Goals of drug therapy for angina
1) prevention of MI and death
2) Prevention of myocardial ischemia and anginal death
Families of drugs: antianginal agents
organic nitrates (nitroglyceride)
Beta blockers (propranolol)
CCB (verapamil)
Ranolazine
Three forms of angina
chronic stable/exertional
variant angina
Unstable angina
Chronic stable angina: patho
caused by emotional excitement, large meals, cold exposure, CAD
Variant angina: patho, treatment, therapeutic agents
Patho: Coronary artery spasm
Treatment strategy: increase oxygen supply
Therapeutic agents: Nitroglycerin, CCB
Unstable angina: patho, treatment
severe CAD complicated by vasospasm
Patho: symptoms of angina at rest, new-onset exertional angina, intensification of existing angina
Treatment strategy: maintain oxygen supply, decrease oxygen demand
Therapeutic agents: anti-ischemic therapy (nitro, bet
Nitroglycerin: uses, actions, adverse effects
vasodilator used for stable and variant angina
Actions: acts directly of VSM to promote vasodilation, dependent on conversion of nitrate to nitric oxide
Adverse effects: headache (diminishes), orthostatic hypotension (due to relaxation of VSM), reflex tac
Nitroglycerin: pharmacokinetics, drug interactions, tolerance
Pharm: highly lipid soluble, rapid degradation by hepatic enzymes
Drug interactions: hypotensive drugs (can intensify effects), phosphodiesterase type 5 inhibitors (ED drugs, absolutely contraindicated), beta blockers, verapamil, diltiazem (suppress nitro
Nitroglycerin: preparations, routes
Sublingual, sustained-release oral tablets, transdermal delivery system, translingual spray, topical ointment, IV infusion
Rapid acting preparations can be used for prophylaxis
Discontinue long acting agents slowly to prevent vasospasm that can occur with
Chronic stable angina: beta blockers
Propanolol, Metoprolol (for asthmatic patients), all beta blockers appear to work equally well
only used for chronic stable angina, no effective against vasospastic angina
Work by decreasing oxygen demand by decreasing heart rate and contractility
Decreas
Calcium channel blockers: angina
Include verapamil, diltiazem, nifedipine
Used for stable and variant angina
SA: reduces cardiac oxygen demand
VA: relaxes coronary artery vasospasm
Adverse effects: dilation of peripheral arterioles, reflex tachy, hypotension, bradycardia, AV block
Use ca
Ranolazine
exact mechanism is unknown but can be combined with other first line agents to increase their effectiveness
Does not reduce heart rate, blood pressure, or vascular resistance
Adverse effects: prolongation of QT wave which increases risk of serious ventric
Revascularization therapy
Considered when all drug therapy fails
CABG: used to increase blood flow, harvest vein and graft to heart to bypass blockage, considered treatment of choice because more effective
PCI: consists of balloon angioplasty coupled with placement of stent
Order of treatment for vasospastic angina
1) CCB or long acting nitrate
2) If ineffective, both
3) if combination fails, CABG
NO BETA BLOCKERS
Order of treatment for chronic angina
1) sublingual nitroglycerin
2) beta blocker (especially in patients with previous MI)
3) CCB added or substituted
4) long acting nitrate added or substituted
5) revascularization surgery
Drugs used to prevent MI and death
Antiplatelet drugs, cholesterol lowering drugs, ACE inhibitors, antianginal agents
Steps to achieve homeostasis
1) formation of platelet plug (platelet aggregation)
2) Coagulation: intrinsic or extrinsic pathway and formation of fibrin
Anticoagulants: general info
Reduce formation of fibrin
Prevent venous thrombi
Two mechanisms of action: inhibits synthesis of clotting factors, inhibits the activity of clotting factors
Heparin: general info
Enhances anti-thrombin which blocks clotting factors Xa and thrombin
Sources: lungs of cattle and intestines of pigs
Pharmacokinetics: must be given by injection only, either IV or sub Q, only used in hospital
Lab monitoring: must monitor aPTT, normal val
Heparin: therapeutic uses
preferred anticoagulant during pregs because it does not cross the placenta, PE, evolving stroke, massive DVT, open heart surgery, renal dialysis, low-dose therapy post operatively, DIC, adjust to thrombolytic therapy
Heparin: adverse effects, contraindications, antidote
Adverse effects: hemorrhage is 10% of patients, heparin-induced thrombocytopenia (HIT), hypersentitivity reactions
Contraindications: thrombocytopenia (platelets <100K), uncontrolled bleeding, during and immediately after surgery of the eye, brain, or spi
LMW heparin: general info
composed of molecules that are shorter than those found in unfractioned heparin
Activation of antithrombin, inactivation of factor Xa
No aPTT monitoring required, can be given subQ at home
Fixed dosage based on body weight
Costs more than unfractioned
LMW heparin: therapeutic uses
prevention of DVT following surgery including hip and knee replacements, treatment of established DVT, prevention of ischemic complications (patients with unstable angina, non-Q wave MI and STEMI)
LMW heparin: adverse effects and interactions
bleeding (less than unfractioned), immune-mediated thrombocytopenia, severe neurologic injury for patients undergoing spinal puncture or spinal epidural
Fondaparinux
synthetic anticoagulant used for selective inhibition of factor Xa
Therapeutic uses: prevention of DVT following surgery, treatment of acute PE and acute DVT in conjunction with warfarin
Adverse effects: bleeding, avoid in patients weighing less than 50kg
Warfarin
Inhibits synthesis of vitamin K dependent clotting factors including prothrombin and factor X
Route: PO
Slow onset
Duration is prolonged
PT measures effectiveness, reported in INR (2-3 is recommended, increase dose if too low)
Vitamin K for overdose
Warfarin: therapeutic uses
not useful in emergencies
Long-term prophylaxis of thrombosis--> prevention of venous thromobosis and associated pulmonary embolism, prevention of thromboemolism in patients with prosthetic heart valves, prevention of thrombosis during arterial fibrilatio
Warfarin: adverse effects
hemorrhage (Vit K for toxicity), fetal hemorrhage and teratogensis from use during pregnancy, enters breast milk during lactation, other adverse effects include GI upset, fever
Warfarin: drug interactions
drugs that increase anticoagulant effects, durgs that promote bleeding, durgs that increase anticoagulant effects, heparin, aspirin, acetaminophen (people taking 4 tablets/wk were 10x's more likely to have high INR
Direct thrombin inhibitors: general info
directly inhibits thrombin, example is dabigatran etexilate (pradaxa), approved in 2010
Is an oral pro-drug that undergoes conversion to dabigatran
Benefits include that it doesn't require monitoring of anticoagulation, little risk of adverse interactions
Bivaliruden
prevents clot formation in combination with aspirin in patients with unstable angina undergoing coronary angioplasty
Mechanism of action: facilitiates action of antithrombin, prevents concersion of fibrinogen to fibrin, prevents activation of factor XIII
Rivaroxaban
oral anticoagulant approved in 2011
Does not require laboratory monitoring
patients who receive this drug were found to be much less likely to experience DVT, VTE, PE, or death
Atnithrombin (AT)
endogenous compound that suppresses coagulation primary by inhibit thrombin and factor Xa
used to prevent thrombosis in patients with inherited AT deficiency
Aspirin: therapeutic uses and adverse effects
ischemic stroke, TIA, chronic stable angina, unstable angina, coronary stenting, acute MI, previous MI, primary prevention of MI
Adverse effects: bleeding, GI bleeding which may not be reduced by enteric coating and hemorrhagic stroke
Clopidogrel
Plavix
Therapeutic uses: prevents blockage of coronary artery stents, reduces thrombotic events in patients with acute coronary syndromes like MI, ischemic stroke, and vascular death
Similar adverse effects to those of aspirin
use with caution in combinat
Glycoprotein IIb/IIIA receptor antagonists
most effective antiplatelet drug, "super aspirin", REVERSIBLE BLOCKADE
Thrombolytic drugs
include streptokinase and alteplase
Major adverse effect is bleeding which can be minor oozing to life-threatening amount, likely sites of bleeding include recent wounds, needle puncture sites, invasive procedure sites
Used in combination with anticoagula
Ways to minimize bleeding
minimize physical manipulation of the patient, avoid subQ and IM injections, minimize invasive procedures, minimize concurrent use of anticoagulants and antiplatelets
Streptokinase
binds to plasminogen to form active complex
therapeutic uses: acute coronary thrombosis (acute MI), DVT, massive pulmonary emboli
Adverse effects: bleeding, antibody production, hypotension, fever
Alteplase
Converts plasminogen to plasmin
given in accelerated schedule
therapeutic uses: MI, ischemic stroke, massive PE
Adverse effects: bleeding (risk for intracranial bleeding higher than with streptokinase), fever
Advantages: does not cause allergic reaction,
Diabetes: general information
Disorder of carbohydrate metabolism caused by either a deficiency of insulin or resistance to the action of insulin
Causes sustained hyperglycemia, polyuria, polydipsia, ketonuria, and weight loss
Type I and type II
DMI: general information
represents 5-10% of all cases
Also called insulin dependent diabetes or juvenile onset diabetes
Caused by destruction of pancreatic beta cells
DMII: general information
most prevalent form of diabetes and it is increasing world wide
approx 22 m americans have it, more common in minorities
Obesity is almost always present
Characterized by insulin resistance and impaired insulin secretion
Complications of DM
Short term: hyper and hypoglycemia
Long term macrovascular damage: heart disease, hypertension, stroke, hyperglycemia, altered lipid metabolism
Long term microvascular damage: retinopathy, nephropathy, neuropathy, gastroparesis, amputation secondary to in
Gestational diabetes
before insulin many babies born to severely diabetic mothers died
factors during pregnancy include: placenta produces hormones that antagonize the actions of insulin, production of cortisol increases three fold (promotes hyperglycemia), glucose can pass f
Diagnosis of diabetes
excessive plasma glucose is diagnostic for diabetes
patient must be tested on two separate days and both tests must be positive
Three tests include: fasting plasma glucose, casual plasma glucose, oral glucose tolerance test
Also test hemoglobin A1C
Prediabetes
impaired fasting plasma glucose between 100-125
Impaired glucose tolerance test
Indicates increased risk of developing DMII
May reduce risk with diet changes and exercise and possible antidiabetic drugs
many people who meet criteria for prediabetes never
Overview of treatment for DM
primary goal is to prevent long term complications
tight control of blood glucose is important
also important to control BP and blood lipids
Treatment for DMI
requires comprehensive plan
integrated program of diet, self-monitoring of blood glucose, exercise, and insulin replacement
dietary measures: total number of carbs is more important than the type of carbs, glycemic index
DMII treatment
similar to type I, requires a comprehensive plan
should be screened and treated for: HTN, nephropathy, retinopathy, neuropathy, dyslipidemia
glycemic control with modified diet and exercise, drug therapy
Insulin: physiology
synthesized by beta cells within the islets of langerhans
increased glucose stimulates secretion
promotes conservation of energy--anabolism
metabolic consequence of deficiency is hyperglycemia
Short duration: rapid acting insulin
insulin lispro (humalog), insulin aspart (novolog), insulin glulisin
Short duration: slower acting
regular insulin
Intermediate duration insulin
neutral protamin hagedorn (NPH) insulin, insulin detemir (levemir)
Long duration insulin
insulin glargine (Lantus)
Insulin: mixing for DMI and concentrations
NPH with short acting insulin
Always draw up short-acting first
Concentration: 100 U/ml or 500 U/ml
Administration of insulin
SubQ injections: syringe and needle, pen injectors, jet injectors
SubQ infusions: portable insulin pumps, implantable insulin pumps
IV insulin infusion (for DKA)
Insulin storeage
unopened vials should be stored under refrigeration until needed and should not be frozen, can be used until expiration date if kept in fridge
after opening can be kept at room temp for a moth
keep out of direct sunlight and excessive heat
mixtures in via
Therapeutic uses for insulin
principle use is DM, required by all type I and some type II, IV insulin for DKA, hyperkalemia (used to promote uptake of insulin into cells), aids in diagnosis of GH deficiency
Complications of insulin treatment
hypoglycemia, lipohypertrophy (rotate site to prevent), allergic reactions, hypokalemia, drug interactions include ethanol, thizide diuretics, beta blockers
oral hypoglycemics
biguanides (metformin)
sulfonylureas: increases insulin release
thiazolindiones: decreases insulin resistance
meglitinides (same MOA as sulfonyureas): increases insulin release)
alpha glucosaide inhibitors (delays absorption of carbs)
gilptins (enhances a
Biguanides
Metformin/glucophage
MOA: inhibits glucose production in the liver, reduces glucose absorption in the gut, sensitizes insulin receptors at target tissue
can be used as monotherapy or in combination, prevention of type II, used in gestational diabetes
side
Exenatide
Byetta
incretin mimetic
Adjunctive therapy to improve glycemic control in patients with DMII, appears to decrease appetite, weekly form available
adverse effects: hypoglycemia and GI effects
Acute complications of poor glycemic control
DKA and HHNS, both are crisis
Glucagon for insulin overdose
preferred treatment is IV glucose because it immediately raises blood sugar
glucagon can be used if IV glucose is not available
Results in delayed elevation of blood glucose by breaking down glycogen stores, but will not work in starvation or malnourishme
Mu receptors
response to activation is analgesia, respiratory depression, euphoria, and sedation
Kappa receptors
response to analgesia, sedation, and decreased GI motility
Delta receptors
respond less to analgesia than the others but may reduce depression
Morphine: therapeutic uses
Mu and Kappa receptors involves
Results in pain relief (used for moderate to severe pain, works better on dull pain but can also be used for sharp/stabbing pain in larger doses), drowsiness, mental clouding, anxiety reduction (esp pre-operatively), cough
Morphine: adverse effects
respiratory depression: infants and elderly especially sensitive to this, tolerance can be developed, increased depression with other CNS depressant drugs, can be very bad for patients with respiratory issues already like asthma or emphysema, constipation
Mophine: pharmacokinetics
administered by several routes, not very lipid soluble and does not cross BBB easily, only small fraction of dose reaches site of analgesia action
Morphine: tolerance and physical dependence
tolerance: increased doses needed to obtain same response, develops with analgesia, euphoria, sedation, respiratory depression, cross tolerance to other opioid agonists, no tolerance to miosis or constipation
Physical dependence: abrupt discontinuation ca
Morphine: precautions
decreased respiratory reserve, pregnancy and L&D (can suppress uterine contractions and cause respiratory depression in neonate), head injury
Morphine: drug interactions
CNS depressents, anticholinergic drugs, hypotensive drugs, MAOI's, agonist-antagonist opioids, opiod antagonists
Morphine toxicity
Clinical manifestations include the classic triad of coma, respiratory depression, pinpoint pupils
Treatment: Naloxone (narcan)
General guidelines: monitor full vitals before giving, give on fixed schedule (not PRN)
Fentanyl
100 times stronger than morphine
Administration: parentral (surgical anesthesia), transdermal (patch, needle free system), transmucosal (lozenge, buccal film and tablets)
Codine
Less analgesia and respiratory depression than morphine and have a somewhat lower potential for abuse (10% converted to morphine in liver)
Used for pain and cough suppression
Formulation is usually oral and may be combined with acetaminophen or aspirin
Oxycodone
analgesic actions equivalent to those of codine
long acting, immediate release
OxyContin abused by crushing and snorting or injecting, OP formulation much harder to crush and does not dissolve in water
Hydrocodone
Vicotin, most commonly prescribed drug in the US
combined with aspirin, tylenol, or ibuprofen
Agonist-antagonist opiods
Pentazocine (used for mild pain and produces no euphoria), nelbuphine, butorphanol all antagonist @ Mu and agonists at Kappa
Buprenorphine is partial agonist at Mu and antagonist @ Kappa
Dosing guidelines for opiods
assessment of pain: should be evaluated before opiod administration and about 1 hour after
Dosage determination: must be accommodated for individual variations
Dosing schedule: should be administered on a fixed schedule
Avoiding withdrawal: if used for ov
Patient controlled analgesia
devices have lock outs so patients can't overdose
Allows patient to have control
patient education should be done
Using opiods in specific settings
postoperative pain relief
obstetric analgesics (meperidine aka Demerol is drug of choice)
MI
head injury
cancer related pain
chronic non-cancer pain
REMS
risk evaluation and mitigation strategy developed by FDA
designed to reduce opioid-related injuries and death
Naloxone/Narcan
used to: treat opioid over dose, relief of opioid induced constipation, reversal of postoperative opioid effects (to acheive adequate ventilation and pain relief), management of opioid addiction, reversal of neonatal respiratory depression
Mechanism of ac
Methylnaltrexone
selective opioid antagonist used for the treatment of opioid induced constipation in late-stage diseases for patients on constant opioids
Non-opioid centrally actin alagesics
relieve pain by mechanisms largely or completely unrelated to opioid receptors
Do not cause respiratory distress, physical dependence, or abuse
Nor regulated by controlled substance act
tramadol
non-opoid, used to treat moderate pain and can be combined with opioid and non-opioid mechanisms
Clonidine
alpha2-adrenergic agonist
used in combination with opioid analgesics
adverse effects are cardiovascular in nature--severe hypotension, rebound hypertension, bradycardia
Ziconotide
non-opioid centrally acting analgesic
shown to be effective in patients who are non-responsive to morphine
distributed through CSF and then transported into systemic circulation
CoX inhibitors: general
uses: suppress inflammation, relieves pain, reduces fever
adverse effects: gastric ulceration, bleeding, renal impairment
Drugs with anti-inflammatory properties: NSAIDS like aspirin, celecoxib, ibuprofen, and naproxen
Drugs without: acetaminophen
First generation NSAIDs
inhibit Cox1 and 2
used to treat inflammatory disorders like RA, OA, and brusitis
relieves mild to moderate pain, suppresses fever, relieve dysmenorrhea
Have serious risks
Aspirin
Nonselective inhibitor of cyclooxygenase
Therapeutic uses: analgesic, antipyretic, anti-inflammatory, suppression of platelet aggregation (protects in thrombic disorders), dysmenorrhea, cancer protection, prevention of alzheimer's disease
Adverse effects:
non-aspirin first generation NSAIDS: general info
have fewer GI, renal, and hemorrhagic effects than aspirin, effects are reversible unlike aspirin
Principle indications include RA and OA
DO NOT protect against MI and stroke, may actually increase the risk of thrombic events
Ibuprofen
Advil, Motrin
works similarly to aspirin but is superior in relief of dysmenorrhea
among the safer NSAIDS to use with anticoagulant therapy but still can pose a risk for MI and stroke
Second generation NSAIDS
just as effective as traditional NSAIDs in suppressing inflammation and pain, somewhat lower risk for GI side effects, can impair renal function and cause HTN and edema, increases risk of MI and stroke
Use of these drugs has declined dramatically
Celecoxib
Celebrex
Because of cardiovascular risks it is the last choice drug for management of chronic pain
Therapeutic uses: OA, RA, acute pain, dysmenorrhea, familial adenomatous polyposis
Adverse effects: dyspepsia, abdominal pain, renal toxicity, sulfonamide a
Acetaminophen
Tylenol
Uses: analgesic, antipyretic, does not have any anti-inflammatory or antirhemetic actions, not associated with Reye's
Action: inhibits prostaglandin synthesis in CNS
Averse effects: very few at therapeutic doses, hepatotoxicity in over dose or pat
Antimicrobials
used to treat infectious diseases
up to 30% of all hospital patients receive antimibrobials
significantly reduce morbidity and mortality from infection
Antimicrobials: selective toxicity
toxic to microbe but not the host
May cause: disruption of cell wall, inhibition of enzyme unique to bacteria, disruption of bacterial protein synthesis
Classification of antimicrobial drugs
classification by susceptible organism: narrow spectrum preferable to broad, antibacterial, antifungal, antiviral
Classification by mechanism of action: cell wall synthesis, cell membrane permeability, protein synthesis, nonlethal inhibitors of protein sy
Antimicrobial resistance: mechanisms
over time organisms may develop resistance
mechanisms: decrease the concentration of a drug at its site of action, inactivate a drug, alter the structure of target molecules, produce a drug antagonist
Acquired resistance by spontaneous mutation (causes re
Antibiotic use and drug resistant microbe emergence
all antibiotics promote resistance
the amount of the antibiotic impacts resistance, nosocomial infections are most difficult to treat, suprainfections (new infection that appears when treatment for primary infection is taking place)
How to delay emergence of drug resistance
vaccinate, get catheters out, target the pathogen, access the experts, practice antimicrobial control, use local data, target infection not contamination or colonization, know when to say no to vanco, stop treatment when infection is cured, isolate pathog
When selecting antibiotic...
identify the organism and know drug sensitivity, consider host factors (site of infection, status of host defenses, age, pregnancy, previous allergic reactions), drug may be ruled out owing to allergy, inability to penetrate the site of infection, patient
Dosage size and duration of antibiotic...
antibiotic must be present at site of infection and for sufficient amount of time, do not discontinue prematurely and educate patient about this
General info about antibiotic combinations
effects may be additive, potentiative (together they are stronger), antagonistic
indications: mixed infections, prevention of resistance, decreased toxicity, enhanced bacterial action
disadvantages: increased risk of allergic reaction, antagonism, increas
prophylactic use of antimicrobials
given to prevent an infection rather than to treat an established infection
indicated in surgery, bacterial endocarditis, neutropenia
Misuses of antimicrobial drugs
attempted treatment of untreatable infections, treatment of fever of unknown origin, improper dosage, treatment in the absence of adequate bacertiological information, omission of surgical drainage
Monitoring antimicrobial therapy
monitor clinical responses and lab results
frequent monitoring should increase with severity of infection
clinical indicators of success include reduction of fever, resolution of signs/symptoms related to the affected organ
monitor serum drug levels for t
Penicillins: general info
active against a variety of bacteria, direct toxicity is very low, principle adverse effect is allergic reaction, all have a beta-lactam ring in their structure
Mechanism of action: wakens cell wall causing bacteria to take up excessive water and rupture,
Penicillinases
enzymes that render penicillin inactive
example is beta-lactamase
Penicillin G
benzylpenicillin, bactericidal to numerous gram positive and some gram negative organisms
Least toxic of all penicillins
Penicillin allergy
types: immediate (2-30 minutes), accelerated (1-72 hours), late (reactions takes days or weeks to develop)
Anaphylaxis is an immediate reaction resulting in laryngeal edema, bronchoconstriction, and severe hypotenstion and is treated with epinephrine and
Penicillin V
similar to pen g but more acid stable so can be used for oral therapy
Penicilinase-resistant penicillins
nafcilin, oxacillin, diloxacillin
All highly resistant to inactivation by beta-lactamases
broad-spectrum penicillins
ampicillin
amoxicillin (can be administered orally because it is more acid stable than ampicillin)
Extended spectrum penicillins
piperacillin, it is penicillinase-sensitive
penicillin combinations
can be combined with beta-lactamase inhibitors like clavulanic acid, taxobactam, or sulbactam
extends the antimicrobial spectrum
Cephalosporins: general info
most widely used group of antibiotics
beta-lactum antibiotics, similar to penicillin in structure, bactericidal, usually give parentrally, toxicity is low
Mechanism of action: binds to penicillin-binding proteins and disrupts cell wall synthesis and cause
classification of cephalosporins
First: cefazolin
Second: cefaclor
Third: cefoperazone
Fourth: cefepime
Cephalosporins
drug interactions: probenecid (delays excretion and increases effects), alcohol, drugs that promote bleeding, calcium and ceftriaxone interact to cause fatal precipitates
Adverse effects: allergy, bleeding, thrombophlebitis
administered parentrally
therap
Carbapenems
beta-lactam antibiotics that have an extremely broad antimicrobial spectrum with low toxicity, however a more narrow spectrum antibiotic should be used first
Not active against MRSA
include: imipenem, meropenem, ertapenem, doripenem
Vancomycin
inhibits cell wall synthesis
Uses: severe infections only including MRSA and C. diff
Adverse effects: renal failure is biggest concern (must test for creatinine clearance), ototoxicity, red man syndrome, thrombophlebitis (common), thrombocytopenia (rare),
Monobactam
binds to penicillin-binding protein 3, has narrow antimicrobial spectrum--gram negative only, must be given parenterally, adverse effects are similar to those of other beta-lactam antibiotics but are safe for patients with beta-lactam allergies
Teicoplanin
similar in structure and actions to vancomycin, does not have beta-lactum ring, MRSA and C. diff are sensitive, not approved in US
Fosfomycin
approved for single dose therapy of uncomplicated UTI's caused by E. coli or E. faecalis
Disrupts synthesis of peptidoglycan polymer strands that compose cell walls
side effects include diarrhea, headache, vaginitis, nausea
Tetracycline: general info
broad spectrum antibiotic that inhibits protein synthesis, increasing antibiotic resistance has emerged
Four members include: tetracycline, demaclyocyline, doxycycline, minocycline
Must not be taken with food--take with large glass of water 1 hour before
Tetracycline: uses
Ricksettsial disease, chlamydia trachomatis, brucellosis, cholera, mycoplasma pneumoniae, lyme disease, anthrax, H. pylori, acne, peptic ulcer disease, peridontal
Tetracycline: adverse effects
GI irritation, effects on bone and teeth include yellowing in children under age of 8, suprainfection (notify provider if diahrrea occurs), hepatoxicity, renal toxicity, photosensitivity
Tertacycline: summary of major precautions
eliminated in urine so will accumulate in patients with kidney disease, discoloration of deciduous and permanent teeth, diarrhea may indicate potentially life threatening suprainfection of the bowel, high dose IV therapy has been associated with liver dam
CNS drugs
agents that work on the brain and spinal cord
Medical uses: psychiatric disorders, suppression of seizures, pain relief, production of anesthesia
Non-medical uses: stimulant, depressant, euphoriant, and other "mind altering" abilities
Development of new psychotherapeutic drugs
1) structural analogs are synthesized
2) biochemical and physiologic screening tests
3) serious toxicity ruled out and then tested in humans
Parkinson's disease: general info
PD is a neurodegenerative disorder of the extrapyramidal system associated with disruption of neurotransmission in the striatum
Proper function of the striatum requires balance between neurotransmitters dopamine and ACh, imbalance indicated degeneration o
Cardinal symptoms of PD
tremor at rest, rigidity, postural instability, bradykeneisa, tremor
In addition to motor symptoms patients can have autonomic disturbances, depression, psychosis, dementia
Also--Lewy bodies are characteristic and only found during autopsy
Dopamine/ACh imbalance in striatum
results from degradation of the neurons that supply dopamine to the striatum
Without adequate dopamine, ACh causes excessive stimulation of GABA-releasing neurons
Overactivity of GABA neurons contributes to the motor symptoms of PD
Therapeutic goals for PD
ideal treatment (reverse neuronal degeneration or prevent further degeneration) does not exist
Goal is to improve patient's ability to carry out activities of daily life
drug selection and dosages are determined by extent to which PD interferes with work,
Drug selection for PD: patient with few symptoms
MAO-B inhibitor, prevents drug breakdown
Drug selection for PD: more severe symptoms
Levodopa/Carbidopa or a dopamine agoninst if previous combination no longer effective
Drug selection for PD: management of motor fluctuations
for "off" times, dopamin agonists, COMT inhibitors, and MAO-B inhibitors
Dyskinesias: amantadine
Levadopa
only given in combination with carbidopa or carbidopa/entacapone
Highly effective but benefits diminish over time
Orally administered and has rapid absorption in small intestine--but remember that food delays absorption, neutral amino acids compete with l
Carbidopa
no adverse effects of it's own, increases availability of leodopa in CNS and allows for 75% decrease in leovdopa dosage, there for reduces CV and GI adverse effects
effects come mainly from levodopa when given in combination
Dopamine agonists
first line drugs for PD and cause direct activation of dopamine receptors
when compared to levodopa: less effective than levodopa, not dependent on enzymatic reaction to become active, does not compete with dietary proteins, lower incidence of response fa
pramipexole
non-ergot derivative used to treat PD
used alone in early PD and with levodopa in advancing PD
Adverse effects in monotherapy include N&V, dizziness, daytime somnolence, insomnia, constipation, weakness, hallucinatioins
Combined: rare instances of patholo
COMT inhibitors
Treatment for PD in combination with levodopa
Inhibits the breakdown of levodopa in the periphery, no direct therapeutic effects of their own, two available: entacapone and tolacapone
Entacapone
selective, reversible inhibitor of COMT, used only with levodopa
Inhibits metabolism of levodopa in intestines and periphery
Prolongs time that levodopa is available to the brain
increases levodopa availability by inhibiting COMT which decreases productio
MAO-B inhibitors
Selegiline
inactivates MAO-B's (enzyme that inactivates dopamine in the striatum)
Used as a monotherapy or with levodopa, shows modest improvement in motor function
can suppress destruction of dopamine derived from levodopa and prolong the effects of levo
Levodopa/Carbidopa/Entacoapone
fixed dose combination sold as stlevo, more conveinient that taking three pills, costs less than all three separately
disadvantages: only available in immediate release, available only in three strengths
non-motor symptoms of PD
autonomic dysfunctions, sleep disturbances, depression, psychosis, dementia
Anticholinergic drugs and PD
relieve symptoms of PD by blocking cholinergic receptors in striatum
Alzheimer's disease: general
devastating illness, progressive memory loss, impaired thinking, neuropsychiatric symptoms, inability to perform ADL's, affects 4.5 m Americans, 4th leading cause of death
AD: patho
degeneration of neurons in hippocampus which affects memory and later cerebral cortex which affects speech, perception, reasoning, and other higher functions
Reduces levels of cholinergic transmission (levels of ACh are 90% below normal levels), beta amyl
AD: risk factors
major risk factors: advancing age, family history
Possible risk factors: females, head injury, low educational level, production of apoE4, high levels of homocystine, low levels of folic acid, estrogen/progestin therapy, nicotine in cig smoke, sedentary l
AD: symptoms
memory loss, confusion, feeling disoriented, impaired judgement, personality changes, difficulty with self care, behavior problems like wandering, pacing, agitation, screaming, "sundowning", inability to recognize family members, inability to communicate
diagnosis of AD
episodic memory loss and at least one AD biomarker as determined by MRI scan, PET neuroimagine, or CSF analysis
Dementia need not be present
Drug therapy for AD
Cholinesterase inhibitors may delay or slow progression of disease but will not stop it
Indicated for mild to moderate AD, prevents breakdown of ACh and may help slow progression of disease
Only three are recommended: donepezil, glantamin, rivastigmine
Ta
Other drugs for AD
drugs for non-psychiatric symptoms like agitation, aggression, delusions, hallucinations
None are very effective
MS: general info
chronic, inflammatory, autoimmune disorder that damages the myelin sheath of neurons in the CNS, exact cause is unknown, causes a wide variety of sensory and motor deficits, most patients experience periods of acute clinical exacerbations alternating with
Subtypes of MS
relapsing-remitting MS (most common)
Secondary progressive
Primary progressive
progressive-relapsing
Signs and symptoms of MS
vary depending on where CNS demyelination occurs and the size and region of demyelination
Parasthesias, muscle or motor problems, visual impairment, bladder and bowel symptoms, sexual dysfunctions, disabling fatigue, emotional lability, depression
Diagnostic tools for MS
Based on clinical presentation (s/s) and lab data
MRI, CSF testing (look at IgG levels to assess immune activity), visual evoked potential
Immunomodulators
sever currently available and 4 include beta interferon
all except natalizumab are recommended as first-line therapy for all patients with relapsing-remitting MS and for those with secondary progressive MS who are experiencing acute exacerbation
decrease
Interferon beta
naturally occuring glycoprotein with antiviral, antiproliferative, and immunomodulatory actions
used to: reduce frequency and severity of attacks, reduce number and size or MRI detectable lesions, and delays progression of disability
Interferon beta side effects
flu-like reactions, hepatoxicity, myelosuppression, injection-site reactions, depression, drug interactions with others that suppress bone marrow or cause liver damage
General info: drug therapy for MS
acute episodes: short course of high-dose IV glucocorticoids, IV gamma globulin
Drug therapy of symptoms: all four subtypes have the same symptoms
Drug therapy for relapsing-remitting MS
this type has most benefits from therapy
treatment should begin as soon as diagnosis is made
all patients should receive immunomodulators like interferon beta, glaritramer acetate, or natalizumab
secondary progressive MS: drug therapy
interferon beta
Mitoxantrone
Primary progressive MS: drug therapy
no drugs are effective
Progressive-relapsing MS: drug therapy
mitoxantrone
Glatiramer acetate
therapeutic uses: long term therapy for relapsing-remitting MS
MOA: protects myelin by inhibiting immune response to myelin basic protein
Adverse effects: well tolerated
Natalizumab
prevents circulating leukocytes from leaving vasculature, generally well tolerated
Only used in relapsing/remitting
mitoxantrone
produces greater immune suppression than immunomodulators
therapeutic uses: decreases neurologic disability and clinical relapses
MOA: binds with DNA and inhibits topoisomerase
adverse effects and drug interactions: myelosuppression, cardiotoxicity, fetal