A.20

Question 1

NSAIDs, except acetylsalicylic acid. Non-opioid and adjuvant analgestics. Drugs for headache syndromes

Answer 1

1. NSAIDs:
   -approximately equal selectivity to COX1 and COX2 inhibition: Ibuprophen, Paracetamol, Sodium salicylate (derivative of aspirin)
   -Relative selective for COX2 inhibition: Meloxicam, Celecoxib
2. Non opiod analgestic: Paracetamol
3. Drugs for headache syndromes: Sumatriptan, Propanolol, Galcanezumab, Cinnarizine, Verapamil, Valproate
   -Tricyclic antidepressant: Amitriptyline

Question 2

Phenylbutazone

Answer 2

MOA: prostaglandin H synthase & Prostacyclin synthase inhibitor;
Effect: reduced production of PGIs→ reduced inflammation;
IND: gout, arthritis;
SEs: BM significant toxicity, leukopenia, anemia;
Extra: rarely used;
ROA: p.o;
DOA: T1/2- more than 6 hours

Question 3

Diclofenac

Answer 3

MOA: COX NS inhibitor;
Effect: ↓PG production→ strong anti-inflammatory drug;
IND: chronic rheumatic pain(accumulates in synovial fluid)→ joints;
SEs: liver damage, potential thrombotic risk;
ROA: p.o, topical use (dose: 2-3X50mg);
DOA: T1/2- less than 6 hours

Question 4

Indomethacin

Answer 4

MOA: COX inhibitor;
Effect: short acting, strong anti-inflammatory;
IND: acute gout attacks, ductus arteriosus closure, BM suppression;
SEs: diarrhea, thrombocytopenia, aplastic anemia, anorexy, depression, confusion, insomnia,;
ROA: p.o;
DOA: T1/2- less than 6 hours

Question 5

(dex)ibuprofen, (dex)ketoprofen

Answer 5

MOA: non-selective COX inhibitor;
Effect: Analgestic+antipyretic (low doses), anti-inflammatory (high doses);
IND: analgestic use in children (safer than aspirin), induces closure of ductus arteriosus;
Dose: 1-4X200-600mg; ;
DOA: T1/2- less than 6 hours;
SEs: GI bleeding, tinnitus, skin rashes,

Question 6

Naproxen

Answer 6

MOA: non-selective COX inhibitor;
Effect: management of dysmenorrhea→ menstrual cramps;
IND: Analgestic use+moderate anti-inflammatory action;
DOA: T1/2- more than 6 hours;
SEs: Increased risk of MI, confusion, headache, drowsiness, dizziness;
ROA: p.o;
Extra: long serum T1/2

Question 7

Metamizole

Answer 7

MOA: COX inhibitor;
Effect: excellent analgestic effect, weak anti-inflammatory drug;
IND: limited use today because of the SEs, can be used in-acute severe pain after trauma/surgery, tumor pain; SEs: BM toxicity→ agranulocytosis

Question 8

Meloxicam

Answer 8

MOA: first generation COX2 inhibitor (safer NSAIDs); Effect: anti-inflammatory;
IND: arthritis (rheumatic diseases, osteoarthritis); ; DOA: T1/2- more than 6 hours

Question 9

Celecoxib

Answer 9

MOA: COX2 selective inhibitor;
ROA: p.o; SEs: anorexy, depression, confusion, insomnia, CV risk is high, GI irritation, prothrombic effect, sulfonamide hypersensitivity;
Extra: not more effective than non-selective COX inhibitor, hepatic metabolism

Question 10

Paracetamol

Answer 10

MOA: COX 1,2 inhibitor;
Effect: inhibition of COX in the CNS;
IND: analgestic, antipyretic, aspirin substitute (→in children with viral infection of those with aspirin hypersensitivity);
SEs: hepatotoxicity (acute liver necrosis), chronic use of alcohol increases liver toxicity, angioedema, leukocytopenia, thrombocytopenia;
Extra: short acting, 2-3h;
ROA: oral 1-4x500-1000mg

Question 11

Sumatriptan

Answer 11

MOA: selective 5-HT1D/1B agonist;
Effect: vasoconstriction of meningeal vessels, prevent release of vasoactive peptides, inhibit pain pathway; IND: 1st line agent in acute migraine attack;
SEs: coronary vasospasm (chest pain), dizziness, muscle weakness;
ROA: p.o, inhaled, parentral

Question 12

Galcanezumab

Answer 12

MOA: monoclonal Ab against CGRP-R;
Effect: ↓inflammation in meninges caused by CGRP; IND: migraine;
SEs: hypersensitivity reactions (from urticaria to anaphylaxis) ;
Extra: Expensive;
ROA: subcutaneous (1/month)

Question 13

Cinnarizine

Answer 13

MOA: Ca2+-blocker, anti-histamine;
Effect: reduce neurogenic inflammation, promote cerebral perfusion;
IND: migraine, prevent nausea associated with motion sickness;
SEs: hypersensitivity reactions;
ROA: p.o

Question 14

Propanolol

Answer 14

MOA: non-selective β-antagonist;
Effect: HR↓→ diastolic perfusion↑→ O2 demand↓;
IND: used in all β-blocker IND, Migraine (prophylaxis), essential tremor, glaucoma, HTN, angina pectoris, anti-arrhythmic class II, hyperthyroidism, pheochromocytoma (after α-blocker administration); SEs: sedation, sleep disturbances;
Extra: lipophilic→ cross BBB, reduces mortality in patients with stable angina;
ROA: p.o, parentral

Question 15

Verapamil

Answer 15

MOA: Cardioselective Ca2+-channel blocker;
Effect: slower AV and SA conduction (Ca2+ dependant cells)→HR↓;
IND: Migraine, supraventricular arrhythmias (AVRT, SVT) angina;
SEs: hypotension, constipation, nausea;
ROA: p.o, parentral

Question 16

Valproate

Answer 16

MOA+Effect: enhances GABA transmission, decreases glutamate, inhibits VG-Na+ channels and T-type Ca2+ ch.;
IND: All seizures (incl. absence of seizures)→ broad spectrum, Bipolar disorders, Migraine;
SEs: Hepatotoxicity, thrombocytopenia, GI symptoms, weight gain, teratogenic;
Extra: inhibits CYTP450→ different from others that induce it→ slows it down and causes build-up of other chemicals

Question 17

Amitriptyline

Answer 17

MOA: inhibits NET, SERT, anti-M-R, anti-α-R, anti-H1-R; ROA: p.o;
IND: Migraine, anxiety, bipolar disorder, IBS, insomnia, interstitial cystitis;
SEs: CNS depression, atropine-like effect (antiM-R), orthostatic hypotension, ECG changes, arrhythmias (α-blokade);
Elimination: hepatic metabolism P450;
T1/2: 8-36h

Question 18

Agranulocytosis

Answer 18

severe reduction in the number of white blood cells (granulocytes) in the circulating blood

Question 19

Advantages of COX-2 selective inhibitors

Answer 19

Less GI SEs
Less bleeding disorders

Question 20

SEs of selective COX-2 inhibitors

Answer 20

Cardiovascular risk
Gastrointestinal - delay of healing
Renal- in elderly can cause renal insufficiency

Question 21

Which drug (according to Semmelweis) is 1st line to treat patent ductus arteriosus?

Answer 21

Ibuprofen