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285 Cards in this Set
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- Back
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CNS depressants (sedative hypnotics) |
Benzodiazepines
Barbituates |
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benzodiazepines characteristics |
-selected for their high anxiolytic potency in relation to their CNS depressive effects -all benzodiazepines possess sedative-hypnotic properties to varying degrees, and these properties are extensively used clinically to facilitate sleep -Because of their safety, benzodiazepines have largely replaced barbiturates as sedative agents. |
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baribituates characteristics |
-have been used for a long time as sedative-hypnotic drugs -However, except for a few specialized uses (i.e., thiopental for anesthesia induction and phenobarbital for epilepsy), they have largely been replaced by benzodiazepines which are considered to be safer drugs. |
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THERAPEUTIC EFFECTS OF SEDATIVE-HYPNOTICS |
sedation hypnosis anesthesia anticonvulsant actions muscle relaxation |
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THERAPEUTIC EFFECTS OF SEDATIVE-HYPNOTICS- sedation characteristics |
-produce sedation, with relief of anxiety -exert anterograde amnesic effects (i.e., the inability to remember events occurring during the drug's action) at sedative doses -amnesic action is a primary reason some benzodiazepines (e.g., midazolam) are commonly used for short duration invasive procedures -DO NOT PROVIDE PAIN RELIEF, however, and must be used in conjunction with analgesics. |
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THERAPEUTIC EFFECTS OF SEDATIVE-HYPNOTICS- hypnosis characteristics |
-promote sleep onset and increase the duration of sleep -will induce sleep if given in high enough doses. -REM leep stages are usually decreased at high doses; "REM rebound" can be detected following termination of sedative/hypnotic drugs. |
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THERAPEUTIC EFFECTS OF SEDATIVE-HYPNOTICS- anesthesia characteristics |
-At high doses, produce a loss of consciousness with amnesia and a suppression of reflexes -can be produced by most barbiturates and some benzodiazepines -frequently used as “induction” agents for general anesthesia -Only 3 (diazepam, midazolam and lorazepam) are formulated for i.v. administration. |
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THERAPEUTIC EFFECTS OF SEDATIVE-HYPNOTICS- anticonvulsant actions characteristics |
-Most can suppress seizure activity at high doses; however, often this occurs along with marked sedation -Several have selective anticonvulsant actions, and can decrease the spread of epileptiform activity without excessive CNS depression -Some are administered by the intravenous route to treat status epilepticus. |
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THERAPEUTIC EFFECTS OF SEDATIVE-HYPNOTICS- muscle relaxation |
-Most sedative-hypnotics produce muscle relaxation at high doses -Diazepam is effective at sedative doses and is useful for treating specific spasticity states, including cerebral palsy. |
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Sedative hypnotics tolerance characteristics |
i.e., a decreased responsiveness to a drug following repeated exposure), commonly occurs with the continued use of sedative-hypnotics.
The mechanisms of tolerance to sedative-hypnotics are not well-understood. |
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Sedative hypnotics tolerance characteristics |
psychological dependence- often occurs with most of the sedative/hypnotics which leads to the compulsive use of these agents to reduce anxiety.
physical dependence- (i.e., the development of a withdrawal syndrome) occurs when these drugs are discontinued. Withdrawal symptoms include: tremors, hyperreflexia, and seizures. Withdrawal symptoms occur more commonly with shorter-acting drugs. |
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barbituates |
thiopental
phenobarbital |
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benzodiazepines |
midazolam
diazepam
lorazepam
alprazolam |
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benzodiazepine antagonist |
flumazenil |
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newer drugs for anxiety and sleep |
buspirone
zolpidem zaleplon eszopicione
ramelteon |
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spasmolytics |
diazepam baclofen tizanidine cyclobenaprine dantrolene botulinum toxin |
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diazepam characteristics |
-benzodiazepine that facilitates GABA inhibition in the CNS -potent action on the GABAA receptor and, at least in part, acts at the level of the spinal cord -effective in treating all types of muscle spasms. -major limitation is sedation seen at muscle relaxant doses. |
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baclofen characteristics |
-orally effective agonist for the presynaptic CNS GABAB receptor -When activated, the presynaptic GABAB receptor causes a decrease in release of excitatory amino acids (i.e., glutamate) and a corresponding decrease in skeletal muscle tone -Patients experience less sedation than with diazepam -used for relief of spasticity caused by multiple scleroses and traumatic spinal cord injury. |
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tizanidine characteristics |
-clonidine-like α2-adrenoceptor stimulant that reduces skeletal muscle spasticity by a CNS inhibitory action but with less hypotension than seen with clonidine -side effects include sedation, asthenia (muscle weakness) and dry mouth. |
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cyclobenazprine characteristics |
-related to the tricyclic antidepressants -used for short-term (2-3 weeks) treatment of muscular spasms associated with musculoskeletal conditions -MOA may be to increase brain stem mediated noradrenergic inhibition of spinal motor neurons -Side effects include atropine-like responses as well as effects produced by inhibition of catecholamine uptake -not effective in treatment of muscle spasms due to spinal cord injury or CP |
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dantrolene characteristics |
-acts directly on skeletal muscle by interfering with excitation-contraction coupling in the muscle fiber (i.e., blocks release of activator calcium) -selective for skeletal muscle and thus the drug does not depress cardiac or smooth muscle function -main adverse effects are generalized muscle weakness and sedation -drug of choice in treatment of malignant hyperthermia |
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botulinum toxin characteristics |
-sometime used (in addition to cosmetic and some ophthalmologic indications) by local injection to treat more generalized spastic disorders such as cerebral palsy -Often one or two limbs are injected, with the effects lasting weeks to months. |
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4 primary symptoms of parkinsons |
1. muscular rigidity 2. tremor 3. bradykinesia 4. postural instability |
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Pharmacological treatment of parkinsons disease is to enhance: |
the action of dopamine in the CNS by a variety of approaches |
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ways to enhance action of dopamine in CNS (long) |
1) by replacement by giving dopamine precursor, Levodopa, combined with peripheral dopa-decarboxylase inhibitor to decrease peripheral side effects. This combo is called sinemet 2) by administration of direct acting dopamine agonists-Dopamine receptor agonists bromocriptine and pramipexole 3) by use of agents that alter dopamine metabolism or synaptic concentration, the MAO-B inhibitor selegiline 4) a depression of unopposed CNS cholinergic systems- anti-cholinergic drugs benztropine |
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L-DOPA drugs |
levodopa
sinemet |
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L-DOPA fxn |
dopamine replacement
combined with carbidopa to decrease side effects |
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dopamine agonists |
bromocripitine
pramipexole |
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dopamine agonists characteristics |
-longer duration of action and are less likely to produce response fluctuations and dyskinesias than levodopa -provide direct stimulation of CNS DA receptors and do not require enzymatic conversion to dopamine -As monotherapy, DA agonists are somewhat less effective than levodopa, but often are used early in treatment to delay use of L-DOPA
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bromocriptine vs pramipexole |
-Bromocriptine is a non-selective dopamine receptor agonist which stimulates both the D1 and D2- like dopamine receptors -newer agents such as pramipexole are more selective stimulants of the D2 dopamine receptor sites and thus, may produce fewer side effects. |
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Monoamine oxidase (MAO) inhibitors |
selegiline |
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selegiline characteristics |
-inhibitor of MAO that increases CNS dopamine levels by reducing its metabolic inactivation -can be used in early stages of Parkinson’s disease, as monotherapy, with very modest effects -combined with levodopa in later stages to allow reduction of levodopa dosages (and attempt to delay the dyskinesias and motor fluctuations seen with chronic L- DOPA therapy). |
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MUSCARINIC RECEPTOR ANTAGONISTS |
benztropine |
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benztropine characteristics |
-act to block cholinergic mechanisms in the striatum that are normally opposed by tonic release of dopamine -other drugs of this class may improve the tremor and rigidity of Parkinsonism, but have little effect on the bradykinesia. -side-effects are as would be expected with muscarinic blockade (e.g., cycloplegia, dry mouth, urinary retention, etc.) -With high doses, CNS effects (confusion, hallucinations, etc.) may occur. |
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arachidonic acid metabolites characteristics |
-Production of prostaglandins and thromboxane via cyclooxygenase pathway cause vasodilation and prolong edema -This is the pathway that non-steroidal anti-inflammatory drugs (NSAIDs) act to exert anti-inflammatory action. |
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Non-steroidal anti-inflammatory drugs (NSAIDS) general properties |
anti-inflammatory
analgesic
antipyretic |
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NSAIDS mechanism of action |
-anti-inflammatory, analgesic and antipyretic properties of NSAIDs are attributed to their ability to inhibit prostaglandin synthesis by inhibiting the enzyme cyclo-oxygenase |
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aspirin (acetylasilicyclic acid) characteristics |
-Aspirin is the prototype drug for peripherally acting analgesic -also the prototypical anti- inflammatory and antipyretic agent -Aspirin was synthesized and found to be an effective treatment for arthritis in 1897 -The mechanism of action was unclear until 1971. |
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aspirin pharmacokinetics characteristics |
Rapidly absorbed and converted to salicylic acid (active form) Given PO, topically, and rectally |
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aspirin MOA |
It is a non-selective COX1 and COX2 inhibitor (irreversible) and does not inhibit lipoxygenase. |
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aspirin effects |
antipyretic effects- can only be demonstrated in a febrile patient antiplatelet effects- aspirin significantly increases bleeding time by inhibiting platelet aggregation anti-inflammatory/analgesic effects- difficult to separate gastrointestinal system- Effects of aspirin on the gut represent the major disadvantage of salicylates. Aspirin interferes with the ability of gastric mucosal cells to resist penetration by acid which may lead to gastric irritation and distress. |
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aspirin general uses characteristics |
-Inflammation (mild anti-inflammatory effects) -Anti-inflammatory effects synergize with opioids to enhance pain relief -Fever -Pain |
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aspirin specific uses characteristics |
- Transient ischemia – due to vasodilatory and anti-platelet effect - Alters the effect of PGI2 and TXA2 on aggregation of platelets and on vascular smooth muscle tone causing relaxation - Unstable angina – anti-platelet effects (clotting triggers vasospasms) - Myocardial infarction (MI)– anti-platelet effects -Prevent re-infarction in patients with high risk of MI
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aspirin adverse effects (at therapeutic doses) |
Gastric upset and gastric ulcer; tinnitus (ringing in ears; especially at moderately high doses); decreased hearing; vertigo; increased uric acid levels; hepatitis (mild, usually asymptomatic); associated with underlying disorders (lupus, juvenile arthritis, and others); decreased glomerular filtration rate – renal toxicity (due to Aspirin’s renal elimination and toxicity, mostly in patients with renal disease) |
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aspirin overdoes toxicity (high doses) characteristics |
-Commonly occurs in children (Reye’s syndrome) and is potentially life threatening. -Symptoms: Depresses respiratory center; Metabolic acidosis; Uncoupling of oxidative respiration |
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aspirin contraindications |
-pregnant women (high doses)- due to effects on PGs
-Aspirin and other salicylates should be contraindicated in children and teenagers with history of recent viral infection (association with Reye’s syndrome). Use acetaminophen or ibuprofen in children. |
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selective COX-2 inhibitors characteristics |
COX-2 inhibitors have analgesic, antipyretic, and anti-inflammatory effects similar to those of nonselective NSAIDS but with fewer GI side effects and have no impact on platelet aggregation, which is mediated by the COX-1 isozyme. |
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selective COX-2 inhibitors |
celecoxib
acetaminophen |
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celecoxib MOA |
selectively inhibit the COX-2 isoform |
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celecoxib effects |
Anti-inflammatory; antipyretic; analgesic; no effect on platelet aggregation and GI system |
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celecoxib use |
Anti-inflammation and pain relief |
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celecoxib pharmacokinetics |
They mostly are metabolized by liver cytochrome P450 enzymes and eliminated by the kidneys |
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celecoxib adverse effects |
-Increased risk of cardiovascular events: two drugs (Rofecoxib and Valdecoxib) have been removed from market due to this reason. -Gastrointestinal (GI) tract: less common than with NSAIDS for the first 6 months of therapy, but similar in incidence overall -Renal toxicity like all NSAIDS |
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clecoxib contraindications |
Celecoxib has a sulfonamide backbone. Therefore it is contraindicated in patients with sulfonamide allergies.
Renal failure
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acetaminophen characteristics |
-has both analgesic and antipyretic activity that is equivalent to that of Aspirin -weak COX-1 and COX-2 inhibitor in peripheral tissues and possesses no significant anti- inflammatory effect -Recent evidence suggests that acetaminophen may inhibit COX-3 in the CNS -more activity in the CNS and less activity in the periphery, which may account for its lack of anti-inflammatory and anti-platelet activity -used to relieve pain and to reduce fever |
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acetaminophen pharmacokinetics |
Peaks in blood in 30-60 mins; metabolized by liver microsomes and excreted in the urine |
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acetaminophen uses |
-Headache, myalgia, postpartum pain, fever
-Used for pain in patients with blood disorders (e.g., hemophilia), GI disease, lung problems (bronchospasm brought on by NSAIDS)
-Children with recent viral illnesses |
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acetaminophen adverse effects and overdose toxicity |
Liver toxicity: seen in patients consuming large quantity of alcohol drinks -target organ of alcohol and acetaminophen plus alcohol increases liver toxicity -most serious effect of acetaminophen overdose, produced by the accumulation of a toxic metabolite -treatment primarily is supportive. |
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other NSAIDS general properties |
Possess most of the properties of aspirin Inhibitors of cyclooxygenase Some affect COX-2 activity more than others All are gastric irritants All can cause renal toxicity, especially with chronic use Contraindicated in persons with severe asthma, nasal polyps, urticaria, or salicylate hypersensitivity The anti-inflammatory activity of most NSAIDS is not very different but the adverse effect profile can be very different. |
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phenylopropionic acid derivatives |
ibuprofen
naproxen
ketoprofen |
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phenylpropionic acid derivatives characteristics |
-largest group of aspirin alternative -produce their anti-inflammatory, analgesic and antipyretic action by inhibiting cyclo-oxygenase and prostaglandin synthesis -generally cause fewer GI side effects than aspirin and, as a result, are being used in place of aspirin. |
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ibuprofen characteristics |
600 mg four times daily (QID) or 800mg three times daily (TID) for adults. Smaller doses reduces anti-inflammatory properties 2 hour half-life Less GI effects than aspirin, less fluid retention than indomethacin |
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naproxen characteristics |
375 mg BID 12-15 hour half-life (twice daily - BID) Less GI effects than aspirin but still double that of ibuprofen |
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ketoprofen inhibits |
Inhibits both cyclooxygenase and lipoxygenase |
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indole and indene derivatives |
indomethacin |
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indomethacin uses |
- Gout, general pain/inflammation, and patent ductus arteriosus |
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indomethacin MOA |
selective COX-1 inhibitor |
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indomethacin toxicity |
Highly effective but more toxic than most other NSAIDs: At high doses, 1/3 of patients must discontinue using the drug |
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indomethacin adverse effects |
Severe GI effects (rare cases of GI perforation and death); headache associated with dizziness, confusion, and depression; thrombocytopenia, aplastic anemia |
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Aspirin and acetaminopehn combination characteristics |
The advantage of this combination is not clear but action of acetaminophen on COX-3 in CNS may be beneficial. |
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NSAIDS and caffeine combo characteristics |
caffeine is considered to be an analgesic adjuvant and the central vasoconstrictive effects of caffeine may help alleviate certain types of headache. |
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NSAIDS and opioids combo characteristics |
-combination of peripherally and centrally acting analgesics -Codeine and hydrocodone are commonly used opioids in combination analgesics -Additive but not synergistic phenomenon supports rationale of the combination -Opioids also contribute a centrally mediated sedative effect. |
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therapeutic concerns with NSAIDS characteristics |
Contraindication to the NSAIDS: Children, patients at a risk from bleeding abnormality or anticoagulant therapy, ulcer, asthma, kidney failure, and liver disease. Drug interactions: NSAIDS interacts with some anti-hypertensive agents (B-blockers, ACE inhibitors and diuretics) and reduce the effects of these drugs. Acetaminophen enhances the anticoagulant effect of warfarin. |
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immunosuppressive drugs |
methotrexate |
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methotrexate characteristics |
-inhibits and kills inflammatory immune cells by inhibiting their DNA synthesis -inhibits dihydrofolate reductase, an enzyme that converts dihydrofolate to tetrahydrofolate, which is necessary for the synthesis of nucleotides (DNA synthesis) -an anti-cancer drug and very toxic -For RA treatment, it is given at lower doses and is the drug of choice for moderated RA |
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anti-malarial drugs |
chloroquine and hydroxychloroquine
sulfasalazine |
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chloroquine and hydroxychloroquine |
-preferred because of lower incidence of ocular toxicity -may take 3-6 weeks to see therapeutic benefit. -often used in patients just starting therapy (mild RA) -may also be used in more severe cases when NSAIDS are no longer effective -In addition to ocular toxicity, other adverse effects include GI and dermatologic disturbances. |
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sulfasalazine characteristics |
-sulfonamide derivative that has been used for the treatment of ulcerative colitis and, in a delayed release form, for the management of RA in patients not adequately responding to NSAIDS. -converted by intestinal gut flora to a sulfonamide (anti-bacterial action) and a salicylate (anti-inflammatory) -lower level of toxicity than most DMARDs. -adverse effects include nausea and vomiting, bloody diarrhea and anorexia -Along with hydroxychloroquine, sulfasalazine is a drug of choice for patients just starting therapy. |
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general concepts of treatment of RA |
begin with an NSAID
Add a DMARD like hydroxychloroquine or sulfasalazine
scale up to methotrexate for moderate to severe RA |
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NSAIDS list |
aspirin acetaminophen celecoxib ibuprofen naproxen ketoprofen indomethacin ketorolac |
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DMARDS |
methotrexate
hydroxychloroquine
sulfasalazine |
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3 primary sites of action for opioids |
A. Spinal cord: Opioids inhibit release of neurotransmitters from primary afferents and also directly inhibit dorsal horn neuronal activity. B. Thalamus and limbic system: Opioids block the perception of pain at the level of the thalamus and limbic system to depress reaction to pain. C. Brainstem: Opioids activate descending inhibitory systems in the brainstem to modulate pain transmission at the level of the spinal cord. |
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mu opioid receptor fxns |
Supraspinal and spinal analgesia; sedation; inhibition of respiration; slowed GI transit; modulation of hormone and neurotransmitter release |
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delta opioid receptor fxns |
Supraspinal and spinal analgesia; modulation of hormone and neurotransmitter release |
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kappa opioid receptor fxns |
Supraspinal and spinal analgesia; psychotomimetic effects; slowed GI transit |
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cellular actions of opioids |
(1) they close voltage-gated Ca2+ channels on pre-synaptic nerve terminals and thereby reduce transmitter release
(2) they hyperpolarize and thus inhibit post-synaptic neurons by opening K+ channels. |
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types of endogenous opioids |
endorphins
enkephalins
dynorphins |
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therapeutic effects of opioids |
analgesia antitussive antidiarrheal acute pulmonary edema sedation/mood elevation anesthesia |
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toxicity and untoward effects of opioids |
CNS (euphoria/dysphoria) respiratory depression constipation physical and psychological dependence miosis |
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opioid tolerance and dependence |
Chronic use of opioids can result in tolerance for the drugs, which means that users must take higher doses to achieve the same initial effects. Long-term use also can lead to physical dependence and addiction |
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opioid withdrawal symptoms |
restlessness, muscle and bone pain, insomnia, diarrhea, vomiting, cold flashes with goose bumps ("cold turkey"), and involuntary leg movements. |
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opioid agonist actions |
Opioid agonists are drugs that act at some or all of the opioid receptors to produce a biological effect. They do not act as antagonists at any of the opioid receptors. |
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opioid agonists examples |
strong- morphine and methadone
moderate- codeine and oxycodone
weak- propoxyphen |
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opioid antagonists actions |
Opioid antagonists are drugs that bind to all or some opioid receptors, but do not produce a physiological effect |
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opioid antagonists example |
naloxone |
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Opioids with Mixed Receptor Actions (agonistic and antagonistic activities) |
roduces its major effects on the CNS and GI tract and induces morphine-like subjective effects and euphoria. Thus, the physical and psychological dependence can develop to pentazocine and the drug has been widely abused. |
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Opioids with Mixed Receptor example |
pentazocine |
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morphine CNS effects |
1. analgesia 2. euphoria 3. sedation 4. cough suppression 5. respiratory depression 6. miosis 7. physical dependence and tolerance |
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morphine peripheral effects |
CV- effective in treating patients with pulmonary edema
GI- decrease secretion and increase the resting tone and decrease propulsive activity in the gastrointestinal tract which leads to constipation
sphincters- can cause biliary colic and postoperative urinary retention due to increased sphincter tone, the latter is a particular problem in patients with prostatic hyperplasia |
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heroin characteristics |
-diacetyl derivative of morphine that has enhanced capacity to enter the CNS and thus has a very high addiction liability -not available in the United States for therapy, but is commonly injected, smoked and snorted as a recreational drug -Practice safe use: don't share needles -Keep tolerance in mind. If you've been off it a while, ease your way back into it. Starting at the same dose you used to use is a good way to OD |
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methadone characteristics |
has an analgesic profile and potency that is similar to that seen with morphine. However, methadone does not produce the peaks and valleys of response due to its long duration of action. Methadone is widely used (given orally) for replacement therapy in patients addicted to heroin and other shorter acting agents. |
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fentanyl characteristics |
synthetic drug. It is 50-80 times more potent than morphine and is widely used for anesthesia and analgesia. Transdermal patch is used in chronic pain management. |
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codeine characteristicsq |
naturally occurring opioid. It is indicated for mild to moderate pain (has 1/10 to 1/5 the potency of morphine) and is used as an antitussive (see below). It is one of the most commonly used opioids and rarely produces addiction. It is usually combined with an NSAID which attacks several mechanisms and allows for the opioid dose to be reduced. |
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Oxycodone and hydrocodone characteristics |
potency similar to codeine. They are used for analgesia; usually in formulations combined with aspirin or acetaminophen. |
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propoxyphene characteristics |
appears to have potency for pain relief similar to aspirin. Although it has a relatively low abuse potential, if taken in high enough doses, it will act like morphine. Death associated with propoxyphene overdose is increasing in incidence, especially in combined use with alcohol or sedative/hypnotic drugs. |
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naloxone characteristics |
-pure opioid receptor antagonist with large substitutions on the N17 positions -blocks all three receptor types with some preference for u receptors -binds to the receptors without activating them. -not efficacious when given orally and has a short (1-2 hr) duration of action when given i.v. -often given for reversal of opioid overdose. |
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pentazocine characteristics |
-k agonist with weak u antagonist -major effects on the CNS and GI tract and induces morphine-like subjective effects and euphoria -treat mild to moderately severe pain (such as used as analgesic for dental extraction) -physical and psychological dependence can develop to pentazocine and the drug has been widely abused |
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clinical use of opioids analgesics |
analgesia acute pulmonary edema anesthesia cough and diarrhea |
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clinical use of opioids contraindications |
impaired pulmonary function, head injury and trauma, pregnancy |
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clinical use of opioids drug interactions |
These include CNS depressants, neuroleptics (antipsychotics), tricyclic antidepressants, and monoamine oxidase inhibitors. The drug interaction with antidepressants may cause CNS depression and orthostatic hypotension |
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type III diabetes characteristics |
Diabetes linked to pancreatic disease, hormonal changes, drug side effects, or genetic defects |
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type IV diabetes characteristics |
gestational diabetes |
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B cell (beta) produces |
insulin, C-peptide, proinsulin, islet amyloid polypeptide (IAPP)
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A cell (alpha) secretory products |
glucagon, proglucagon |
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Where does insulin fxn? |
1. liver
2. muscle
3. adipose |
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insulin rule of thumb |
insulin promotes growth and storage of energy and stops depletion of energy stores |
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Insulin fxns in liver |
1. Reversal of catabolic activity Inhibits Glycogenolysis 2. Anabolic actions Promotes glucose storage as glycogen |
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insulin fxns in muscle |
1. Increases protein synthesis Increases amino acid transport and ribosomal protein synthesis 2. Increase glycogen synthesis Increases glucose transport and glycogen synthase Inhibits phosphorylase |
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insulin fxn in adipose |
1. Increased triglyceride storage Induces lipoprotein lipase to hydrolyze triglycerides from lipoproteins |
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anabolic definition |
synthesis of molecules as a means for storing energy |
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catabolic definition |
breaking down molecules, usually for energy |
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glycogen definition |
"stored energy" in liver and muscle, derived from glucose |
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glycogen synthase definition |
a key enzyme glycogen synthesis |
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glycogenolysis definition |
process of releasing glucose from glycogen by cleaving and phosphorylating a residue from the nonreducing end of glycogen chains |
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phosphorylase definition |
enzyme involved in the breakdown of glycogen to glucose |
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keto acids definition |
by product of fatty acid and amino acid conversion to glucose (due to absence of CHO) |
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triglyceride definition |
stored fat in a cell and can be used later as an energy source |
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glycerol phosphate definition |
phosphorylate glycerol upon entry into the cell to produce glycerol 3 phospate. Glycerol 3 phosphate enters the glycolytic pathway and is ultimately used for energy |
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hyperglycemia definition |
high blood glucose |
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hypoglycemia definition |
low blood glucose |
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ultra short acting insulin |
lispro insulin/aspart insulin |
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Lispro Insulin/Aspart Insulin characteristics |
-recombinant, with low tendency to form hexamers due to point mutations in the C-terminus of the B-chain, efficacious 5 min after injection -duration of these preparations is seldom more than 3-4 hours. Enhances glycemic control as compared to regular insulin. |
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short-acting insulin |
regular human insulin |
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regular human insulin characteristics |
-crystalline zinc insulin, most effective 30 min after injection -only form of insulin that can be given intravenously under physician’s supervision i.e. during surgery -As part of chronic administration, it is given IM (like all preparations). |
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intermediate-acting insulin |
NPH insulin
lente insulin |
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NPH insulin characteristics |
(Neutral protamine Hagedon): onset of action is delayed by combining insulin and protamine in a ratio (1:10 – protamine:insulin) so that neither is present in an uncomplexed form. Lente insulin is also in this group. |
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Lente insulin characteristics |
(insulin zinc suspension): an intermediate-acting insulin consisting of porcine or human insulin with a zinc salt added such that the solid phase of the suspension contains a 7:3 ratio of crystalline to amorphous insulin. |
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Long acting insulin |
ultralente insulin
glargine lantus |
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ultralente insulin characteristic |
poorly soluble crystal of zinc insulin with delayed onset of action |
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glargine lantus characteristics |
-bioengineered form of insulin is soluble at pH 4, but precipitates at physiologic pH -When the clear solution is injected, it forms microprecipitates in the body, delaying its absorption and prolonging its onset and duration of action. |
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Source of insulin preparations |
Bovine and porcine – historically the source of
insulin from animals Human insulin – is made using recombinant DNA technology (expressed in bioengineering yeast or bacteria followed by biochemical purification) |
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insulin units definition |
a measure of insulin activity – from times when purification of insulin from animal sources was as predictable. |
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insulin therapy benefits |
Type I – decreased glycated hemoglobin, diabetic retinopathy, nephropathy, neuropathy |
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Insulin therapy complications |
Hypoglycemia Immunopathology Lipodystrophy at injection site |
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Drugs for type 1 diabetes |
Aspart Insulin Lispro Insulin Regular Insulin NPH Insulin Lente Insulin Ultralente Insulin Glargine Insulin |
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Pharmacology of Type II diabetes therapeutic goals |
1) Insulin release 3) Decrease blood glucose |
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insulin secretagogues |
sulfonylureas
meglitinides |
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sulfonylureas examples |
tolbutamide
glipizide |
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sulfonylureas characteristics |
-binds the surfonylurea receptor that associates with a B cell inward rectifier-type ATP sensitive potassium channel -Binding inhibits the influx of potassium ions through the channel causing depolarization. -Depolarization opens the voltage gated calcium channel; increasing cellular calcium and releasing preformed insulin |
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meglitinides characteristics |
modulate insulin release by modulating B cell insulin through changes potassium channel influx. |
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meglitinides example |
Repaglinide (Prandin) |
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insulin sensitizers |
biguanides
thiazolidinediones |
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biguanides characteristics |
molecular mechanism is unknown, but causes a decrease in blood glucose levels. (Ex. Metformin) |
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Thiazolidinediones characteristics |
function by enhancing insulin target tissue sensitivity by enhancing activity of the peroxisome prolierator-activated receptor-gamma (PPAR-y) nuclear receptor. |
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enzymatic inhibitors |
alpha glucosidase inhibitors |
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alpha glucosidase inhibitors characteristics |
nhibits the enteric enzymes of the brush border of the intestinal cells. Prevents the breakdown of complex starches, oligosaccharides, and disaccharides. |
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factors affecting insulin absorption |
diet
exercise |
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adverse reactions type II diabetes treatment |
ketoacidosis |
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thyroid gland physiological fxn |
to normalize growth and development, body temperature, and energy levels |
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Hyperthyroidism (thyrotoxicosis) definition |
expression of too much thyroid hormone (example: Grave’s Disease) – too much activation of bodily functions and energy |
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hypothyroidism definition |
too little thyroid hormone, decrease in body energy |
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Treatment of hypothyroidism characteristics |
Replacement therapy – Levothyroxine (Synthyroid)
Because of long t1/2 of Levothyroxine, it takes 6-8 weeks after starting therapy until steady-state levels are reached. |
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Treatment of hyperthyroidism |
Anti-thyroid drugs – Thioamides: Methimazole Thyroidectomy – surgical removal of the thyroid Radioactive iodine (131I) – concentrates in the thyroid, and shrinks the size of the thyroid gland |
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hyperthyroidism effects on skin and appendages |
Warm, moist skin; sweating; heat intolerance; fine, thin hair; Plummer's nails; pretibial dermopathy (Graves' disease) |
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hypothyroidism effects on skin and appendages |
Pale, cool, puffy skin; dry and brittle hair; brittle nails |
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hyperthyroidism effects on eyes, face |
Retraction of upper lid with wide stare; periorbital edema; exophthalmos; diplopia (Graves' disease) |
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hypothyroidism effects on eyes, face |
Drooping of eyelids; periorbital edema; loss of temporal aspects of eyebrows; puffy, nonpitting facies; large tongue |
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hyperthyroidism effects on CV system |
Decreased peripheral vascular resistance, increased heart rate, stroke volume, cardiac output, pulse pressure; high-output congestive heart failure; increased inotropic and chronotropic effects; arrhythmias; angina |
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hypothyroidism effects on CV system |
Increased peripheral vascular resistance; decreased heart rate, stroke volume, cardiac output, pulse pressure; low-output congestive heart failure; ECG: bradycardia, prolonged PR interval, flat T wave, low voltage; pericardial effusion |
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hyperthyroidism effects on respiratory system |
Dyspnea; decreased vital capacity |
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hypothyroidism effects on respiratory system |
Pleural effusions; hypoventilation and CO2 retention |
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hyperthyroidism effects on GI system |
Increased appetite; increased frequency of bowel movements; hypoproteinemia |
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hypothyroidism effects on GI system |
Decreased appetite; decreased frequency of bowel movements; ascites |
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hyperthyroidism effects on CNS |
nervousness; hyperkinesia; emotional lability |
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hypothyroidism effects on CNS |
Lethargy; general slowing of mental processes; neuropathies |
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hyperthyroidism effects on musculoskeletal system |
Weakness and muscle fatigue; increased deep tendon reflexes; hypercalcemia; osteoporosis |
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hypothryroidism effects on musculoskeletal system |
Stiffness and muscle fatigue; decreased deep tendon reflexes; increased alkaline phosphatase, LDH, AST |
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hyperthyroidism effects on renal system |
Mild polyuria; increased renal blood flow; increased glomerular filtration rate |
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hypothyroidism effects on renal system |
Impaired water excretion; decreased renal blood flow; decreased glomerular filtration rate |
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hyperthyroidism hematopoietic system effects |
increased erythropoiesis, anemia 1 |
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hypothryroidism hematopoietic system effects |
decreased erythropoiesis; anemia 1 |
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hyperthyroidism effects on reproductive system |
Menstrual irregularities; decreased fertility; increased gonadal steroid metabolism |
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hypothyroidism effects on reproductive system |
Hypermenorrhea; infertility; decreased libido; impotence; oligospermia; decreased gonadal steroid metabolism |
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hyperthyroidism effects on metabolic system |
Increased basal metabolic rate; negative nitrogen balance; hyperglycemia; increased free fatty acids; decreased cholesterol and triglycerides; increased hormone degradation; increased requirements for fat- and water-soluble vitamins; increased drug detoxification |
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hypothryroidism effects on metabolic system |
Decreased basal metabolic rate; slight positive nitrogen balance; delayed degradation of insulin, with increased sensitivity; increased cholesterol and triglycerides; decreased hormone degradation; decreased requirements for fat-and water- soluble vitamins; decreased drug detoxification |
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Resperine characteristics |
-Reserpine, a drug used for hypertension and schizophrenia, was found to cause depression |
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tricyclic antidepressants (TCAs) MOA |
1. Non-specifically target the serotonin and norepinephrine receptors |
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TCAs uses |
a) A previous responder to another TCA |
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TCAs adverse effects |
1. Anticholinergic (anti-SLUD) effects: blurred vision, dry mouth, |
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SSRIS SELECTIVE SEROTONIN REUPTAKE INHIBITORS |
1. Fluoxetine (Prozac) – prototypical agent
(These weren't in bold, may not be necessary to remember) |
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SSRIS MOA |
Specifically increase serotonin levels in the brain by inhibiting its reuptake |
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SSRIS Uses |
1. Probably the drugs of choice for initial treatment of depression |
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SSRIs adverse effects |
1. N&V, dry mouth |
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drug of choice for bipolar disorder? |
Lithium |
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Lithium MOA |
Is an ion: |
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Lithium effects in CNS |
A. overactivity of neurotransmitters thought to contribute to mania |
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Lithium adverse effects |
V. ADVERSE EFFECTS: |
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Lithium interactions |
1. NSAIDs, tetracycline: decrease clearance of lithium |
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Schizophrenia symtoms |
•Positive: hallucinations, delusion, thought disorders, insomnia, bizarre behavior
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Goals for schizophrenia treatment |
•Alleviate perception abnormalities such as delusions and hallucinations |
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Traditional antipsychotic agents prototypical agent |
A. Chlorpromazine (Thorazine) |
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traditional antipsychotic agents MOA |
A. Non-specifically inhibit dopamine (D2 receptor) |
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traditional antipsychotic agents uses |
used in patients not responding to other agents |
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traditional antipsychotic agents extrapyramidal (EPS) side effects |
1. Early–onset EPS - sometimes reversible |
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Neuroleptic Malignant syndrome (NMS) characteristics |
1. Due to dopamine blockade |
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Non-traditional/apical antipsychotic agents |
1. Risperidone (Risperdal) |
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haloperidol characteristics |
A. Potent D2 blocker |
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Atypical (non-traditional antipsychotic agents): |
1. Risperidone (Risperdal) |
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Atypical (non-traditional antipsychotic agents): MOA |
1. variable - block serotonin receptors as well as dopamine |
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Atypical (non-traditional antipsychotic agents): Uses |
1. first line agents for the treatment of schizophrenia |
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Atypical (non-traditional antipsychotic agents): ADRs |
1. much MUCH less than with typical agents |
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antiepileptics |
PHENYTOIN (1938) ETHOSUXIMIDE CARBAMAZEPINE (OXCARBAZEPINE - analog) (1970s) VALPROATE (VALPROIC ACID) and DIVALPROEX GABAPENTIN (1990s) LAMOTRIGINE |
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phenytoin uses |
•Still one of the most effective (or perhaps THE most effective) AEDs against |
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phenytoin MOA |
•Alters multiple channels, in particular Na+ and to a lesser extent Ca++ |
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phenytoin ADRs |
1. Drowsiness |
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phenytoin interactions |
Potent inducer of many liver enzymes (P450s, MFOs) – many interactions due to this property |
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ETHOSUXIMIDE uses |
A drug of choice in absence seizures |
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ETHOSUXIMIDE MOA |
reduces the low-threshold calcium current in neurons – reduces discharge from thalamic neurons |
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ETHOSUXIMIDE ADRs |
• Most common: GI distress, weight loss, lethargy |
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CARBAMAZEPINE (OXCARBAZEPINE - analog) (1970s) uses |
• A drug of choice for Tonic-Clonic and Partial Seizures |
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CARBAMAZEPINE (OXCARBAZEPINE - analog) (1970s) MOA |
Alters conductance through several channels, in particular sodium channels of neurons |
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CARBAMAZEPINE (OXCARBAZEPINE - analog) (1970s) ADRs |
• Most common: diplopia (double vision) and ataxia |
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CARBAMAZEPINE (OXCARBAZEPINE - analog) (1970s) interactions |
• Induces metabolism of valproic acid, TCAs, haloperidol, lamotrigine and |
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VALPROATE (VALPROIC ACID) and DIVALPROEX (coated form for |
-BROADEST SPECTRUM AED - was at one time used for about every seizure type |
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VALPROATE (VALPROIC ACID) and DIVALPROEX (coated form for |
Affects sodium and calcium channels and increases GABA availability to synapse |
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VALPROATE (VALPROIC ACID) and DIVALPROEX ADRs |
Most common: |
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VALPROATE (VALPROIC ACID) and DIVALPROEX interactions |
Displaces phenytoin from PP binding, especially at high doses |
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Gabapentin uses |
•Back-up in partial seizures |
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Gabapentin MOA |
does NOT act on GABA receptor
binds to calcium channels to downregulate neurotransmission |
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Gabapentin interactions |
•May increase phenytoin blood levels at higher doses (probably not P450- |
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Lamotrigine uses |
A drug of choice in Partial and Atypical Absence Seizures
IMPROVES DEPRESSION in patients with epilepsy (unknown MOA) |
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Lamotrigine MOA |
Like phenytoin, suppresses sustained rapid firing of neurons through sodium channels |
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Lamotrigine ADRs |
· Most common: diplopia, blurred vision, rhinitis |
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mast cells fxn |
important initiators of allergic reactions |
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Histamine dominant actions |
The dominant actions of histamine are on blood vessels, other smooth muscles, afferent nerve endings (H1 receptors) and the secretion of |
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Histamine's vascular action "triple response" |
red spot (vasodilatation)
wheal (fluid leakage causing edema)
flare (diffuse redness due to nerve stimulation) |
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Histamine constricts nonvascular smooth muscle where? |
Histamine constricts nonvascular smooth muscle including bronchioles, gut and urinary bladder |
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allergic response to the release of leukotrienes and histamine characteristics |
-ranges from hives and itching to anaphylactic shock -latter is lifethreatening because of bronchiolar constriction and swelling of larynx |
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Antihistamines- H1 receptor antagonists |
Diphenhydramine (BENADRYL) |
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H1 receptor antagonists fxn |
-antagonize all of the components of the "triple response": vasodilatation, increased capillary permeability, and stimulation of nerve endings -antagonize bronchiolar constriction from histamine but not that caused by -action on bronchioles occurs too slowly to be of benefit for treatment of an acute asthma attack |
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Antihistamines- H2 receptor antagonists |
Cimetidine (TAGAMET) |
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H2 receptor antagonists important for |
H2 histamine receptors are important for gastric acid secretion, thus these antagonists are used in ulcer therapy, esophageal reflux and hypersecretory states. |
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quick-relief medications for asthma |
1. Inhaled beta2adrenoceptor agonists: albuterol
2. Anticholinergic: ipratropium
3. Systemic corticosteroids: prednisone
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Albuterol indication |
– Relief of acute symptoms/bronchospasm
Preventive treatment prior to exercise induced asthma (2 hours duration; >80% patients) |
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albuterol adverse effects |
– Acute: have not been able to separate tremor from bronchodilation
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ipratropium indications |
– Relief of acute bronchospasm, may provide additive effects to a beta2-agonist. |
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ipratropium mechanism |
– Bronchodilation by competitive inhibition of muscarinic cholinergic receptors |
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ipratropium adverse effects |
– Drying of mouth and respiratory secretions |
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prednisone indications |
– For short-term (3-10 days) “burst” to gain control, speed recovery and prevent recurrence of persistent asthma. |
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prednisone mechanism |
– Antiinflammatory by reduced airway hyperresponsiveness, block late reaction to allergens |
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prednisone adverse effects |
– Reversible abnormalities in glucose metabolism |
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Long-term controllers of asthma |
1. Inhaled corticosteroids 2. “Histamine Release Inhibitors” 3. Leukotriene modifiers oral 4. Long-acting inhaled Beta2adrenoceptor agonists: Salmeterol 5. Systemic corticosteroids 6. Methylxanthine
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inhaled corticosteroids |
Beclomethasone
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inhaled corticosteroids indication |
– Long-term prevention of symptoms; suppression, control and reversal of inflammation. |
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inhaled corticosteroids mechanism |
– Same as systemic corticosteroids |
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inhaled corticosteroids adverse effects |
– Cough |
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histamine release inhibitors |
cromolyn |
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histamine release inhibitors (cromolyn) indications |
– Long-term prevention of symptoms; may modify inflammation. |
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histamine release inhibitors (cromolyn) mechanism |
– Stabilize mast cell membranes & inhibit activation and release of mediators from eosinophils and epithelial cells |
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histamine release inhibitors (cromolyn) adverse effects |
– Safety is primary advantage |
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Leukotriene modifiers oral |
Zafirlukast
zileuton |
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Zafirlukast and Montelukast indications |
– Prevention of mild persistent asthma |
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Zafirlukast and Montelukast mechanism |
– Leukotriene inhibitor: LT D4 and LT E4 receptors |
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zileuton indications |
– Prevention of mild persistent asthma |
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zileuton mechanism |
– 5-lipoxygenase inhibitor |
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Long-acting inhaled Beta2adrenoceptor agonists: |
Salmeterol |
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salmeterol indications |
– Long-term prevention of symptoms, especially nocturnal symptoms
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salmeterol mechanism |
– Bronchodilation by adenylate cyclase activation and increase in cyclic AMP
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salmeterol adverse effects |
– Skeletal muscle tremor, tachycardia, hypokalemia |
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salmeterol therapeutic concerns |
– Not to be used to treat acute symptoms or exacerbations.
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prednisone indications |
– Long-term prevention of symptoms in severe persistent asthma: suppression, control, and reversal of inflammation |
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systemic corticosteroids |
prednisone |
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prednisone mechanism |
– Antiinflammatory by reduced airway hyperresponsiveness, block late reaction of antigens |
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prednisone adverse effects |
– Adrenal axis suppression
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methylxanthine |
theophylline sustained release |
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theophylline sustained release indications |
– Prevention of symptoms especially nocturnal symptoms |
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theophylline sustained release mechanism |
– Bronchodilation from phosphodiesterase inhibition and adenosine antagonism
– Serum concentration monitoring is essential due to significant toxicity, narrow therapeutic |
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Antacids |
Magnesium hydroxide plus aluminum hydroxide |
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H2 receptor antagonists |
Cimetidine (TAGAMET) |
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proton pump inhibitors |
Esomeprazole (NEXIUM) |
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proton pump inhibitors vs. H2 receptor antagonists |
When contrasted with the actions of H2 antagonists, proton pump inhibitors provide more effective ulcer healing and faster relief of symptoms. They heal more than 90% of duodenal ulcers within a month and most gastric ulcers within two months. |
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protokinetic drugs |
metoclopramide |
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metoclopramide characteristics |
-improves gastric emptying -Drug induced GI motility increase is mediated through stimulation of muscarinic receptors |
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antiemetic drugs |
ondansetron
prochlorperazine
dronabinol |
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antidiarrheal agents |
loperamide
diphenoxylate |
