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360 Cards in this Set
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how do Locals work (effect)?
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stop Na channels
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Local structure?
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lipophilic part and charged amine segment connected by amide or ester link
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As molecular weight and lipid solubility increases for a Local, what happens?
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1. more potency as local
2. bind Na channel longer 3. more toxic if in systemic circulation |
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Examples of ester linked locals?
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Procaine (short-acing)
Tetracaine (Long) |
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Examples of amide linked locals (a short, medium and long acting ex.)?
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1. Lidocaine (short)
2. Mepivacaine (moderacte acting) 3. Bupivacaine (long) |
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unique for naming difference between esters and amides?
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amides always have an A and and I before caine. esters do not have both.
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Toxicity of local depends on? termination depends on?
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plasma concentration
tissue blood flow |
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how does cocaine differ from the other locals?
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it produces constriction instead of dilation..
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how are ester locals degraded? the amides?
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plasma esterases (pseudocholinesterase)
liver for amides |
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bad side effect of the amide locals?
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can produce gran mal seizures and depress respiration
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what % of locals are excreted uncharged?
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5%
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What is the order of sensitivity to local blockade for nerve functions?
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1. pain 2. touch 3. adrenergic vasoconstriction 4. temperature 5. proprioception 6. motor function
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which type (ester or amide) of local is more likely to produce acute anaphylaxis? (examples)
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Ester types with p-aminobenzoate (procaine, tetracaine)
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systemic toxic affects what in the body?
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1. CNS
2. Cardiovascular system |
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what is the limit on amount of lidocaine?
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500mg (for full sized individual)
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Locals, if cause a death, is generally b/c
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1. locals used in pt with a CNS depressant (barbituates or opiates)
2. Clinician not prepared for a respiratory depression |
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what faciliates seizure activity?
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Hypercapnia (too much CO2) and acidosis
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If dentist needs to use inticonvulsive drug, should sue?
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IV of lorazepam or diazepam
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what on procaine leads to anaphylaxis sometimes?
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p-aminobenzoic acid
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procaine is ___acting? type? metabolized by?
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short
ester plasma cholinesterase |
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tetracain is ___acting? type? downside?
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long
ester more toxic |
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Lidocaine other uses besides loca?
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antiarrhythmic drug
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Lidocaine is ___acting? type? metabolized by?
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short
amide in liver |
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lidocaine is metabolized into?
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two metabolites
1. one with no antiarrhythmic activity 2. one with CNS stimulatory activity |
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Mepivacaine is ___acting? type? uses?
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moderate
amide Local, nerve block (spinal/epidural) |
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Bupivacaine is ___acting? type? main side effect?
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long
amide cardiovascular toxicity |
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use for cocaine?
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topical for surgery (b/c of its vasoconstiction, decreasing NE uptake into neurons)
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Benzocaine is unique because?
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non-amine local without +charge.
needs high concentrations to work (over 10%) |
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alternate administration for lidocaine?
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iontophoresis: dirct electrical charge forces drug into cutaneous tissues
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General anesthesia is?
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reversible loss of consciousness with
1. analgesia 2. amnesia 3. inhibition of sensory and autonomic reflexes 4. decreased skeletan muscle tone |
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conscious sedation is
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altered/diminished state of consciousness with
1. analgesia 2. amnesia 3. retained responsiveness to verbal commands |
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analgesia is
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loss of response to pain
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stages of general anesthesia are?
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1. analgesia without loss of consciousness
2. excitation 3. surgical anesthesia 4. Medullary depression |
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How does stage 2 excitation differ from stage 3 surgical anaesthesia?
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stage 2 BP and respiration can be irregular and pt. can vomit, hold breath, etc.
3. is regular respiration and BP with reflexes suppressed |
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Stage 4 of general anesthesia represents?
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relative overdosage.
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examples of volatile anesthetics?
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desflurane, isoflurane and sevoflurane (halogenated hydrocarbons)
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NO is a ___anesthetic? characteristics?
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Gaseous. colorless, odorless, non-flammable gas lacking potency
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maximal safe inspired concentration of NO is? if above this?
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70%.
above this can produce hypoxia |
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NO is good for?
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analgesic and amnestic without useful muscle relaxation (so a good supplement)
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why does NO have a quick onset ad offest?
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low blood sulbility
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Diffusion hypoxia is? how treat it
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when NO is stopped, the quick rate of diffusion to the lungs blocks the O2 eschange
use 100% O2. |
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long-term exposure to NO can do?
caused by? |
blood dyscrasias, bone marrow suppression, peripheral neuropathies, and increase in spontaneous absorption
Methionine synthase inhibition |
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IV anesthetic types?
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Barbiturates
benzodiazepines Propofol |
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Examples of Barbiturates?
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thiopental, thiamylal, methohexital
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Barbiturates ____acting? useful for?
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very short. produce unconsciousness within 30 sec (IV) and last 20-30 min.
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how do barbiturates wear off?
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redistribuion, not metabolism and then renal excretion
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if barbiturates are administered to rapidly or in too large a dose?
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respiratiory and CV depression
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barbiturate effects?
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loss of consciousness and amnesia not anesthesia
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Benzodiazepine examples?
which is prefered? |
diazepam, midazolam, lorazepam
midazolam is prefered |
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Benzodiazepine uses?
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surgical anesthesia or conscious sedation
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benzodiazepines are terminated by?
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specific benzodazepine receptor antagonist: flumazenil
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Propofol is for?
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IV anesthetic that is rapid onset and anesthesia
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propofol half life is?
termination time? |
alpha: 2-8 min
beta: 30-60 min 10-20 minutes |
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side effects of propofol are?
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anaphylactoid reactions due to emulsifying agent, not active agent.
inhibits platelet function and increases bleeding times |
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Bone contains __% of calcium and phosphate in body?
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98% calcium
85%phosphate |
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Calcium concentrations in serum range from? what if there is a50%or more change in Ca concentration?
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8-10mg/dl
life threatening hypo/hypercalcemia |
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Risk factors for osteoporosis 7?
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1. female 2. smoking 3. underweight 4. lack exercise 5. excessive alcohol 6. glucocorticoid use 7. calcium intake
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what has a better absorption rate, Ca or P?
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P!
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What % of Ca and P are excreted from filtrate?
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2%Ca
15%P |
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where is Ca absorbed? P?
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Duodenum and upper jejunum (secreted from ileum)
P: jejunum (more efficient) |
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what commonly leads to osteroperosis?
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small bowel disease and kidney disease
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what hormones regulate Ca and P metabolism?
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1. PTH: poly peptide (84 AA)
2. Vitamin D: made in skin, ingested |
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Vitamin D and PTH affect?
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D: gut, bone
PTH: bone only |
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PTH's principle action ?
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increase serum Ca and reduce serum P
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low doses of PTH do?
High doses of PTH do? |
Low: decrease bone reabsorption (or bone formation) (increases osteoblast activity)
High: increase bone reabsorption (or bone loss) (increases activity of osteoclasts) |
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Direct renal actions of PTH?
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1. increase Ca and Mg reabsorption
2. decrease in P reabsorption 3. Increased renal formation of Vit D3 |
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how treat Osteoporosis?
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Teriparatide (a receptor agonist for PTH) adminsitered subQ
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Vit D3 formed from
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7-dehydrocholesterol in skin under sunlight
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Vit D3 and D2 can be obtained?
activated by? |
in normal diet
activatd by hydroxylation in the liver (25) and in kidney (at 1 or 24) |
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Vit D3 defficiency does?
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Rickets
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principal actions of Vit D?
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1. increase serum ca and P concentrations
2. increase intestinal absorption of Ca and P 3. decrease Ca and P excretion |
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24,25 Vit D differs from 1,25 Vit D effects to bone by?
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24: can increase bone formation through stimulation of osteoblastic activity
1: increase osteoclastic activity |
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how does 1,25 Vit D increaes Ca absorption in the Jejunum
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synthesis of new Ca binding proteins
increased ca transport |
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What is Calcitonin and where is it made?
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Peptide (32 AA) made by Parafollicular cells of Thyroid
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Calcitonin action?
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reduces serum calcium and serum phosphate (reduce reabsorption in the kidney)
reduce osteclastic activity so increased bone formation |
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Calcitonin administration/
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parenterally or inhaled
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reloxifene is ? does? risks?
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estrogen type supplement
reduce bone loss in pts with osteoporosis 1. increaed risk for endometrial carcinoma 2. facilitation fo growth for breast cancer (low risk) |
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why is reloxifene unique?
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agonist of alpha estrogen receptor but antagonist for beta estrogen receptor
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Thiazide diuretics do to ca? other good uses?
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increase ca ion reabsorption
reduce oxalic acid excretion and reduce the formation of renal caluli (Kidney stones) |
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high ceiling diuretics (furosemide) differ in Ca effect by?
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promoting calciuria and an increased excretion of calcium
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Fl- for osteoporosis pts?
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stimulateds new bone formation with increase in Ca content and bone volume
decreased bone fractures |
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Side effects of Fl use orally (large doses)?
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nausea, vomiting, GI blood loss, and arthralgia
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Bisphosphonate stucture?
does? |
like Pyrophosphate but PCP bond instead of POP
decrease rate of osteoclastic dissolution of hydroxyapatite in bone (maybe toxic to osteoclasts) so slows resorption of bone |
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bisphosphonate drugs ex?
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alendronate (oral)
zolendronate (IV) |
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Why not take bisphosphonates orally/
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only about 10% of them can be absorbed with oral administration
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bisphosphonate administration if orally must?
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1. be with 6 oz water on empty stomach
2. pt must be standing, sitting upright for 2hours |
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bisphosphonate contraindications?
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peptic ulcers, reduced renal function
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acute vs. chronic inflammation?
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A: short lasting (a few days)
C:longer with infiltration of lymphocyte, macrophages, plasma cells, and tissue destruction by inflammatory cells and self repairing attempts with fibrosis and angiogenesis |
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What are the mediators of acute inflammation for vasodilation
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Bradykinin, prostaglandins, histamine and serotonin a little
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Which mediators of acute inflammation cause vascular permeability?
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histamine, leukotrienes a lot
serotonin, bradykinin and prostaglandins some |
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which mediators of acute inflammation cause chemotaxis?
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prostaglandins and leukotrienes
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which mediators of acute inflammation signal pain
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Bradykinin a lot and prostaglandins some
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what are the sources of interleukins 1-3?
what are their effects? |
macrophages and t-cells
lymphocyte activation, prostaglandin production |
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GM-CSF ceoms from?
does? |
t-cells, endothelial cells, fibroblasts
macrophages and granulcyte activation |
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TNF-alpha is from?
Does? |
macrophages
prostaglandin production |
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Interfeons are from?
Do? |
Macrophages, endothelial cells and t-cells
macrophages and granulocyte activation |
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PDGF is from?
Do? |
macrophages, endothelial cells, fibroblasts, platelets
fibroblast chemotaxis and proliferation |
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what are the metabolites of arachidonic acid?
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leukotrienes, prostacyclin, prostaglandins, thromboxane
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what do prostaglandins and thromboxane do?
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vasodilation and prolong edema
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besides cox, what is teh other pathway for Arachidonic acid?
drugs that inhibit this pathway? |
Lipoxygenase activity (makes leukotrienes)
Zileuton, later on Zafirlukast |
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what do leukotrienes do?
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increase bronchial tone
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what do prostacyclins do?
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decrease: platelet a ggregation, vascular tone, bronchial tone, uterine tone
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Prostaglandins do?
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increase uterine tone and decrase vascular tone and bronchial tone
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what does thromboxane do?
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increase: platelet aggregation, vascular tone and bronchial tone
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what is the purpose of drug therapy for arachidonic acid pathways?
drug categories? |
pain relief and tx of tissue-damaging processes
NSAIDs, Corticosteroids, slow-acting anti-rheumatic drugs (SAARDS) Disease-modifying ant-rheumatic drugs (DMARDS) |
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what do NSAIDS do specifically?
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1. Anti-inflammatory
2. Analgesic 3. Antipyretic (fever reducing) |
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what are the 3 types of COX?
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1: constitutively expressed
2. induced by cytokines 3. maybe like type 1, but in CNS type 2 is the one we want to stop |
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Aspirin aka? it is prototypical for?
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acetylsalicylic acid
analgesic, anti-inflammatory and antipyretic |
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absorption rate of aspirin
elimination? |
rapid, and converted to salicylic acid (active)
urine as salicylic acid or as glucuronic acid conjugate |
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aspirin action?
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non-selective COX1 and 2 irreversible inhibitor (does not inhibit lipoxygenase
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antipyretic of aspirin effects are limited to?
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those with a fever
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Antiplatelet effects of aspirin?
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1 tablet can doulbe bleeding time (325 mg)
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GI effects of asprin?
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major disadvantage: interferes with ability of gastric mucosal cells to resist penetration by acid which may lead to gastric irritation and distress
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general uses of aspirin?
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mild anti-inflammatory effects that can synergize with opioids to enhance pain relief
fever and pain |
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specific uses of aspirin?
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1. transient ischemia
2. alters the effect of PGI2 and TXA2 (vascular smooth muscle tone relaxation) unstable angina (anti-platelet effects) myocardial infarction (anti platelet) prevent re-infarction in patients with high risk of MI |
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side effects of aspirin?
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GI upset, Tinnitus (ringing in ears), decreased hearing, vertigo, increased uric acid levels, hepatitis,
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aspirin overdose does?
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reyes sydrome get it
depresses respiratory center, metabolic acidosis, uncoupling of oxidative respiration |
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contraindications of aspirin?
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pregnacy, other salicylates for teeenagers with recent viral infection (reye's)
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examples of selective COX2 inhibitors?
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celecoxib, valdecoxib, meloxicam (order from most to least selective)
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Selective Cox2 inhibitors metabolized by? eliminated by?
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cytochrome p450 and eliminated by kidney
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Adverse effects of COX2 inhibitors?
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GI: same after 6 mo
nothing on platelets renal toxicity same as NSAIDS increase in edema and hypertension |
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contraindications of COX2 inhibitors?
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pts with sulfonamide allergies (celecoxib has sulfonamide backbone)
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Aceaminophen effects?
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analgeis and antipyretic but only weak cox inhibitor (no anti-inflam or anti platelet) maybe cox3 inhibition (thus CNS effect)
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uses of acetaminophen?
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relieve pain and reduce fever
headache, myalgia, postpartum pain, fever |
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acetaminophen time to peak in blood?
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30-60 min? metabolized by liver microsomes and excred in the urine
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adverse effects / overdose of acetaminophen?
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liver toxicity (especially with alcohol)
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other NSAIDS?
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like aspirin
cause renal toxicity (chronic use) contraindicated with asthma, nasal pulyps, |
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largest group of aspirin alternatives is?
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phenylpropionic acid derivatives
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what do phenylpropionic acid derivatives do?
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inhibiting COX and prostaglandin synthesis
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side effects of phenylpropionic acid derivatives?
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less GI problems than aspirin
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examples of phenylpropionic acid derivatives?
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Ibuprofen, naproxen,indole, and indene
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prescription of ibuprofen? is usually?
half life? side effects differ from aspirin in that? |
600mg: QID
800mg: TID 2 hours less GI bleeding and less fluid retention that indomethacin |
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Naproxen prescription?
side effects compared to Aspirin and ibuprofen |
375 mg BID
12-15 hour half life which is why BID less GI effects than aspirin but double that of ibuprofen |
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prescription variants of ibuprophen
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fenoprofen: rare adverse effect is interstitial nephritis
flurbiprofen: Topical ophthalmic formula for intraoperative miosis Ketoprofen: inhibits COX and Lipoxygenase |
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The Indole and indene derivatives ex?
uses? |
indomethacin (Rx only)
Patent ductus arteriosus, gout, and general pain/inflam |
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Action of indomethacin? how differ from other NSAIDS?
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Selective COX-1 inhibition
highly effective but more toxic |
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Adverse effects of indomethacin?
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Sever GI bleeds, headache w/ dizziness, confusion and depression
Thrombocytopenia, anemia |
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Pyrrole derivative ex?
uses? |
ketorolac
Analgesic for post op pain (opioid level). supposedly equal to morphine w/o drowsiness, nausea, vomiting |
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Adverse effects of Ketorolac?
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GI (more serious and faster onset)
Bleeding (platelet inhibition) |
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combo of aspirin and acetaminophen benefit??
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not clear
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NSAIDS and Caffeine combo benefit?
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Caffeine is analgesic adjuvant and CNS vasoconstricive effects may alleviate some headaches
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NSAIDS and Opioids combo benefit?
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Combo of centrally and peripherally acting analgesics
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Contraindications of NSAIDS?
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Children, pts with risk of bleeding, ulcers, kidney failure, liver disease
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Drug interactions of NSAIDS?
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some anti-hypertensive agents (beta-blockers, ACE inhibitors, diuretics) reduce the effects of these drugs
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Which NSAID cannot block sourse of pain? source is?
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acetaminophen
inflammation |
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what do opioids cause that NSAIDS do not?
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drowsiness, dizziness, nausea, and vomiting
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When do you prescribe solo drugs vs combos?
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Mild pain: solo
moderate/severe: combos |
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What type of drugs are used for arthritis? when?
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DMARDS (disease modifying anti-rheumatic drugs)
rapidly progressing or refractory cases (low doses) Actually it is an anti-cancer drug |
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Ex. of immunosuppressive DMARDS?
how does it work? |
Methotrexate
inhibits DNA synthesis of inflammatory immune cells (inhibits dihydrofolate reductase stopping dihydrofolate -->tetrahydrofolate and thus stops DNA synthesis) |
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Anti-malarial drugs DMARDS exs?
uses? |
Chloroquine and hydroxychloroquine
pts with mild RA, or severe cases when NSAIDS are no longer effective |
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chloroquine and hydrochloroquine adverse effects?
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GI and dermatologic disturbances
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Penicillamine as a DMARDS does?
when use? |
immuosuppressive and immunostimulant properties but no antibacterial
cases RA taht are refractory to salicylates or related compounds |
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Adverse side effects of penicillamine?
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Skin rash, GI disturbances and nephropathy
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Sulfasalazine as DMARDS when?
how work? |
NSAIDS no longer working.
converted by intestinal gut flora to a sulfonaminde (anti-bacterial) and a salicylate (anti-inflammatory). |
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Sulfasalazine differs from other DMARDS by?
adverse effects? (RA cases to use it with?) |
lower toxicity
nausea, vomiting, bloody diarrhea and anorexia (use with mild RA) |
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Anti-TNF alpha drugs made by ? activated by?
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macrophages. T-cells activate it.
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Anti-TNF alpha does?
the drug ex that inhibits this? |
stimulates release of inflammatory cytokines from other cells.
Infliximad (expensive but long half life) |
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For, RA, the drug order is?
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NSAIDs, then DMARds, later methotrexate (moderate to severe)
if it fails, then add TNFalpha to methotrexate |
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Gout is due to?
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increased concentration of uric acid in body fluids due to increased production or decreased excretion
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why gout has pain?
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excess uric acid/salt precipitates out and deposits in joints and urinary tract
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Tx of gout mechanisms?
|
uricosuric drugs to increase renal urate clearance or inhibiting synthesis
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Uricosurics do?
adverse effects? |
block tubular reabsorption of uric acid thus increasing urinary excretion of uric acid. (chronic gout)
GI irritation and allergic dermatitis |
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Allopurinol inhibits?
Does? |
Zanthine oxidase (rate limiting enzyme in uric acid formation)
decreases synthesis of Uric acid and lowers blood/urine concentration |
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allopurinol is for chronic/acute gout?
adverse effects? |
chronic
acute attack of gouty arthritis, skin rash and GI intolerance |
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drug interactions of allopurinol?
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increases effects of anti-cancer drugs
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Indomethacin drug of choice for?
|
tx acute gouty arthritis, reducing pain and inflammation
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types of neurotransmitters in CNS?
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1. AA
2. Acetylcholine 3. Monoamines 4. Others |
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Ex. of AA neurotransmitters?
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1. Glutamic acid
2. Gaba |
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Exs of monoamines as neurotransmitters in CNS?
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1. NE, Epi
2. Serotonin (5-HT) 3. Dopamine |
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ungrouped Neurotransmitters for CNS?
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Peptides, histamine, Nitric acid,
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Drugs for gran mal seizures?
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phenytoin
Carbamazepine Valproic acid |
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Absence seizures (petit mal) drugs?
|
ethosuximide
Valproic acid |
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Benzodiazepines are?
|
sedative hypnotic drugs
|
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ex. of Benzodiazepines ?
|
Diazepam
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Drug for tx of dementia-alzheimer's disease?
|
Donepezil
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Antidepressant agents?
|
Tricyclics: amitriptyline
Selective serotonin reuptake inhibitors (SSRI): fluoxetine |
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CNS stimulants drugs?
|
cocaine, amphetamines, methylphenidate
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dopamine pathways for:
emotions? Prolactin release? CTZ; emesis? extrapyramidal motor system? retina and olfactory bulb? |
emotions: mesolimbic/mesocortical
tuberoinfundibular (prolactin release) Chemoreceptor trigger zone (CNZ; emesis) Nigrostriatal (extrapyramidal motor system) Ultrashort pathways (retina and olfactory bulb) |
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Drugs for parkinson's disease and each work by?
|
Bromocriptine: dopamine receptor stimulation
Selegiline MAO inhibtion and Entacapone COMT inhibition (dopamine breakdown) Levodopa and carbidopa:Dopamine replacement |
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Drugs for Schizophrenia?
|
haloperidol and risperidone
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drugs for manic-depressive syndrome?
|
lithium and valproic acid
|
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Drugs for emesis? each do?
|
Haloperidol: block dopamine at CTZ
ondansetron: block CNS 5-HT receptors promethazine:Block CNS histamine receptors |
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drug for tx of migraines and does?
|
Sumatriptan: stimulation of 5-HT receptor
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opioids contain what that makes them do what they do?
|
alkaloids (natural plant derived chemicals) {morphine and codeine}
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what happens if they add a methyl group to codeine?
|
Reduces first pass hepatic metabolism (ie. increases that available through oral administration)
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Codeine substitution with allyl group and a hydroxyl group?
|
Naloxone, antagonist
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what are the two mechanisms to stop pain?
|
1.interrupt transmission of ascending pathways for pain
2. modulation of feed back circuits in descending |
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3 sites of action for opioids and how each works?
|
1. spinal cord: inhibit release of neurotransmitters (primary afferents)
2. Thalamus and limbic system: block perception of pain 3. Brainstem: activate descending inhibitory systems to modulate pain |
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what does u (mu) opioid receptors do?
|
supraspinal/spinal analgesia, sedation, inhibit respiration, slow GI, modulate hormone/NT release
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what does the delta opioid receptor do?
|
Supraspinal and spinal analgesia
modulation of hormone release |
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what does the kappa opioid receptor do?
|
supraspinal and spinal analgesia
psychotomimetic effects slow GI |
|
|
what is the family for the opioid receptors?
what are the 2 actions that these activated receptors perform? |
G protein
1. close Voltage gated Ca channels (presynaptic nerve terminals) 2. hyperpolarize and thus inhibit post synaptic neurons by opening K channels |
|
|
What are the families of endogenous opioids?
|
1. endorphins
2. enkephalins 3. dynorphins |
|
|
Endorphines made of __AAs? which receptors do they activate?
function? |
31 mu (u)
function as neurohormones and mediate psychological responses to pain and stress |
|
|
enkephalins are __AAs? where found?
functions? receptors? |
5 brain, spine,
neurotransmitters. kappa (k) |
|
|
Dynorphins are ___AAs?
function as? receptors? |
17.
neurotransmitters. kappa (k) |
|
|
what are the therapeutic effects of opioids?
|
analgesia, antitussive, antidiarrheal, acute pulmonary edema, sedation/mood elevation, anesthesia
|
|
|
what are the untoward efects of opioids?
|
CNS euphoria/disphoria
respiratory depression constipation addiction miosis |
|
|
which untoward effects are caused by activation of the mu receptor?
|
all of them
|
|
|
which effects are caused by activation of delta receptor?
|
analgesia
|
|
|
which effects are caused by activation of kappa receptor?
|
analgesia, miosis, sedation, dysphoria, addiction, altering GI motility pattern
|
|
|
agonists of opioid receptors (strong and moderate levels?)
|
strong: morphine, meperidine, methadone
Moderate: codeine, oxycodone, propoxyphene |
|
|
Antagonists of opioid receptors?
|
Naloxone
|
|
|
opioids taht are mixed actions on receptors? where effect?
|
Pentazocine: k agonist and weak u antagonist (or partial agonst)
CNS effects with euphoria so it can be abused |
|
|
Antitussives for opioid receptors?
|
(blocks cough). codeine. dextromethorphan is selective for this
|
|
|
Antidiarrheal opioids/
|
diphenoxylate nad loperamide
|
|
|
what is the prototypes opioid drug?
|
morphine
|
|
|
How does the analgesia for morphine work?
|
selective effect, not affecting other senses. suppress perception and reaction to pain most effectively on visceral pain
|
|
|
Euphoria or dysphoria with morphine?
|
Euphoria unless nove/non-pain users
|
|
|
What type of sedation comes from morphine?
|
drowsiness and mental clouding
|
|
|
How does morphine suppress cough?
|
cough reflex center in medulla (codeine is really good at this)
|
|
|
where is the respiratory depression caused at?
|
brainstem, decreasing response to CO2.
|
|
|
Why does morphine cause miosis?
|
stimulate oculomotor nucleus for pinpoint pupil production
|
|
|
which CNS effects of morphine can you develop tolerance to?
|
analgesia, euphoria, sedative, and respiratory depression
|
|
|
how does morphine effect the CV system?
|
can cuase histamine release in local area: itching, bronchspasm, vasodilation
can be used to tx pt with pulmonary edema |
|
|
who does morphine effect the GI system?
why does this matter? |
decrease secretions, increase the resting tone, decrease propulsive activity of GI (constipation)
b/c no tolerance develops so effects pts. using morphine long term |
|
|
morphines effects on the sphincters?
|
biliary colic, post op urinary retention (increased tone), constipation too
|
|
|
what is heroin?
why not used in US |
diacetyle derivative of morphine
readily enters CNS and thus is very addictive |
|
|
Meperidine is?
|
derivative of morphine with rapid onset and short duration. used for atropine-like actions
|
|
|
Methadone differs from mophine by?
how administered? used for? |
no peaks and valleys of response b/c it has long duration of action
orally: for pts addicted to heroin, etc. |
|
|
Fentanyl is like what other drug?
how does it differ from morphine? used for? |
meperidine
50-80 times more potent anesthesia and analgesia, chronic pain |
|
|
Tramadol effects which receptor?
also effects? uses? |
u
serotonin, and NE uptake in CNS neurons pain relief b/c of less addiction liability |
|
|
Moderate agonists include?
|
1. codeine 2. oxycodone/hydrocodone
|
|
|
codeine is used for?
usually combined with? |
mild-moderate pain (1/10 to 1/5 potency of morphine)
antitussive NSAID |
|
|
oxycodone and hydrocodone are used for?
combined with? |
analgesia
aspirin or acetaminophen |
|
|
weak agonists of morphine ?
|
propoxyphene
|
|
|
propoxyphene is similar to? to be like morphine, needs?
death can occur if? |
aspirin
very high doses high doses with alcohol/hypnotic drugs |
|
|
Antagonists of morphine?
type of receptor preference? |
naloxone
u |
|
|
naloxone duration? how given?
|
1-2 hrs, IV
|
|
|
Which drugs are antidiarrheals?
|
Diphenoxylate and loperamine
|
|
|
what type of pain is stopped by opioids?
|
constant pain, not intermittent sharp
|
|
|
what is the half life of methadone?
|
24 hours
|
|
|
what are some contraindications for opioid use?
|
impared pulmonary function, head injury/trauma, pregnancy
|
|
|
What are teh drug interactions for opioids?
|
CNS depressnats, neuroleptics (antipsychotics), TCAs, monoamine oxidase inhibitors
|
|
|
opioids taken with antidepressants can cause?
|
CNS depression and orthostatic hypotension
|
|
|
meperidine taken wtih a monoamine oxidase inhibitor can result in?
|
excitation, rigidity, hypertension and death
|
|
|
how long can pt take opioids without fear of addiction?
|
7 days or less
|
|
|
why are benzodiazepines chosen?
can also be used for? |
anxiolytic potency related to CNS depressive effects
sedative-hypnotic (sleep) |
|
|
Barbiturates used as?
|
seative hypnotid (sleep)
but mosty replaced by benzodiazepines |
|
|
Phenobarbital is?
thiopental is? |
barbiturate used for epilepsy
thiopental is for anesthesia |
|
|
in addition to anxiolytic and sedative qualities of benzodiazepines, what other effects do they have?
|
anterograde amnesia.
hypnosis anesthesia (high doses) Anticonvulsant muscle relazation |
|
|
how long does it take to build tolerance to hypnosis from benzodiazepines?
|
2 weeks
|
|
|
what are teh clinical sues of sedative-hypnotics?
|
anxiety, long lasting
sleep, short lasting muscle spasticity: diazepam phobic anxiety: alprazolam Anesthesia: thiopental, midazolam Detoxification: long lasting |
|
|
What are the benzodiazepines?
|
midazolam, lorazepam, alprazolam, diazepam and chlordiazepoxide
|
|
|
what are teh benzodiazepime antagonists?
|
flumazenil
|
|
|
Drugs for anxiety and sleep?
|
buspirone, zolpidem, zaleplon, eszopiclone, ramelteon
|
|
|
parkinsons, ALS, alzheimers, huntington's are due to what?
|
progressive and selective loss of neurons from specific parts of brain
|
|
|
Parkinsons is what type of disorder?
what are the 4 primary symptoms? |
hypokinetic, idiopathic
1. muscular rigidity 2. tremor 3. bradykinesia 4. postural instability |
|
|
how common is parkinsons?
how long does it last till pts can no longer care for themselves? |
1% of those over 55
5-10 yrs |
|
|
what is lost in parkinsons?
|
>80% loss of dopamine containing cells of pars compact and substantia niagra.
|
|
|
how tx parkinsons?
|
enhance action of dopamine in CNS
1. replace dopamine (L-dopa) 2. direct acting dopamine agonists 3. alter dopamine metabolism/concentration |
|
|
Levodopa is?
why used? |
L-dopa
b/c dopamine does not cross BBB |
|
|
what % of L-dopa enters brain?
|
1%
|
|
|
what is given to increase l-dopa that gets to brain?
how much difference does this make to the dose? |
given with carbidopa (peripheral dopa decarboxylase inhibitor) {sinemet}
70-80% reduction in dose needed! |
|
|
what % of pts have good reaction to L-dopa?
|
50%. and it gets worse at time of tx goes on
|
|
|
how to avoid CNS side effects of L-dopa?
|
3days to 3 weeks off at a tiem can help neurological effects
|
|
|
What are 2 exs. of dopamine agonists?
|
bromocriptine
pramipexole |
|
|
how are dopamine agonists better than L-dopa?
downsides? |
longer duration, less fluctuations and dyskinesias, and do not require enzymatic conversion
not quite as effective as L-dopa |
|
|
whey use agonists of dopamine?
|
in the beginning to prolong beginning L-dopa
use to help with on-off problems seen with L-dopa later on |
|
|
Bromocriptine does vs pramipexole?
|
stimulates D1 and D2 receptors
pram is more selective for D2 (fewer side effects) |
|
|
what do MAO inhibitors do? ex?
|
increases striatal CNS dopamine by inhibiting MAO (breadown)
Selegiline |
|
|
COMT inhibitors exs (2)?
|
entacapone
tolcapone |
|
|
COMT does?
COMT inhibitors do? |
inactivates L-dopa
increase L-dopa in peripheral system |
|
|
entacapone vs tolcapone?
|
E: peripheral only
Tol: both CNS and peripheral and a longer duration |
|
|
why is tolcapone not used?
|
hepatoxicity-->death!
|
|
|
why use muscarinic receptor antagonists for parkinsons?
ex drug? |
block cholinergic actions in striatum that normally oppose tonic release of dopamine
benztropine |
|
|
benztropine is unique because?
|
only drug effective for tx of anti-psychotic drug induced parkinsonism
|
|
|
benztropine side effects?
|
cycloplegia, dry mouth, urinary retention.
High doses: confusion, hallucinations, etc |
|
|
muscarinic receptor blocking drugs should be avoided in pts with?
|
prostatic hyperplasis
angle-closure glaucoma |
|
|
what % of people in us are depressed?
what % have depressive episode in lifetime? |
5-6%
10% |
|
|
Reserpine does?
|
causes depression (was for schizo and hypertension)
inhibit storage of amine NTs |
|
|
What is the prototype TCA?
chemical structure? |
amitriptyline
3 ring nucleus |
|
|
How are TCAs cleared?
|
rapidly from first pass metabolism in the liver
|
|
|
elimination half life range of TCAs?
how may half live for stead state levels? |
12-72 hrs
5 |
|
|
mechanism of action of TCAs?
mechanism of adverse effects? |
1.non-specificly target serotonin and NE receptors in CNS
2. Bind a-adrenergic, histaminergic, and cholinergic receptors (causing adverse effects) |
|
|
TCAs should be used with pts? (qualifications)
|
1. previous responder to other TCA
2. medically healthy 3. non-suicidal 4. refractory to newer agents (like SSRIs) |
|
|
what are the adverse effects of TCAs?
|
Anti-cholinergic (anti-slud): blurry vision, dry mouth, urinary retention, constipation
a-adrenergic block: orthostatic hypotension, impotence, dizzyness antihistamine: sedative |
|
|
SSRIs are?
|
selective serotonin reuptake inhibitors
|
|
|
ex of SSRIs?
|
1.fluoxetine
2. paroxetine 3. citalopram 4. Sertraline |
|
|
prototypical SSRI?
how long to see effect take place? |
fluoxetine
2-3 wks |
|
|
SSRIs metabolized by?
|
cytochrome p450
|
|
|
Method of action of SSRIs?
|
increase serotonin levels in brain (inhibit reuptake)
|
|
|
adverse effects of SSRIs?
|
1. dry mouth
2. insomnia/drowsiness 3.Sexual dysfunction |
|
|
Lithium is drug of choice for tx of?
|
Bipolar disorder
|
|
|
Method of action of Lithium?
|
competes with K, Mg, Ca, Na in body
in CNS, decreases overactivity of neurotransmitters (to decrease mania) increasing catecholamine destruction, decreasing NT release, and decreasing sensitivity of postsynaptic receptors to NTs |
|
|
adverse effects of lithium?
|
Dizziness, lethargy, memory loss
dry mouth hand tremors, muscle weakness reversible leukocytosis |
|
|
interactions of Lithium?
|
NSAIDs, tetracycline (decreased clearance)
|
|
|
what % of population is schizo?
cost of tx a yr? |
1%
40 billion! (lots are homeless) |
|
|
symptoms of schizo?
|
Positive:hallucinations, delusion, thought disorders, insomnia, bizarre behavior
Negative: apathy, amotivation, anhedonia (no plearsure), asocial |
|
|
prototypical agent for schizo?
|
chlorpromazine
|
|
|
Chemistry for schizo drugs based on?
|
phenothiazines (PTZs)
|
|
|
method of action of schizo drugs?
|
inhibit dopamine
|
|
|
adverse effects of chlorpromazine?
|
Extrapyramidal effects: muscle spasms, grimaced face, restlessness
parkinsonism: shuffling gait, rigidity, etc Tardive dyskinesia: abnormal body movts, Neuroleptic malignant syndrome: dopamine blockade |
|
|
what are the non-traditional antipsychotic agents?
|
Haloperidol
risperdone (inhibit serotonin) |
|
|
Anit-epileptic drugs (AEDs)?
|
1. Carbamazepine
2. Ethsuximide 3. Gabapentin 4.Phenobarbital 5. Phenytoin 6.Valproate |
|
|
What % of epileptics in US are controlled?
|
80%. although well controlled, these people are not free of seizures
|
|
|
Etiology of epilepsy?
|
neurological diseases, infections, cancer, head injury, drugs, heredity, hypocalcemia
|
|
|
Phenobarbital/rpimidone is a ?
|
barbiturate
|
|
|
Primidone is?
|
prodrug of phenobarbital
|
|
|
half life of phenobarbital?
primidone? |
100 hrs
24hrs |
|
|
Method of Action of phenobarbital?
|
GABA potentiation
|
|
|
phenobarbital/primidone some think should only be used for?
|
children, even though it causes cognitive effects for them (if long term use)
|
|
|
Adverse drug effects?
|
sedation, dependence, tolerance, induction of p450 enzymes, cognitive, learning problems.
|
|
|
phenytoin taken how?
|
PO or IV (but PO is crummy/varriable)
|
|
|
dilanting is?
|
extended release phenytoin
|
|
|
metabolism of phenytoin is?
|
non-linear
|
|
|
what is the effectiveness of phenytoin?
|
most effective of all for tonic-clonic and partial seizures
|
|
|
MOA of phenytoin?
|
alters Na channels, and some Ca channels
has antiarrhythmic activity |
|
|
ADRs of phenytoin?
|
drowsiness, gingival hyperplasia, nystagmus, hirsuitism (hair growth), rash/fever, lymphadenopathy (may be fatal)
|
|
|
interactions of phenytoin??
|
potent inducer of p450/MFOs
|
|
|
Ethosuximide chemistry is ?
|
succinamide
|
|
|
ethosuximide is taken by?
|
PO, and then metabolized to hydroxylated metabolites
|
|
|
uses of ethosuximide?
|
drug of choice in absence of seizures
|
|
|
MOA of ethosuximide?
|
reduces low-threshold ca current,
reduces discharge from thalamic neurons |
|
|
ADRs of ethosuximide?
|
GI distress, weightloss, lethargy
rarer: blood dyscrasias |
|
|
Carbamazepine chemistry related to
|
TCAs
|
|
|
Carbamazepine is take via?
|
PO, metabolized through P450s
|
|
|
uses of carbamazepine?
|
tonic-clonic and partial seizures
trigeminal neuralgia |
|
|
MOA of carbamazeine?
|
alters conductance of Na channels (and others)
|
|
|
ADRs of carbamazepine?
|
diplopia, ataxia
memory loss if long term use (50% of pts) |
|
|
Valproate and divalproex uses?
|
broad spectrum AED (seizures)
for absence/atypical absence of seizures migraine, bipolar disorder |
|
|
MOA of valproate?
|
effects Na channes
increases GABA availability |
|
|
ADRs of valproate?
|
Gi upset (use divalproex b/c is coated)
rarely: hepatoxicity and thrombocytopenia |
|
|
drug interactions of valproate?
|
displaces phenytoin from PP binding (high doses)
|
|
|
Gabapentin chemistry is?
|
AA analog of GABA
|
|
|
Gabapentin blood levels peak?
|
1-3 hrs
|
|
|
uses of gabapentin
|
back up in partial seizures
chronic pain, bipolar |
|
|
MOA of gabapentin?
|
may alter gaba metabolsim, transport
|
|
|
ADRs of gabapentin?
|
ataxia, drowsiness, dizziness, fatugue
(less than others!) |
|
|
interactions of gabapentin?
|
increase phenytoin blood levels at higher doses
|
|
|
detoxification requires?
|
longer lasting
orally active pharmacologically equivalent stabilize pt slowly withdrawl |
|
|
heroin effects last?
|
3-5 hrs
|
|
|
how tx opioid withdrawl?
|
methadone: long acting, orally active drug
|
|
|
barbiturate abuse is similar to ?
dependence is? |
ethanol
psychological |
|
|
Stimulants that are abused?
|
Caffeine, nicotine
|
|
|
caffeine effects?
Dose for withdrawl effects? |
CNS, CV system (tachycardia)
600mg/day: when off, get lethargy, irritability, HA |
|
|
Nicotine is most widely used ___ drug?
|
licit
|
|
|
tolerance to nicotine is? depenence is?
|
rapidly developing and psychologican dependence is high
|
|
|
% adults smoke?
% of all deaths due to smoking? % of cancer deaths? |
28%
20% 30% |
|
|
Cocine is?
taken via? |
local anesthetic that penetrates CNS
snorted as hydrochloride salt or as free base (crack). |
|
|
Amphetamines MOA ?
|
catecholamine release
|
|
|
what is major amphetamine?
|
dextroamphetamine (methamphetamine is prefered for abuse. also, or methyphenidate)
|
|
|
Ecstacy is?
|
methylendedioxymethamphetamine (MDMA)
hallucinogen |
|
|
Crank is?
|
meth crystal that are smoked
|
|
|
stimulant withdrawl symptoms are?
how tx? |
depresion, flue like,
bupropion for depression |
|
|
LSD is a ?
other exs? |
hallucinogen
mescaline, psilocybin (found in nature) |
|
|
effects of LSD?
|
somatic, perceptual, psychologic effets
over activity of SNS and CNS stimulation |
|
|
phencyclidine is?
works by? |
PCP: dissocaitive anesthetic
makes pts insensitive to pain by separating their bodily functions from minds |
|
|
phencyclidine is used for?
|
animals
|
|
|
phencyclidind was replaced by?
|
Ketamine (humans and animals)
|
|
|
phencyclidine is taken by?
|
smoke, orally, snorted, or IV
|
|
|
marajuana is a?
other exs? |
cannabinoids
cannabidiol (CBD) 9-tetrahydrocannabinol cannabinol (CBN) |
|
|
effects of marijuana?
|
high: euphoria, laugh, etc
later: relaxed, dram like, (thinking is difficult) |
|
|
signs of marijuana use?
|
increased pulse
red eyes (can have anti-emetic effect and decrease of intraocular pressure) |
|
|
tolerance to marijuana?
withdrawl syndroms? health hazards? |
only for heavy, long term users
mild unclear |
|
|
types of inhalants?
|
1. anesthetics (aerosols): NO
2. Industrial solvents: gas, paint thinner 3. Organic nitrates: amyl nitrate, butyl |
|
|
NO effects?
|
difficulty concentrating, dreaminess, euphoria, numbness, visual disterbances
|
|
|
Effects of industrial solvents?
|
hepatotoxicity, peripheral and CNS damage
|
|
|
effects of organic nitrates?
|
giddiness, rapid heart rate, flushing of skin
methemoblobinemia (rare) |
|
|
Steroids effects?
|
Myocardial infarction, liver:aminotransferases), acne
behavioral:aggression, libido and sexual functions changed, mood, violent, cognitive impairment:distractibility, fogetful, confusion |
