Pharmacology - Prostaglandins and Autacoids Flashcards
1
Q
What is an autacoid?
A
An endogenous compound secreted by one type of cell but its effect is to modulate function of another cell within the same area.
2
Q
What are Eicosanoid’s function?
A
- Function in the body, are also potential disease mediators.
3
Q
What are the seven types of Eicosanoids?
A
Prostaglandins( in endothelial cells) Prostacycylins Thromboxane (Produced in platelets) Leukotrienes (asthma) Lipoxins Isoprostanes EETs
4
Q
How are Eicosanoids created?
A
An inflammatory response–> Arachidonic acid is cleaved by phosolipase A and depending on the enzymes that its available in or the tissues its located in it will differentiate into a specific Eicosanoid
5
Q
In arthritis (rheumatoid, osteoarthritis) what are the two main autacoids?
A
COX2 and PGE2
6
Q
In asthma what are the 4 autacoids that are significant?
A
PGD2 and LTB4
LTC4 and LTD4
7
Q
In Crohn’s disease and UC what are the main autacoids?
A
- and increase in LTB4 in affected mucosa leading to leukocytes infiltration
8
Q
In cancer what is the significance of autacoids?
A
only circumstancial evidence only
9
Q
In Dysmenorrha what are the main autacoids?
A
Endometrium –> PGE2 and PGF2a
10
Q
In Glomerulonephritis what are the main autacoids?
A
Abnormal elevation of LTB4 due to complement proteins. In cysteinyl leukotrienes there is a decrease in glomerular filtration.
11
Q
In cardiovascular disease what are the autacoids that can make the condition worsen?
A
- increased levels of thromboxane which will constrict blood vessels.
12
Q
What Eicosanoids can Erectile dysfunction be treated with?
A
- PGE1
13
Q
What Eicosanoids are used for labor and abortion?
A
Induction of labor –>PGE2 and PGF2a
14
Q
What Eicosanoid are used to treat Glaucoma?
A
PGE2 used to dilate increasing passage and allow vitreous humor to escape.
15
Q
What Eicosanoid is used to keep a ductus arteriosus open?
A
- PGE2
16
Q
What Eicosanoid is used to treat pulmonary hypertension?
A
PGI2
17
Q
What are the class of anti-Eicosanoids?
A
Corticosteroids (Prednisone, Dexamethasone)
NSAIDS (aspirin, indomethacin, ibuprofen)
Inhibitors of leukotrienes ( Zafirlukast, montelukast)
Inhibitors of thromboxanes (Dazoxiben, pirmagrel)
18
Q
What is the mechanism of action of corticosteroids?
A
Decrease immune response and decrease inflammatory response - via an increased expression of IL-10 and receptors in the bronchials. They also increase the expression of IL-1 receptor antagonist thats main goal is to decrease expression of IL-2 - IL-6 (IL-4 stimulates beta cells to produce IgE with IL-5 are the potent recruiter of eosinophils (inflammation). Also inhibit cyclooxygenase inhibitors. Without phospholipase A will not have arachondonic acid inhibits phospholipase A indirectly via lipocortin.
19
Q
What are some types of Corticosteroids?
A
Prednisone, betamethasone, dexamethasone, triamcinolone.
20
Q
What are some clinical applications of Corticosteroids?
A
Asthma (inhaled formulations) - inhibition of IL-4 and IL-5. Will not treat just suppress
- Arthritis (rheumatoid, osteoarthritis)
- Systemic lupus erythematosus
21
Q
What are some types of Thromboxane
antagonists?
- What are the clinical application?
What might an adverse effect be?
A
Dazoxiben, Pirmagrel, Ridogrel
- Similar to aspirin
- Bleeding
22
Q
What are some common properties of NSAIDS?
What is the MOA?
A
- Properties: Found in synovial fluid, inhibit platelets and suppress inflammation, analgesic and antipyretic, gastric irritation, nephrotoxity, and heptotoxicity (diclofenac and sulindac)
- Nonselective COX inhibitor
23
Q
What is the COX selectivity for NSAID?
A
- COX1 > COX2 (indometacin, sulindac)
- COX1 = COX2 (meclofenamate, ibuprofen)
- COX1 < COX2 (celecoxib, rofecoxib)
24
Q
What is the nmonemic for cox selectivity?
A
If you like 1 cox over 2 you are either in love or sullen. If you can’t decide if you want 1 cox or 2 you propably have a headache or meclofenamate, and if you like 2 cox rather than one you were probably celebrant and want it rofe!!
25
What are the clinical application for aspirin?
| What is the MOA?
- Mild to moderat pain, headache, myalgia, arthralgia, prophylaxis for stroke and myocardial infarction
- Cox1 and Cox2 inhibition
26
What are the adversed effects of aspirin?
- GI ULCERS
- BLEEDING
- asthma exacerbation
- bronchospasm
- angioedema
27
What are the types of propionic acid drugs?
| What are the clinical applications to drugs that have propionic acid?
- Ibuprofen, naproxen, ketoprofen, fluprofen
| - mild to moderate pain, fever, Osteoarthritis, rheumatoid arthritis, dysmenorrhea, and gout
28
What are the adverse effects of drugs that use Propionic acid?
- GI hemorrhage, ulceration, perforation, nephrotoxicity, stevens-johnsons syndrome ( immune reaction)
29
What are the Acetic acid derivatives of the anti-eicosanoids?
- What are the clinical applications of drugs that are acetic acid derivatives?
- What are the adverse effects?
- Indomethacin, Sulindac, etodolac, diclofenac, ketorolac
- Clinical app: long term treatment of rheumatoid arthritis, closure of patent ductus arterioles,
- Adverse effects: GI disturbances, tinnitus
30
What types of drugs are oxicams?
What are they used for?
What are the adverse effects?
- Piroxicam (bad b/c it can cause more GI bleeding than aspirin)
- For Rheumatoid, osteoarthritis, primary dysmenorrhea
- Adverse effects: GI bleeding > aspirin
31
What type of drug is a ketone anti-eicosanoid?
- Nabumetone
32
What are some COX2 selective antagonist?
| What are some clinical applications?
Celecoxib (only one used), Rofecoxib
| -Osteoarthritis, rheumatoid arthritis, primary dysmenrrheal, acute pain in adults familial adenomatous polyposis.
33
What are some adverse effect of COX2 selective antagonist?
- MYOCARDIAL INFARCTION
- GI bleeding
- peripheral edema
- asthma
34
What are the applications and MOA of Acetaminophen?
| What are some adverse effects?
- Application: Fever mild to moderate pain
- MOA: COX3 inhibition
- Adverse effects: hepatotoxicity, nephrotoxicity and hypothermia
35
What is the only Lipoxygenase inhibitor that we need to freaking know and what the hell is it used for?
How can is Screw up your shit?
- Zileuton: used for Asthma (not as effective as other forms of treatment)
- Adverse effects: Urticaria (rash of round, red welts on skin that itch intensely), abdominal discomfort, dizziness, and insomnia.
36
What does lipoxygenase inhibitors do?
- neutrophils produce lipoxygenase which converts arachdonic acid lipoxine
37
What are some LT receptor antagonists?
| What are some clinical applications of LT (Leukotriene) receptor antagonists?
- Montelukast and Zafirlukast
| - Chronic asthma, perennial allergic rhinitis and seasonal allergic rhinitis (montelukast)
38
What are some adverse effects of LT receptor antagonists?
- GI distress, hallucination and agitation, allergic granulomatosis angiitis, hepatitis
39
What are the two receptor types that can terminate pregnancy at any stage secondary to uterine contraction?
- What is the one PGE2 drug used in the USA?
- What does it do?
- PGE2 and PGF2a
- Dinoprostone
- Obstetric: induction of labor at term (ripens the cervix), 2nd trimester abortion, missed abortion, benign hydatidiform mole.
- Caution: prolonged vaginal bleeding and severe menstrual cramps occur if used for menstral regulation or early abortion
40
What type of drug is misoprostol?
- What does it treat?
- What does it need to be combined with to be an abortifacient?
"Morning after pill"
- PGE1
- Peptic ulcer
- Mifepristone
41
What type of drug is carboprost?
What are it's applications?
What are its adverse effect?
- PGF2a agonists
- 2nd trimester abortion, resistant postpartum hemorrhage
- Adverse effects: GI distrubances, dystonia and Pulmonary edema
42
What can cause dysmenorrhea and what is its treatment?
- High levels of PGE2 and PGF2a during menstruation leading to contraction of uterus resulting in menstrual pain. Dysmenorrhea is easily treated with NSAIDs
43
What does Alprostadil treat?
| What is a possible adverse effect?
- Alprostadil (PGE1) is a second line drug used to treat erectile dysfunction (ED). Administer via intravacernosal injection or urethral suppository.
- May cause penile pain
44
What drugs can be used to treat pulmonary hypertension?
- Treprostinil (PGI2) approved for treatment of pulmonary hypertension and administered by subcutaneous infusion
- Epoprostenol (PGI2) - for pulmonary hypertension.(adverse effect- hypotension, rash, GI disturbances, muscle pain)
45
What is another name for PGI2?
| What do PRE1 and PGI2 do?
- Prostacycline
| - Vasodilate ( PGE1 [penis] PGI2 [pulmonary|)
46
What drug would you give to maintain the patent ductus arteriosus?
- What are adverse effects of said drug?
- When is said drug contraindicated?
- Alprostadil (PGE1)
- Side effects may include apnea, bradycardia, hypotension, and hyperpyrexia.
- Contraindicated in sickle cell anemia
47
What are the two Eicosanoid drugs effective against asthma?
Zafirlukast and montelukast are effective against asthma. Zileuton is not as effective even though it has been used.
48
What are two groups of drugs used to treat Glaucoma/Ocular hypertension?
- Latanoprost (stable long-acting PGF2a)
| - Bimatoprost, travoprost, and unoprostone (newer focuses on decreasing pressure)
49
What are some adverse effects of Ecinosoids that treat Glaucoma/ ocular hypertension?
- IRREVERSIBLE BROWN PIGMENTATION of the iris and eyelashes, conjunctivitis, blurred vision, and drying eyes.
50
Where is histamine synthesizes and stored?
- Mast cells, basophils, neurons, cells of gastric mucosa, and cells in regenerative or rapidly growing tissues
51
By what mechanisms is Histamine released?
- Immunologic release: IgE/Fc-mediated --> type I allergic reaction
- Mechanical: Na+ causes release of histamine from granules when mast cells are injured
- Drug induced release (tubercurine, morphine, vancomycin [red man syndrome]) Venom
52
What are the functions of endogenous histamine in the immune system?
Allergy and inflammation
53
What is the function of endogenous histamine in the CNS?
```
- Circadian rhythms,
increase in wakefulness and decrease in appetite
-Thirst, ADH release & body temp
-Pain perception and bp control
Anxiety, aggression, & locomotion
```
54
What does reaction does histamine have on the nervous system?
What reaction does Histamine have on the cardiovascular system?
What reaction does Histamine have on the Bronchiolar system?
- Nervous system: Pain and itching (urticaria, bites and stings), H3 agonists decrease release Ach, amines and peptide transmitter in CNS and PNS.
- Cardiovasc: decrease systolic and diastolic bp, increase heart rate and contractility, Vasodilation in endothelium, and Edema.
- Bronch: constriction--> asthma
- GI: Gastric acid secretion
55
What effect does histamine have during anaphylaxis/ pregnancy?
histamine induced contractions
56
What drugs are first generation antihistamine?
| What are there big adverse effects?
- Ethanolamines, Phenothiazine, piperazines, piperdines, alkylamines, ethelenediamine,
- Sedation dizziness
57
What are the secondary drugs?
- Piperazine (Certirizine)
- Alkylamines (Acrivastine)
- Piperdine (Loratadine and Fexofenadine)-
- PHTHLAZINONES (Axelastine)
58
What are the uses and the advese effect of Certirizine?
- Uses: Allergic rhitinitis, allergic urticaria
| - Adverse effects (somnolence, dry mouth, headache, fatigue)
59
What are the uses of Loratadine and Fexofenadine?
Allergic rhitinitis and urticaria
60
What are the clinical uses of Azelastine?
- Allergic conjunctivitis and rhitinitis
61
What are 4 H2 blockers?
Cimetidine, Ranintidine, fomotidine, nisatidine
62
What is a type of serotonin receptor agonist and what are its effects?
-What are its major advantage over benzodiazepines?
- Buspirone: an anxiolytic agent that relieves anxiety without causing sedative, hypnotic, and euphoric effects.
- Does not affect driving skills and causes less psychomotor impairment
63
What are the side effects of serotonin agonist?
- Tachycardia, palpitation, nervousness, GI distress, and paresthesia.
64
The Serotonin receptor agonist triptans is used to treat what?
What can be its adverse effects?
When are they contraindicated?
- Used to treat acute migraine and cluster headache attacks
- May cause coronary artery vasospasm and are contraindicated in patients with coronary artery disease.
- Contraindicated in hepatic and renal insufficiency
65
What is the serotonin receptor agonist Tegaserod?
Tegaserod: effective treatment of irritable bowel syndrome
66
What is the serotonin receptor antagonist Ondansetron useful in treating?
-useful in preventing nausea and vomiting with surgery and chemotherapy
67
What are some common properties of NSAIDS?
| What is the MOA?
- Properties: Found in synovial fluid, inhibit platelets and suppress inflammation, analgesic and antipyretic, gastric irritation, nephrotoxity, and heptotoxicity (diclofenac and sulindac)
- Nonselective COX inhibitor
68
What is the COX selectivity for NSAID?
- COX1 > COX2 (indometacin, sulindac)
- COX1 = COX2 (meclofenamate, ibuprofen)
- COX1 < COX2 (celecoxib, rofecoxib)
69
What is the nmonemic for cox selectivity?
If you like 1 cox over 2 you are either in love (cause idomethacin fills the hole in your heart) or sullen. If you can't decide if you want 1 cox or 2 you propably have a headache (ibuprofen) or a feminist (meclofenamate), and if you like 2 cox rather than one you were probably celebrant due to heartbreak (celecoxib adverse reaction is MI) or like it rough (rofecoxib)!!
70
What are the clinical application for aspirin?
| What is the MOA?
- Mild to moderat pain, headache, myalgia, arthralgia, prophylaxis for stroke and myocardial infarction
- Cox1 and Cox2 inhibition
71
What are the adversed effects of aspirin?
- GI ULCERS
- BLEEDING
- asthma exacerbation
- bronchospasm
- angioedema
72
What are the types of propionic acid drugs?
| What are the clinical applications to drugs that have propionic acid?
- Ibuprofen, naproxen, ketoprofen, fluprofen
| - mild to moderate pain, fever, Osteoarthritis, rheumatoid arthritis, dysmenorrhea, and gout
73
What are the adverse effects of drugs that use Propionic acid?
- GI hemorrhage, ulceration, perforation, nephrotoxicity, stevens-johnsons syndrome ( immune reaction)
74
What are the Acetic acid derivatives of the anti-eicosanoids?
- What are the clinical applications of drugs that are acetic acid derivatives?
- What are the adverse effects?
- Indomethacin, Sulindac, etodolac, diclofenac, ketorolac
- Clinical app: long term treatment of rheumatoid arthritis, closure of patent ductus arterioles,
- Adverse effects: GI disturbances, tinnitus
75
What types of drugs are oxicams?
What are they used for?
What are the adverse effects?
- Piroxicam (bad b/c it can cause more GI bleeding than aspirin)
- For Rheumatoid, osteoarthritis, primary dysmenorrhea
- Adverse effects: GI bleeding > aspirin
76
What type of drug is a ketone anti-eicosanoid?
- Nabumetone
77
What are some COX2 selective antagonist?
| What are some clinical applications?
Celecoxib (only one used), Rofecoxib
| -Osteoarthritis, rheumatoid arthritis, primary dysmenrrheal, acute pain in adults familial adenomatous polyposis.
78
What are some adverse effect of COX2 selective antagonist?
- MYOCARDIAL INFARCTION
- GI bleeding
- peripheral edema
- asthma
79
What are the applications and MOA of Acetaminophen?
| What are some adverse effects?
- Application: Fever mild to moderate pain
- MOA: COX3 inhibition
- Adverse effects: hepatotoxicity, nephrotoxicity and hypothermia
80
What is the only Lipoxygenase inhibitor that we need to freaking know and what the hell is it used for?
How can is Screw up your shit?
- Zileuton: used for Asthma (not as effective as other forms of treatment)
- Adverse effects: Urticaria (rash of round, red welts on skin that itch intensely), abdominal discomfort, dizziness, and insomnia.
81
What does lipoxygenase inhibitors do?
- neutrophils produce lipoxygenase which converts arachdonic acid lipoxine
82
What are some LT receptor antagonists?
| What are some clinical applications of LT (Leukotriene) receptor antagonists?
- Montelukast and Zafirlukast
| - Chronic asthma, perennial allergic rhinitis and seasonal allergic rhinitis (montelukast)
83
What are some adverse effects of LT receptor antagonists?
- GI distress, hallucination and agitation, allergic granulomatosis angiitis, hepatitis
84
What are the two receptor types that can terminate pregnancy at any stage secondary to uterine contraction?
- What is the one PGE2 drug used in the USA?
- What does it do?
- PGE2 and PGF2a
- Dinoprostone
- Obstetric: induction of labor at term (ripens the cervix), 2nd trimester abortion, missed abortion, benign hydatidiform mole.
- Caution: prolonged vaginal bleeding and severe menstrual cramps occur if used for menstral regulation or early abortion
85
What type of drug is misoprostol?
- What does it treat?
- What does it need to be combined with to be an abortifacient?
"Morning after pill"
- PGE1
- Peptic ulcer
- Mifepristone
86
What type of drug is carboprost?
What are it's applications?
What are its adverse effect?
- PGF2a agonists
- 2nd trimester abortion, resistant postpartum hemorrhage
- Adverse effects: GI distrubances, dystonia and Pulmonary edema
87
What can cause dysmenorrhea and what is its treatment?
- High levels of PGE2 and PGF2a during menstruation leading to contraction of uterus resulting in menstrual pain. Dysmenorrhea is easily treated with NSAIDs
88
What does Alprostadil treat?
| What is a possible adverse effect?
- Alprostadil (PGE1) is a second line drug used to treat erectile dysfunction (ED). Administer via intravacernosal injection or urethral suppository.
- May cause penile pain
89
What drugs can be used to treat pulmonary hypertension?
- Treprostinil (PGI2) approved for treatment of pulmonary hypertension and administered by subcutaneous infusion
- Epoprostenol (PGI2) - for pulmonary hypertension.(adverse effect- hypotension, rash, GI disturbances, muscle pain)
90
What is another name for PGI2?
| What do PRE1 and PGI2 do?
- Prostacycline
| - Vasodilate ( PGE1 [penis] PGI2 [pulmonary|)
91
What drug would you give to maintain the patent ductus arteriosus?
- What are adverse effects of said drug?
- When is said drug contraindicated?
- Alprostadil (PGE1)
- Side effects may include apnea, bradycardia, hypotension, and hyperpyrexia.
- Contraindicated in sickle cell anemia
92
What are the two Eicosanoid drugs effective against asthma?
Zafirlukast and montelukast are effective against asthma. Zileuton is not as effective even though it has been used.
93
What are two groups of drugs used to treat Glaucoma/Ocular hypertension?
- Latanoprost (stable long-acting PGF2a)
| - Bimatoprost, travoprost, and unoprostone (newer focuses on decreasing pressure)
94
What are some adverse effects of Ecinosoids that treat Glaucoma/ ocular hypertension?
- IRREVERSIBLE BROWN PIGMENTATION of the iris and eyelashes, conjunctivitis, blurred vision, and drying eyes.
95
Where is histamine synthesizes and stored?
- Mast cells, basophils, neurons, cells of gastric mucosa, and cells in regenerative or rapidly growing tissues
96
By what mechanisms is Histamine released?
- Immunologic release: IgE/Fc-mediated --> type I allergic reaction
- Mechanical: Na+ causes release of histamine from granules when mast cells are injured
- Drug induced release (tubercurine, morphine, vancomycin [red man syndrome]) Venom
97
What are the functions of endogenous histamine in the immune system?
Allergy and inflammation
98
What is the function of endogenous histamine in the CNS?
```
- Circadian rhythms,
increase in wakefulness and decrease in appetite
-Thirst, ADH release & body temp
-Pain perception and bp control
Anxiety, aggression, & locomotion
```
99
What does reaction does histamine have on the nervous system?
What reaction does Histamine have on the cardiovascular system?
What reaction does Histamine have on the Bronchiolar system?
- Nervous system: Pain and itching (urticaria, bites and stings), H3 agonists decrease release Ach, amines and peptide transmitter in CNS and PNS.
- Cardiovasc: decrease systolic and diastolic bp, increase heart rate and contractility, Vasodilation in endothelium, and Edema.
- Bronch: constriction--> asthma
- GI: Gastric acid secretion
100
What effect does histamine have during anaphylaxis/ pregnancy?
histamine induced contractions
101
What drugs are first generation antihistamine?
| What are there big adverse effects?
- Ethanolamines, Phenothiazine, piperazines, piperdines, alkylamines, ethelenediamine,
- Sedation dizziness
102
What are the secondary drugs?
- Piperazine (Certirizine)
- Alkylamines (Acrivastine)
- Piperdine (Loratadine and Fexofenadine)-
- PHTHLAZINONES (Axelastine)
103
What are the uses and the advese effect of Certirizine?
- Uses: Allergic rhitinitis, allergic urticaria
| - Adverse effects (somnolence, dry mouth, headache, fatigue)
104
What are the uses of Loratadine and Fexofenadine?
Allergic rhitinitis and urticaria
105
What are the clinical uses of Azelastine?
- Allergic conjunctivitis and rhitinitis
106
What are 4 H2 blockers?
Cimetidine, Ranintidine, fomotidine, nisatidine
107
What is a type of serotonin receptor agonist and what are its effects?
-What are its major advantage over benzodiazepines?
- Buspirone: an anxiolytic agent that relieves anxiety without causing sedative, hypnotic, and euphoric effects.
- Does not affect driving skills and causes less psychomotor impairment
108
What are the side effects of serotonin agonist?
- Tachycardia, palpitation, nervousness, GI distress, and paresthesia.
109
The Serotonin receptor agonist triptans is used to treat what?
What can be its adverse effects?
When are they contraindicated?
- Used to treat acute migraine and cluster headache attacks
- May cause coronary artery vasospasm and are contraindicated in patients with coronary artery disease.
- Contraindicated in hepatic and renal insufficiency
110
What is the serotonin receptor agonist Tegaserod?
Tegaserod: effective treatment of irritable bowel syndrome
111
What is the serotonin receptor antagonist Ondansetron useful in treating?
-useful in preventing nausea and vomiting with surgery and chemotherapy
