Professional Documents
Culture Documents
Drugs
Drugs
Drugs
Mechanism
Furosemide
1. Block active transport of ions in the
Ascending Loop of Henle by
blocking the luminal Na-K-2Cl
cotransporter.
2. This leads to less reabsorption of
Ca2+ and Mg2+.
3. Leads to equal proportional loss
of water and sodium, so NO effect
on plasma osmolality.
Torsemide
Name
Mechanism
Hydrochlorothiazide
(HCTZ)
Chlorthalidone
Name
Indapamide
Mechanism
Weak blockade of Na+
reabsorption in the proximal
tubule
Metolazone
Name
Mechanism
Spironolactone
Aldosterone Antagonist in the
principal cells of the Collecting
Tubule
Eplerenone
Amiloride
Traimterene
CA
Name
Mechanism
Acetazolamide
Name
Mechanism
Mannitol
LOOP DIURETICS
Clinical Uses
THIAZIDE DIURETICS
Clinical Uses
1. Hypertension
a. Should get a 10-15mmHg fall in pressure
b. Reduce blood volume (Volume returns to near
normal over 6-8 weeks, but antihypertensive effect
remains)
c. Reduce vascular resistance by relaxation of
arterioles (Na+ increases vessel stiffness, so
reducing Na+ relaxes arterioles)
d. Reduce responsiveness of arterioles to NE (also
because of lower Na+)
e. Combat sodium retention (Many antihypertensives promote Na+ retention, particularly
the vasodilators and alpha-blockers)
f. Potentiate effects of other antihypertensive
drugs when used in combination
g. Used in Blacks (and Non-Blacks) Under 60
2. Diabetes Insipidus
a. Thiazides decrease urine output by about 50%
in these patients
3. Non-emergency edematous states (Cyclical
edema with menstruation)
4. Hypercalciuria
a. Volume contraction caused by the thiazide
diuretics stimulates proximal tubule reabsorption of
Ca2+
THIAZIDE-LIKE DIURETICS
Clinical Uses
When loop diuretics fail, the addition of one of these
agents with the loop diuretic may again produce
diuresis.
POTASSIUM-SPARING DIURETICS
Clinical Uses
1. Heart failure
2. Prevent K+ loss by other diuretics
-Counteract this side-effect of thiazides and loops
-Hyperaldosteroneism syndromes (rare
occurrence)
1. ***GLAUCOMA***
-Decreases production of aqueous humor
-Given topically, so it does not gain access to
systemic circulation in high enough dose to effect
the kidneys.
2. Alkalization of the urine
-Useful in nephrolithiasis, caused by uric acid
and cystine stones, both of which are poorly
soluble in acidic pH.
-Cystinuria is rare (pH has to be raised to 7.5 to
avoid)
-Uric acid stones are more common (pH only has
to be raised to 6-6.5)
-In either condition, too aggressive aliklization of
urine promotes Ca2+ stones.
3. Mountain Sickness (Above 9,000 ft)
-CSF is formed in part because bicarb is secreted
from blood into CSF space, and water follows
-CAIs reduce brain edema in part by CSF
mechanism and in part by causing a systemic
metabolic acidosis (Stimulates deep breathing to
compensate)
-Best tx is to move to low altitude and gradual
acclimation
-If CAIs used, must be given prophylactically
4. Epilepsy
-Tolerance develops quickly
-Typically used in emergency settings for 1-2 days
OSMOTIC DIURETICS
Clinical Uses
LOOP DIURETICS
Side Effects
Contraindications
THIAZIDE DIURETICS
Side Effects
Contraindications
HIAZIDE-LIKE DIURETICS
Side Effects
Contraindications
SSIUM-SPARING DIURETICS
Side Effects
Contraindications
1. Hyperkalemia
-Especially with ACEI's, NSAIDS, and Beta-blockers
-Most common when co-administered with K+
supplement
2. Anti-androgen effect
-Gynecomastia (Typically irreversible)
-Impotence
-Steroid structure leads to competitive inhibition of
androgen receptors
-Stronger with Spironolactone
1.
2.
3.
4.
GI (Nausea/Vomiting)
Dizziness
Leg cramps ("Charlie-horse")
Nephrolthiasis (Triamterene)
Contraindications
1. Metabolic acidosis
-Secondary to reduced plasma bicarbonate
2. Hypokalemia
3. Renal stones (Calcium-containing stones)
4. Hypersensitivity reactions (rare)
-Rash
-Fever
-Bone marrow suppression
Sulfa allergy
OSMOTIC DIURETICS
Side Effects
Contraindications
Notes
1. Standard drug of this
class
2. Loops can increase
fractional Na+ excretion
to 20-25% of glomerular
filtrate and diminish
interstitial fluid
osmolality (countercurrent mechanism).
Notes
Drug Interactions
1. Aminoglycosides
-Ototoxicity
2. Digitalis
(Digoxin/Digitoxin)
-Enhanced efficacy of
digitalis, but enhanced
likelihood of arrhythmias.
3. Sulfonylureas used for DM
Type II
-Hyperglycemia
4. Lithium (Used for bipolar
disorder)
-Na+ is preferentially
excreted
5. NSAIDs
-NSAIDs can blunt the
diuretic response by reducing
glomerular filtration
6. Thiazides
-Diuretic synergism
Drug Interactions
Notes
Drug Interactions
Notes
Drug Interactions
Notes
Drug Interactions
Notes
Drug Interactions
Name
Mechanism
Hydrochlorothiazide
(HCTZ)
Chlorthalidone
Name
Mechanism
ANGIO
Name
Mechanism
Captopril
Enalapril
Lisinopril
A
Name
Mechanism
Candesartan
Valsartan
Losartan
Name
Labetalol
Clevidipine &
Nicardipine
Mechanism
Both alpha and beta blocker
Calcium channel blockers
Nitroprusside
Fenoldopam
Name
Mechanism
Name
Mechanism
Magnesium
Name
Mechanism
Aliskiren (Tekturna)
Name
Propranolol
Metoprolol
Atenolol
Name
Mechanism
Mechanism
Prazosin
Terazosin &
Doxazosin
Name
Clonidine
Mechanism
1. CNS-Active, Alpha-2 Agonist
a. In the periphery, alpha-2 receptor is an
autoreceptor on norepinephrine nerve
terminals, and when stimulated, it decreases
release of norepinephrine.
b. In the CNS, stimulation of alpha-2 receptors in
the brainstem decreases the responsiveness of
the sympathetic system.
c. The brainstem is the main site of action as an
anti-hypertensive.
2. Part of the effect may be via Imidazoline
receptors in the brainstem.
Name
Nitric Oxide (NO)
Mechanism
Direct-acting vasodilator
THIAZIDE DIURETICS
Clinical Uses
1. Hypertension
a. Should get a 10-15mmHg fall in pressure
b. Reduce blood volume (Volume returns to near normal
over 6-8 weeks, but antihypertensive effect remains)
c. Reduce vascular resistance by relaxation of arterioles
(Na+ increases vessel stiffness, so reducing Na+ relaxes
arterioles)
d. Reduce responsiveness of arterioles to NE (also
because of lower Na+)
e. Combat sodium retention (Many anti-hypertensives
promote Na+ retention, particularly the vasodilators and
alpha-blockers)
f. Potentiate effects of other antihypertensive
drugs when used in combination
g. Used in Blacks (and Non-Blacks) Under 60
2. Diabetes Insipidus
a. Thiazides decrease urine output by about 50% in
these patients
3. Non-emergency edematous states (Cyclical edema
with menstruation)
4. Hypercalciuria
a. Volume contraction caused by the thiazide diuretics
stimulates proximal tubule reabsorption of Ca2+
Hypertension
a. Used in Blacks (and Non-Blacks) Under 60
a. Decreases mortality
b. Used for this effect even in the absece of HTN
6. Blacks and Elderly may not respond well
1. Hypertension
a. First-choice agents for Non-Black, Under 60
population
Emergent Hypertension
a. High BP (>180/120) with end-organ damage (i.e.
retinal hemorrhage)
b. Pressure must be reduced quickly
c. Want agents that are very short-acting and given
IV, so if BP is unintentionally reduced too much, stopping
administration allows pressure to rise quickly.
TREATMENT OF PREECLAMPSIA
Clinical Uses
Preeclampsia
a. The sudden emergence of hypertension during
pregnancy.
b. In the worst forms, Eclampsia, the hypertension is so
severe the CNS is grossly affected.
c. Even in preeclampsia, seizures are possible.
RENIN ANTAGONISTS
Clinical Uses
Hypertension
a. Effects are comparable to ACE-Is or ARBs
b. No documented efficacy for improving
morbidity/mortality
BETA-BLOCKERS ("olol")
Clinical Uses
1. Hypertension
2. Used for preventing arrhythmias
a. Especially after Myocardial Infarction (MI)
3. Improve mortality in heart failure
1. Hypertension
a. Not first-line drugs
b. Use in combination with other classes
2. Benign Prostatic Hypertrophy (BPH)
DIRECT-ACTING VASODILATORS
Clinical Uses
1. Angina
2. Pulmonary Edema
3. Hypertension
1. Isosorbide Dinitrate and Hydralazine are used in
combination in some heart failure patients to improve
morbidity and mortality
2. Hypertension
E DIURETICS
Side Effects
1.
2.
3.
4.
When the dose is kept low, side-effects are usually not a problem.
Hypokalemia
Hypokalemic Metabolic Alkalosis
Hyperuricemia
a. Can produce gout attack in patients with a history or family
history of gout.
b. Without such a history, they almost never cause gout.
5. Hyponatremia with or without Hypovolemia (Usually without)
a. Water loss is non-ADH dependent
b. Common in elderly and frail patients
c. Causes weakness (seizures occur in severe hyponatremia)
d. Watch for this in patients who have been stable on Thiazides, but
who for some reason (i.e. viral illness) suddenly decrease their salt
intake.
e. Dizziness and lightheadedness in the first few days of use
(initial response to lowering of plasma Na+ with subsequent
adaptation).
6. Hyperlipidemia (5-15mg/dL)
a. But no increase in morbidity or mortality
7. Hyperglycemia
a. Decrease insulin secretion (May reveal latent DM)
b. Usually clinically important only at high dose
c. Usually reversible with correction of hypokalemia
d. Avoiding this effect is often why another antihypertensive is
added to patient's regimen when a thiazide is already being used to
maximum reasonable dose.
8. Allergic reactions (Sulfa)
a. Contraindicated in Sulfa allergy
9. ERECTILE DYSFUNCTION (Impotence)
-Frequency is even greater than with Beta-blockers
1. ***Cough***
a. Caused by elevated bradykinin in the lungs
b. Dry, non-productive
c. Irritating
d. Dose-related, but seen in the therapeutic range
e. Not seen with ARBs, which do not elevate bradykinin
2. First-dose hypotension
a. Especially if hypovolemic
b. Relatively common if a full dose is given
c. Work dose up gradually
3. Skin rashes
a. Captopril seems worse than others because it contains an SH
group, which has a greater propensity for allergy
4. Acute renal failure in renal artery stenosis
a. Since renin levels are high in renal artery stenosis, ACE-Is will
further dilate the efferent arteriole, resulting in even less pressure in the
glomerulus.
b. Significant danger of acute renal failure because pressure in the
capsule is too low to cause filtration.
5. Angioneurotic edema (Angioedema)
a. Rapid swelling of dermal tissue
b. If in the upper respiratory tract, such as the tongue, it can be lifethreatening.
c. Typically occurs within the first week of therapy, often with first
dose
d. IgG reaction
e. NOT IgE immune-mediated (NOT anaphylaxis)
6. Hyperkalemia
ERGENT HYPERTENSION
Side Effects
Avoid in typical contraindication patients (i.e. asthmatics)
REDATING PREGNANCY
Side Effects
1. Various side-effects
2. ***Rebound hypertension***
a. If the drug is discontinued too rapidly
3. Sleepiness/tiredness
OF PREECLAMPSIA
Side Effects
NTAGONISTS
Side Effects
Contraindicated in pregnancy
CKERS ("olol")
Side Effects
AGONISTS ("zosin")
Side Effects
ALPHA-2 AGONISTS
Side Effects
1. Various side-effects
2. ***Rebound hypertension***
a. If the drug is discontinued too rapidly
3. Sleepiness/tiredness
NG VASODILATORS
Side Effects
1. Hypotension
2. Orthostatic Hypotension
Notes
Notes
Notes
1. No SH groups
a. Less allergy than Captopril
Notes
1. Candesartan:
a. Shorter acting than other ARBs
b. Multiple daily dosing is undesirable
2. Many authorities would prefer ACE-Is or ARBs in
Diabetes.
a. They more selectively reduce pressure in the
glomeruli
b. They dilate the efferent arteriole, thus reducing
pressure in the capsule.
c. This should provide better protection against
diabetes-induced damage of the capsule.
3. Whether Black or not, ACE-Is and ARBs are
the starting drugs for patients with
Hypertension and Chronic Kidney Disease.
a. Prolongs kidney function
b. Most patients with HTN and CKD require
more than one antihypertensive.
c. Many patients also require a diuretic.
d. In chronic renal failure, Thiazides are not
efficacious enough as diuretics; have to use loop
diuretics.
4. ***Don't combine ACE-Is and ARBs***
a. Causes profound hyperkalemia
b. Act through similar mechanisms, so their
mechanisms basically cancel each other out.
Notes
Very short duration of action
Very short-acting (1-2 minutes)
Notes
1. All antihypertensives cross the placenta.
2. Many are known to be teratogenic.
a. ACE-Is, ARBs, and Anti-Renin agents are
contraindicated.
3. Choices are usually:
a. Calcium Channel Blockers (CCBs)
b. Methyl-DOPA (Alpha Methyldopa)
c. Beta-blockers
Notes
1. Magnesium is the drug of choice to prevent
eclampsia.
2. From a treatment standpoint, this condition tends
to occur later in pregnancies, so first therapy is
delivery, if possible.
3. Because the fetus is more developed, a variety of
drug therapies are available.
a. ACE-Is and ARBs are still contraindicated.
Notes
Notes
1. Non-selective beta-blocker
2. Prototype agent of this class
3. Advantages:
a. Cheap
b. Efficacious
c. Extensive history
Notes
1. Prototype
2. Short-acting
Notes
Notes
Although effective in reducing BP, side-effects
generally limit prescription.
1. Long-acting
2. Orally active
Name
Alirocumab
(Praluent)
Ezetimibe (Zetia)
Name
Lovastatin
(Mevacor)
Name
Gemfibrozil
(Lopid) &
Fenofibrate
Niacin
Omega-3 Fatty
Acids (Fish Oils)
LD
Mechanism
1. PCSK9 inhibitor
a. PCSK9 is a protein that binds to and causes degradation of the liver receptor
for low density lipoprotein (LDLR).
b. PCSK9 results in less binding of LDL-C to LDLR, so the amount of plasma
LDL-C increases.
c. PCSK9 inhibitor increases hepatic LDLR, resulting in markedly reduced
LDL-C.
1. Inhibits cholesterol absorption
2. Phytol receptor blocker
a. Blocks cholesterol uptake from diet to any degree desired
b. Inhibits absorption of phytosterols and cholesterol by acting on
intestinal wall receptors
3. Excreted with the bile and acts at the brush border of the small
intestine to inhibit the uptake of dietary and biliary cholesterol into the
enterocytes.
a. Unlike bile acid binders, this drug does NOT decrease absorption of
other fatty substances.
b. Well tolerated
4. No inhibition of cholesterol synthesis in the liver.
5. No increase in bile acid secretion.
Mechanism
F
Mechanism
1. Decreases triglycerides
2. Increases activity of lipoprotein lipase
a. Cleaves free fatty acids from triglycerides more readily
b. Promotes delivery of triglycerides to adipose tissue
3. Decreases VLDL formation in the liver
a. Modest reduction in LDL (May increase in some patients)
b. Rise in HDL
Raises HDL
STATINS
Clinical Uses
Side Effects
Side Effects
1. Frequency of toxicities is generally low, and most are reversible on discontinuation of the
drug.
2. Hyperglycemia and increased HbA1c.
3. Cognitive impairment in the elderly
a. Usually mild and reversible
4. Hepatic damage
a. Frequent (1-2%)
b. Elevated serum hepatic enzymes occur, with the possibility of hepatitis; incidence,
however, is relatively low
c. Contraindicated in hepatic disease
5. Peripheral neuropathies
a. Reversible upon discontinuation of drug
6. Most frequent untoward effect is ***Myalgia*** (1-5%- Muscle pan is common on these
Side Effects
1. Low incidence
2. GI problems
3. Liver enzyme abnormalities
a. Usually transient
4. Myositis
a. Myopathy and Rhabdomyolysis are reported when combined with HMG-CoA
reductase inhibitors
b. Increased myopathy risk at least 10-fold when combined with a Statin
5. ***Gallstones***
a. Increased biliary excretion
b. Do NOT use in patients with gallbladder problems
Name
Mechanism
Aspirin (ASA)
Clopidogrel
(Plavix)
Prasugrel
(Effient)
Ticagrelor
(Brilinta)
Dipyridamole
Abciximab
Tirofiban &
Eptifibatide
Name
Mechanism
Heparin
LMWH
(Enoxaparin,
Dalteparin,
Ardeparin,
Danaparoid)
Warfarin
Warfarin
Rivaroxaban
(Xarelto)
Dabigatran
(Pradaxa)
Name
factors:
a. Thrombin (II)
b. VII
c. X
d. Proteins C and S
3. Without addition of the gamma
carboxyglutamic acid residue, the clotting
factors cannot bind Calcium and are
inactive.
Mechanism
tPA
(Recombinant
Tissue
Plasminogen
Activator, rtPA,
Alteplase,
Activase)
Reteplase
1. Normal fibrinolysis:
a. Clots are dissolved by the action of
the protease Plasmin
b. Plasmin is formed from inactive
Plasminogen by tissue Plasminogen
Activator (tPA)
c. Produces fibrinolysis
d. Fibrinolysis is controlled by fast
clearance of tPA by a circulating inhibitor of
tPA
2. Objective of Thrombolytic Therapy:
a. Dissolve pathological blood clots by
injecting a fibrinolytic enzyme or an
activator of endogenous fibrinolysis without
uncontrolled bleeding.
ANTIPLATELETS (ARTERIAL)
Clinical Uses
ANTICOAGULANTS (VENOUS)
Clinical Uses
1.
2.
3.
4.
5.
1. ***Overlap
with Heparin/LMWH
therapy to avoid long delay in onset
of Warfarin action when switching
from Heparin/LMWH to Warfarin***
2.
3.
4.
5.
6.
THROMBOLYTIC/FIBRINOLYTIC AGEN
Clinical Uses
ANTIPLATELETS (ARTERIAL)
Side Effects
1. Benign
2. GI upset
3. Dizziness and Headache
a. Common untoward effects with vasodilation
b. Relatively low frequency
ANTICOAGULANTS (VENOUS)
Side Effects
1. ***Hemorrhage***
a. Inadvertent overdose
b. Undiagnosed disease site
2. Hematoma at site of injection
3. Thrombocytopenia (Heparin-induced thrombocytopenia; HIT)
a. Platelet-factor 4 is released by activated platlets to block the anticoagulant effects of Heparin.
b. The closer to the clot, the greater the concentration of this factor, which
tends to promote clotting within an appropriate area.
c. These antigen-antibody complexes bind to Fc receptors on adjacent
platelets, causing:
i. Aggregation
ii. Platelet activation
iii. Paradoxical thrombosis
d. Occurs in about 5-7 days after starting treatment.
4. Hyperkalemia due to Aldosterone antagonist
a. Watch for patients on ACE-Is, ARBs, Potassium-sparing diuretics, and
Potassium supplements.
5. Contraindications:
a. Any site of active or potential bleeding
b. Severe HTN or known vascular aneurysm
c. Recent surgery of head, eye, or spinal cord
d. Head trauma
e. Lumbar puncture or regional anesthetic block
f. Tuberculosis
g. Visceral carcinoma
h. GI ulcers
6. Less common side effects:
a. Platelet aggregation
b. Acute Hypersensitivity
c. Alopecia
d. Osteoporosis
e. Priapism
1. ***Hemorrhage***
2. Anorexia, nausea, vomiting, and diarrhea
3. Drug-drug interactions:
a. Warfarin is a classic exaple for many types of drug-drug interaction
b. Inhibition or acceleration of Warfarin metabolism
c. Displacement from plasma protein binding sites (Albumin)
d. Interference with mechanism of action
e. Interference with absorption
4. Skin necrosis
a. Rare
b. Result of extensive microvascular thrombosis within subcutaneous
fat (stasis).
c. Caused by depletion of Protein C and/or Protein S
d. Usually occurs within 3-6 days of initiating therapy with painful
discoloration of breast, buttocks, thigh, or penis
e. Lesions progress to frank necrosis with black eschar
5. Contraindications:
a. Pregnant patients: Congenital abnormalities
b. Unreliable/Uncompliant patient
c. Any recent bleeding
d. Recent head, eye, brain, or spinal cord injury
e. Severe HTN or known vascular aneurysm
4. Skin necrosis
a. Rare
b. Result of extensive microvascular thrombosis within subcutaneous
fat (stasis).
c. Caused by depletion of Protein C and/or Protein S
d. Usually occurs within 3-6 days of initiating therapy with painful
discoloration of breast, buttocks, thigh, or penis
e. Lesions progress to frank necrosis with black eschar
5. Contraindications:
a. Pregnant patients: Congenital abnormalities
b. Unreliable/Uncompliant patient
c. Any recent bleeding
d. Recent head, eye, brain, or spinal cord injury
e. Severe HTN or known vascular aneurysm
***Bleeding***
1. Generally well-tolerated
2. ***Bleeding***
a. As compared to Heparin and Warfarin, no test is available to monitor the
extent of reduced clotting when these agents are used.
b. Occurs in about 10% of patients
ROMBOLYTIC/FIBRINOLYTIC AGENTS
Side Effects
***Hemorrhage***
Notes
1. Generic; OTC
2. Prototype drug
3. Salicylic Acid derivative
1. Prodrug
a. Metabolized in the liver by Cytochrome CYP2, which is
not a frequent target for drug interactions
2. Slow onset (2 hours)
3. Same indications as ASA, but marginally better outcomes
4. Costs more than ASA
1. Prodrug
a. Metabolized in the liver by Cytochrome CYP3A/4
Notes
1. Routes of Administration:
a. Continuous IV
-Often preceded by IV bolus
b. Subcutaneous Minidose
-Post-surgery prophylaxis
c. NOT given IM
-Hematoma potential
d. NOT given Orally
-Too polar to cross into plasma
2. Pharmacokinetics:
a. Onset:
i. IV Bolus- Immediate anticoagulant
ii. SC- Begins in 20-30 minutes
iii. Continuous IV infusion- 2-3 hour delay, unless an
initial bolus injection is administered
b. Termination:
-Metabolized in the liver or excreted unchanged
3. Negatively charged polysaccharide
4. In the native extracted form, it is unfractionated.
5. Treatment of Heparin Overdose:
a. Stop administration
b. Protamine Sulfate
i. Binds to and inactivates Heparin
ii. Must be given slowly IV
c. Infusion of fresh-frozen plasma
1. Route of Administration:
a. Only given orally
2. Out-patient
a. Noncompliant and unreliable patients are NOT good
candidates for Warfarin therapy
3. Pharmacokinetics:
a. Onset:
i. Considerably delayed (36-72 hours)
ii. Pre-existing clotting factors are slowly cleared from the
blood
b. Duration:
i. Prolonged
ii. Proportional to the elimination half-life (~25-60 hours)
c. Distribution:
i. Rapid and complete absorption
ii. Highly fat soluble
iii. 99% bound to plasma albumin (Tremendous potential
for drug interactions)
d. Termination:
i. Delayed (2-5 days)
ii. Long elimination half-life (Liver and kidney)
iii. New, active clotting factor must be synthesized
4. Therapeutic Use:
a. Initial doses followed by maintenance dose and are adjusted
according to PT time (INR)
b. Determine PT time (INR):
i. Prior to starting therapy
ii. Daily until response stablized
iii. Weekly until maintenance dose established
c. Warfarin is often administered concurrently with Heparin until
target INR is achieved, and then the patient is maintained on
Warfarin
5. INR (Interntional Normalization Ratio)
a. Used to standardize PT times between different batches of
Thromboplastin and between different laboratories
b. 1 is normal clotting time
c. 2 is twice as long as normal
6. Treatment of Warfarin (Warfarin Antidote):
a. "Routine" Warfarin Overdose:
i. Hold Warfarin and give Vitamin K replacement
ii. Often continued for several days (even with adequate
Vitamin K present, the body has to synthesize clotting
components)
b. "Superwarfarin" Toxicity (Intentional- Suicide attempt;
Unintentional- Confusion, drug displacement, etc.)
i. Fresh frozen plasma
ii. Packed RBCs
iii. Vitamin K
1. Oral anticoagulant
2. Once daily dosing
3. Predictable pharmacokinetics and limited number of targets in
the clotting cascade, so clotting time does not need to be
monitored.
4. Treatment:
a. No approved treatment for Rivaroxaban overdose
1. Orally active anticoagulant
2. Once daily dosing
3. Treatment:
a. Idarucizumab (Praxibind)
i. Antibody fragment against Dabigatran
ii. Approved for uncontrolled bleeding when
Dabigatran is involved
iii. Adverse reaction comparable to placebo
Notes
Name
Mechanism
NSAIDs
NSAIDs
Name
Mechanism
Aspirin (ASA)
Indomethacin
(Indocin)
Ketorolac (Toradol)
Name
Mechanism
Name
Acetaminophen
(Tylenol)
Mechanism
1. Analgesia
a. PGE2 sensitizes pain nerve endings to the actions of
bradykinin, histamine, and substance P.
b. Mild analgesics, effective against pain of low-tomoderate intensity.
c. NSAIDs can be superior to intermediate efficacy opioids
for relief of some forms of post-operative pain,
particularly when pain is associated with inflammation.
d. Efficacy of pain relief by NSAIDs is lower than with
high-efficacy opioids (NSAIDs + Opioids provide greater
pain relief than intermediate opioids alone).
e. NSAIDs do NOT produce opioids effects of:
a. Respiratory depression
b. Development of physical tolerance/dependence or
use for abuse
c. Production of constipation
2. Antipyretic Effects
a. Temperature control center in the hypothalamus
regulates body temperature
b. Pyrogens (cytokines) from lymphocytes lead to higher
temperature set point (i.e. fever).
c. Heat generation (metabolism) increases and heat loss
(vasodilation) decreases.
d. NSAIDs effectively suppress this response.
3. Anti-Inflammatory Effects
-PGE2 and PGI2 cause vasodilation and are important
mediators of localized erythema and edema in
inflammation.
a. Respiratory depression
b. Development of physical tolerance/dependence or
use for abuse
c. Production of constipation
2. Antipyretic Effects
a. Temperature control center in the hypothalamus
regulates body temperature
b. Pyrogens (cytokines) from lymphocytes lead to higher
temperature set point (i.e. fever).
c. Heat generation (metabolism) increases and heat loss
(vasodilation) decreases.
d. NSAIDs effectively suppress this response.
3. Anti-Inflammatory Effects
-PGE2 and PGI2 cause vasodilation and are important
mediators of localized erythema and edema in
inflammation.
NON-NSAID ANTIPYRETIC/ANALGESIC
Clinical Uses
ERTIES OF NSAIDs
Side Effects
1. GI Irritation Effects (As a salicylic acid derivative, ASA does this more so than
most other NSAIDs):
a. Epigastric distress
b. Nausea
c. Vomiting
d. Microhemorrhage (Doesn't cause gross blood in vomit/Hematemesis)
e. Ulceration
f. Anemia
2. Effects on the Kidney:
a. Little effect in normal subjects
b. In situations where there are high levels of circulating vasoconstrictors
(i.e. compensated CHF, Chronic renal disease), NSAIDs can reduce the renal
blood flow, precipitating acute kidney injury (AKI).
c. Retention of sodium and water. Reduced effectiveness of hypertensive
regimens.
d. NSAIDs and COX-2s should be used with caution in patients with:
i. Reduced renal function
ii. Heart failure
iii. Liver dysfunction
iv. Patients on ACE inhibitors or diuretics, especially elderly patients
3. Overt Toxicity:
a. Increased risk of serious CV events (Class effect: Both selective and nonselective NSAIDs increase risk)
b. Salicylism- Mild Intoxication
i. Nausea
ii. Vomiting
iii. Tinnitus
iv. Hyperventilation
v. HA
vi. Mental confusion
vii. Dizziness
c. Overdose- Acute medical emergency (Children especially vulnerable)
i. Fever
ii. Dehydration
iii. Delirium
iv. Hallucination
v. Convulsions
vi. Coma
vii. Respiratory and Metabolic Acidosis
viii. Death
4. Adverse Effects during Pregnancy
-Avoid use during third trimester unless absolutely necessary
a. Low birth weight
b. Increased perinatal mortality
c. Anemia
d. Antepartum and Postpartum hemorrhage
a. Increased risk of serious CV events (Class effect: Both selective and nonselective NSAIDs increase risk)
b. Salicylism- Mild Intoxication
i. Nausea
ii. Vomiting
iii. Tinnitus
iv. Hyperventilation
v. HA
vi. Mental confusion
vii. Dizziness
c. Overdose- Acute medical emergency (Children especially vulnerable)
i. Fever
ii. Dehydration
iii. Delirium
iv. Hallucination
v. Convulsions
vi. Coma
vii. Respiratory and Metabolic Acidosis
viii. Death
4. Adverse Effects during Pregnancy
-Avoid use during third trimester unless absolutely necessary
a. Low birth weight
b. Increased perinatal mortality
c. Anemia
d. Antepartum and Postpartum hemorrhage
e. Prolonged gestation
f. Premature closure of ductus arteriosus
E COX INHIBITORS
Side Effects
High rates of GI bleeds prevent the drug from being used chronically in arthritis
(Has to be used episodically).
OX-2 INHIBITORS
Side Effects
1 By leaving COX-1 unaffected, a number of benefits are available:
a. Significantly fewer GI ulcers (but by endoscopy, decreased GI bleeding with
Celecoxib is still unproven).
b. Does not impact platelets and bleeding time.
2. Contraindicated in ASA allergy and 3rd trimester pregnancy
PYRETIC/ANALGESIC
Side Effects
Notes
Notes
1. Generic; OTC
2. Prototype drug
3. Salicylic Acid derivative
Notes
Notes
1. A non-narcotic analgesic
2. Mechanism of Acetaminophen
Toxicity:
a. Depletion of Glutathione
b. Major Pathways: Sulfation and
Glucuronidation
c. Minor Pathways: Particularly in
overdose, Glutathione can be
depleted, and hepatic damage occurs.
3. Treatment of Acetaminophen
Overdose:
a. Glutathione does not cross cell
membranes readily.
b. N-acetylcysteine substitutes for
glutathione, and this compound can be
administered to treat toxicity.
GENERA
Name
Mechanism
Opioids
1. Endorphins
a. Usually associated with ***mu*** receptor
activation
b. Derived from Prepro-opiomelanocortin (POMC)
i. Gives met-enkephalin, beta-endorphin, ACTH, etc.
2. Enkephalins
a. Usually associated with ***delta/mu*** receptor
activation
b. Methionine (met-enkephalin) and Leucine (leuenkephalin) containing pentapeptides
c. Derived from Preproenkephalin
i. 6 copies of met-enkephalin and 1 copy of leuenkephalin
3. Dynorphins
a. Usually associated with ***kappa*** receptor
activation
b. Derived from Prodynorphin
i. Dynorphin A and B
4. Endogenous Peptide Activity:
a. Mu- Endorphins > Enkephalins > Dynorphins
b. Kappa- Dynorphins >> All others
Opioids
Name
Mechanism
Morphine
Meperidine
(Demerol)
Methadone
(Dolophine)
Fentanyl
(Sublimaze;
Duragesic)
Name
Mechanism
Butorphanol
(Stadol)
Nalbuphine
(Nubain)
Name
Mechanism
Hydrocodone
Oxycodone
(Percodan;
Percocet;
OxyContin)
Pentazocine
(Talwin)
Name
Mechanism
Buprenorphine
(Buprenex)
Codeine
1. Codeine is a pro-drug.
2. The analgesic effects of the drug come from the slow
conversion of Codeine to Morphine by
demethylation via cytochrome CYP2D6
Name
Mechanism
Tramadol
1. Weak Mu agonist
a. Metabolite is a somewhat more efficacious Mu
agonist than the parent compound
2. CNS Serotonin Releaser
a. In pain management programs, drugs that block
serotonin re-uptake (Older antidepresants) are often the
cornerstones of therapy
3. Norepinephrine re-uptake inhibitor
4. Several other actions as well (NOT an NSAID)
Name
Naloxone (Narcan)
Mechanism
1. Short acting
2. Not absorbed orally, so main use is parenterally
Name
Mechanism
Name
Docusate
Mineral Oil
Mechanism
Facilitates water and fat entering the stool
By coating the stool, holds water inside
Name
Mechanism
Methylnaltrexone
Peripherally active opioid antagonist
(Relistor)
MISCELLANEOUS MU AGENTS
Clinical Uses
OPIOID ANTAGONISTS
Clinical Uses
Useful for opioid overdose (Coma,
Respiratory depression, and Miosis)
1. Opioid treatment programs
a. Poorly tolerated by patients
2. Adjuvant in alcohol treatment
a. Decreases craving
COUGH SUPPRESSORS
Clinical Uses
Cough
constipation***
ii. Tolerance to other effects develops essentially in parallel (equal degree to
sedation, respiratory depression, etc.)
f. Tolerance can be profound (as great as 35-fold)
3. Opioid Dependence:
a. Accompanies tolerance development
ii. Analgesia
iii. Sedation
iv. Vasodilation (Morphine is the most efficacious for this effect)
v. Increased urinary output
vi. Less respiratory depression and miosis than mu agonists
vii. Psychotomimetic responses (Disoriented or depersonalized feelings)
viii. Less involvement in abuse potential and physical dependence
2. Opioid Tolerance:
a. Occurs even with the lowest therapeutic doses and increases as dose and duration
of treatment increase
b. Tolerance, with cross-tolerance, can develop to all opioid agonists (If you become
tolerant to one Mu agonist, you can be cross-tolerant to all Mu agonists)
c. Rate of development varies among agents, but generally develops faster with more
potent drugs and/or higher doses
d. Starts with first dose, but doesn't become clinically relevant for 2-3 weeks
(at normal therapeutic doses)
e. There is specificity of tolerance development:
i. ***No or very little tolerance to miosis and
constipation***
ii. Tolerance to other effects develops essentially in parallel (equal degree to
sedation, respiratory depression, etc.)
f. Tolerance can be profound (as great as 35-fold)
3. Opioid Dependence:
a. Accompanies tolerance development
b. May include both physical and psychological dependence
c. Withdrawal syndrome is seen upon cessation of drug use or upon treatment
with opioid antagonists or mixed agonist/antagonists (Precipitated withdrawal)
d. Withdrawal is extremely unpleasant, but for patients in even relatively normal health,
it should never be life-threatening
4. Opioid Overdose:
a. Primary Triad:
i. ***Lethargy or Coma***
ii. ***Respiratory
Depression***
iii. ***Miosis (Pinpoint Pupils)***
b. Secondary:
i. Hypotension
ii. Hypothermia with cold or clammy skin
iii. Pulmonary edema
iv. Convulsions (Primarily in children)
v. Dilated pupils (Caused by hypoxia, but this is a very near death event; usually
see miosis)
FFICACY MU OPIOIDS
Side Effects
Metabolite (Normeperidine) can cause Seizures if the drug is taken for significant
periods
Highly lipid soluble opioids when given I.V. quickly can cause truncal rigidity
***Dysphoria***
H INTERMEDIATE EFFICACY
Side Effects
Schedule II (High abuse potential) drug
LANEOUS MU AGENTS
Side Effects
1. High doses can cause seizures (Most frequently seen as a consequence of misuse)
2. Physical dependence/withdrawal of the opioid type, but relatively minor in intensity
3. Very little respiratory depression on its own, but enhances that effect in other
respiratory depressants (i.e. alcohol)
4. It has so few typical Mu agonist effects that it is a DEA Schedule IV agent
OID ANTAGONISTS
Side Effects
Precipitates withdrawal syndrome in chonic users of opioids
GH SUPPRESSORS
Side Effects
Overdose can cause respiratory depression
SOFTENING AGENTS
Side Effects
Chronic use may decrease fat-soluble vitamins (A, D, E, & K), which can be treated
with vitamin supplements
Drug Interactions
Drug Interactions
Drug Interactions
Drug Interactions
Efficacy is enhanced by adding
Aspirin or Acetaminophen (Vicodin;
Lortab)
Drug Interactions
Not readily reversible by an opioid
antagonist
Drug Interactions
Many patients are on SerotoninSelective Reuptake Inhibitors
(SSRIs) for the treatment of depression
and/or anxiety. Because Tramadol
increases the release of Serotonin, the
potential exists for provocation of
***Serotonin Syndrome***:
a. Tremor and perhaps clonus
b. Hyperreflexia
c. ***Hyperpyresis***
(Elevated temperature can be deadly)
Drug Interactions
Reverses the action or blocks the
action of agonists
Drug Interactions
When used with opioids, this drug
increases the cough suppressant
effects of the opioid.
Drug Interactions
***Do NOT treat opioid-induced
constipation with Fiber***
Drug Interactions
***Do NOT treat opioid-induced
constipation with Fiber***