Pharmacological Aspects of Immunology 1 Flashcards

Question

How many hospital admissions and deaths from NSAIDs? (yearly)

Answer 1

12,000 admissions, 2600 deaths

Answer 2

* Use for pain and inflammation limited by * **GI** toxicity * **Tinnitus** – mechanism obscure, usually reversible * **Reye’s** syndrome (fulminant hepatic failure in children) * Anti-platelet effect * Primary and secondary prevention eg stroke and MI * Treatment of acute MI and stroke

Answer 3

* Use for pain and inflammation limited by * GI toxicity * Tinnitus – mechanism obscure, usually **reversible** * Reye’s syndrome (fulminant hepatic failure in children) * Anti-**platelet** effect * Primary and secondary prevention eg **stroke** and MI * Treatment of acute MI and stroke

Answer 4

fulminant hepatic failure in children

Answer 5

primary and secondary prevention e.g. stroke and MI, also treatment of acute MI and stroke (anti-platelet effect)

Answer 6

* GI toxicity * Tinnitus - mechanism obscure, usually reversible * Reye's syndrome (fulminant hepatic failure in children) *

Answer 7

* In the GI tract **prostaglandins** E2 and I2 * **Decrease** acid production * **Increase** mucus production * **Increase** blood supply * NSAID inhibition in stomach and duodenum * Irritation * **Ulcers** (gastric 15-30%, duodenal 10%) * Bleeding * Similar effect in the colon * Colitis – esp with local preps e.g. rectal diclofenac

Answer 8

* In the GI tract prostaglandins **E2** and I2 * Decrease **acid** production * Increase **mucus** production * Increase **blood** supply * NSAID inhibition in stomach and duodenum * Irritation * Ulcers (gastric 15-30%, duodenal 10%) * Bleeding * Similar effect in the colon * Colitis – esp with local preps e.g. rectal diclofenac

Answer 9

* In the GI tract prostaglandins E2 and **I2** * Decrease acid production * Increase mucus production * Increase blood supply * NSAID inhibition in stomach and duodenum * Irritation * Ulcers (gastric 15-30%, duodenal 10%) * **Bleeding** * Similar effect in the colon * **Colitis** – esp with local preps e.g. rectal diclofenac

Answer 10

They inhibit them in stomach and duodenum leading to irritation, ulcers (gastric 15-30%, duodenal 10%) and bleeding

Answer 11

NSAIDS inhibit GI tract prostaglandins E2 and I2 in stomach and duodenum leading to **irritation, ulcers (gastric 15-30%, duodenal 10%) and bleeding**

Answer 12

* **Upper** GI **bleeding** * Relative Risk 4.7 all users * Azapropazone = 23.4 * Piroxicam = 18.0 * Small differences between others… * Biggest risk factor for GI bleed = previous GI bleed * Also * Age * Chronic disease (e.g.rheumatoid disease) * Steroids

Answer 13

* Upper GI bleeding * Relative Risk 4.7 all users * Azapropazone = 23.4 * Piroxicam = 18.0 * Small differences between others… * Biggest risk factor for GI bleed = **previous GI bleed** * Also * **Age** * Chronic disease (e.g.rheumatoid disease) * **Steroids**

Answer 14

**Relative Risk 4.7 all users**

Answer 15

* Upper GI bleeding * Relative Risk 4.7 all users * Azapropazone = 23.4 * Piroxicam = 18.0 * Small differences between others… * Biggest risk factor for GI bleed = previous GI bleed * Also * Age * Chronic disease (e.g.rheumatoid disease) * Steroids

Answer 16

previous GI bleed

Answer 17

* Primarily related to changes in glomerular blood flow * Decreased **glomerular filtration rate** * **Sodium** retention * Hyperkalaemia * Papillary **necrosis** * Acute renal failure 0.5-1% * Avoid or dose adjust in renal **failure** * Avoid in patients likely to develop renal **failure**

Answer 18

* Primarily related to changes in glomerular blood flow * **Decreased** glomerular filtration rate * Sodium retention * **Hyperkalaemia** * Papillary necrosis * Acute renal failure **0.5-1%** * Avoid or dose adjust in renal failure * Avoid in patients likely to develop renal failure

Answer 19

Acute renal failure in **0.5-1%** of people using NSAID

Answer 20

Avoid or dose adjust in renal failure and avoid in patients likely to develop it

Answer 21

* About **10**% of asthmatics experience bronchospasm following NSAID – perhaps because of **arachidonic** acid is shunted down the 5LPO pathway when COX is inhibited

Answer 22

* About 10% of asthmatics experience **bronchospasm** following NSAID – perhaps because of arachidonic acid is shunted down the 5LPO pathway when **COX** is inhibited

Answer 23

* Is an NSAID the answer (paracetamol, opioids, COX2 inhibitor, non-pharmacological?) * Consider risk factors eg age, renal impairment, previous peptic ulcer disease * Avoid or dose adjust in **renal impairment** * Consider co-administration of **gastroprotection** with proton pump inhibitor

Answer 24

* Is an NSAID the answer (**paracetamol**, opioids, COX2 inhibitor, non-pharmacological?) * Consider **risk factors eg age, renal impairment, previous peptic ulcer disease** * Avoid or dose adjust in renal impairment * Consider co-administration of gastroprotection with **proton pump** inhibitor

Answer 25

* Proably the four NSAIDS I’d recommend you know are these * Ibuprofen available over the counter is demonstrably the least associated with side-effects * Naproxen is similar but probably slightly more prone to side-effects * The most widely prescribed NSAID for more severe short term analgesis is probably diclofenac – often referred to by its trade name * Indomethacin may be slightly more potent again and is generally reserved for specialist use in diseases like gout where marked inflammation ispresent

Answer 26

* Proably the four NSAIDS I’d recommend you know are these * **Ibuprofen** available over the counter is demonstrably the least associated with side-effects * **Naproxen** is similar but probably slightly more prone to side-effects * The most widely prescribed NSAID for more severe short term analgesis is probably **diclofenac** – often referred to by its trade name * **Indomethacin** may be slightly more potent again and is generally reserved for specialist use in diseases like gout where marked inflammation ispresent

Answer 27

* Proably the four NSAIDS I’d recommend you know are these * **Ibuprofen** available over the counter is demonstrably the least associated with side-effects * **Naproxen** is similar but probably slightly more prone to side-effects * The most widely prescribed NSAID for more **severe short** term analgesis is probably diclofenac – often referred to by its trade name * Indomethacin may be slightly more potent again and is generally reserved for specialist use in diseases like **gout** where marked inflammation ispresent

Answer 28

* 27 different NSAIDs licensed in the UK, some over the counter * Toxicity generally increases with analgesic potency

Answer 29

* Not classically a member of the **NSAID** group * Minimal anti-**inflammatory** effects, but good analgesic/ anti-pyretic * Very well-tolerated with almost no contraindications * Mechanism of action is **controversial** * Doesn’t bind COX1 or 2; weak inhibitor of prostoglandin * May inhibit COX3 (CNS only) but relevance controversial * Dangerous in overdose

Answer 30

* Not classically a member of the **NSAID** group * Minimal anti-inflammatory effects, but good **analgesic**/ anti-pyretic * **Very** well-tolerated with almost no contraindications * Mechanism of action is controversial * Doesn’t bind COX1 or 2; weak inhibitor of prostoglandin * May inhibit COX3 (CNS only) but relevance controversial * Dangerous in **overdose**

Answer 31

* Not classically a member of the NSAID group * Minimal anti-inflammatory effects, but good analgesic/ anti-**pyretic** * Very well-tolerated with almost no **contraindications** * Mechanism of action is controversial * Doesn’t bind **COX1 or 2;** weak inhibitor of **prostaglandin** * May inhibit **COX3** (CNS only) but relevance controversial * Dangerous in overdose

Answer 32

* **Minimal anti-inflammatory effects, but good analgesic/ anti-pyretic** * **Very well-tolerated with almost no contraindications**

Answer 33

* In overdose, can go from managing paracetamol that is taken to having saturation pathway with production of NAPQI - problem with this is that it is hepatotoxic and causes delayed hepatic **necrosis** - classic overdose story = present **late** (maybe days later) and too late to do anything, potential liver transplant * Overdose is much **less** common now - harder to get lots of packs in one go

Answer 34

hepatic necrosis - typically present a few days later when it is too late

Answer 35

* **N-acetylcysteine (glutathione precursor)**

Answer 36

**N-acetylcysteine (glutathione precursor)**

Answer 37

* Selective inhibition of COX-2 in vitro and in vivo * Anti-**inflammatory** and **analgesic** in humans * Objective evidence of selectivity (GI, platelets) at \> anti-inflammatory doses * **Comparable** efficacy (not superior) to non-selective NSAIDs in * Acute pain * Dysmenorrhoea * Inflammatory joint disease * Controversy due to apparent increased risk of MI – but may have been a result of absence of anti-platelet effect * Currently only recommended in high-risk patients and after cardiovascular risk assessment

Answer 38

* Selective inhibition of COX-2 in vitro and in vivo * Anti-inflammatory and analgesic in humans * Objective evidence of selectivity (GI, platelets) at \> anti-inflammatory doses * Comparable efficacy (not superior) to non-selective NSAIDs in * Acute pain * Dysmenorrhoea * Inflammatory joint disease * Controversy due to apparent increased risk of **MI** – but may have been a result of absence of **anti-platelet** effect * Currently only recommended in **high**-risk patients and after **cardiovascular** risk assessment

Answer 39

* Selective inhibition of COX-2 in vitro and in vivo * Anti-inflammatory and analgesic in humans * Objective evidence of selectivity (GI, platelets) at \> anti-inflammatory doses * Comparable efficacy (not superior) to non-selective NSAIDs in * **Acute** pain * **Dysmenorrhoea** * **Inflammatory** joint disease * Controversy due to apparent increased risk of MI – but may have been a result of absence of anti-platelet effect * Currently only recommended in high-risk patients and after cardiovascular risk assessment

Answer 40

* NO - Comparable efficacy (not superior)

Answer 41

* **Controversy due to apparent increased risk of MI – but may have been a result of absence of anti-platelet effect** * *Currently only recommended in high-risk patients and after cardiovascular risk assessment*

Answer 42

* Population based retrospective study * 1.3 million people aged 66 years or older in Ontario * 365,000 (28%) had a prescription for an NSAID * **NSAIDs had highest rate**

Answer 43

* **Cortisol** (hydrocortisone) – predominant endogenous glucocorticoid * Carbohydrate and protein **metabolism** * Fluid and electrolyte **balance** (mineralocorticoid effects) * Lipid metabolism * Psychological effects * Bone metabolism * Profound modulator of immune response

Answer 44

* Cortisol (**hydrocortisone**) – predominant endogenous glucocorticoid * Carbohydrate and protein metabolism * Fluid and electrolyte balance (mineralocorticoid effects) * Lipid metabolism * **Psychological** effects * **Bone** metabolism * Profound modulator of **immune** response

Answer 45

**Cortisol (hydrocortisone)**

Answer 46

**Corticosteroids** are the most profound global modulator of the immune response

Answer 47

* Steroids **reduce** immune activation by altering gene expression in numerous cell types, including T cells, B cells and cells of the innate immune system. * Their onset of action is **delayed** and they must be taken regularly

Answer 48

* Steroids reduce **immune** activation by altering gene expression in numerous cell types, including T cells, B cells and cells of the **innate immune** system. Their onset of action is delayed and they must be taken **regularly**

Answer 49

* Cell **trafficking** * Lymphopenia, monocytopenia (redistribution) * Neutrophilia and impaired phagocyte migration * Cell **function** * T cell hyporesponsiveness * Inhibited B cell maturation * Decreased IL1, IL6 and TNFa production (monocytes) * Widespread inhibition of Th1 and Th2 cytokines * Inhibition of COX - prostaglandins * Impaired phagocyte killing * ↓collagenases, elastases etc * **Don’t** effect * Immunoglobulin levels * Complement

Answer 50

* Cell trafficking * Lymphopenia, monocytopenia (redistribution) * Neutrophilia and impaired **phagocyte** migration * Cell function * T cell **hyporesponsiveness** * **Inhibited** B cell maturation * **Decreased** IL1, IL6 and TNFa production (monocytes) * Widespread inhibition of Th1 and Th2 cytokines * Inhibition of **COX** - prostaglandins * **Impaired** phagocyte killing * ↓collagenases, elastases etc * Don’t effect * Immunoglobulin levels * Complement

Answer 51

* **Immunoglobulin levels** * **Complement**

Answer 52

* Cell trafficking * Lymphopenia, monocytopenia (redistribution) * **Neutrophilia** and impaired phagocyte migration * Cell function * **T** cell hyporesponsiveness * Inhibited **B** cell maturation * Decreased IL1, IL6 and TNFa production (monocytes) * Widespread **inhibition** of Th1 and Th2 cytokines * Inhibition of COX - **prostaglandins** * Impaired phagocyte **killing** * ↓collagenases, elastases etc * Don’t effect * Immunoglobulin levels * Complement

Answer 53

* To suppress **inflammation** of all kinds, particularly in **acute** disease but also in **maintenance** therapy * Asthma, Crohn’s / UC, Eczema, Multiple sclerosis, Sarcoid, allergy, **rheumatoid** arthritis, systemic lupus **erythematosis** etc etc * Replacement therapy in hypoadrenalism * Myriad preparations, and also routes * Systemic (oral and parenteral) * Topical (skin, joint injections, inhaled, enteric coated, rectal)

Answer 54

* To suppress inflammation of all kinds, particularly in acute disease but also in maintenance therapy * Asthma, Crohn’s / UC, Eczema, Multiple sclerosis, Sarcoid, allergy, rheumatoid arthritis, systemic lupus erythematosis etc etc * Replacement therapy in hypoadrenalism * **Myriad** preparations, and also routes * **Systemic** (oral and parenteral) * **Topical** (skin, joint injections, inhaled, enteric coated, rectal)

Answer 55

* To suppress inflammation of all kinds, particularly in acute disease but also in maintenance **therapy** * Asthma, **Crohn’s** / UC, Eczema, Multiple **sclerosis**, Sarcoid, allergy, rheumatoid arthritis, systemic lupus **erythematosis** etc etc * Replacement therapy in hypoadrenalism * Myriad preparations, and also routes * Systemic (oral and **parenteral**) * Topical (skin, joint injections, inhaled, enteric coated, rectal)

Answer 56

* Predictable from steroid actions * Early * Weight **gain** * **Glucose** intolerance * **Mood** change * **Suppression** of ACTH release * Later * Proximal muscle **weakness** * Osteoporosis * Skin changes * Body shape changes * Hypertension * Cataracts * Adrenal **suppression**

Answer 57

* Predictable from steroid actions * Early * Weight gain * Glucose intolerance * Mood change * Suppression of **ACTH** release * Later * Proximal muscle weakness * **Osteoporosis** * Skin changes * Body **shape** changes * **Hypertension** * Cataracts * **Adrenal** suppression

Answer 58

* Prednisolone is a type of medicine known as a **corticosteroid or steroid.** * **Medium** potency * Good lipid solubility * Anti-**inflammatory** * Oral steroid, also available as enemas

Answer 59

* Prednisolone is a type of medicine known as a corticosteroid or steroid. * **Medium** potency * Good lipid solubility * Anti-inflammatory * **Oral** steroid, also available as **enemas**

Answer 60

* Hydrocortisone is a steroid (corticosteroid) medicine * **Low** potency * **Good** lipid solubility * **Replacement** therapy for hypoadrenalism, occasionaly also used for treatment in some indications * Skin topically, also injections into joint

Answer 61

* Hydrocortisone is a steroid (corticosteroid) medicine * Low potency * Good lipid solubility * Replacement therapy for **hypoadrenalism**, occasionaly also used for **treatment** in some indications * **Skin** topically, also **injections** into joint

Answer 62

* Beclometasone is a type of medicine known as a corticosteroid (or steroid). * **Medium** potency * **Poor** lipid solubility * **Brown** Inhaler for asthma * Topically in Crohn's

Answer 63

* Beclometasone is a type of medicine known as a corticosteroid (or steroid). * **Medium** potency * Poor lipid solubility * Brown Inhaler for **asthma** * Topically in **Crohn's**

Answer 64

* Dexamethasone is a corticosteroid * **High** potency - IV and oral * **Good** lipid solubility * Cerebral **oedema**

Answer 65

* Dexamethasone is a corticosteroid * High potency - **IV** and oral * Good lipid solubility * **Cerebral** oedema

Answer 66

* Dexamethasone is a corticosteroid * High potency - IV and **oral** * **Good** lipid solubility * Cerebral oedema

Answer 67

* Triamcinolone is a corticosteroid - typically used for **skin** and **joints** * High potency * Poor lipid solubility

Answer 68

* Triamcinolone is a corticosteroid - typically used for skin and joints * **High** potency * **Poor** lipid solubility

Answer 69

* High-dose exogenous corticosteroids suppress endogenous production within **1 week** * After prolonged therapy, the adrenal cortex begins to **atrophy** and endogenous production takes some time to recover upon cessation * Abrupt withdrawal below **replacement** dose reduces ability to deal with physiological stress – eg infection – and may precipitate an adrenal crisis * Steroid warning card * Tail dose slowly * Increase dose during acute illness and prior to surgery

Answer 70

* High-dose exogenous corticosteroids **suppress** endogenous production within 1 week * After prolonged therapy, the adrenal cortex begins to atrophy and endogenous production takes some time to recover upon cessation * Abrupt withdrawal below replacement dose reduces ability to deal with **physiological** stress – eg infection – and may precipitate an adrenal crisis * Steroid **warning** card * Tail dose **slowly** * **Increase** dose during **acute** illness and prior to surgery

Answer 71

High-dose exogenous corticosteroids suppress **endogenous** production within 1 week (After prolonged therapy, the adrenal cortex begins to atrophy and endogenous production takes some time to recover upon cessation)

Answer 72

* Early * Weight gain * Glucose intolerance * Mood change * Suppression of ACTH release * Later * Proximal muscle weakness * Osteoporosis * Skin changes * Body shape changes * Hypertension * Cataracts * Adrenal suppression

Answer 73

* Risk is related to **cumulative dose** * Early risk - **Phagocytic** defects * Bacterial infection – S. aureus, enteric bacteria etc * Fungal infection – candida, aspergillus * Later risk - Cell mediated defects * Intracellular pathogens * TB * Varicella * Listeria * Pneumocystis

Answer 74

* Risk is related to cumulative dose * Early risk - Phagocytic defects * **Bacterial** infection – S. aureus, enteric bacteria etc * **Fungal** infection – candida, aspergillus * Later risk - Cell **mediated** defects * Intracellular pathogens * TB * Varicella * Listeria * Pneumocystis

Answer 75

* Risk is related to cumulative dose * Early risk - **Phagocytic** defects * Bacterial infection – S. aureus, enteric bacteria etc * Fungal infection – candida, aspergillus * Later risk - Cell mediated defects * **Intracellular** pathogens * TB * Varicella * Listeria * Pneumocystis

Answer 76

* Risk is related to **cumulative** dose * Early risk - Phagocytic defects * Bacterial infection – S. aureus, enteric bacteria etc * Fungal infection – candida, aspergillus * Later risk - Cell mediated defects * Intracellular pathogens * **TB** * Varicella * **Listeria** * Pneumocystis

Answer 77

* A diverse group of drugs that target the **immune system** * Derive name from use in **rheumatoid** arthritis, but also used in transplantation and myriad other autoimmune and inflammatory disorders; also sometimes (in higher doses) for **cancer chemotherapy** * To be distinguished from: * NSAIDS: despite name, not disease-modifying * **Steroids**: the idea of DMARDS is that they’re ‘**steroid**-sparing’ * Biologics: newer class of drugs resembling naturally-occurring molecules

Answer 78

* A diverse group of drugs that target the immune system * Derive name from use in rheumatoid arthritis, but also used in **transplantation** and **myriad** other autoimmune and inflammatory disorders; also sometimes (in higher doses) for cancer chemotherapy * To be distinguished from: * **NSAIDS**: despite name, not disease-modifying * Steroids: the idea of DMARDS is that they’re ‘steroid-sparing’ * **Biologics**: newer class of drugs resembling naturally-occurring molecules

Answer 79

DMARDS are a diverse group of drugs that target the **immune system**

Answer 80

* Competitive inhibitor of **dihydrofolate** **reductase** (DHR), therefore anti-folate action * Folate needed for purine synthesis in DNA * This reduces T cell activity, and also (in higher doses) tumour synthesis * Main indications * Rheumatoid arthritis * **Psoriasis** * **Crohns** disease * Main toxicities * Hepatotoxicity * **Leucopenia** * Pulmonary **fibrosis** * Teratogenic * NOTE **weekly** dosing; errors have caused major toxicity

Answer 81

* **Competitive** inhibitor of dihydrofolate reductase (DHR), therefore anti-folate action * Folate needed for **purine** synthesis in DNA * This **reduces** T cell activity, and also (in higher doses) tumour synthesis * Main indications * Rheumatoid arthritis * Psoriasis * Crohns disease * Main toxicities * **Hepatotoxicity** * Leucopenia * Pulmonary fibrosis * **Teratogenic** * NOTE weekly dosing; errors have caused major toxicity

Answer 82

weekly dosing - errors have caused major toxicity

Answer 83

* DHR (Dihydrofolate reductase) - therefore anti-folate action - folate is needed for purine synthesis in DNA. * This reduces T cell activity, and also (in higher doses) tumour synthesis

Answer 84

Methotrexate **reduces** T cell activity, and also (in higher doses) tumour **synthesis**

Answer 85

* Rheumatoid arthritis * Psoriasis * Crohns disease

Answer 86

* Hepatotoxicity * Leucopenia * Pulmonary fibrosis * Teratogenic

Answer 87

* Inhibits **thiopurine** S methyltransferase (TPMT), so also inhibits **purine** synthesis * Similar indications to **methotrexate**; more widely used in transplantation compared to methotrexate * Toxicities similar to **methotrexate**; GI upset very common when starting

Answer 88

* Inhibits thiopurine S methyltransferase (TPMT), so also inhibits purine **synthesis** * Similar indications to methotrexate; more widely used in **transplantation** compared to methotrexate * Toxicities similar to methotrexate; **GI** upset very common when starting

Answer 89

* Inhibits **calcineurin**, which in turn reduces T lymphocyte activity * Similar indications to aza/ metho, but used more in **Dermatology** and transplantation * Main toxicities * Nephrotoxic * Hepatotoxic * Gum hyperplasia * Hirsuitism * Note tacrolimus (newer formulation) is easier to take, and available for **topical** use (esp eczema)

Answer 90

* Inhibits calcineurin, which in turn **reduces** T lymphocyte activity * Similar indications to aza/ metho, but used more in Dermatology and **transplantation** * Main toxicities * Nephrotoxic * Hepatotoxic * Gum hyperplasia * Hirsuitism * Note **tacrolimus** (newer formulation) is easier to take, and available for topical use (esp eczema)

Answer 91

* Nephrotoxic * Hepatotoxic * Gum hyperplasia * Hirsuitism

Answer 92

Tacrolimus (newer formulation of ciclosporin) is easier to take, and available for **topical** use (esp **eczema**)

Answer 93

calcineurin - which in turn reduces T lymphocyte activity

Answer 94

Ciclosporin has similar indications to azathioprine / methotrexate, but used more in **dermatology and transplantation**

Pharmacological Aspects of Immunology 1 Flashcards

(127 cards)