Narcotics & Nsaids

Front 1

Morphine: Pharmacokinetics

Back 1

1. high first pass metabolism
2. mostly excreted by kidneys as morphine-3 or morphine-6 glucuronide (latter is an active metabolite)
Half-life: 2-3 hours

Front 2

Morphine: Clinical Considerations

Back 2

1. better for continuous dull pain & moderate to severe pain rather than intermittent sharp pain
2. Tolerance & dependence rare under "normal" conditions; more common with long-term treatment for chronic conditions

Front 3

Morphine: Adverse Effects

Back 3

1. sedation
2. euphoria/dysphoria
3. miosis
4. decrease rate & volume of respiration
5. stimulation of chemoreceptor trigger zone - nausea & vomiting
6. depresses cough center
7. constipation - decreased stomach secretion of HCl; increased sphincter tone; decreased peristalsis
8. constricts smooth muscle in biliary, bronchial, urinary tracts & uterus
9. increased CO2 causes cerebral vasodilation

Front 4

Codeine: Advantages

Back 4

1. less first pass metabolism
2. best combination of low abuse, cough suppressant, sedative & analgesic
3. oxycodone + ASA (percodan) and oxycodone + acetaminophen (percocet) very effective

Front 5

Codeine: Disadvantages

Back 5

requires metabolism from CYP2D6 (many polymorphisms & some drugs inhibit or induce)

Front 6

Demerol: Characteristics

Back 6

1. most abused drug in health profession
2. orally effective, rapid onset, peaks 1 hour
3. less effect on uterus and biliary smooth muscle
4. does not suppress cough reflex
5. tolerance to euphoria develops slowly
6. severe reactions with amphetamines, MAOIs (elevated temperatures, convulsions, respiratory distress)
7. mechanism not well known

Front 7

Naloxone (short-acting) & Naltrexone (long-acting)

Back 7

- antagonist at mu, kappa, and delta but not sigma
- immediate withdrawal symptoms will be seen in those that are opiate dependent
- implanted slow-release naltrexone pellets may be used to prevent effects of illicit heroine and reduce alcohol cravings in small number of people

Front 8

Petanzocine (Talwin or Talwin NX)

Back 8

- weak partial agonist at mu receptor; produces analgesia via activation of kappa receptor
- used in chronic pain and those with drug abuse history
- withdrawal may be seen with morphine users
- low abuse potential due to kappa action & oral formulation contains naloxone which is destroyed orally but not after IV administration

Front 9

Methadone

Back 9

- better absorption after oral
- OD more difficult to manage
- less sedation, euphoria, respiratory effects
- tolerance develops more slowly
- withdrawal symtoms appear more slowly and are less severe, but they last longer
- IV abuse liability equals that of morphine

Front 10

Steroids (Ex: Hydrocortisone & Prednisone)

Back 10

- reduce pain caused by inflammation
- inhibit phospholipase A2 synthesis of arachidonic acid and block induction of COX-2

Front 11

NSAIDS: Therapeutic Effects

Back 11

Inhibition of COX-2: anti-inflammatory effects (inhibition of conversion of arachidonic acid to endoperoxides)

Inhibition of COX-1: antipyretic effects due to superficial dilation; block thromboxane production which is involved in platelet aggregation

Unclear whether analgesic effects are brought on by inhibition of COX-1 or COX-2

Uricosuric Effect:
1. block tubular reabsorption and secretion of uric acid at high doses
2. useful for gout (Indomethacin drug of choice)

Front 12

Examples of non-selective COX-1 and COX-2 inhibitors:

Back 12

1. aspirin
2. dicofenac
3. indomethacin
4. ibuprofen
5. naproxen
6. ketorlac
7. meclofenamate
8. paroxicam
9. sulindac

Front 13

NSAIDS: Adverse Effects

Back 13

1. Gastric upset, bleeding, gastritis and intolerance; possibly due to inhibtion of COX-1 which produces protective prostaglandins in the gut

2. inhibition of platelet aggregation

3. may disturb acid base balance: increase in respiration --> decrease CO2 --> respiratory alkalosis --> decreased in respiration --> increase in CO2 --> acidosis

4. inhibit uterine mobility and PG mediated renal function

5. NSAIDS and ASA hypersensitivity worst in chilren w/ Reye's syndrome who have a viral infection

Front 14

Acetaminophen - weak COX inhibitor but NOT an NSAID

Back 14

- no effect on platelets, bleeding time, no gastric irritation or effect on CV, respiratory system or acid-balance

- analgesic & antipyretic possibly due to inhibtion of COX-3 (COX-1b)

- excreted in urine after hepatic glucuronic acid conjugation

Front 15

Acetaminophen OD and Tx

Back 15

OD:
- N-hydroxylation to N-acetyl-benzoquinoneimine which reacts with SH (most common is glutathione)
- once glutathione is depleted, will begin to attack SH groups in hepatic proteins --> possible hepatic necrosis

Tx:
- administer N-acetylcysteine to provide exogenous SH groups