LEC 7 - Opioid Analgesics Flashcards Preview

Pharmacology II > LEC 7 - Opioid Analgesics > Flashcards

Flashcards in LEC 7 - Opioid Analgesics Deck (124):
1

Full agonists (8)

Morphine 

Methadone 

Oxymorphone 

Hydromorphone 

Fentanyl 

Alfentanil 

Sufentanil

Carfentanil 

2

Partial agonists (1) 

butorphanol 

3

Agonist - Antagonist (2) 

Buprenorphine 

Nalbuphine

4

Antagonists (2)

Nalozone 

Naltrexone 

5

mu-agonist 5-HT NE reuptake inhibitor (1)

Tramadol 

6

Drugs that inhibit preception (5)

General anesthetics 

Opioids 

alpha2 agonists 

Benzodiazepines 

Phenothiazines

7

Drugs that inhibit transmission (2)

Local anesthetics 

Alpha2 agonists

8

Drugs that inhibit peripheral sensitazation of nociceptors (transduction) (4)

Local anesthetics 

Opioids 

NSAID's 

Corticosteroids

9

Drugs that modulate the spinal pathway (7)

Local anesthetics 

Opioids 

Alpha 2 

Tricyclic antidepressants 

NMDA antagonits 

NSAIDs 

Anticonvulsants 

10

What are the opioid receptors linked to?

Gi proteins 

11

What does Gi protein stimulus cause?

decrease cAMP 

12

What effects does opioids have on ion channels?

Close - Presynaptic Ca2+ channels (u + d + K) 

Open - postsynaptic K+ channels (u) 

13

What effects does closing the Ca2+ channels have?

Decrease NT release 

ACh 

NE 

Glutamate 

5-HT 

Substance P 

14

What is the effect of opening post-synaptic K+ channels?

Hyperpolarization 

15

What are the major overall effects of opioids?

INhibition of pain transmitting ascending systems 

Stimulating descending pain transmission inhibiting neurons

16

What are the actions of opioids at the presynaptic terminal?

u/d/k receptors 

decrease gCa2+ 

decrease NT release 

17

What effects does opioids have post-synaptically?

u receptors 

Increase gK+ - IPSP 

18

Where in the body are mu receptors found?

Brain 

Dorsal horn of spinal cord

19

What are the effects of mu receptor activation?

Supraspinal + Spinal analgesia 

Euphoria 

Sedation 

Miosis 

Respiratory depression

Chemical dependence 

Decrease GI motility (ACh effect) 

20

What NT are effected by mu receptors?

ACh 

Dopamine 

21

Where in the body are kappa receptors found?

Cerebral cortex 

Spinal cord 

Brain regions

22

What is the result of kappa receptor activation?

Spinal + Supraspinal analgesia 

Mild sedation 

Dysphoria 

Miosis 

23

What NT is affected by kappa? What is the result?

Vasopressin 

Stops release to induce diuresis

24

Where are the delta receptors found?

Limbic system 

Cerebral cortex

Spinal cord

25

What occurs with delta receptor activation?

Spinal + Supraspinal analgesia 

Cardiovascular depression 

26

What NT is affected by delta receptors?

Dopamine 

27

What are the three endogenous opioids?

Endorphins 

Enkephalins 

Dynorphins

28

What levels of analgesia occur with opioid administration?

Brain 

Spinal cord 

(rarely peripherial) 

29

What receptor has the largest analgesic effects?

Mu 

30

What is the relationship between duration of action and 1/2 life with opioids? Why?

Duration of action normally shorted then 1/2 life 

Desensitization + Down regulation of receptors

31

What CNS occur with opioids at high and low concentrations?

Low - Depression 

High - Excitation 

32

What respiratory effects are seen with opioids?

mu receptors = depressants 

will see panting due to change in thermoregulatory set point 

33

What is the effect of the respiratory depression seen with opioids?

Increase in arterial CO2 tension 

Decreate in arterial O2 tension

Decrease in pH 

34

What are the cardiovascular effects of opiods?

For the most part spare the CV system 

Hypotension can occur 

35

What can be seen in dogs with opioid administration that effects heart rate?

Vagal stimulation 

Bradycardia 

Induce barorecptor response

36

Why do you see vasodilation with opioid administration?

Histamine release

37

What are the GI effects of opioid administration?

IM - vomiting dogs 

IV decreases this effect 

Constipation + decrease gastric emptying 

38

What are the pupilary effects of opioids?

Mioisis

Mydriasis - Cats + Horses

39

Morphine - Vomit induction in Dogs 

Stimulate chemoreceptor trigger zone

40

Morphine - Uses

Acute pain - dogs, cats, horses 

Sedative to reduce pacing + standing procedures - horse 

Antitussive - Dogs 

41

Morphine - BA 

<20 % - dogs given PO 

Due to first pass effect 

42

Morphine -  Excretion 

Renal 

43

Morphine - Metabolism

Glucuronidation

44

Morphine - Adverse effects

Hyperexcitability 

Hypotension 

Cerebral hemorrhage/edema

Abnormal body temp 

45

What animals see hyperthermia with morphine?

Cats 

Horses 

Ruminants 

46

Why is cerebral hemorrhage + edema a concern with morphine?

Respiration depressed 

Arterial CO2 increase 

INcrease cerebral blood flow - increased pressure 

47

What animals see hypothermia with morphine?

Rabbits 

Dogs 

Primates

48

Tramadol  - Mechanism

mu-receptor agonist 

inhibits reuptake of serotonin + NE 

49

What contributes to tramadols analgesic effects?

Inhibition of serotonin + NE 

50

Tramadol  - use

Anlagesic + Antitussive 

51

Tramadol  - Admin

PO

52

Tramadol  - BA

65% cats/dogs

53

Tramadol  - Metabolism

Liver 

54

Tramadol  - 1/2 life

Dogs 

Cats 

Horses

Dogs = 0.8 to 1.7 hours 

Cats - 3 to 5 hours 

Horses = 1.5 to 4 hours 

55

Methadone - Mechanism

mu-agonist 

May have NMDA receptor antagonist activity 

56

Methadone - Admin

IV + IM + SC 

57

Methadone - Use

Pre-med or Analgesic alternative in dogs/cats

58

Methadone - BA 

80% SC 

very low with PO 

59

Methadone -  Protein binding 

Albulmin - 60 yo 90% 

60

Methadone - Metabolism

Liver - Cytochrome P450 

61

Methadone - Adverse side effects

Less sedation + vomiting compared to morphine

62

Oxymorphone/Hydromorphone - Potency 

ten times that of morphine

63

Oxymorphone/Hydromorphone - Uses

Analgesia 

Pre-meg 

Neruoleptanalgesia 

Anesthesia 

64

Oxymorphone/Hydromorphone - Admin

IV + IM + SC + Rectal 

65

Fentanyl - Mechanism 

Potent mu-agonist

66

Fentanyl - Admin

IV + Patch 

67

Fentanyl - Duration of Action 

Patch - 72 hours

68

Fentanyl -  Use

Anesthetic induction 

Potent analgesic 

69

Fentanyl - Pain control

Intraoperative 

Postoperative 

Chornic pain 

70

Fentanyl - Onset

More rapid then morphine due to increase lipid solubility 

71

Fentanyl - Metabolism

CYP450 

72

Fentanyl - Excretion 

urine

73

Fentanyl - Adverse effects

Sensitive to noise 

Panting + defecation + flatulence 

Bradycardia 

Hypersalivation 

74

How can bradycardia + hypersalivation due to fentanyl be treated?

Anticholinergic drug

75

Alfentanil - Potency 

4x's less potent then fentanyl 

76

Alfentanil - Mechanism 

mu-receptor antagonist 

77

Alfentanil - Admi

IV + IM + SC

78

Alfentanil - Metabolism

Liver - P450

79

Alfentanil - Use

Analgesic + Sedative 

Adjunctive anesthesia (cats) 

80

Sufentanil - Potency

5 to 10x's more potent then fentanyl 

81

Sufentanil - Admin

IV + IM + SC + Epidural 

 

82

Sufentanil - Use

Adjunctive anesthesia 

Epidular analgesia 

Postoperative analgesia 

 

83

Sufentanil - Metabolism

Liver - 

Small Intestine via O-demethylation

84

Sufentanil - Adverse effect

CNS + respiratory depression 

85

Carfentanil - Potency

10,000 x's more then morphine

86

Carfentanil - Admin

IM 

87

Carfentanil - 1/2 life 

2 to 24 hours 

needs a reversal due to this 

88

Carfentanil - Adeverse effects

Disruption of body temp 

CNS + respiratory depression 

 

89

Carfentanil - Reversal Agent 

Naltrexone 

Longer duration of action 

90

Butorphanol - Mechanism

Parital agonist for mu-receptor 

Full Agonist for kappa-receptor 

91

Butorphanol - Use 

Not a great alnalgesic 

Opioid reversal - reverses mu-receptor effects 

(sedation + respiratory depression) 

Antitussive - Dogs with chronic cough 

Analgesia in cats + cattle 

Colic 

Anti-emetic for chemotherapy 

Chemical resitrant in cattle

92

Butorphanol - Withdrawl

5 days meat withdrwal 

93

Butorphanol - BA 

Horses - 37% via IM in adults 

67% in Foals

94

Butorphanol - 1/2 life 

Horses 

6 hours - adults 

2 hours - foals

95

Butorphanol - Adverse effects in horses

Transient ataxia 

Sedation/Excitement 

Ileus 

Startle to loud Noises 

96

Butorphanol - Dogs elimination

P-glycoprotein mediates elimination from CNS 

97

Butorphanol - Adverse effects in Dogs

MDR1 mutation 

hets - 25% reduction in dose 

homos - 50% reduction in dose

98

What are the subtypes of the opioid agonist/antagonists?

1 - antagonize mu + activate kappa 

2 -partial agonist for mu + antagonist for kappa 

99

Buprenorphine - Potency 

30x's the analgesic effect compared to morphine

100

Buprenorphine - Mechanism

Partial Agonist for mu 

Antagonist for kappa 

Very strong affinitiy for mu 

101

Buprenorphine - Reversals

Resistant to Naloxone due to strong mu affinity 

102

Buprenorphine - Admin

IV + IM + SC + Transmucosal + Topical 

103

Buprenorphine - Use

Analgesic/Premed in Small Animals 

Analgesic in horses

104

Buprenorphine - Protein binding

96% binding 

 

105

Buprenorphine - 1/2 life 

5 to 6 hours 

Horses 

Cats 

Dogs

106

Buprenorphine - Metabolism

Liver via 

N-dealkylation 

Glucuronidation 

107

Buprenorphine - Adverse effects 

respiratory depression + sedation 

108

Nalbuphine - Mechanism

Antagonist for mu-receptor 

Agonist for kappa-receptor 

109

Nalbuphine - Potency 

equal to morphine

110

Nalbuphine - Admin

IM 

topically

111

Nalbuphine - Use

Mild to moderate pain 

Pre-med

Corceal ulcerations

112

Nalbuphine - Duration of action

Dogs = 45 minutes 

Cats = 2 to 3 hours

113

Nalbuphine -  Protein binding 

does not bind

114

Nalbuphine - Metabolism

Liver - Glucoronidation 

115

Nalbuphine - Excretion

Urine 

116

Nalbuphine - 1/2 life 

Dogs = 1.2 hours

117

Naloxone - Mechanism

High affinity for mu-receptor 

Low affinity for kappa + delta 

Antagonist 

118

Naloxone - Use 

Post-op reverseal 

119

Naloxone - Metabolism

Liver - CYP450 

 

120

Naloxone - Excretion

Urine

121

Naltrexone - Mechanism

Long- acting antagonist 

mu/kappa/delta 

122

Naltrexone - use 

reversal 

123

Naltrexone - Admin

IV + IM 

Oral 

124

When is naltrexone given orally to dogs? How?

To treat behavioral problems in dogs 

Reduced endorphine binding