Term
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Definition
proximal tubule (urine alkalinizing)
MOA: reversible inhibition of carbonic anhydrase
PD: inhibits reabsorption of HCO3- in proximal tubule
PK: well absorbed orally; effect beings within 30 min and is maximal within 2 hrs; duration=12 hrs; renal secretion via organic acid transporter
AE: metabolic acidosis, hypokalemia, calcium phosphate stones, drowsiness, parethesias and hypersensitivity rxns
ConIn: cirrhosis (impairs NH4+ excretion)
CI: diuretic agent (weak), glaucoma, urinary alkalinization (drug overdose/stones), acute mountain sickness |
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Term
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Definition
loop diuretic
MOA: inhibits Na+/K+/Cl- cotransporter, vasodilation
PD: reduce reabsorption of Na+, K+, Cl-, also Ca2+ and Mg2+; renal vasodilation improves renal blood flow
PK: oral absorption rapid but variable, ½ life short=1.5-2hrs, duration=2-3hrs, renal secretion, oral acid transporter
AE: hyponatremia, hypokalemia, hypomagnesia, dehydration, metabolic alkalosis, hyperuricemia, ototoxicity, hypersensitivity rxns
CI: acute pulmonary edema, edema associated w/ CHF, acute hypercalcemia, acute hyperkalemia, acute renal failure? |
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Term
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Definition
loop diuretic
40x more potent than furosemide
shorter ½ life than furosemide (~1hr)
50% metabolized by liver |
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Term
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Definition
loop diuretic
longer ½ life than furosemide (~3hrs)
longer duration of action (~5-6hrs)
better oral absorption than furosemide
80% metabolized by liver |
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Term
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Definition
loop diuretic
last resort-used only when others exhibit sulfur hypersensitivity
nephrotoxic and ototoxic |
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Term
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Definition
potassium-sparing
MOA: competitive inhibitor of aldosterone; anti-andronergic effects (decrease testosterone synthesis, competitive inhibition of DHT receptor)
PD: mild diuresis due to decreased Na+ reabsorption secondary to aldosterone inhibition, sparing of K+ and H+ also secondary to aldosterone inhibition
PK: slow onset of action-days to take effect, liver metabolism to several active metabolites
AE: hyperkalemia, metabolic acidosis, gynecomastia, impotence, decreased libido, GI upset (peptic ulcers), CNS effects-headache, fatigue, confusion
CI: liver cirrhosis, primary and secondary hyperaldosteronism, hypertension |
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Term
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Definition
potassium-sparing
brand new (expensive) alternative to spironolactone
same action as spironolactone |
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Term
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Definition
potassium-sparing
MOA: blocks Na+ channels in principal cells
PD: blocking Na+ influx decrases driving force for K+ efflux so K+ is “spared”
PK: 1/2 life=21 hrs, secreted into tubule via organic base transporter, excreted unchanged by kidney
AE: hyperkalemia (NSAIDs can exacerbate), GI upset (nausea, vomiting, diarrhea), muscle cramps, CNS effects (headache, dizziness)
CI: edema, hypertension, combo with other diuretics to reduce K+ loss, adjunct for lithium Tx (mania) to decrease diabetes insipidus |
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Term
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Definition
potassium-sparing
MOA: blocks Na+ channels in the principal cells
PD: blocking Na+ influx decrases driving force for K+ efflux so K+ is “spared”; active form can precipitate in the tubules and obstruct flow
PK: ½ life=4hrs, 10x less potent than amiloride, liver metabolizes drug to active form -> secreted using the organic base transporter |
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Term
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Definition
thiazide
MOA: inhibition of Na+/Cl- cotransporter in distal tubule
PD: relatively mild diuresis, increased Ca2+ reabsorption
PK: good oral absorption and renal elimination; ½ life=2.5hrs
AE: hyponatremia and hypokalemia, dehydration, metabolic alkalosis, hyperuricemia, hyperglycemia, hyperlipidemia (increased LDL), weakness, fatigue, paresthesias and hypersensitivity rxns
CI: hypertension, CHF, idiopathic hypercalciuria, nephrogenic diabetes insipidus |
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Term
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Definition
thiazide
10x more potent than hydrochlorothiazide
½ life=4-5hrs |
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Term
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Definition
thiazide
20x more potent than hydrochlorothiazide
½ life=10-22hrs, metabolized extensively by liver |
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Term
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Definition
thiazide
same potency as hydrochlorothiazide
½ life=44hrs |
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Term
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Definition
osmotic agent
MOA: major osmotic effects in proximal tubule and loop of Henle
PD: IV admin causes expansion of intravascular volume, powerful diuretic effect once it reaches kidney
PK: not orally absorbed-must be injected IV to reach kidney, bolus excreted within 30-60min
AE: acute pulmonary edema, dehydration, hypernatremia, headache, nausea, and vomiting
ConIn: CHF, pulmonary edem
CI: increased intracranial pressure, renal excretion of toxic substances (contrast dye, myoglobinemia) |
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Term
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Definition
vasopressin (ADH) antagonist
selective V2 receptor antagonist-renal ADH receptors |
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Term
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Definition
vasopressin (ADH) antagonist
V1A and V2 receptor antagonist-vasodilator and ADH antagonist |
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Term
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Definition
renin inhibitor
lower elevated blood pressure, combo w/ ACE inhibitors, ARBs, aldosterone antagonists -> synergistic effects |
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Term
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Definition
Transmitter depleter
Crosses BBB so central effects as well as depleting NE in SNS
Many SEs including depression
Long acting |
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Term
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Definition
Transmitter depleter
Depletes NE peripherally
Potent
Many SEs |
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Term
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Definition
Centrally-acting alpha-2 agonist
MOA: act on post-synaptic alpha-2A receptors in NTS and Imidazoline receptors in RVLM
SE: sedation, dry mouth, decreased libido, no CNS SEs like alpha-methyl-DOPA, some minimal ortho-hypo, rebound HT (abrupt withdrawal)
USE: drug and nicotine plans
Reduce left-ventricle hypertrophy and lower total cholesterol w/o reducing HDL |
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Term
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Definition
Centrally-acting alpha-2 agonist
MOA: prodrug metabolized to alpha-methyl-NE intra-neuronally -> released as false NT
Activity @ alpha-2A receptor > alpha-1 receptor
USE: decreases SNS, moderately potent anti-HT, can be used safely during pregnancy
SE: dry mouth, nasal congestion, + Coombs test (resolves), sedation, EPS, lactation, decreased libido, ortho-hypotension
Reduce left-ventricle hypertrophy and lower total cholesterol w/o reducing HDL |
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Term
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Definition
Alpha-1 antagonists
MOA: alpha-1 and alpha-2B selective
SE: syncope (during 1st admin and dose increases), minimal ortho-hypo, headaches, priapism
USE: more severe HT, usually in combo
Decreases total cholesterol w/o effect on HDL
Caution: arrythmias -> sudden death |
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Term
Propanolol and Labetolol (nonselective)
Acebutolol, Atenolol, Metoprolol (beta-1 cardioselective) |
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Definition
Beta-blockers
MOA: decrease renin, decrease CO, block presynaptic beta receptors?
May produce rapid drop in BP, or have more slowly developing anti-HT effect
Used for mild to moderate HT, and in combo for more severe HT
SE: myocardial depression, bronchial constriction, potentiation of hypoglycemia, withdrawal rebound, impaired exercise tolerance, increase TGs and decrease HDLs
DI: NSAIDs may block or reduce anti-HT effect of beta-blockers
Not good at preventing stroke like ACE inhibitors, ARBs, Ca2+ channel blockers -> use other first unless pt has cardiac issues for which you need to use beta-blockers |
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Term
| Hydrochorothiazide, Chlorthalidone, Spironolactone, Amiloride |
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Definition
saluretics
MOA: mild diuretic effect, possibly reduce Na+ in VSM to reduce contractility
Very well tolerated, very inexpensive, as good/better than more expensive agents for mild HT and in combo for more severe HT
Chlorthalidone as effective as Ca2+ channel blocker or ACE inhibitor in preventing fatal CHD or non-fatal MI, also more effective in preventing heart failure
No orthostatic hypotension
Many options available
Hydrochlorthiazide: overall anti-HT effect is mild and plateaus (ceiling effect-efficacy maxed out at 15mmHg)
Does not lower BP in normotensive, high sodium intake can reverse anti-HT effects
SE: hypokalemia, hyperglycemia, hyperuricemia, increased cholesterol and TGs |
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Term
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Definition
Overall anti-HT effect is mild and plateaus (ceiling effect)
Does not lower BP in normotensive, high sodium intake can reverse anti-HT effects
SE: hypokalemia, hyperglycemia, hyperuricemia, increased cholesterol and TGs |
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Term
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Definition
Smooth muscle vasodilator
MOA: increased NO, increased K+ permeability
SEs (if used alone): tachycardia, headache, fluid retention, edema, nausea, lupus-like syndrome (resolves with DQ)
USE: generally used with severe HT in combo
Reflexes intact, little or no otho-hypo
-give with beta blocker to counter tachycardia |
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Term
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Definition
Smooth muscle vasodilator
MOA: increased K+ channel opening
USE: very potent, used in severe HT-usually in combo
SEs like hydralazine, also hirsutism and edema
-give with beta blocker and diuretic |
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Term
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Definition
Smooth muscle vasodilator
MOA: metabolized to NO
Very potent, unstable compound, prepared fresh and given IV
SE: headache and nausea
Used for HT crisis, gives moment to moment control of BP, cheap |
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Term
| Captopril, Enalapril, Fosinopril |
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Definition
ACE inhibitors
MOA: prevent conversion of A1 to A2, increase bradykinin, increase PGI and NO
USE: mild or moderate HT, well tolerated
Do not interfere with reflexes -> no ortho-hypotension
SE: cough, bronchospasm, ageusia (mainly captopril), renal complications (long term, kidney excretion), hypotension with volume depletion, fetal mortality (2nd and 3rd trimesters), birth defects seen in 1st trimester, angioedema: rare -> DQ drug, resolves in hours
DI: dangerous hyperkalemia if combined w/ K+ sparing agent, oral contraceptives increase A1 levels, NSAIDs can reduce anti-HT and may increase kidney complications, increase Li2+ retention (bipolar pts)
In heart failure -> slow progession of disease and prolong survival
In diabetics -> decrease development of glomerulopathies
Less effective in African Americans |
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Term
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Definition
Angiotension receptor blockers (ARBs)
In terms of efficacy, patient tolerance, and SEs -> similar to ACE-Is
Advantage: no cough
SE: dizziness, fetal toxicity, hyperkalemia
Less effective in African Americans |
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Term
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Definition
Renin inhibitor
MOA: binds rennin, inhibits cleaving of angiotensinogen to produce angio-1
Does not increase plasma renin activity
BP reduction similar to ARBs
Expect other effects similar to ACE-Is and ARBs (heart, kidney) -> but not known
No or little cough
Long ½ life=24 hrs
SE: rash, increased uric acid , gout (low incidence)
Do not use during pregnany
-sometimes see unexpected beneficial effects or deleterious effects |
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Term
Nifedipine (arteriolar)
Verapamil and Diltiazem (arteriolar and cardiac) |
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Definition
Calcium channel blockers
MOA: reduce VSM tone to decrease PR
Numerous SEs including adverse cardiac events including sudden death (more common in short acting)
Nifedipine-good vasodilation with little cardiac depression, but significant reflex tachycardia
Verapamil and Diltiazem-little reflex tachycardia, but do produce cardiac depression
Works well in African Americans |
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Term
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Definition
PDE5 inhibitor
MOA: prolongs cGMP presence, vasodilation
USE: pulmonary arterial HT
Danger: unexpected presence of NO
Limitation: requires cognitive activation
SE: retinal cGMP |
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Term
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Definition
Phenanthrene (strong agonist)
MOA: natural opioid, affects MOR
PK: hydrophilic, poor lipid solubility, ½ life=2hrs, lower absorption and CNS entry; oral admin-1st pass metabolism, 25% bioavailabilty, less effective than paraenteral but easier
Metabolism: CYP450 -> morphine-3 and morphine-6 glucuronide (2x potent), sustained release formulation used for 8-12hr analgesia
Effects: analgesia, sedation, euphoria (sometimes dysphoria)
USE: MI pain (anxiolytic and sedating), epidural anesthesia (long-lasting), cancer pain, antitussive
SE: respiratory depression -> respiratory arrest, high potential for abuse, prolong labor, miosis, constipation
DI: MAOI, alcohol |
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Term
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Definition
Phenylpiperidine (strong agonist)
MOA: very potent MOR agonist (~100x morphine)
Less nausea, more muscle rigidity
PK: highly lipophilic, faster absorption and CNS entry
Multiple routes available: paraenteral (I.V., epidural, intrathecal; oral mucosa (lozenge lollipop); transdermal patches for 72 hr analgesia
USE: anesthetic (combined with droperidol)-greater hemodynamic stability and no histamine release
Derivatives: sufentanil, alfentanil -> anesthetic adjuvants, epidural
DI: several (aprepitant, antibiotics, diltazem, verapamil) |
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Term
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Definition
Phenylheptalamine (strong agonist)
MOA: potent MOR agonist, racemic mix also blocks NMDAR
USE: analgesia, instead of heroin addiction
PK: better bioavailability than morphine, long-lasting; long ½ life=25-52hrs (strong binding to protein -> accumulation, maintained low conc. when discontinued)
Milder, but more prolonged withdrawal than morphine
If taken as prescribed, minimal euphoria and prevents withdrawal SEs
Risk of opioid OD if taken with heroin |
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Term
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Definition
Phenylpiperidine (strong agonist)
MOA: MOR agonist
PK: less potent and shorter acting than morphine-faster onset (~10min) and duration (1.5-3hr)
Unusual profile compared to morphine-does not prolong labor, not antitussive, less constipation
Not recommended for chronic pain (>48hrs) -> toxic metabolite normeperidine can accumulate -> dysphoria, irritability, tremors, myoclonus, seizures
DI: MAOIs -> cerebral edema (5-HT syndrome)
Anti-muscarinic activity can lead to tachycardia -> not used for MI |
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Term
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Definition
Phenanthrene (mild to moderate agonist)
MOA: weak MOR, but metabolized to morphine (~10% of population have polymorphims of CYP2D6 -> do not efficiently convert codeine to morphine
PK: excellent oral bioavailabilty (~60%) -> less 1st pass metabolism
USE: mild-moderate pain, antitussive; doses exert minimal SEs, histamine release -> itching, usually combo w/ acetaminophen or aspirin for pain relief |
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Term
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Definition
Phenylheptylamine (mild to moderate agonist)
MOA: MOR agonist chemically related to methadone
USE: mild-moderate pain
Orally less potent than codeine-combined with aspirin, effective analgesia; sometimes used because of overconcern of abuse liability of codeine
Adverse interactions with alcohol and sedatives can be fatal
Irritant when IV or subcutaneous; buildup in body -> toxic psychosis, pulmonary edema, cardiotoxicity
Reduced use because other equally efficacious medications available without adverse interactions
Risk of fatal overdose |
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Term
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Definition
Phenanthrene (mild to moderate agonist)
MOA: MOR receptor agonist
USE: Mild-moderate pain
PK: better oral availability than morphine; used in lower doses in combo w/ aspirin or acetaminophen; synergistic pain relief (Percodan or Percocet)
Metabolism by CYP450, CYP2D6 system – potential drug interactions
Widespread abuse of sustained release OxyContin |
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Term
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Definition
Benzomorphan (mixed agonist-antagonist and partial agonist)
MOA: KOR agonist, weak MOR antagonist/partial agonist
USE: moderate pain -> only for pts not using other opioids, ceiling effects for analgesia and respiratory depression
Formulated with naloxone (IV -> prevents euphoria, oral -> doesn’t block)
Less nausea than morphine
SE: sedation, sweating, dizziness, psychomimetic effects, anxiety, increase HR/BP |
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Term
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Definition
Morphinan (mixed agonist-antagonist and partial agonist)
MOA: similar to pentazocine, 30x more potent than pentazocine as an agonist at KOR and 20x more potent as an analgesic
USE: moderate-severe pain
Better for acute than chronic pain |
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Term
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Definition
Phenanthrene (mixed agonist-antagonists and partial agonists)
Similar to naloxone
When admin paraenterally -> eqipotent to morphine and 5x more potent than pentazocine
Fewer psychotomimetic effects than pentazocine, greater MOR antagonist activity |
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Term
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Definition
Phenanthrene (antagonist)
Fast onset (min) and offset (1-2hr)
Multiple injections may be needed to treat OD
Minimal oral bioavailabilty-almost complete 1st pass metabolism
If given alone to opioid-naïve person -> little effect |
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Term
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Definition
Phenanthrene (antagonist)
More potent than naloxone
Longer duration of action (1/2 life=10 hrs, effect for days)
Greater oral bioavail than naloxone
Helpful in drug addiction -> alcohol dependence, reduced heroin-seeking |
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Term
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Definition
(strong agonist)
similar to codeine but with lower affinity for opioid receptors
MOA: unique dual mechanism of pain relief- weak MOR agonist and monoaminergic reuptake blockade
less potential for abuse or respiratory depression
post-operative analgesic equivalent to codeine
cancer pain management-tramadol is moderate agent |
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