Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
208 Cards in this Set
- Front
- Back
|
Describe RA
|
- Chronic progressive autoimmune inflammatory disease
- Unknown etiology - Attacks synovial tissue - Leading to irreversible joint damage, chronic pain and functional impairment - Ages 30-60 years old, 75 % women |
|
|
Is there a cure for RA
|
No, but progression of disease can be stopped with DMARDS
|
|
|
Describe genetic component of RA
|
- Association with HLA-DR4, chromosome 6 - strong association with RA and juvenile diabetes
|
|
|
RA symptoms
|
- Inflammation of joints
- Swelling - Difficulty moving and pain - Loss of appetite - Fever - Loss of energy - Anemia (10-20% mild anemia) |
|
|
RF
|
Rheumatoid factor - immunologic complex - binds to IgG - most patients with RA have it
|
|
|
Negative RF test with RA symptoms means _
|
Mild disease
|
|
|
Describe progression of RA
|
RF antigen presents to IgG or other antibody - inflammatory response - PMN's, leukocytes , monocytes, lymphocytes congregate - phagocytosis of immune complexes - release of lysosomal enzymes - destruction of cartilage and subchondral bone erosion
At the same time inflammatory response causes angiogenesis in synovium, synovial cell proliferation and pannus invasion, which also leads to destruction of the joint |
|
|
Pannus
|
1. B cell activity
2. Plasma cell activity 3. Activation of synovial fibroblasts |
|
|
Synovitis in RA can be attributed to _
|
Pro-inflammatory cytokines - IL1, TNF alpha and other cytokines
|
|
|
In addition to joint problems RA patients should also be checked for _
|
Osteopenia due to increased bone resorption by osteoclasts
|
|
|
One of the most common extra-articular manifestations of RA
|
Nodules - associated with presence of RF (occurs in high titer RF)
|
|
|
What do you see on x ray in people with RA
|
- Decreased joint space
- Bony erosions (overproduction of TNF alpha, IL1) - Joint deformities - Thinning of bones around joints - juxtarticular osteoporosis - Soft tissue swelling (early RA) |
|
|
How do you prevent radiological damage in RA
|
Early RA - major window of opportunity for disease control - apply DMARDS in this phase
Radiographic damage occurs in 1-2 years after disease onset |
|
|
Which enzyme is inhibited by corticosteroids
|
Phospholipase A2
|
|
|
Which enzyme is inhibited by NSAIDS
|
Cyclooxygenase
|
|
|
NSAIDS side effects
|
-GI IRRITATION - most common
- Skin reactions and rashes - Increased blood coagulation time (PT test) - Reversible hepatocellular toxicity (check liver enzymes) - Impaired renal function (especially if patient is on diuretics - check BUN + creatinine) |
|
|
Are NSAIDS effective in treatment of RA
|
While NSAIDS relieve pain and inflammation of RA, they do nothing to halt loss of bone associated with this disease
|
|
|
Corticosteroid side effects
|
- Diabetes (long time users)
- Weight gain - Osteoporosis - Hypertension - Mood changes (very common, 95%) - Increased risk of infection - Bone damage - osteonecrosis |
|
|
Major classes of DMARDS
|
- Antimalarial drugs
- Gold compounds - Penicilamine - Sulfasalazine - BRM - biologic response modifiers |
|
|
IL1 role in RA
|
- Dominant cytokine associated with RA
- Produced in response to inflammatory stimuli - Mediates inflammatory and immunological responses - Broad range of activity including cartilage degeneration and stimulation of bone resorption - Abundant in synovial fluid of RA patients |
|
|
Relationship of IL1 and TNF alpha
|
IL 1 and TNF alpha induce production of each other and they act synergistically
|
|
|
Functions of IL1
|
- Activates monocytes and macrophages - inflammation
- Induces fibroblast proliferation - synovial pannus formation - Activates chondrocytes - cartilage breakdown - Activates osteoclasts - bone resorption |
|
|
Name drug that is recombinant version of human IL1 receptor antagonist (IL1- Ra)
|
ANAKINRA - blocks biologic activity of IL1, identical to normal human IL1 - Ra - a single aa methionine has been added at N terminus which stabilizes it
|
|
|
How long does it take for Anakinra to work
|
2-4 weeks
|
|
|
Pharmokinetics of Anakinra
|
- Well absorbed after subcutaneous injection
- T 1/2 4-6 hours |
|
|
Indication for Anakinra
|
For the reduction of signs and symptoms of moderately to severe active RA in patients 18 or older who have failed AT LEAST 1 or more DMARDS
|
|
|
Adverse effects for Anakinra
|
- The most common adverse event is transient mild local injection site reaction which lasts 14-28 days
|
|
|
How is ANAKINRA used (alone, combination, etc)
|
ANAKINRA can be used alone or in combination with DMARDS other then TNF alpha blocking agents
|
|
|
Describe AZATHIOPRINE
|
- Has been used since mid 1960's to treat RA and SLE
- Derivative of mercaptopurine - functions as structural analog or antimetabolite (acts on precursors of DNA and RNA) - Alters Ab production and suppression of T cell effects (immunosuppressive) |
|
|
Adverse effects for AZATHIOPRINE
|
- Nausea, vomitting
- Leukopenia - Thrombocytopenia - Hepatotoxicity (High serum APT and mild jaundice) - SEVERE BM SUPPRESSION - particularly in patients with renal insufficiency |
|
|
Drug interactions for AZATHIOPRINE
|
- Allopurinol - increases serum levels 3-4 folds
- ACE inhibitors (enalapril, captopril) - can cause severe leukopenia |
|
|
Contraindications for AZATHIOPRINE
|
- Contraindicated in pregnancy
- Severe leukopenia and thrombocytopenia may occur during treatment - CBC!!! - Risk of infection during treatment - May increase risk of neoplasia |
|
|
Describe HYDROXYCHLOROQUINE
|
- Antimalarial drug discovered in early 50's
- Decreases inflammation of RA - Decreases joint pain and inflammation in 60% patients with RA |
|
|
Drug which most rheumatologists consider to be "safe but weaker second line drugs"
|
HYDROXYCHLOROQUINE (PLAQUENIL)
|
|
|
Adverse effects of HYDROXYCHLOROQUINE
|
- Headache
- Dizziness - Abnormal skin pigmentation - Visual disturbances - Edema - Blood dyscrasia - Nervousness - Anorexia - Weight loss |
|
|
Most important toxicity of HYDROXYCHLOROQUINE
|
OCULAR - should see ophthalmologist every 3 months
|
|
|
Describe LEFLUNOMIDE
|
- FDA approval October 1998
- Similar efficacy to MTX - Used for patients with definite active RA when aggressive treatment is needed - Usual time to effect - 4-8 weeks |
|
|
LEFLUNOMIDE MOA
|
- Decreases inflammation by inhibition of enzymes necessary for production of pyrimidines - tyrosine kinase and dihydropteorate dehydrogenase
T1/2 - 15 days |
|
|
Toxicities for LEFLUNOMIDE
|
- Elevation of liver enzymes with some risk of liver damage
- Renal impairment - Teratogenic effect - Low frequency of cardiovascular effects ( angina, tachycardia) was reported in clinical trials |
|
|
Drug interactions for LEFLUNOMIDE
|
- RIFAMPIN - blood levels of leflunomide can increase to toxic levels
- TOLBUTAMINE - blodd levels of leflunomide may increase to toxic levels |
|
|
SULFASALAZINE FDA indications
|
- Mildly to moderately acute ulcerative colitis - DOC
- Treatment of RA in patients who have not responded to salicylates or other NSAID's - Treatment of children with polyarticular juvenile RA that have not responded to salicylates or other NSAIDs |
|
|
Describe SULFASALAZINE
|
- Combination of 2 different medications - 5-aminosalicylic acid and sulfapyridine, starts working 6-12 weeks, 1/3 of people starting it have to stop because of side effects
|
|
|
SULFASALAZINE MOA
|
- Split by intestinal bacteria into active metabolies sulfapyridine and mesalamine - BLOCK CYCLOOXYGENASE and inhibit prostaglandin formation which would decrease formation of AA metabolites
|
|
|
SULFASALAZINE adverse effects
|
- Anorexia
- Headache - Reversible oligospermia - CAN CAUSE HYPERSENSITIVITY reactions due to sulfa allergy - allergic reactions include fever and rash |
|
|
SULFASALAZINE drug interactions
|
May reduce absorption of DIGOXIN and FOLIC ACID
|
|
|
Contraindications for SULFASALAZINE
|
- Contraindicated in patients with hypersensitivity to salicylates
- Use with caution in patients with renal and hepatic dysfunction, blood dyscrasias and bronchial asthma |
|
|
PENICILLAMINE - describe
|
- For acute and severe RA (seldom used)
- Unknown MOA - Response delayed (4-12 weeks) - Can also chelate copper and so used to treat Wilsons disease, mercury or lead poisoning |
|
|
Common side effects for PENICILLAMINE
|
- Rashes+ dermatitis - most common
- Severe nausea and vomitting - Mild to moderate thrombocytopenia and leukopenia - Mild proteinuria which can progress to nephrotic syndrome - DO UA!!! Side effects rapidly disappear if therapy discontinued |
|
|
Most widely prescribed and most commonly used DMARD
|
MTX - methotrexate
|
|
|
MTX indications
|
- RA
- Psoriasis - Psoriatic arthritis - SLE - Sarcoidosis ADDITIONAL USE - anticancer and immunosuppressive if used in high doses |
|
|
Why MTX is the first line DMARD
|
- Early onset of action (4-6 weeks)
- Good efficacy - Favorable toxicity profile - Ease of administration - Low cost |
|
|
Describe MOA of MTX
|
- FOLATE ANTIMETABOLITE - inhibits dihydrofolate reductase
- Inhibits folate-dependent enzymes involved in ADENOSINE degeneration increasing concentration of extracellular ADENOSINE which inhibits formation of pro-inflammatory cytokines - TNF alpha and IL1 |
|
|
Adverse effects of MTX
|
- Usually mild and can be managed by temporarily stopping the drug or reducing dose
- Nausea - STOMATITIS - GI DISCOMFORT - MILD ALOPECIA Those three related to folic acid antagonism - RASH - common - Diarrhea - Headache SEVERE BUT RARE SE - Hepatotoxicity progressing to cirrhosis - Pneumonitis progressing to pulmonary fibrosis - Bone marrow depression - anemia, leukopenia, thrombocytopenia |
|
|
Why is it recommended to use folic acid supplementation together with MTX
|
Stomatitis, GI discomfort and mild alopecia are connected to folic acid antagonism, so folic acid supplementation can help to reduce those side effects
|
|
|
Which population is at higher risk for toxicity from MTX
|
Elderly due to decreased renal and hepatic function
|
|
|
Contraindications for MTX
|
- TERATOGENIC - contraindicated during pregnancy or breast feeding
- Kidney disease - Lung disease - Liver disease - Immunodefficiency - Blood dyscrasias - Type III hypersensitivity |
|
|
Drug interactions for MTX
|
MTX clearance can be decreased by administration of NSAIDS - not problem with low doses of MTX to treat RA
- Can be displaced from plasma protein binding by phenylbutazone, phenytoin and sulfonylureas |
|
|
Two IM preps of GOLD COMPOUNDS available in US
|
- Gold sodium thiomalate
- Aurothioglucose |
|
|
The only oral prep GOLD COMPOUND available in US
|
AURANOFIN - limited efficacy
|
|
|
GOLD COMPOUNDS MOA
|
- Not fully understood
- Suppresses increased phagocytic activity - either inhibits macrophages or prevents release of LYSOSOMAL ENZYMES in the joint - main thing responsible for erosion |
|
|
Most common adverse reaction with GOLD COMPOUNDS IS
|
RASH
|
|
|
Adverse effects for GOLD COMPOUNDS
|
- DERMATITIS - accompanied by pruritus
- STOMATITIS - may be preceded by metallic taste in mouth - BLUE OR GRAY SKIN DISCOLORATION - from gold deposition in that tissue, PHOTOSENSITIVITY may also occur - Mild proteinuria - if severe may indicate toxic nephritis |
|
|
In what case GOLD COMPOUND therapy should be stopped
|
If proteinuria exceeds 500 mg in 24 hours - glomerular filtration is down - can lead to renal failure, hepatotoxicity and CNS toxicity
|
|
|
Most common hematologic abnormality with GOLD COMPOUNDS is _
|
EOSINOPHILIA
if this or any other hematologic abnormalities occur - discontinue therapy |
|
|
How do you alleviate signs and symptoms of toxicity with GOLD COMPOUNDS
|
Chelating agents - DIMERCARPOL and PENICILLAMINE
|
|
|
Contraindications for GOLD COMPOUNDS
|
Patients with
- SLE - Sjogren syndrome - Severe debilitation - Uncontrolled CHF and hypertension - Should be used cautiously in patients receiving drugs that can cause NEPHROTOXICITY |
|
|
Criteria for diagnosis of RA
|
- Morning stiffness
- Arthritis of 3 or more joint areas - at least 6 weeks - Arthritis of hand joints - at least 6 weeks - Symmetrical arthritis - at least 6 weeks - Rheumatic nodules - Serum RF - X ray changes |
|
|
DMARDS that are MODERATELY EFFECTIVE and employed in milder disease
|
- Hydroxychloroquine
- Sulfasalazine - Auranofin - Minocycline |
|
|
DMARDS that are VERY EFFECTIVE and are used in moderate to severe RA
|
MTX - most popular
- Leflunomide - TNF blockers - Remicade, Humira, Enbrel - IL 1 blocker - Anakinra - Azathioprine - IM Gold compound - Cyclosporine (immunosuppressive) |
|
|
Which lab tests are important when assessing for RA
|
- CBC
- RF - C-reactive protein - indicaiton of inflammation - ESR - erythrocyte sedimentation rate - X ray |
|
|
Primary palliative agents in treatment of RA
|
NSAIDS - do not significantly alter course of disease - analgesic and anti-inflammatory
|
|
|
What is the problem with conventional DMARDs
|
Long term tolerability
|
|
|
Name Biological Response Modifiers (BRM)
|
ETANERCEPT - reduces circulatory TNF alpha levels, for patients who are treatment-naive, with DMARD-refractory RA and those with moderately to severe active RA, not recommended in patients with CHF or with demyelinating disease
INFLIXIMAB - monoclonal Ab, for use in refractory DMARD RA, combination with MTX, associated with cytokine release syndrome - fever, chills, headache - infusion related |
|
|
How do you ensure clinical outcome with DMARDS
|
- Radiologic evidence of clinical efficacy
- Improvement of clinical symptoms |
|
|
At low doses aspirin plays what role
|
ANTI PLATELET AGENT - widely used to reduce risk of MI and stroke - targets cyclooxygenase - non selective - both COX 1 and COX 2
|
|
|
At moderate doses NSAID's are effective as what
|
- Mild analgesics for conditions such as headache and muscle aches and also reduce fever
|
|
|
At high doses NSAID's are used as what _
|
- Anti -inflammatory and are heavily used for arthritis
NSAIDS DO NOT SLOW PROGRESSION OF JOINT DISEASE (use DMARD's for that) |
|
|
Describe steps of inflammation
|
- Exudation of fluid from vessels to site of injury
- Attraction of leukocytes to the site of injury for destruction of bacteria, tissue debris, etc - Activation of chemical mediators - Restoration of injured tissue to normal structure and function |
|
|
Cardinal signs of inflammation
|
Rubor = redness
Dolor = pain Calor = heat Tumor =swelling Functio laesa = loss of function |
|
|
Major causes of inflammation
|
- Infection
- Trauma - Physical injuries - Chemical injuries - Immunologic injuries - Tissue death (necrosis, not apoptosis) |
|
|
3 types of inflammation
|
- Acute (neutrophils)
- Immune response - Chronic (macrophage) |
|
|
Mediators of acute inflammation
|
- Histamine
- Leukotrienes (can block with corticosteroids) - Bradykinin - Prostaglandin (block with aspirin) - Serotonin |
|
|
Immune response inflammation provides two outcomes _
|
- Beneficial - invading organisms can be eliminated by phagocytosis and neutralization
- Harmful - can lead to chronic inflammation without resolution of underlying infectious process |
|
|
Mediators of chronic inflammation
|
- IL1, 2, 3 - activate lymphocytes and prostaglandin production
- Granulocyte-macrophage-colony stimulating factors for activation of macrophages and granulocytes |
|
|
Cyclooxygenase (COX) pathway of AA metabolism produces _
|
- Prostaglandins
- Thromboxane |
|
|
COX 1
|
- More involved in homeostatic function and is non-selective
|
|
|
COX 2
|
Induced during inflammation and cause facilitation of inflammatory response
|
|
|
Lipooxygenase pathway of AA metabolism produces _
|
Leuotrienes - effect eosinophils, neutrophils, macrophages, cause bronchoconstriction and alteration in vascular permeability
|
|
|
Most widely prescribed corticosteroid
|
Prednisone
|
|
|
Agents that reduce inflammation and relieve pain
|
- NSAIDS
- Non-opioid analgesics - Glucocorticoids |
|
|
Major adverse effects of salicylates
|
- Hepatotoxicity
- Nephrotoxicity - GI irritation SHOULD NOT BE COMBINED WITH NSAIDS |
|
|
Name non- selective COX inhibitors
|
- Aspirin
- Ibuprofen - Indomethacin - Ketoprofen - Ketorolac - Naproxen - Diclofenac |
|
|
Selective COX 2 inhibitors
|
- Celecoxib (CELEBREX) - only one that is still on market but can be prescribed only by specialists
- BEXTRA and others have been removed off market because of serious cardiac complications |
|
|
Historically _ has been DOC against inflammatory condition but now _ is DOC
|
Aspirin
Ibuprofen |
|
|
3 effects of aspirin
|
- Analgesic - reduces mild to moderate pain
- Antipyretic - reducing fever - Antiplatelet |
|
|
Selective property of aspirin
|
- Decreases incidence of TIA, unstable angina, coronary artery thrombosis with MI and colon cancer
- Incidence of MI can be reduced by giving 325 mg every other day |
|
|
Which drug should be discontinued week prior to surgery to avoid bleding complication
|
ASPIRIN
|
|
|
Why is aspirin contraindicated in viral infections in kids
|
REYES SYNDROME
|
|
|
Adverse effects of aspirin
|
- Gastritis (take with meal or water)
- increase incidence of gastric ulcers - Vomitting, tinnitus, vertigo - in case of overdose - SALICYLISM - Unnoticed fecal blood loss - Respiratory alkalosis due to increased ventilation |
|
|
Aspirin is contraindicated in _
|
Hemophilic patients
|
|
|
Ketoprofen MOA
|
Inhibits COX and lipooxygenase activity - can also be used for gout and dysmenorrhea
|
|
|
Ketoprofen adverse effects
|
GI dyscomfort + nervous system effects
|
|
|
Which NSAID is like aspirin - has analgesic, anti-inflammatory and antipyretic activity - BUT DOES NOT ACT ON PLATELETS
|
DICLOFENAC
|
|
|
Non selective COX inhibitor that may affect TNF
|
FLURBIPROFEN
|
|
|
Which NSAID is used as topical ophthalmic preparation for inhibition of intraoperative miosis
|
FLURBIPROFEN
|
|
|
Ibuprofen is contraindicated in patients with _
|
- Nasal polyps
- Angioedema - Bronchospastic reactivity to aspirin |
|
|
Indomethacin
|
- Gout
- Ankylosing spondylitis - RA - Patent ductus arteriosus |
|
|
Adverse effects of INDOMETHACIN
|
- ABDOMINAL PAIN
- HEMORRHAGE - PANCREATITIS - DEPRESSION - Diarrhea - Headache - Dizzines, confusion RARE - hyperkalemia, thrombocytopenia, aplastic anemia |
|
|
Ketorolac is mainly used as _
|
ANALGESIC
|
|
|
Where is KETOROLAC used
|
- To replace morphine in situations with mild to moderate post surgical pain
- Ophtalmic preparation |
|
|
KETOROLAC adverse effect
|
- Increased incidence of peptic ulcer
- Renal failure if used for postsurgical pain for more then 5 days |
|
|
FENOPROFEN is less used due to _
|
Association with interstitial nephritis
|
|
|
DICLOFENAC is associated with _ toxicity
|
LIVER
|
|
|
DMARD with shortest half life
|
ANAKINRA - 4-6 hours
|
|
|
DMARD with longest half life
|
LEFLUNOMIDE - 15 days
|
|
|
SULFASALAZINE should not be used in people with _
|
G6PD defficiency
|
|
|
Which DMARD can chelate copper so can be used to treat Wilsons disease
|
PENICILLAMINE
|
|
|
Neuromuscular blocking drugs
|
Used to produce muscle paralysis in order to FACILITATE SURGERY or ARTIFICIAL VENTILLATION
|
|
|
Spasmolytic drugs
|
A drug that reduces abnormally elevated MUSCLE TONE (SPASM)without paralysis - Baclofen, dentrolene
|
|
|
Describe pathophysiology of spasms
|
SPASMS - sudden violent painful involuntary CONTRACTIONS of muscle or group of muscles
- Involvement of MOTOR NEURONS (balance between muskuloskeletal movement and body posture) - ACTION POTENTIALS by motor neurons are conducted directly to nerve terminals in muscle fibers that form synapses called NEUROMUSCULAR JUNCTIONS (NMJ) - ACH is released from nerve terminal and stimulated NICOTINIC RECEPTORS ON MUSCLE producing CONTRACTION |
|
|
Describe pathophysiology of spacsticity
|
- In contrast to spasm spasticity is INCREASE IN PASSIVE STRETCH RESISTANCE of muscle or muscle group - INCREASED MUSCLE TONE OR CONTRACTIONS cause movement to be STIFF AND AWKWARD
- SPASTICITY IS CONSIDERED TO BE PERMANENT CONDITION and may progress to disabling condition of therapy is not instituted |
|
|
Common causes of spasticity
|
- Close head injuries
- Cerebral palsy - MS - Stroke |
|
|
Two major classes of skeletal muscle relaxants
|
- Neuromuscular blockers
- Spasmolytics |
|
|
How do neuromuscular blockers act
|
Interfere with TRANSMISSION at neuromuscular end plate and ARE NOT CENTRALLY ACTING DRUGS
|
|
|
Spasmolytics are centrally acting muscle relaxants EXCEPT _ which is peripheral drug
|
DANTROLENE
|
|
|
Major use of skeletal muscle relaxants
|
Muscle strains
Back pain |
|
|
Name centrally acting muscle relaxants used to treat spasticity
|
Baclofen
Botulinum toxin type A (BOTOX) Diazepam (VALIUM) Tizanidine |
|
|
Peripherally acting drug for spasticity
|
DANTROLENE
|
|
|
Name centrally acting drugs for spasms
|
Carisoprodol
Chlorphenesin Chlorzoxazone Cyclobenzoprine Diazepam Metaxalone Methocarbamol Vigabatrin |
|
|
Spasm is mediated by _ while spasticity is mediated by _
|
Spasm - LOWER MOTOR NEURONS
Spasticity - UPPER MOTOR NEURONS |
|
|
BACLOFEN MOA
|
- Acts within spinal cord to SUPPRESS HYPERACTIVE REFLEXES involved in regulation of muscle movement
- Structural analog of GABA (mimics action of GABA on spinal neurons) ACTS ON THE LEVEL OF SPINAL CORD TO RESTORE INHIBITING TONE!!! |
|
|
Therapeutic use of BACLOFEN
|
- Can REDUCE SPASTICITY associated with MS, spinal cord injury and cerebral palsy
- Not effective in stroke - Drug decreases FLEXOR AND EXTENSOR SPASMS and suppresses resistance to passive movement - reduces discomfort of spasticity and allows increased performance - PREFERRED TO DANTROLENE in patients whose spasticity is associated with significant muscle weakness - DOES NOT relieve spasticity of Parkinsons disease |
|
|
Adverse effects of BACLOFEN
|
- MOST COMMON - GI and CNS effects
- CNS effects - CNS depressant, causes DROWSINESS AND DIZZINESS (should not be driving), weakness and fatigue - especially in early stage |
|
|
Contraindications for BACLOFEN
|
- SHOULD NOT BE USED WITH ALCOHOL AND OTHER CNS DEPRESSORS
|
|
|
Max amount of BACLOFEN
|
80 mg/D (20 qid)
|
|
|
Overdose with BACLOFEN can lead to _
|
COMA and RESPIRATORY DEPRESSION - no antidote, supportive treatment
|
|
|
DIAZEPAM
|
- ANTI-ANXIETY DRUG
- Member of BENZODIAZEPINE family - Acts within CNS by facilitating GABA mediated PRESYNAPTIC INHIBITION (mimics action of GABA in spinal cord and brain) - Can be used in patients with muscle spasm of almost any origin including local muscle trauma - Produces SEDATION |
|
|
Side effects of DIAZEPAM
|
SEDATION (MOST COMMON)- to minimize sedation initiate therapy at lower dose
|
|
|
MOA DANTROLENE
|
Suppression of Ca release from SR - decrease in ability of skeletal muscle to contract
|
|
|
Therapeutic advantage of DANTROLENE
|
Minimal effect on smooth and cardiac muscle
|
|
|
Therapeutic use of DANTROLENE
|
- Spasticity
- MALIGNANT HYPERTHERMIA |
|
|
Describe malignant hyperthermia
|
- Life threatening syndrome that can be triggered by any general anesthetic and by succinylcholine - neuromuscular blocker.
- Prominent symptoms - muscle rigidity and profound elevation of temp - Heat of malignant hyperthermia is generated by muscle contraction occuring secondary to massive release of Ca from SR - DANTROLENE relieves symptoms by acting on SR to block Ca release |
|
|
DANTROLENE adverse effects
|
- HEPATIC - dose related liver damage - MOST SERIOUS TOXICITY (1/1000) - test liver function before and during treatment
- Also CNS effects - Increased urinary frequency |
|
|
Drug interaction of DANTROLENE
|
Increased toxicity:
- Estrogen -Warfarin - CNS depressants - Clindamycin - Verapamil - Tolbutamine |
|
|
Which drug used for local acute muscle spasms has longest half life and most protein binding
|
CYCLOBENZAPRINE
DANTROLENE |
|
|
CYCLOBENZAPRINE IS CONTRAINDICATED IN PATIENTS WITH HISTORY OF _
|
PORPHYRIA
|
|
|
Arachidonic acid is derived from _
|
CELL MEMBRANE LIPIDS
|
|
|
Name natural EICOSANOIDS
|
Prostaglandins
Thromboxanes Leukotrienes Lipoxins |
|
|
Lipid derived autocoids derived from AA formed from _
|
DIETARY LINOLEIC ACID
|
|
|
EICOSANOIDS are stored in cells - T/F
|
FALSE - they are not stored in cells, synthesis depends on release of AA from membrane lipids by phospholipases that are activated by physical, chemical or hormonal stimuli
|
|
|
Prostaglandin chemical structure
|
Modified fatty acid attached to 5 membered ring
|
|
|
Therapeutic use of prostaglandinds
|
- Obstetric
- Cytoprotection of stomach - Pediatrics (patent ductus arteriosus) - Impotence - Glaucoma (relieve intraocular pressure) - Pulmonary hypertension |
|
|
Which prostaglandin has most broad multiorgan application
|
PGE2
|
|
|
Describe use of PGE2
|
- CYTOPROTECTIVE - inhibits gastric acid secretion, increases bicarbonate
- VASODILATOR - maintains kidney function by increasing glomerular filtration and increasing sodium and H2O excretion - RELAXES RESPIRATORY SMOOTH MUSCLE - INHIBITS PLATELET AGGREGATION - CAUSES STRONG UTERINE CONTRACTION - labor induction - INCREASES BODY TEMP - increases cAMP and triggers hypothalamus to increase body temp - INFLAMMATORY MEDIATOR |
|
|
Describe use of PGI2
|
- INHIBITS PLATELET AGGREGATION and causes hypotension
- VASODILATOR - RELAXES UTERINE MUSCLE - CYTOPROTECTION |
|
|
Describe main function of TXA2
|
- Potent STIMULATOR OF PLATELET AGGREGATION
- Potent VASOCONSTRICTOR - Potent BRONCHOCONSTRICTOR |
|
|
TXA 2 can be blocked by _ which will cause _
|
Aspirin
Inhibition of platelet aggregation |
|
|
Name EICOSANOIDS as therapeutic agents
|
- Alprostadil
- Carboprost - Caverject - Dinoprostone - Prostacycline - Misoprostol |
|
|
Which two EICOSANOIDS are used for 1st and 2nd trimester abortions
|
CARBOPROST - IM
DINOPROSTONE - intravaginally |
|
|
Which EICOSANOID is used to control postpartum hemorrhage and uterine atony
|
CARBOPROST
|
|
|
Which EICOSANOID is used in pediatrics to maintain patency of ductus arteriosus in neonates with congenital heart defects - pulmonary atresia, tetralogy of Fallot, transposition of great vessels, aortic coarctation, interruption of aortic arch
|
ALPROSTADIL - IV infusion can be used until surgery can be performed, only temporarily, has toxic effects
|
|
|
Forms of DINOPROSTONE
|
PROSTIN E2 - vaginal suppository used for abortions, also used to induce labor, causes cervical ripening and also to control postpartum hemorrhage and uterine atony
PREPEDIL GEL - gel used to ripen cervix and induce labor CERVIDIL - vaginal insert |
|
|
Which EICOSANOID is used orally to prevent peptic ulcers in patients on chronic NSAIDS toxicity
|
MISOPROSTOL
|
|
|
Adverse effects of ALPROSTADIL
|
- Prolonged treatment can rupture ductus
- APNEA - 10-20% of neonates - Other SE - flushing, hypotension, fever, seizures, diarrhea, hemorrhage, rarely cardiac arrest |
|
|
Which EICOSANOID is used for treatment of impotence
|
Alprostadil (CAVERJECT) - naturally occuring from PGE1, ACTS AS SMOOTH MUSCLE RELAXANT LOCALLY, injected via cavernous arteries - PRODUCES ERECTION with 5-20 min lasting about 1 hour
|
|
|
Side effects of CAVERJECT (Alprostadil)
|
PROLONGED ERECTION
Bleeding at injection site Penile pain CONTINUED USE CAN CAUSE PENILE FIBROSIS |
|
|
Which APROSTADIL form is used for treatment of OPEN ANGLE GLAUCOMA
|
XALATAN - PGF2 analog that reduces elevated IOP
- PRODRUG hydrolyzed by esterases in cornea to active LATANOPROST ACID |
|
|
Which EICOSANOID is used IV for treatment of PRIMARY PULMONARY HYPERTENSION
|
EPOPROSTENOL (high pulmonary artery pressure causes R ventricular hypertrophy)
- Causes vasodilation and inhibition of platelet aggregation |
|
|
EPOPROSTENOL adverse effects
|
BROAD ADVERSE EFFECT PROFILE
FLUSHING - common, headache, nausea, diarrhea, vomitting, tachycardia, jaw pain, fever, hypotension, anxiety, etc |
|
|
Name drugs that inhibit LEUKOTRIENES
|
5-LO INHIBITORS - ZILEUTIN
Lekotriene receptor antagonists - anti-asthmatics - ZAFIRLEUKAST and MONTELEUKAST - Also corticosteroids |
|
|
Which drugs inhibits prostaglandins
|
NSAIDS - inhibit COX
CORTICOSTEROIDS - inhibit PLA2 - NOT DIRECTLY - stimulate synthesis of lipocortins that inhibit phospholipase A2 |
|
|
Describe GOUT
|
Clinical syndrome - deposition of monosodium urate monohydrate crystals in tissue - accompanying inflammation - degeneration of joints and soft tissues
|
|
|
Gout in men vs women
|
Women have lower incidence and later onset of gout - attributed to better urate excretion, attack before age 30 is rare and suggests genetic metabolic disorder
|
|
|
GOUT is associated with
|
HYPERURICEMIA
|
|
|
Drugs used for treatment of acute gout
|
COLCHICINE
NSAIDS GLUCOCORTICOIDS ANALGESICS |
|
|
Drugs used in treatment of chronic gout
|
URICOSURICS
ALLOPURINOL |
|
|
Drug of choice for treatment of chronic gout
|
ALLOPURINOL
|
|
|
Why does uric acid deposit in tissues
|
URIC ACID is the end product of purine metabolism and is POORLY SOLUBLE especially in acidic environment
|
|
|
TOPHI
|
URIC ACID DEPOSITS under the skin around affected joint, cartilage of ear, tendons or other tissues (can also deposit in kidney resulting in chronic kidney failure)
|
|
|
Tophi are a sign of _ gout
|
CHRONIC
|
|
|
Symptoms of gout
|
- Appears as ACUTE ATTACK often coming overnight
- Within 12-24 hours there is SEVERE PAIN and swelling in affected joint - SKIN over joint may be RED AND SHINY |
|
|
What is the concentration of uric acid necessary for DIAGNOSIS OF GOUT to be made
|
- More then 7 mg/dL in men
- More then 6 mg/dL in women |
|
|
Manifestations of Hyperuricemia
|
- Subcutaneous tophaceous deposits
- Urolithiasis - crystals in urine combine to form stones - Nephrolithiasis - kidney stones - Renal diseases involving tubules, interstitium, glomeruli |
|
|
4 clinical phases of GOUT
|
- Asymptomatic hyperuricemia
- Acute gouty arthritis - Intercritical gout (intervals between acute attacks) - Chronic tophaceous (UA deposits) gout |
|
|
Gouty arthritis
|
- Arthritis especially of BIG TOE as a result of gout, often precipitated by TRAUMA, INFECTION, SURGERY.
- Initial attacks are usually monoarticular but later attacks are polyarticular |
|
|
Causes of GOUT
|
- EXCESS OF URIC ACID due to either decreased excretion or increased production
- HYPERURICEMIA - high levels of uric acid in blood - RECURRENT ATTACKS OF GOUTY ARTHRITIS - deposition of uric acid crystals in joints URIC ACID DEPOSITS CAN ALSO OCCUR IN KIDNEY CAUSING KIDNEY STONES - OBESITY - High ALCOHOL intake - High intake of food containing PURINES - DIURETICS - cause volume depletion - Longstanding KIDNEY DISEASE |
|
|
Foods that are high in purines
|
- Offal foods such as liver, kidney, tripe, sweetbreads and tongue
- Excessive amounts of red meet - Shellfish, fish roe and scallops - Peas, lentils and beans |
|
|
Hyperuricemia ALWAYS LEADS to GOUT - T/F
|
FALSE - hyperuricemia DOES NOT always lead to gout, but GOUT is ALWAYS preceded by hyperuricemia
|
|
|
How does uric acid form
|
Purine is converted to HYPOXANTHINE by XANTHINE OXIDASE and the HYPOXANTHINE is converted to XANTHINE by XANTHINE OXIDASE and XANTHINE is converted to URIC ACID
|
|
|
Therapeutic strategies for treatment of gout
|
- Interfere with uric acid synthesis with ALLOPURINOL
- Increasing uric acid secretion with PROBENECID or SULFINPYRAZONE - Inhibiting leukocyte entry into affected joints with COLCHICINE - Anti- inflammation - NSAIDS |
|
|
Goals of drug therapy of GOUT
|
- To PREVENT OR REDUCE INFLAMMATION and pain of acute attack
- To REDUCE BLOOD URATE LEVELS either by increasing urate excretion or by decreasing urate production |
|
|
DOC for treatment of acute gout
|
COLCHICINE
|
|
|
Drugs that INCREASE URATE EXCRETION
|
PROBENECID
SULFINPYRAZONE |
|
|
Drugs that DECREASE URIC ACID PRODUCTION
|
ALLOPURINOL
|
|
|
MOA of COLCHICINE
|
BINDS TO TUBULIN AND INHIBITS MICROTUBULE ASSEMBLY - microtubules in granulocytes and inflammatory cells are affected and granulocytes cannot migrate to inflamed area
NET EFFECT - decrease release of LACTIC ACID - decreases inflammation and further urate deposit caused by lactate-induced low pH is prevented |
|
|
Use of COLCHICINE in treatment of GOUT
|
- DIAGNOSTIC - results in dramatic relief
- PROPHYLACTIC - very low doses to decrease risk of acute attacks - TREATMENT OF ACUTE GOUT |
|
|
COLCHICINE toxicity
|
- GI symptoms of nausea, vomitting, abdominal pain,diarrhea are common - 80% of patients get those
- HEMORRHAGIC GASTROENTERITIS in case of OVERDOSE - if not stopped can progress to vascular damage, renal toxicity, muscular depression and depression of CNS |
|
|
MAXIMUM AMOUNT OF COLCHICINE PER DAY
|
6 MG !!!!!!!!!!
|
|
|
DRUG OF CHOICE FROM NSAIDS for treatment of acute gout attacks
|
INDOMETHACIN
|
|
|
MOA URICOSURICS
|
BLOCK REABSORPTION OF URATE IN RENAL PROXIMAL TUBULE - also block urate tubular secretion
NET RESULT - INCREASED URATE EXCRETION IN URINE |
|
|
NAME URICOSURICS
|
PROBENECID
SULFINPYRAZONE |
|
|
Adverse effects of URICOSURICS
|
- Initiation of therapy may precipitate acute gout attack - prevent by prophylactic use of colchicine or NSAID
- Best not to start treatment with uricosuric until 1-2 weeks after acute gout attack - Strongly bound to plasma albumin - potential for drug-drug interaction - Tend to PRODUCE URIC ACID STONES - should be taken with plenty of water |
|
|
Sulfinylpyrazone should be taken with _
|
FOOD OR MILK to avoid common GI irritation
|
|
|
Other then for treatment of gout PROBENECID is also used where?
|
- As adjunct in penicillin therapy - doubles levels of penicillin
|
|
|
MOA of ALLOPURINOL
|
- INHIBITS XANTHINE OXIDASE which converts hypoxanthine to xanthine and xanthine to uric acid
- Drug is oxidized to OXYPURINOL - which is an irreversible "suicide substrate" inhibitor of XO - RESULT IN INCREASED CONCENTRATIONS OF MORE WATER SOLUBLE HYPOXANTHINE - less likely that uric acid crystals will precipitate in joints and tissues |
|
|
Therapeutic uses of ALLOPURINOL
|
- Generally used in SEVERE CHRONIC GOUT
- Also valuable in PREVENTION OF HYPERURICEMIA in patients with leukemia and some other cancers undergoing chemotherapy with cytotoxic agents - Also used TO PREVENT RECURRENCE OF URIC ACID KIDNEY STONES |
|
|
ALLOPURINOL side effects
|
- SKIN RASH - can become serious if therapy is continued - higher incidence of rash when used with AMPICILLIN
- Rare BM depression, hepatotoxicity, interstitial nephritis, peripheral neuritis and cataracts |
|
|
Drug interactions for ALLOPURINOL
|
- Xanthine oxidase inactivates 6-MERCAPTOPURINE AND AZATHIOPRINE - doses of these drugs must be reduced to 1/3 or 1/4 of usual dose
- In some patients it may interfere with hepatic inactivation of ORAL ANTICOAGULANTS - MONITOR PT - May increase concentration of THEOPHYLLINE metabolite (anti-asthmatic drug) |
