphate levels, which bind Ca and precipitate.
- Hypocalcemia leads to increase in PTH.
- More Ca and Phos reabsorbed, which MAKES THE PROBLEM WORSE.
- Low Vitamin D levels also increase PTH secretion.
9
Q
CKD Related Mineral & Bone Disorders (3)
A
Parathyroid Hyperplasia: Result from renal osteodystrophy. Leads to resistance to calcium and vitamin D therapy.
Osteitis fibrosa cystica: High bone turnover disease. Leads to fibrosis of bone marrow and decreased erythropoiesis.
Osteomalacia: softening of bones
10
Q
S/S CKD
A
- Uremic symptoms cause fatigue, weakness, confusion, SOB
- Peripheral neuropathies
- Edema
- Change in urine, foaming of urine
- Abdominal distension from ascites
11
Q
Hemodialysis
A
Will have a fistula that connects artery and vein in arm. Allows for blood to be taken out of artery, goes through filtrate system, and is put back into the body through the vein.
4 hrs, 3x a week
12
Q
Peritoneal Dialysis
A
Putting dialysate solution into the peritoneal space. Passive diffusion, blood transmits waste into the peritoneal space.
In several hours, take the waste out through a drain. Takes 20-30mins.
13
Q
Management of CKD Diet
A
Limit protein to 0.8 g/kg/day
Limit sodium intake to <2g/day
Stop smoking
Start exercising
14
Q
How do you tx a diabetic with CKD?
A
ACEI or ARB to prevent progression, titrate the drug until GFR drops or you have a significant elevation in serum K occur.
Metformin for diabetes, continued until GFR <30ml/min or SCr >1.5 in males or 1.4 in females.
Stop the drug or it can accumulate at higher levels and form fatal lactic acidosis. :(
15
Q
How do you treat a patient with CKD and HTN?
A
- ACEI or ARB = 1st line in DM
- Thiazide diuretics if not sufficient to control BP.
- Manage BP - 140/90 to decrease albumin excretion, 130/80 if possible.
16
Q
How do you treat anemia in CKD?
A
Decreased production of erythropoietin from interstitial fibroblasts, which are damaged. Develop normochromic, normocytic anemia.
Tx: Erythropoiesis stimulating agents (ESA) and iron supplementation.
Need to take both for ESA to be effective.
Monitor: oxyhemoglobin
17
Q
Target Hemoglobin in Anemia Tx:
A
Pt w/ hemoglobin b/w 9-10, ESA should be considered.
D/C ESA when Hgb is above 10 (11 in RRT pts).
If you continue treating above 13g/dL of hemoglobin = increased mortality, due to thrombosis.
Dose ESA w/ iron.
18
Q
What are the Erythropoiesis Stimulating Agents?
A
Epoetin alfa (Epogen, Procrit) Darbepoetin alfa (Aranesp)
Black box warning:
- Increased risk of death, MI, stroke, VTE (sludging of blood, leads to clotting off).
- Increased risk of cancer.
Dose 3-4x a week.
ADR: HTN and vascular access thrombosis.
19
Q
What do you monitor in CKD patient receiving ESA?
A
Monitor iron status.
Also, make sure you have adequate intake of B12 and folate - can be diminished by RRT.
Oral intake of iron alone may be insufficient for CKD patients, because their absorption is decreased to 10% (100% in those who are healthy).
20
Q
Iron Preparations
A
Oral. Different doses of elemental iron in each.
- Ferrous sulfate
- Ferrous gluconate
- Ferrous fumarate
IV
- Iron Dextran
- Sodium ferric gluconate
- Iron sucrose (most commonly used)
- Ferumoxytol
21
Q
ADR of Iron Preps
A
Constipation, nausea, abdominal cramping, black discoloration of stool
TELL PATIENT THEIR STOOL WILL BE BLACK.
Allergic reactions: Hypotension, headaches, and dizziness. Can be fixed by lowering the infusion rate!
TEST Q!
Can also develop arthralgia and arthritis.
22
Q
How do you select an iron prep?
A
- Oral therapy if possible. Has less side effects.
- RRT patients are more likely to need IV prep.
Monitor:
- Iron status every 3 months while on ESA.
- Monthly, when titrating dose.
-Hgb, measure every 3 months, but monthly in RRT. When alterring, monitor weekly.
23
Q
Treatment goals for CKD Related Mineral & Bone Disorders
A
- Normalize biochemical parameters.
- Prevent dentrimental consequences.
Limit Ca * P product to <55
Less chance of crystal formation
24
Q
Nonpharmacologic therapy for CKD Related Mineral & Bone Disorders
A
Limit dietary phosphate intake <800mg per day.
Avoid cola, nuts, beer.
Dialysis won’t pull phosphate out.
25
What drugs treat CKD related mineral and bone disorder?
Phosphate binders:
- Calcium carbonate
- Calcium Acetate
- Sevelamer Carbonate
- Lanthanum Carbonate
- Aluminum Hydroxide
Bind to phosphate ingested through GI tract and prevent it from being absorbed.
- Used for hypocalcemia in early CKD.
- Calcium Carbonate: Give prior to meals
26
Why is Aluminum Hydroxide limited use in B&M disorders in CKD?
Aluminum will accumulate and can cause toxicity.
27
Sevelamer Carbonate
Phosphate binder
- Nonabsorbable hydrogel
- Lowers LDL, raises HDL
- Nice side effect
28
ADR phosphate binders
- N/V, diarrhea, constipation
- Hypercalcemia with calcium based products
Drug to drug interactions
- Calcium salts can bind to iron, zinc, and FQ.
- Take one hour before or 3 hours after.
29
Vitamin D Therapy
Ergocalciferol and cholecalciferol must be converted by the kidney to active form.
Calcitriol is an active form - stimulates absorption of calcium.
Leads to hypercalcemia and hyperphosphatemia.
Paracalcitrol - actives PTH receptors, but does NOT increase calcium and phosphate absorption.
30
Cinacalcet (Sensipar)
Sensitizes PTH receptors to effects of calcium.
Reduces PTH concentrations.
Will have enough calcium and not have as much PTH.
31
Manifestations of DIKD
```
AB abnormalities
Electrolyte imbalance
Urine sediment
Proteinuria
Pyuria
Hematuria
Decreased GFR*
```
32
Clinical manifestation, signs, and symptoms of DIKD
- Decline in GFR
- Rise in SCr and BUN
-Anorexia, malaise, vommiting, SOB, edema
- Decreased urine output, with progression to HTN and volume overload.
- Esp with NSAIDs, ACEI, and contrast induced nephropathy (CIN).
33
Signs of PCT injury
Metabolic acidosis with bicarbonaturia, glycosuria, hypophosphatemia, and hypokalemia.
34
Signs of DCT injury
Polyuria due to impaired urinary concentration, metabolic acidosis from impaired acidification and hyperkalemia.
35
What can cause ATN?
```
Aminoglycosides
Radio contrast media
Cisplatin
Amphotericin B
Foscarnet
Pentamidine
Foscarnet
Osmotically active agents, like colloids and mannitol
```
36
What drugs can cause osmotic nephrosis?
Mannitol
Dextran
IV immunoglobulin
37
What drugs can cause hemodynamically mediated kidney injury?
ACEI
ARBS
NSAIDs
Cephalosporins, tacrolimus
38
What drugs causes obstructive nephropathy?
```
Acyclovir
Sulfonamides
Indinavir
Foscarnet
Methotrexate
```
39
What drugs cause nephrolithiasis?
Sulfonamides
Triamterene
Indinavir
40
What drugs causes glomerular disease?
Lithium
NSAIDs
Pamidronate
41
What drugs can cause acute allergic interstitial nephritis?
```
PCNs
Cipro
NSAIDs
PPIs
Loops
```
42
What drugs can cause vasculitis or thrombosis?
Hydralazine
Allopurinol for gout
Methamphetamines
Cyclosporine
43
What drugs can cause cholesterol emboli?
warfarin
| thrombolytics
44
Aminoglycosides and ATN
Tobramycin
Gentamycin
ATN occurs in 10% of patients, 58% of those critcally ill. - Happens when there is cumulation of drug in proximal epithelial cells. Generates reactive oxygen species that damage the mitochondria.
Will have progressive increase in BUN and Cr.
Reversible if you discontinue therapy.
Risk factors
- large total dose
- prolonged therapy
- trough >2mcg/mL
- concurrent nephrotoxins with use
45
How do you prevent aminoglycoside damage to the kidney?
Careful patient selection, alternative antibiotic use if possible.
Limit concurrent nephrotoxic usage.
- Pharmacokinetic monitoring to achieve certain troughs.
- Once daily doses are used now, rather than 3x per day.
If ATN develops, discontinue.
46
Radiographic contrast media and ATN
Presentation: 24-48hrs after administration of contrast. Oliguria.
Contrast will induce a 50% reduction in blood flow causing renal ischemia and direct cellular toxicity. Occurs with high osmolar agents.
47
How do you avoid contrast induced ATN?
Isotonic Crystalloids - Used to maintain normal blood volume prior to contrast exposure and continued 6-24 hours after exposure.
AVOID ATN by using smallest dose possible, non-iodonated contrast agent, or low isoosmolar agent.
Other preventative agents to use:
- Sodium bicarbonate, but wasn't very helpful.
- N-acetylcysteine (Mucomyst) - benefits patients at high risk for contrast induced nephropathy. Also good for tylenol OD.
48
Cysplatin Nephrotoxicity
Used for solid tumors. Doses are limited by nephrotoxicity.
Impairs tubular reabsorption.
Decreased urinary concentration ability.
Leads to polyuria, decreased GFR, and electrolyte wasting.
Drug accumulates in proximal epithelial tubular cells causing necrosis.
49
How do you prevent cysplatin induced nephropathy?
Prevent by doing dose reduction and decreased frequency of admin.
Avoid concurrent nephrotoxins.
Vigorous hydration with NS can flush the kidneys.
50
What is the antidote used to chelate cisplatin in normal cells?
Amifostine (Ethyol)
Give 30mins before cisplatin to avoid kidney injury in high risk patients.
Need supportive care and hemodialysis to replace electrolytes.
51
Amphotericin B and ATN
Used for severe fungal infections.
Leads to renal tubular acidosis and wasting of K, Na, and Mg. Occurs days to weeks after initiation.
Causes direct tubular cell damage. Interacts with ergosterol in cell membrane to kill fungal cells, but damages our cells as well.
52
How do you prevent amphotericin B ATN?
Liposomal formations (AmBisome)
Embed the drug within the bilayer of the liposome med instead of your own cells. Expensive therapy.
Also need adequate hydration, longer infusion times, and can do electrolyte repalcement PRN.
53
Intratubular obstruction
Direct precipitation of drug crystals, which causes obstruction, nephritis, and acute tubular necrosis.
Can cause preciptation of tissue degradation products like tumor lysis syndrome and rhabdomyolysis.
54
How do you prevent tumor lysis syndrome from intratbular obstruction?
Can cause precipitation of uric acid crystals.
Avoid by staying hydrated and allopurinol (Zyloprim).
55
How does rhabdomyolysis cause intratubular obstruction?
Can cause precipitation of myoglobin.
Can be caused by by using HMG-CoA reductase inhibitors and CYP3A4 inhibitors.
56
AKI is a cause of drug precipitation - Why? What drugs?
it causes low urine volumes, low drug solubility, and volume depletion.
Can be caused by acyclovir, foscarnet (precipitations calcium), and methotrexate.
57
Total Body Water
Intracellular compartment
- Potassium
- Organic and inorganic phosphates
Extracellular compartment
- Sodium
- Chloride
- Bicarbonate
Balance maintained by Na-K-ATPase pump.
Osmolality equal in ICF and ECF.
58
Isotonic fluids (0.9% NaCl)
No net shift in ICF and ECF
59
Hypertonic solutions
| >0.9% NaCl
Decrease in ICF and increase in ECF.
Water shunts out of the cell, ICF, and into the intravascular space, ECF.
Good for cerebral edema to draw water out of the space pushing on the brain.
60
Hypotonic solution
| <0.9% NaCl
Increase in ICF and decrease in ECF.
61
D5W
Free water; doesn't have solutes in it to keep it in intravascular space.
Will have 40% in the extracellular space and 60% in the intracellular fluid.
62
0.45% NaCl
Hypotonic solution, larger volume stays in extracellular space with some intracellular.
63
0.9% NaCl
Isotonic; all of it stays in the extracelluar fluid. Same concentration as blood.
64
3% NaCl
Will draw water out of the intracellular space and shuttle to extracellular fluid.
65
Serum Sodium
tightly regulated; determines plasma osmolality and blood volume.
Kidney regulates water extration via hypothalamaus.
Also affected by glucose and BUN.
66
Arginine Vasopressin (AVP)
Also known as ADH.
Released from pituitary when increased response in osmolality. Too high solute content (dehydrated), will release AVP.
Inserts aquaporin channels into tubular lumen for water to be reabsorbed.
Increases thirst.
Stimulates RAAS, which increase BP and amount of water retention.
67
Hypertonic Hyponatremia
- Excess effective osmoles
- Dilute sodium in blood
- Seen with glucose > 500.
- Glucose switches osmolality to ECF.
Every increase in glucose, drops the serum sodium. Can be caused by other osmotic agents like mannnitol.
68
Hypovolemic Hypotonic Hyponatremia
Due to excessive fluid loss, from diarrhea, vomiting, and diuretics.
Stimulates release of AVP. High urine osmolality, because AVP concentrates it.
Common with thiazides.
69
Euvolemic Hypotonic Hyponatremia
Normal amount of ECF Na, increases TBW and ECF volume.
Most often caused by SIADH (syndrome of inapropriate ADH secretion).
- Small cell lung, pancreatic cancer
- Pulmonary disease, TB, PNA, ARDS
- Polydipsia
- Head trauma, stroke
70
Drug induced causes of SIADH
Nicotine, tricyclic antidepressants, opioids, haloperidol
71
Increased sensitivity to ADH
acetaminopehn, carbamazepine, Iamotrigine, NSAIDs
72
MIXED of increased ADH release and sensitivity to ADH
Methylenedioxymethamphetamine
ACEI
SSRI
73
Hypervolemic Hypotonic Hyponatremia
Volume overload
Kidney sodium and water excretion are impaired.
See sodium retention, volume expansion, and edema.
Seen in cirrhosis, CHF and nephrotic syndrome.
- Acute
- Chronic (>48hrs)
S/S depend on magnitude.
Mild: Nausea, malaise
Mod: Headache, lethargy, disorientation
Sever: Seizures, coma, brainstem herniation
74
Hyponatremia lab tests
Serum sodium <135mEq/L
Plasma osmolality and urine sodium
Serum glucose, lipids, kidney and thyroid function tests help determine cause.
75
Cerebral edema
Related to speed and degree of change in serum osmolality. Brain takes 48hrs to compensate.
Low serum osmolality causes inward shift of fluid to CNS which puts pressure on brainstem and can lead to herniation.
76
Why is it bad to correct hyponatremia too quickly?
Correction of hyponatremia too quickly can lead to neuro consequences.
Water rushes out of the brain and there's an ICF contraction. Acute decrease in brain cell volume leads to osmotic demyelination (central pontine myelinolysis).
77
osmotic demyelination syndrome
Can cause hyperreflexia, para or quadriparesis, parkinsonism, pseudobulbar palsy, locked-in syndrome, and death 1-7 days after treatment.
78
Tx of Hyponatremia
- Treat underlying cause
| - Balance risk of hyponatremia vs. osmotic demyelination syndrome
79
How do you correct hypovolemic hyponatremia?
NS = main therapy
80
How do you collect euvolemic/hypervolemic hyponatremia?
- Manage with water restriction
- Demeclocycine
- AVP receptor antagonists
- or NS + loop diuretic
Concentrated NaCl can manage symptoms of severe hyponatremia.
81
How do you treat acute or severely symptomatic hypotonic hyponatremia?
3% NaCl or 0.9% NaCl
Target 120mEq/L (5% increase)
Compare urinary sodium to corrective fluid. 0.9% can sometimes worsen hyponatremia in patients with SIADH.
Loops used to prevent fluid overload.
82
How do you treat severely symptomatic hypotonic hyponatremia?
NaCl at 0.9% is higher than what the patient has (150mEq/L).
Need normal saline to correct them.
83
How do you treat hypervolemic hyponatremia patients?
May need loop diuretics and hypertonic saline (3% NaCl), which is more concentrated.
84
What's the main rule when calculating sodium chloride infusion?
Do NOT correct faster than 12 mEq/L in the first 24hrs!!!!!!
Goal is to achieve 125-130mEq/L. :)
TBW = 0.6L/kg in men, 0.5L/kg in women.
85
66Y/O female presents to ED with vertigo and disorientation. She started carbamazepine 10 days ago. Serum Na is 108mEq/L. What do you do?
1. Stop carbamazepine
2. Desired serum sodium? 120mEq/L
3. Determine how much 3% NaCl to infuse (math).
What if we wanted to infuse 0.9% NaCl?
...More math...
86
How do you treat non-emergent hypovolemic hypotonic hyponatremia?
Use 0.9% NaCl - limits the risk of correcting too quickly, especially if a nurse hangs it at the wrong rate ;)
Helps replenish both volume and sodium.
87
If you have a patient with euvolemic hypertonic hypernatremia, what is the most likely culprit and how do you treat it?
Caused by SIADH.
- Restrict water to 1000- 1200ml/day
- Correct underlying cause.
- D/C offending drugs.
Sodium chloride tablets and loop diuretics can be used to increase sodium intake and augment amount of kidney water retention.
88
How do you combat oversecretion of ADH in SIADH?
Demeclocycline (tetracycline derivative)
Inhibits tubular AVP activity.
Induces DI.
Takes 3-6 days to work; bad for patients with liver disease or compromised fluid intake. Can cause AKI or renal tubular toxicity.
Don't give to kids under 8 or pregnant woman.
89
If demecloclycine didn't work to manage SIADH hyponatremia (or it was a more severe hyponatremia), what could you give"?
V-2 antagonists (Vaptans)
Decrease water reabsoprtion in the kidneys. Aquaretics.
Conivaptan - IV only
Tolvaptan - available for home use, PO
Metabolized by CYP3A4
CI: Not good if patient isn't producing urine.
Used for chronic correction, not acute.
90
How do you treat a non-emergent hypervolemic hypotonic hyponatremia?
Need to have a negative water balance while minimizing changes to the intracellular volume.
Correct the underlying cause, limit fluid intake, limit sodium intake.
Need to improve cardiac contractility in CHF, via digoxin.
ACEI or ARB can reduce afterload.
91
Hypernatremia
Occurs from renal or extra-renal fluid loss.
Can be caused by hypertonic fluids, excess sodium ingestion.
Water loss is from insensible losses - expired breath or sweat.
- DI can have decreased release of AVP (central) or less kidney response (nephrogenic).
- Causes large volumes of excreted and dilute urine.
92
What causes hypovolemic hypernatremia?
Renal loss of water, diuretic use, post-op diuresis
93
What causes euvolemic hypernatremia?
Diabetes insipidus - excreting water, primary polydipsia
94
What causes hypervolemic hypernatremia?
Sodium overload from sodium bicarbonate, salt tablets, concentrated tube feedings, and sodium containing medications.
95
(Hypernatremia) Central causes of DI
Ethanol ingestion, which decreases ADH/AVP secretion.
Neurosurgery, head trauma, CNS malignancy.
96
(Hypernatremia) Nephrogenic causes of DI
Lithium, amphotericin B, demeclocycline, vaptans
Make AVP work less effectively in their mechanisms.
97
Clinical presentation of Hypernatremia
In hypernatremia, ICF => ECF. Will have polyuria.
Decreased neuronal cell volume leads to weakness, lethargy, restlessness, irritability, confusion.
Acute onset is more symptomatic than chronic.
98
Treatment goals of hypernatremia
Correct sodium to 145mEq/L
Rapid correction can lead to cerebral edema.
Restrict sodium and fluids to prevent recurrence.
99
How do you treat hypovolemic hypernatremia?
0.9% NaCl until the volume is restored, then 0.45% NaCl (more hypotonic) or D5W.
Correction should not exceed 10-12mEq/L a day.`
100
How do you treat a central diabetes insipidus; hypernatremia?
Replace AVP with desmopressin.
Has poor oral bioavailability; given as a nasal spray.
"Sniffin desmopressin" lol.
Adjust dose to achieve adequate urinary concentrations during sleep to prevent nocturia.
Goal:
- Urine 1.5-2L per day
- Serum Na 147-142
RISK of water intoxication and excess water retention!!!!
101
How do you treat a nephrogenic diabetes insipidus; hypernatremia?
- D/C causative agent
- Correct electrolyte disturbances.
- Induce mild ECF defecit to cut urine volume by 50%. Defecit wll cut urine volume by 50%.
Indomethacin (Indocin) which increases AVP activity.
102
How do you treat sodium overload?
Limit intake
Loop diuretics to excrete sodium
D5W (free water)
103
Physiology of Erections
Penis has 2 corpus cavernosum. Flaccid state has balanced venous and arterial flow.
During erections
- increased arterial flow
- decreased venous outflow
104
What enhances arterial flow to the corpus cavernosum?
Enhanced by acetylcholine mediated vasodilation, cGMP, cAMP, and vasoactive intestinal polypeptide.
Nitric oxide is stimulated/released in epithelial cells.
cGMP decreases calcium in smooth muscle, leading to vasodilation = more blood flow to penis.
Acetylcholine or prostaglandin E enhance cAMP.
105
Where does psychogenic stimuli to penis come from?
- Sacral nerve reflex arc; nerve impulse is carried down the spinal cord to the peripheral cholinergic nerves.
- Hypothalamus integrates external stimuli, uses dopamine (pro-erection)
-A2 receptors - when stimulated, can INHIBIT erections.
106
What drug can cause erectile dysfunction, why?
Clonidine
Acts on A2 receptors
Inhibits erection
107
What causes detumescense?
Detumescense: fancy word for penis deflation lol
Mediated by NE
Contracts the vascular smooth muscle, which decreases that arterial flow. Allows venous outflow (drainage) to increase.
108
Testosterone
Decreases after 40Y/O
| Important to stimulate libido.
109
5-alpha reductase
Enzyme
Converts testosterone to DHT
Enlarges size of prostate
Small amounts can convert to estradiol, which causes gynecomastia in men.
110
What medications cause ED?
Anticholinergics:
- Antihistamines
- Anti-parkinsonian drugs
- TCA's
- Phenothiazines
Dopamine antagonists:
- Phenothiazines
- Metoclopramide
Blocking Ach receptors makes it difficult to achieve erection.
111
How do you avoid antihistamines caused by ED?
Use a second generation antihistamines; don't penetrate the BB barrier.
112
What antidepressant medication has lowest incidence of ED?
Buproprion
113
Why do dopamine antagonists cause ED?
The blockade of dopamine increases prolactin levels, which decreases the production of testosterone.
114
What medications supress testosterone mediated libido stimulation?
- Estrogens
- Anti-androgens
- Digoxin
- Spirnolactone
- Ketoconazole
- Cimetidine
115
What CNS depressants suppress the perception of external psychogenic stimuli?
- Benzodiazepines
- Opiates
- Large doses of ethanol
- Anticonvulsants
Suppressed perception of psychogenic stimuli.
116
What agents decrease penile blood flow?
- Diuretics
- Beta antagonists
- Central sympatholytics (Clonidine, Methyldopa)
117
Vacuum Erection Device
Negative pressure in the cylinder draws arterial blood into the corpus cavernosa.
Onset 3-20mins.
60-80% satisfaction, but aren't discreet.
Good for patients who can't use PDE-5 inhibitors or other agents.
118
Phosphodiesterase Inhibitors MOA
Sildenafil (Viagra)
Vardenafil (Levitra)
Tadalafil (Cialis)
Avanafil (Stendra) *new
Non-hydrolyzable analogs of cGMP
Sexual stimulation to patient releases nitric oxide from nerves, which stimulates increased levels of cGMP to produce erection. By giving PDE-5 inhibitor, you inhibit breakdown of cGMP, which leads to higher levels to have an erection.
119
Which PDE inhibitor has a long half-life?
- Tadalafil has the longest half-life and duration of action
- Can last through the weekend
-Make sure you tell patient drugs take 30-60mins for onset to work.
120
PDE inhibitors: Place in Therapy?
First line therapy, especially for younger patients.
They're discreet.
50-80% effective.
Poor responders usually have comorbid conditions.
121
Therapeutic failures of PDE inhibitors
Educate the patient on food interactions (ex: Can't have a fatty meal and take Viagra, so would prescribe Cialis which you can have a fatty meal with).
Patient should try 5-8 doses, before saying its a failure.
Titrate up dose as needed.
Tell patient to avoid XS alcohol.
122
When are PDE inhibitors contraindicated?
Avoid in healthy patients, sickle cell, leukemia, multiple myeloma, or other therapies.
Risk for priapism goes up with these drugs!
123
PDE-6
Founds in rods and cones of eye.
When inhibited, can see blurry vision and cyanopsia (blue vision)
Seen in sildenafil (worse), followed by vardenafil, avanafil, and tadalafil (least).
124
PDE-11
Located on striated muscles.
When inhibited, leads to myalgias. Seen in Tadalafil.
125
What PDE inhibitor causes myalgias?
Tadalafil
126
What PDE inhibitor causes cyanopsia?
Sildenafil
127
What PDE inhibitors have a slower onset when consumed with food?
Sildenafil
Vardenafil
Slowed onset if they're taken within two hours of food. Will then have a 1-2 hour onset.
128
Tadalafil
Has the slowest onset
| Longest duration of action (36hrs)
129
PDE5 are metabolized by?
CYP3A4
130
What PDE inhibitors need to be renally adjusted?
Sildenafil
| Tadalafil
131
Most common ADR of PDE inhibitors?
The vasodilation can cause facial flushing, headache, dyspepsia, nasal congestion, and dizziness.
Patient's BP will have 8-10mmHg drop in systolic BP. Usually asymptomatic.
132
Who do you NEVER ever prescribe PDE inhibitors to?
People on nitrates and antihypertensives
Don't use on high risk cardiac patients.
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What ADR does Sildenafil have, specifically?
PDE-6 effects (Sildenafil)
- photophobia
- blurred vision
- loss of blue-green color discrimination
Reversible, if you switch to a different agent.
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What is a severe ADR of PDE inhibitors that you have to warn your patients of?
Nonarteritic anterior ischemic optic neuropathy (NAION)
Sudden, unilateral painless blindness that may be irreversible.
Due to drop in blood flow to the optic nerve.
Tell patient to stop taking medication right away if it happens.
135
What ADR does Tadalafil have, specifically?
Produces back and limb muscle pain, bc of PDE-11 effects.
136
What ADR does Vardenafil have, specifically?
QTc prolongation
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Priapism
Not seen frequently with PDE inhibitors, but can be seen with higher doses and other pro-erectogenic drugs.
138
Do not use nitrates when on phosphodiesterase inhibitors. Why?
Synergistic effects with cGMP can cause severe hypotension.
No nitrates for 24 hours after use of PDE inhibitors (or 48hrs after tadalafil).
If you have to treat angina, use other agents.
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If hypotension occurs from PDE inhibitors, how do you treat?
Trendelenburg position and fluids
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Alprostadil, prostaglandin E1
If patient can't take PDE inhibitor, you can use a prostaglandin E1, called Alprostadil.
- Caverject, Edex - intracavernous injection. Patient administer themselves.
- MUSE - medicated urethral system for erection; intraurethral insert.
MOA: Stimulate adenylyl cyclase to increase cAMP and decrease intracellular Ca, allowing smooth muscle to relax for blow to flow in.
141
Why is Alprostadil good for diabetics?
The drug is not nitric oxide dependent, so good for patients with impaired nitric oxide pathway.
- diabetic nephropathy
- prostatectomy
- failed PDE inhibitor treatment
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Intracavernosal injections
- More efficacious than the intraurethral insert, but is more painful to give.
- Excellent bioavailability.
- Preferred over other agents
- Less risk of priapism.
- Mean duration of action: 12-44 minutes
Psychogenic ED needs a lower dose than a vasculogenic ED.
No tolerance can develop to this therapy.
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How do you inject Alprostadil?
- Inject into one cavernosa (one side).
- Duration greater than 1 hour is not expected
- Metabolized quick in cavernosa; limited systemic effects
Administer 5-10mins prior o intercourse. Use aseptic technique.
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Alprostadil ADR
May have local tissue damage with injection, but improves with better technique as they get used to it.
Cavernosal plaques or fibrotic areas that can occur. Don't use injections until they're resolved.
- Local burning discomfort or pain
- Priapism
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Intraurethral injection ADR
Risk for urethral strictures and difficulty voiding.
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Penile prostheses ADR
Inflatable prosthetics that are surgically implanted.
Most common ADR is infection.
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Prostate epithelial glandular tissue
Produces secretions
| Stimulated by androgens (DHT, testosterone)
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Prostate stromal tissue
smooth muscle
| embedded with alpha 1 adrenergic receptors
149
Prostate capsule
fibrous connective tissue
| contains adrenergic receptors
150
BPH summary
Testosterone converted by 5-alpha reductase to DHT; causes prostate enlargement, acne, and hair growth.
Some testosterone is converted to estrogen by aromatase, whcih leads to stromal growth.
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Static factors
Prostate blocks urinary flow, usually due to androgen stimulating the epithelial tissue or estrogen stimulating the stromal tissue.
152
Dynamic factors
Excessive a-adrenergic tone on stromal tissue, bladder neck, or posterior urethra.
Triggered during stress or pain.
153
What medications can cause symptoms of BPH?
- Testosterone replacement, bc the new testosterone substrate is converted to DHT.
- Adrenergic agonists, like pseudoephedrine, ephedrine, phenylephedrine
- Anticholinergics, which decrease the detrusor muscle contraction. Can have urine retained when not fully contracted.
154
Prostatic smooth muscle relaxers
A1 adrenergic antagonists, usually used as a first-line therapy for BPH.
Do not decrease size of prostate, but reduce the adrenergic effects.
155
Reducing testosterone stimulatory effects
5-alpha reductase inhibitors, which decrease the amount of DHT that affects the prostate.
156
Agents relaxing bladder and detrusor muscle:
Antimuscarinics
| Reduces irritable voiding symptoms
157
What is the first line treatment for BPH?
Alpha 1 antagonists
158
What treatment is preferred for cardiovascular patients with BPH or a severely enlarged prostate?
5-alpha reductase inhibitors
159
How do you treat a patient with ED and BPH?
PDE inhibitor, first line
| May not be as effective for BPH, but treats both.
160
How do you treat a patient with mostly irritative symptoms from BPH?
Anticholinergic drugs added to other therapies
Make sure they don't have a high post void residual - otherwise, meds will cause urinary retention.
161
Alpha-1 Adrenergic Antagonists
FIRST Generation
Phenoxybenzamine
- Not used often
- Cause tachycardia and arrythmias
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Alpha-1 Adrenergic Antagonists
SECOND Generation
Prazosin
Terazosin
Doxazosin
Alfuzosin (more used for BPH)
Don't have alpha-2 antagonism... problematic.
Main ADR:
- First dose syncope
- Orthostatic hypotension
- Dizziness
Start low, titrate up over several weeks. Dose at bedtime, so they won't experience syncope or hypotension during the day.
Monitor BP, might have synergy with antihypertensives
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Alpha-1 Adrenergic Antagonists
THIRD Generation
Tamsulosin
Silodosin
Uroselective for alpha-1A adrenergic receptor, which is found in prostate.
Have fewer side effects than first generation. Probably used the most. :)
164
Why do we refrain from using Prazosin for BPH?
Has a lot of CV effects, not recommended
165
Why is Alfuzosin recommended for BPH?
Has lowest incidence of systemic side effects; no dose titration needed.
166
How do you take Tamsulosin?
- Needs to be taken on an empty stomach.
- Avoid in patients with SULFA allergies.
Silodosin not used, bc of the dug interactions and organ impairment.
167
If a patient has ED, but you are treating his BPH - Why do you need to be careful?
PDE inhibitors for ED can have synergistic drops in BP when prescribed with alpha-1 adrenergic antagonists for BPH.
Less likely to see if you use tadalafil and tamsulosin.
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5-Alpha Reductase Inhibitors
Finasteride
Dutasteride
Act on type 2, 5-alpha reductase in prostate to stop conversion of testosterone to DHT. Useful to reduce large prostate size.
May lead to sexual dysfunction, decreases prostate excretions, ED from reduced nitric oxide pathway, and decreased libido.
Pregnancy Category X - Women should not even handle these pills bc of the effects on potential fetus.
169
When do you prescribe 5-Alpha Reductase Inhibitors for BPH?
Good for patients who can't tolerate A1-antagonists. Reduce prostate size by 25%.
CONS:
Slower onset
Higher incidence of sexual side effects
Second line for sexually active males.
170
BPH + ED = PDEI
May counteract effects of alpha-1 antagonists and 5-a reductase inhibitors.
Use Tadalafil most frequently
171
When BPH isn't responsive to treatment, what do you do?
Prostatectomy
172
What medications cause urethral hyperactivity?
TCAs
| Alpha-agonists
173
What medications decrease bladder contractility?
Anticholinergics
TCAs
CCBs
Antipsychotics
174
What's the first line therapy for urinary incontinence?
Non-pharmacologic therapy
Behavioral intervention
Toilet scheduling regimen
Pelvic floor rehab
175
How do you treat urge urinary incontinence?
Anticholinergics - enhance bladder storage
- oxybutinin - used a lot
- tolterodine- used a lot
- tropsium
- solifenacin
- darifenacin
- fesoterodine
ADR: anticholinergic reaction - dry mouth, decreased secretions, cutaneous flushing, blurry vision, hyperthermia
Don't use with urinary retention, gastric retention, myasthenia gravis.
Can cause mental status change in elderly.
176
When do you avoid tolterodine?
Don't give to patients with a creatinine clearance under 10ml/min.
Reduce the dose if patient is on CYP3A4 inhibitors.
177
What's a risk with using oxybutynin for urge incontinence?
May have orthostatic hypotension from alpha blockade.
Comes in XL formulation, first line because it minimizes the side effects (less dry mouth).
Do NOT crush or chew, bc it will break the XR formulation.
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Tropsium
Second generation anticholinergic for urge incontinence.
Poor bioavailabilty, have to take on an empty stomach
Don't give to a renally impaired patient.
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Botulinum toxin A
Potent neurotoxin that paralyzes smooth and striated muscle. Inject into detrusor muscle, to prevent release of Ach.
ADR include hematuria, UTI, retention, dysuria.
Use if failed the other therapies.
180
How do you treat urethral underactivity?
Increase urethral closure with estrogens, which increase proliferation of urethral epithelium.
Alpha receptor agonists
181
What alpha receptor antagonist was removed from the market for stroke risk? Was originally used to treat urethral underactivity.
Phenylpropanolamine
182
Cymbalta
Selective NE reuptake inhibitor. Used to increase urethral tone.
