PHARMACOLOGY STUDY GUIDE
PHARMACOLOGY
STUDY GUIDE
Cummulative Section
I. Introduction:
Pharmacology: The study of drugs and their interactions
with living systems
Encompasses the study of the physical and chemical
properties of drugs as well as their biochemical and physiological effects.
Clinical
Pharmacology: Study of drugs in
humans (includes study of drugs in
patients as well as healthy volunteers).
DRUGS:
Effectiveness: Most important! Elicits the response for which the drug is
given. Current US
marketing.
Safety:
One that cannot produce harmful effects (there is no such thing as
a SAFE drug)
Selectivity: Elicits only the response for which it is given thus no side
effects (No such thing as a selective drug).
Pharmacotherapeutics:
The medical use of drugs (use to dx, prevent or treat
disease, or prevent pregnancy)
Pharmacokinetics: The study of the movement of drugs through the body.
Four
Basic Processses
1. Absorption (think
stomach)
2. Distrubution (think blood flow)
3. Metabolism (think liver)
4. Excretion (think kidney)
Process is
determined by the concentration of a
drug at the site of action à determines intensity and time course of responses.
Movement through
the body: drugs must cross membranes,
most commonly by dissolving directly into the lipid bilayer of the membrane to
cross (lipid soluble drugs can cross membranes, but polar or ionized cannot).
Other pathways to cross membranes: 1)
passing through the pores
2)
undergoing transport
3)
penetrating membrane directly (common)
Absorption : the movement of a drug from its site of
administration into the blood.
o
Enhanced
absorption occurs by rapid drug dissolution, high lipid solubility, a large
surface area, and high blood flow at the site of administration.
Distribution : defined as the movement of drugs throughout the
body.
o
In most tissues,
drugs can easily leave the vasculature through spaces between the cells that
compose the capillary wall.
o
Many drugs
reversibly bind to albumin. While bound to albumin, drug molecules cannot leave
the vascular system.
Metabolism : Biotransformation. Enzymatic alteration of drug
struction
o
most takes place
in the liver and is catalyzed by cytochrome p450 system of enzymes.
o
Most important
consequence of drug metabolism is promotion of renal drug excretion
o
Other
consequences include à conversion of drugs to less active (or inactive) forms. Conversion of
drugs to more active forms. Conversion of prodrugs to their active forms.
Conversion of drugs to more toxic or less toxic forms.
o
First-Pass
Effect: rapid
inactivation of some oral drugs as they pass through the liver after being
absorbed. Essentially, how much drug is
left available after passing through the liver. Used to determine dosage
and intensity.
Excretion : Most drugs are excreted by the kidney.
o
Renal drug
exretion has 3-steps: glomerular filtration, passive tubular reabsortion, and
active tubular secretion.
o
Drugs that are
highly lipid soluble cannot be reabsorbed back into the kidney
o
Drugs can be
excreted into breast milk.
Bioavailabilty: free-circulating drug system (post-first pass) even
after binding.
Half-Life: Time required for the amount of drug in the body to
decline by 50%. Shorter the half-life, the more frequent the administration.
Time to reach plateau is about 4 half-lives. Drugs with a long half-life may
need a loading dose to reach plateau.
Pharmacokincetic
tolerance: results from a accelerated
drug metabolism.
Pharmacodynamics: What drugs do to the body.
The study of biochemical and physiologic effects of
drugs and molecular mechanisms by which those drugs are produce.
Reducing risk
of adverse interactions: minimize #
of drugs the patient is on. Take a thorough drug history. Adjust dosages when
using an inducing agent. Adjust timing of administration to reduce absorption
problems. Monitor for early signs of toxicity. Be vigilant when a patient is on
a drug with a low therapeutic index.
Pharmacodynamic
tolerance: results from adaptive
changes that occur in response to prolonged exposure. It increases the MEC of a
drug.
Allergic
Drug Reaction: an immune response.
Estimated <10% of adverse
reaction are allergice type. Intensity of reaction is
dependent on degree of immune sensitization not dose size.
Medication Errors: “Any preventable event that may cause or lead to
inappropriate medication use or
patient harm, while the medication is in the control of the healthcare
professional, patient, or consumer”
Medication
Errors : Major cause of morbidity and
mortality. Can be made by
many people, incuding pharmaceutic workers,
pharmacists, physicians, transcriptionists, nurses, patients and patients
families.
3 Common
types of Fatal Med Errors : Human
factor, Miscommunication,
Confusion caused by similarities in drug names.
(Others include packaging, formulations, delivery devices, labeling and
reference materials).
Effective
measures for reducing med Errors: using safety checklist for high alert
drugs. Replacing handwritten med orders with
computerized order entry system. Having a clinical pharmacist accompany ICU
docs on rounds. Avoid error-prone abbreviations. Use a computer bar-code
system.
Therapeutic
Index: (LD50: ED50) A measure of a drug’s safety.
Drugs with a high
TI are presumably safe.
FDA Drug Approval Process:
Preclinical
testing (in anmials)
Toxicity
Pharmacokinetics
Possible
Useful effects
|
Investigational
New Drug (IND
|
Clinical
Testing (in humans)
Phase I
subjects: normal
volunteers ; tests: metabolism and
biologic effects
|
Phase II
subjects: patients ; tests: therapeutic utility and dosage
range
|
Phase III
subjects: patients ; tests: safety and effectiveness
|
Conditional Approval of New Drug
Application (NDA)
|
Phase IV: postmarketing Surveillance
II. CNS:
v Except for
local anesthetics, all neuropharmacologic drugs act by altering synaptic
transmissions. High selectivity.
v Three
different effects of transmitter synthesis:
o
Increase transmitter synthesis - storage
vesicles will contain transmitter in abnormally high amounts.
o
Decrease transmitter synthesis – cause the transmitter content of vesicles to decline.
o
Synthesis transmitter molecules that are more
effective than the natural transmitter itself – converts to a “super” transmitter.
Peripheral Nervous System: two major divisions – A) Autonomic Nervous System
B) Somatic Nervous System
Employs
three major transmittors à ACh, Norepi, Epi
Autonomic Nervous System: regulates many
involuntary processes
two major divisions – A)
Parasympathetic “housekeeping”
B) Sympathetic “fight or flight”
Parasympathetic
Nervous System (functions):
Slowing heart rate
Increased
gastric secretion
Emptying
of the bladder
Emptying
of the bowel
Focusing
the eye for near vision
Constricting the pupil
Constricting the pupil
Contracting
bronchial smooth muscle
Sympathetic Nervous System (functions):
Regulating the cardiovascular system
Maintenance
of blood flow to the brain
Redistribution of blood flow during
exercise
Compensation for loss of blood, primarily
by causing vasoconstriction
Regulating
body temperature
By
regulating blood flow to the skin
Sympatietic nerves to sweat glands
promote secretion of sweat, thereby
helping the
body cool
By inducing erection of hair,
sympathetic nerves can promote heat
conservation
Implementing
the “fight-or-flight” reaction
Increases
heart rate and blood pressure
Shunts blood away from skin and viscera
and into skeletal muscles
Dilates
the bronchi to improve oxygenation
Dilates the pupils (perhaps
to enhance visual acuity)
Mobilizing stored energy, therby providing
glucose for the brain and fatty
acids for muscles
Parkinson’s
Disease: neurologic
disorder characterized by tremor at rest, rigidity, postural
instability and bradykinesia.
Primary pathology is a degeneration of neurons in the
substantia nigra that supply dopamine to the striatum. Result is an imbalance
between dopamine and ACh. Disorder of the extrapyramidial system. Disrupts the
balance between dopamine and ACh à dopamine is inhibited, ACh “runs amuck” [normally dopamine regulates ACh which
controls mov’ts] Anticholinergics used to primarily treat tremors;
Levodopa is most common treatment of the disease. COMT inhibiters prevent
breakdown of levodopa.
Classes of
drugs to treat Parkinson’s:
Anticholinergics – block the cholinergic
receptors
Dopaminergics – convert to
dopamine
Dopamine Agonists – stimulate the dopamine
MAO-B Inhibitors
- inhibit MAO-B enzyme which interferes
with dopmaine
COMT Inhibitors – which inbits
the COMT enzymw that maturates dopamine
v Levodopa/Carbidopa [Sinemet]: produces symptoms by promoting
synthesis of dopamine in striatum. Follws via active transport into the brain
across the BBB. Levodopa is needed because dopamine cannot cross into the brain
alone – decarboxylase convert levodopa into dopamine in the brain. Relieves symptoms
by undergoing conversion to dopamine in surviving nerve terminals in the
striatum. Carbidopa enhances the effects of levodopa by preventing the
decarboxylation of levodopa in intestine and peripheral tissues. Since
carbidopa cannot cross the BB, it does not prevent the conversion of levodopa
to dopamine in the brain.
Class: Dopamine agonist
Indication: Goal of treatment is to improve the patient’s ability
to carry out ADLs, does
not
cure but delays the progression.
Pharmacodynamics/Kinetics: variable duration 6-12hrs. Administered orally and
undergoes rapid absorption from small intestine. Only
a fraction of each dose reaches the brain. Levodopa crosses by active
transport.
Adverse
Effect: Nausea, vomiting,
dyskinesias, cardiovascular (orthostatic hypotension,
arrhythmia, chest pain, hypertension, syncope,
palpation), psychosis, darkening sweat and urine.“On-Off” phenomenon.
Drug Interactions: MAOIs (interaction causes hypertensive crisis),
antipsychotics,
anticholinergics, high protein meals (competes with
protein)
Combination with carbidopa allows levodopa dose to
reduce by 75%, which can
reduce some side effects
Contraindications: hypersenstivity to levodopa, carbidopa or any
component of the forumlation
Precautions: pregnancy (c), diabetes, glaucoma, melanoma (or
history of), renal/hepatic/cardiac
disease, respiratory disease, MI, convulsions, peptic
ulcer, lactation, depression.
Alzheimer’s
Disease: A relentless
illness characterized by progressive memory loss, impaired thinking,
neuropsychiatric symptoms, and inability to preform routine tasks of daily
living. Characterized by neuritic plaques, neurofibrillary tangles, and
degeneration of cholinergic neurons in the hippocampus and cerebral cortex.
Major risk
factors: known risk factor is
advancing age. Symptoms usually begin after
after
age 65. Family history is the only other known risk factor.
Treatment: Donepezil [Aricept] –
cholinesterase inhibitors; increases the availability of ACh at
the cholinergic synapses and thereby enhance
transmission by cholinergic neurons that have not yet been destroyed by
Alzheimer’s. Produces modest improvement in cognition, behavior and function in
30-60% of patients. Does not cure, but slow progression for a time.
Choice drug for mild to moderate AD. Well absorbed by oral administration,
metabolized by hepatic enzymes, elimination is mainly urine and partly in the
bile. Prolonged plasma half-life (about 60hrs), administered once a day. Adverse Effects: GI upset, nausea,
dizziness, headache, diarrhea, bronchoconstriction, use with caution in COPD
and asthma patients. Interactions:
drugs that block cholinergic receptors can reduce the effects.
Memantine [Namenda] – 1st representative of new class of
drugs. Works on the NMDA receptor antagonists. Approved for moderate to severe
AD, only modest beneficial effects. Appears devoid of significant adverse effects; constipation,
dizziness, confusion, headaches. PO , well absorbed. Largely excreted unchanged in urine.
Long half-life (60-80hrs). Plasma levels peak (3-7hrs). Interactions: undesirable effect when combination with other NDMA
antagonists.
Seizures:
Intiated by
discharge from a group of hyperexcitable neurons, called a focus.
Partial seizures:excitation undergoes
limited spread from the focus to adjacent cortical areas
Generalized seizures: excitation spreads
widely throughout both hemispheres of the brain
Antiepileptic drugs: act through four basic mechanisms
1) blockade of sodium channels
2) blockade of calcium channels
3) blockade of receptors for glutemate
4) potentiation of GABA
Traditional AEDs à well established, extensive experience, less expensive, less tolerated,
less safe
Newer AEDs à introduced in late 1993 or later, equally good but less established,
safer,limited
interactions, less extensive, more
expensive
Goal of Epilepsy: goal is reduction
seizures to an extent that enables the patient to live a normal or
near-normal life. Complete
elimination of seizures may not be possible without cauing intolerable side
effects.
Selective per seizure: Many AEDs are
selective for particular seizures, and hence, successful
treatment depends on choosing the
correct drug.
Withdrawal: must be done very gradually because most cause
CNS depression and abrupt
withdrawal can trigger Status Epilepticus.
v
Phenytoin [Dilatin]: active against partial seizures and tonic-clonic. Not
active against absence seizures. Capacity of liver to metabolize is limited, so
doses only slightly greater than those needed for therapeutic effects can push
phenytoin levels into toxic range [small
therapeutic range]
Therapeutic range: 10-20mcg/ml
Levels
> 20mcg/ml results in CNS toxicity. S/S include: nystagmus, sedation,
ataxia, diplopia, and
cognitive impairment. Adverse effects: also includes gingivial
hyperplasia in 20% of patients
Class:
Antiarrhythmic agent, anticonvulsant (suppresses Na+ influx)
Indication:
active against partial seizures, as well as primary tonic-clonic
Mechanism:
Causes selective inhibition of sodium channels, but slowing the recovery of Na+
channels from inactive state to active
state.
Pharmacokinetics: Absorption varies,
liver has a limited capacity to metabolize. Small changes
in dose can disproportionately affect
serum levels à small increases cause toxicity,
small decreases cause therapeutic failuer. Half-life varies.
Adverse Effects: CNS effects
(nystagmus, diplopia, ataxia), Gingival hyperplasia, skin rash,
hypotension, dysrrhythmias.
Valporic Acid [Depakote]: Very broad spectrum antiepileptic.
Active against parital seizures and most generalized seizures, including
tonic-clonic, absence, atonic and
myoclonic. Can cause potentially fatal liver injury. Can also cause potentially
fatal pancreatitis. Therapeutic level: 50-100mcg/ml
III. Cardiovascular Thereapies : CAD, CHF, HTN, Cholesterol,
Anticoagulation
Remodeling: theprocess in which the ventricles dilate and
hypertrophy, thus increasing
wall stress and reducing left ventricular ejection
fraction.
Preload:
the work imposed on the heart before the contraction begins. The amount of
blood pumped with each beat.
Afterload:
the pressure that the heart muscle must generate to move blood into the
aorta.
The work presented to the heart after contraction has
finished.
Starling’s
Law: SV = CO x HR
Ejection
Fraction: direct indicator of left
ventricular function [the amount of
blood pumped at of the left ventricle into systemic
system]. 65% or greater EV is normal.
ACE-Inhibitors: Affects
the angiotensin-aldosterone system. Used in the treatment of HTN, HF,
and diabetic neuropathy. Reduces levels of angiotensin
II [a potent vasoconstrictor] – this causes vasodilation, reduces blood volume,
reduces cardiac and vascular remodeling, causes potassium rentention and fetal
injury; it also increases levels of bradykinin[vasodilation] – which results in
vasodilation, cough and angioedema (rare). Only med that improves ventricular function (works on cardiac afterload
reduction, which increases cardiac output). Adverse
effects: hypotension, persistent cough, hyperkalemia, renal failure, Fetal injury,
angioedema. Contraindicated:
pregnancy (2nd or 3rd trimester) [ex: Captopril, Lisinopril]
ARB’s: Similar to ACE except there is no cough. Work by blocking angiotension,
but do not
work on bradykinin so there is no cough or
hyperkalemia. These decrease the release of aldosterone and increase renal
excretion of Na+ and water. [ex:
Losartan, Valsartan]
Calcium-Channel
Blockers: Prevent calcium from entering cells. When calcium channels
are
blocked, contraction will be prevented and
vasodilation will result. In the heart it causes myocardium (decreases
myocardial contractility), SA Node (reduces heart rate) and AV Node (decreases velocity
of conduction through the AV node). In stable angina, CCB work to decrease
oxygen deman by dilating arterioles, which decrease afterload, and by
decreasing heart rate and contractility.
Adverse effects: constipation, peripheral edema, hypotension, AV-block.
Used as first line therapy in African-Americans because Beta-Blockers are ineffective.
Nitrates: Indicated
for HTN, Angina, HF, and MI.in stable angina they decrease oxygen demand
by dilating veings, which decreases preload. In
variant angina they increase oxygen supply by relaxing coronary vasospasm.
Lipid soluble, administration PO / SL.
Metabolized in the liver. Adverse
effects: postural hypotension, relflex
tachycardia [ex: nitroglycerin]
· In event of CP: take one tablet, wait 5 min, another
tablet, if no relief
call 911, take a 3rd tablet in five minute
while waiting for paramedics
Statins: (HMG-CoA reductase
inhibitors)Reduction of LDL cholesterol,
possible elevation of
HDL cholesterol. Nonlipid beneficial cardiovascular
actions reduce the risk of CV events,
increased bone formation. Mechanism of reducing cholesterol is complex and
dependent non the increasing of LDL receptors on hepatocytes. Adverse effects: headache, rash, GI
upset, myopathy/rhabdomyolysis(rare), hepatotoxicity (rare). Interactions: Fibrates
and ezetimibe, Agents that inhibt CYP3A4.
Contraindicated: Pregnacy [ex:
Atrovastatin (lipitor), Simvastatin (zocor)]
· FYI: when a person comes into the ED with an MI,
they are immediately placed on Zocar to lower
LDL
Diuretics: Drugs that can increase the output of urine. Used for
the treatment of HTN,
mobilization of edematous fluid, prevention of renal
failure. They work by blocking Na+ and Cl- reabsorption. By blocking the
reabsorption of solutes, diurectics create osmotic pressure within the nephron
that prevents the passive reabsorption of water. The increase in urine flow is
directly related to the amount of Na+ and Cl- reabsorption it blocks. Drugs
whose site of action is early in the nephron block the great amount of solute
reabsorption and produces the greatest amount of diuresis. Adverse effects: hypovolemia, acid-base imbalance, disturbance
of electrolyte levels.
LOOP
DIURECTCS: most
effective diurectics available. Produce more loss of fluid and electrolytes.
Site of action: Loop of Henle. [ex:
Furosemide (Lasix)] THIAZIDE
DIURECTICS: Similar effects to loop diuretics. Increases renal
excretion of Na+, Cl-, K+ and water. Elevate plasma levels of uric acid and
glucose. Diuresis is considerably lower than loop diuretics. [ex:
Hydrocholorthiazide (HCTZ) ] POTASSIUM-SPARING
DIURETICS: produce a modest increase in urine produce a substantial decrease in K+
excretion. Blocks the actions of aldosterone in the distal nephron: causing retention of K+ and increased
excretion of Na+. [ex:
Spironalactone (Aldectone)].
Beta Blockers: Beta blockers work to balance oxygen demand by
slowing the heart rate and
contractility,
which allows for a more effect contraction, reducing cardiac output.
They also
can suppress reflex tachycardia. Long term use reduces peripheral vascular
resistance. The major consequences
of beta blockers include: 1) reduced heart
rate 2)
reduced force of contraction and 3)
reduced velocity of impulse of conduction
through AV-node. They are
used int the treatment of HTN, but also HF, hyperthyroid,
migraines
and stage fright. Biggest side effect is fatigue, these patients are very
hypotensive.
Adverse effects: Bradycardia, AV-hear
tblock, HF, bronchoconstriction,
CNS
effects. They can mask the signs of hypoglycemia so routine blood sugar levels
should be
taken. [ex: metoprolol (lopressor), propranolol (inderol)]
Vasodilators: Indicated for HTN, angina, HF and MI. Adverse effects: postural hypotension,
reflex
tachycardia. [ex: Hydralazine
(Apesoline)]
v
Furosemide [Lasix]: Inhibits
reabsorption of sodium and chloride channels at proximal and distal tubule and
in the loop of henle.
Class: Loop diuretic
Indication: Treatment/management of pulmonary edema, edema
in CHF.
Hepatic disease, nephrotic syndrome,
ascites, HTN
Pharmacokinetics: Onset:
diuresis PO 30-60mins IM 30mins IV 5mins
Peak: PO 1-2hrrs.
Duration: PO 6-8hrs IV 2hrs. Absorption: PO 60% -67%. Protein binding >68%. Metabolism:
minimally hepatic. Half-life in normal renal function: 0.5-1.1hrs, ESRD 9hrs.
Excretion: Urine within 24hrs (PO 50%), feces
as unchanged drug. Crosses the placenta and is excreted into breast milk.
Adverse Effects: Headache, fatigue, acute hypotension,
Ototoxicity, electrolyte
disturbances, acid-base imbalances, renal
failure, hypergylcemia.
Precautions: Pregnancy (c), diabetes,
dehydration, severe renal disease,
cirrhosis, ascites.
Contraindications: Hypersensitivity to
sulfonamides, anuria, hypovolemia,
infants, lactation, electrolyte depletion.
v Digoxin [Digitek]: Indicated for HF and control of
dysrhythmias. When used for HF, it can reduce symptoms, increase exercise
tolerance and decrease hospitalizations. However in women, may shorten life.
Exerts a positive inotropic aciton on the heart which increases the force of
ventricular contraction and increase CO. Kickstarts the heart. Typically given with a loading dose of
1.25mg in 4 doses within 24hours. Hold digoxin if HR<50. You would expect to
give a PT presenting with CHF in the ED a loading dose.
Therapeutic levels: 0.8 - 2
Class: Antiarrhythmic agent, Cardiac glycoside
Indication: Treatment of CHF, and to slow ventricular rate in
tachyarrhythmias
such as Afib, Aflutter, and supraventric
tachyc; cardiogenic shock.
Pharmacokinetics:
PO onset: 30m-2hrs, peak 6-8hrs, duration 3-4days
IV onset: 5-30mins, peak 1-5hrs, duration variable.
Absorption is by passive nonsaturable diffusion in the upper small intestine. Distribution in normal renal function is
6-7L/kg, in chronic renal failure its only 4-6L/kg. Extensive peripheral tissue
distriubtion. Hyperkalemia/hyponatremia causes a decreased digoxin distribution
to heart and muscles. Metabolism is via sequential sugar hydrolysis in stomach
or by reduction of lactone ring in intestinal bacteria. Metabolism is reduced
in CHF. Bioavailability is 70-80% tablet. Half-life depends on age, renal and
cardiac function. Half-life elimination
is about 1.5 days, excreted via urine.
Adverse Effects: Headace, fatigue,
drowsniess, 1st or 2nd degree heart block
(wenckebach). Dysrrhythymias, hypotension, nausea,
vomiting. Dig-toxicity: extreme vomiting.
Precautions: Pregnancy (c), renal
disease, acute MI, AV-block, severe
respiratory disease, hypothyroidism, geriatric sinus
nodal disease, lactation, hypokalemia.
Contraindications: Hypersensitivity to digoxin, Vfib, ventricular
tachycardia,
carotid sinus syndrome, 2nd or
3rd degree heart block.
Interactions: Beta-Blockers increase
bradycardia,
Diuretics/corticosteroids/certain antibiotics cause
hypokalemia and dig toxicity. Thiazides and IV calcium cause hypercalcemia, dig
toxicity.
v Warfarin [Coumadin]: Goal is to prevent thrombosis without inducing spontaneous
bleeding. Gold standard treatment for Afib. Baseline assessment: Medical
history, VS, INR, CBC, History of alcohol abuse. Give orally and monitor INR closely. Adverse effects: Bleeding and hemorrhage.
· Long-term treatment decisions: typically standard of
care, keep on coumadin for 6 months, then discuss pros & cons, if goes off
and has a recurrence then back on for life.
· Antagonist of vitamin K. Blocks four clotting factors
that are dependent on vitamin K. Overdose can be overcome with vitamin K.
· Binds 99% with albumin. This binding provides basis of
several drug interactions
·
INR is a blood test that measures coumadin levels.
Therapeutic ranges: 1.6 – 2.0 joint
replacement/abdominal surgery
2.0–3.0 Afib, CVA, recurrent DVT , PE
2.5 – 3.5 Mechanical Valve Repair
Class: Anticoagulant
Indication: prophylaxis and
treatment of thromboembolic disorders and
embolic
complications arising from atrial fibrillation. Adjunct to reduce risk of
systemic embolism after myocardial infarction.
Mechanism: Supresses coagulation by acting as an antagonist of
vitamin K. By
antagonizing
vitamin K, warfarin blocks the biosynthesis of vitamin K-dependent clotting
factors (VII, IX, X and prothrombin), which reduces fibrin production.
Pharmacokinetics: Binds 99% to
albumin in the blood. Unbound molecules
can readily cross membranes (including placenta and
milk-glands). Undergoes hepatic metabolism and is excreted in urine and feces.
Onset: 24-72hrs, peak (full therapeutic effect) 5-7days, duration 2-5 days,
absorption: rapid and complete, distribution: 0.14L/kg, half-life elimination
20-60hrs [1.5-2days].
Adverse
Effects: Bleeding and hemorrhaging
Precautions:
Breast-feeding
Contraindications:
pregnancy (X), hemorrhagic tendencies, spinal
cord/eye/brain surgeries.
Interactions: drugs that increase
the effects of warfarin [ex: aspirin,
sulfonamides, acetaminophen], drugs that promote bleeding [ex: aspirin, heparin,
glucocorticoids] and drugs that decrease
effects of warfarin [ex: phenytoin, rifampin, vitamin K, OCPs, carbamazepine,
phenobarbital]
v Heparin: rapid acting anticoagulant. Unable to cross membranes (including GI
tract), must be given subQ or IV. Goal is to prevent thrombosis without
spontaneous bleeding. Must guac stools everytime PT moves bowels. Assess BP,
HR, CBC, platelet counts, PTT. Before you start heparin you want to you normal
clotting abilities. Heparin specifically enchances the activity of antithrombin,
which is a protein that inactivates thrombin and factor Xa [production of
fibrin becomes reduced and clotting is suppressed].
·
Preferred
anticoagulant for use during pregnancy
·
aPTT = activated partial thromboplastin time (IV
heparin monitoring)
·
normal
value is 40secs for someone not heparin
·
No
monitoring for subQ
Therapeutic Ranges: 60-80secs
Levels
<60: dosage needs to increase
Levels >80: dosage needs to
decrease
Class: Anticoagulant
Indication: prophylaxis and treatment of thromboembolic disorders
Mechanism: Inactivates antithrombin which supresses thrombin and
factor Xa
leading to a reduction in the production
of fibrin.
Pharmcokinetics: unable to cross
membranes, cannot be absorbed orally. Must
be given IV or subQ. Does not enter placenta or breast
milke. Binds nonspecifically to plasma proteins. Plasma levels of free heparin
can be IV or subQ. Hepatic metabolism,
renal excretion. Half-life is short (1.5hrs).
Adverse effects: hemorrhage and
thrombocytopenia
Precautions: People who have a high
likelihood of bleeding, severe disease of
the liver and kidney.
Contraindicated: thrombocytopenia and uncontrolled bleeding. Also in people
post-surgery of eye, brain or spinal cord.
Interactions: Any drugs that depress platelet function (ex:
aspirin) will weaken
this defense and must be employed with
caution
Low-weight Molecular Heparin [Lovaenox
and Fragmin]: unfractionated
heparin. Advantages are that they are given on a fixed
schedule, may be used at home, are dosed once a day, based on body weight. No
monitoring necessary, SubQ administration, more expensive.
v Spironolactone [Aldactone]: Blocks the actions of aldosterone in the distal
nephron. By inhibiting aldosterone there is a retention of potassium and an
excretion. Diuresis is minimal.
Class: potassium-sparing
diuretic
Indication: Primarily
hypertension and edema, CHF, hypokalemia, ascites or
liver disease accompanied by edema or
ascites.
Pharmacokinetics: Onset 24-48hr, peak 48-72hr, metabolized by
liver,
excreted in urine, crosses placenta.
Protein binding 91% - 98%. Hepatic
metabolism. Half-life elimination 78-84hr.
Excretion urine and feces.
Adverse Effects: Hyperkalemia, which can cause fatal dysrhythmias.
Discontinue if K+ rises above 5 or if
signs of hyperkalemia develop.
(injection of insulin can help reduce K+
levels)
Precautions: dehydration, liver
disease, renal impairment, electrolyte
imbalances, metabolic acidosis, lactation
Contraindications:
pregnancy (D), hyperkalemia, renal
disease, anuria,
Hypersensitivy.
Interactions: Thiazide and loop
diuretics counteract potassium-wasting effects.
ACE-inhibitors and other drugs that raise K+ levels. Never combine
with K+ supplements or salt substitutes.
IV. Diabetes and Thyroid
Thyroid
hormone: stimulates energy use
(metabolism), stimulates heart, promotes
growth and development.
Feedback
Loop : TRH à TSH à TH [amount of TH shuts on or off TRH/TSH]
Increased TSH : hypothyroidism. (the anterior pituitary releases increased TSH to
stimulate thyroid gland to decrease TH in blood)
Decreased TSH: hyperthyroidism.
(too much T3 and T4 in circulation which is an
inhibitor of release of TSH)
Hypothyroidism: slows body down. Gain weight, fatigue, lethargy,
puffy face, britle
hair, heart rate lowered.
v Levothyroxine: Thyroid hormone replacement therapy. Converted T3 in the
body. Highly protein-bound. Prolonged half-life (7 days). Requires one month to
reach plasma levels. Structure is identical to natural TH.
· Monitor serum TSH levels.
· Normal TSH levels 0.3 – 6.
· Less than
0.3 is hyper; greater than 6 is hypo
class: thyroid hormone-replacement
indication: hypothyroidism, myedema coma, some thyroid cancers
action: increases metabolic rate, controls protein syntehsis,
increase CO, renal blood flow, and oxygen consumption. Increases body temp,
blood volume, growth development. Exact mechanisms are unknown.
pharmacokinetics:
oral onset 3-5days, IV onset 6-8hrs,
duration 1-3wks, peak 6-8wk. Oral absorption is erractic, take in morning
30mins before meals to enhance absorption. Protein binding >99%, hepatic
metabolism. Half-life 3-4 days. Doesn’t readily cross placenta, minimal amounts
in breast milk. Excreted in feces via bile.
Adverse
Effects: Thyroid storm, anxiety,
insomia, tremors, headache, tachycardia, cardiac arrest, palpitations,
diarrhea, heat intolerance, weight loss [similar to hyperthyroidism]
Precautions:
pregnancy, geriatric, angina, lactation,
renal insufficiency, diabetes, CAD, hypertension, ischemia.
Contraindications: Adrenal insufficiency, recent MI, alcohol
intolerance, thyrotoxicosis
Interactions:
Iron supplements [give 2 hrs after
dosage], maalox, calcium-supplements (tums), questran Reduce drug absorption Coumadin, catecholimines (dopamine, epi),
zoloft, tegretal, dilantin Accelerate
effects of drug.
Thyroid storm: critical, life-threatening,
hyperthermia, tachycardia, restlessness,
afitation and tremor. Extreme exacerbation
of thyrotoxicosis.
Diabetes I: beta-cell destruction usually leads to absolute
deficiency. Polyuria,
polydipsia,
polyphagia, weight loss. Usually
juvenile, abrupt onset. Insulin is sole treatment for survival.
Diabetes II: insulin-resistance
and ineffective insulin secretion which reduces
binding of insulin to receptors, reduces receptor
number and reduces receptor responsiveness. Eventually hyperglycemia leads to
destruction of pancreatic beta-cells and insulin production and secretion
decline. Usually over 40, gradual onset, family history, asymptomatic,
frequently obses, excerise and lifestyle changes are essential
Short-term complications: hyper-, hypo-glycemia, ketoacidosis
Long-term complications: Micro [renal, retino, nephro] and macro
[cardio]vascular complications.
· Insulin is
required and only treatment for gestational diabetes (pregnancy).
· HgA1C < 7 à 3 month-look back
blood glucose control
· Proper diet: carbs + monosaturated fats 60-70% of energy intake
Protein 15-20% of energy intake
Polysaturated
fats 10% of daily energy intake
Saturated fats <10% of energy intake
Cholesterol limited to 300 mcg/day
v Rapid-acting [lispro/humalog]: Onset
= 15 – 30mins
Peak =
30mins – 2.5hrs
Duration = 3 – 6.5 hrs
Eat within 15
mins of administration. Feed insulin.
v Short-Acting [regular/Humalin R]:
Onset : 30mins – 60mins
Peak : 1 – 5hrs
Duration : 6 -10hrs
Only type of insulin that can be given
IV
v Intermediate-Acting [NPH/Humalin
N]: Onset : 60 – 120mins
Peak : 6 – 14hrs
Duration: 16 – 24hrs
Clear to
cloudy when mixing, roll the vial
v Long-Acting [Lantus/Glargine]:
Onset: 70mins
Peak: none
Duration: 24hrs
Never mix Lantus with anything
For all insulins monitor for signs and
symptoms of hypoglycemia
v Metformin [Glucafage]: oral agent for type II diabetes. Balances out the body by
increasing insulin uptake in the muscles and decrease glucose production by
liver. Does not cause hypoglycemia. Number one side effect diarrhea.
Class: biguamide,
antidiabetic
Indication: type
II diabetes
Pharmacokinetics: Onset within days, max up to 2wks. Distrubtion by
RBCs, absorbed slowly in
Small Intestine. Not metabolized by
liver. Bioavailibilty
absolute. Plasma half-life 6.2hrs, blood
half-life 17.6hrs.
Excreted by the kidneys (urine). Extended
release take with biggest
meal, regardless of what time of day.
Adverse Effects: Diarrhea, GI upset, headache, lactic acidosis, nausea,
Vomiting.
Precautions:
Pregnancy (use insulin), hypersensitivity, geriatric,
thyroid disorder.
Contradindications: Creatinine over 1.5
(males), 1.4 (females), renal
disease, CHF, alcoholism, history of
lactic acidosis, cardiopulmonary disorder. No contrast for CT scan, hold for 48
hrs prior, check renal function post-scan.
Interactions: increase metformin levels Tagamet, digoxin, alcohol,
morphine, vanco. Increase hypoglycemia Tagamet, calcium
channel blockers,
corticosteroids, estrogens, diuretics, dilantin
V. COPD/Asthma
Short
acting vs long acting inhaler usage
Albuterol
[short acting]: Beta-2 agonist used for
patients with asthma and COPD. Usually PRN
for athsma attacks. Adverse effects: tachycardia, angina and tremor. Bronchodilates in
a reversible airway obstruction “opens airway:, prevention of exercise-induced
bronchospasm. Always watch vitals. Most patients administer incorrectly. Use
only for ongoing, acute attacks (or prevention of exercise-induced). 2 puffs
every 4-6hrs. Wait one minute between each puff.
If
administering a short and long-acting inhaled med, take the short-acting first to
open airways then administer the long-acting (aka albuterol first then
steroid).
Salmeterol
[long acting]: Beta-2 agonist long term control.
Dosed on fixed schedule. Not used
for acute episodes. When incorrectly may increase risk
of athsma related death.
Not first agents for long-term control, should be used
alone. Use in combination
steroid treatments (advair). One inhalation every 12
hours.
Inhaled
Glucocorticoids: Suppresses
inflammation. Decreases synthesis and release of
inflammatory mediators. Decreases infiltration and
activity of inflammatory
cells. Decreases edema of the airway mucosa.
Combination of Fluticasone with Salmerterol is Advair. Typically in powder
form. Adverse effects: Oralpharyngeal
candidiasis (thrush) and dysphonia (hoarseness). Patient needs to gargle after
administration. Check blood sugar with diabetes because steroids can increase
blood glucose levels.
VI. RA/OA/Osteoporosis
General meds used for treatment of Osteoarthritis
(pain in tendons and joints):
· NSAIDs [asprin] (COX-I inhibitors) – great risk
of GI bleed, alleviate mild to moderate pain and inflammation
· Celecoxib [celebrex] (COX-II inhibitor) – reduced risk
of GI bleed because does not decrease platelet aggregation, works on pain
and inflammation
· Acetaminophen – lacks anti-inflammatory properties,
works to reduce pain
General meds for treament of RA:
· DMARDS [disease modifying anti-rheumatic drugs)
Acetominophen [tylenol]: Anti-pyretic,
non-opioid analgesic. Indicated in mild pain and fever.
Does not suppress platelet aggregation, does not
suppress renal blood flow, does not cause renal impairment, does not cause
gastric ulceration. Mechanism of action: inhibits synthesis of prostaglandins
that may serve as mediators of pain and fever primarily in the CNS. Well
absorbed orally, crosses placenta and breast milk (in low concentrations),
widely distributed, metabolized in liver, metabolites may be toxic in overdose
concentrations, half-life 2hrs, excreted in urine. Overdose can cause severe liver damage. No more than 4g/day, always count. Use with
caution in hepatic disease, renal disease, alcoholism, malnutrition. Interacts
with alcohol because consumption increases risk of liver injury. Interacts with
Coumadin, puts at risk for bleeding. Interacts propanolol, decreases metabolism
and may increase effects. Concurrent NSAIDS increase risk of renal effects.
Monitor LFTs.
Alendronate[Fosamax]: Bisphosphonate, treatment of osteoporosis. Inhibits bone reabsorptions
by increasing activity of osteoclasts. Food decreases
absorption. Adverse effects:
difficulty swallowing [esophogitis], esophageal ulcers, dysphagia,
constipation. Contraindicated in renal insufficiency, pregnancy, lactation.
Patient education includes, take first thing in the AM 30 mins before food or
other meds. Take with a full glass of
water and do not lay back down for 30 mins (keep patient upright) to prevent
reflux – could leave hole in esophagus. Interactions
include calcium supplements, antacids and oral meds that may decrease
absorption. Dose 10mg/day.
NSAID Therapies [Asprin, Ibuprofen, Celebrex]: Non-steroid
anti-inflammatory. Used for
treatment of osteoarthritis, rheumatoid arthritis, and
gout. (Cox-1 mediates housekeeping chores: gastric protection, kidney function,
platelets. Mediates beneficial processes. Cox-2 primarilty at the site of
tissue injury, mediates inflammation and sensitizes receptors to pain. Mediates
harmful processes.) NSAIDs are COX-inhibitors. Huge risk for GI bleed, except
Celebrex has a lower risk because does not suppress platelet aggregation. Cox-2
inhibitors can impair renal function and cause HTN and edema, increase the risk
of MI and stroke. Aspring can cause tinnitus (ringing in ears) with levels
above 200mcg/ml.
Ø LAB VALUES
K+
3.5 – 5.0
Cr
0.5 - 1.2
BUN
10 – 30
Na+
135 – 145
BNP
0 - 100 [know for HF]
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