Autacoids Flashcards
Examples of first generation H1 antihistamines
Diphenhydamine
Promethazine
Cyclizine
Meclizine
Examples of second generation H1 antihistamines
Cetrizine
Levocitrizine
Pharmacological actions of antihistamines
- Antagonism of histamine
- Anti allergic
- CNS depression
- Anticholinergic action
- Overall fall in BP
- Local anesthetic
Difference between first gen and second gen H1 antihistamines
Second generation
1. Have no Anticholinergic action
2. No anitemetic property
3. No cns depression as it doesn’t cross bbb
4. Expensive
6. Do not impair psychomotor performance
Difference between first gen and second gen H1 antihistamines (uses)
First Gen uses for
1. Motion sickness
2. Drug induced parkinsonism
3. Muscular dystrophy
4. Allergy
Second gen used for
1. Only allergy
Uses of antihistamines
- Allergic disorders
- Insect bite and ivy poisoning
- Common cold
- Antipruritic
- Motion sickness
- Morning sickness
- Vertigo
- Pre anesthetic medication
- Cough
- Parkinsonism
- Acute muscle dystonia l
- Sedative in children
Vertigo use of antihistamines
Used as labrynthine suppressants
It suppresses end organ receptors and inhibit cholinergic pathway.
Used commonly In miniere disease
Eg: Cinnarizine
Action of prostaglandins in CNS
In CNs: sedation, rigidity, rise in body temperature
Inhibition of NA
Sensitize afferent nerves to pain
Action of prostaglandins in Eye
Decreases IOP by increases trabecular outflow
Action of prostaglandins in lungs
PGF PGD TXA2 bronchoconstrictors
PGI2 PGE2 bronchodilators
Action of prostaglandins in CVS
PGI2 vasodilation hence hypotensive
PGF vasoconstriction
PGE2 F2 stimulate heart. CO increases
Action of prostaglandins in GIT
- Muscle of gut contractions. Propulsive activity hence can cause diarrhea
- Decreases acid secretion, volume of pepsin and juice also decreased
Action of prostaglandins in Kidney
PGE2 PGI2 vasodilates hence diuretic action
PGD F TXA2 renal vasoconstrictions and release of renin
Action of prostaglandins in FGS
Uterine contraction
Cervical softening
Action of prostaglandins in MGS
Increases male sperm motility
Action of prostaglandins in bone
Increases bone resorption hence increase plasma ca2+
Action of prostaglandins in platelets
TXA2 cause platelet aggregation
PGI2 inhibits platelet aggregation
PGE2 at low doses causes and at high doses inhibits
Action of prostaglandins in endocrine
Increase release of acth insulin gh
Two classes of PG
Natural: dinoprostone, dinoprost, prostacyclin
Analogues: carboprost, misoprost, latanoprost
Uses of PG
- FGS:
Abortion
Induce labor
Cervical ripening/priming
Postpartum hemorrhage - MGS: impotency
- Glaucoma
- Pulmonary hypertension
- Peptic ulcer
- To avoid platelet aggregation in hemodialysis
- Peripheral vascular disease
How many classes of NSAIDs are there and which are they
4 classes
Non selective cox inhibitor
Preferential cox 2 inhibitors
Selective cox 2 inhibitors
Antipyretic analgesic with poor anti inflammatory action
Expand non selective cox inhibitors
Salicylates: aspirin
Propionic acid derivatives: ibuprofen, naproxen, ketoprofen
Fenamate: mephenamic acid
Acetic acid derivatives: indomethacin, ketorolac
Pyrazolone derivatives: phenylbutazone, oxyphenbutazone
Enolic acid derivatives: piroxicam, tenoxicam
Examples of preferential cox 2 inhibitors
Diclophenac
Aceclophenac
Nimesulide
Examples of selective cox 2 inhibitors
Celecoxib
Paracoxib
Examples of analgesic antipyretic with poor anti inflammatory action
Para amino phenol: paracetamol
Benzoxazocine der: nefopam
General Actions of NSAID
Antipyretic
Analgesic
Anti inflammatory
Dysmenorrhea
Closure of ductus arteriosus
Antiplatelet aggregatory
General Side effects of nsaids
- Prolong Labour
- Gastric mucosal damage
- Renal effects
- Analgesic nephropathy
- Asthma
- Anaphylactoid reactions
- Bleeding
Advantages of using selective cox 2 inhibitors ahead of non selective cox inhibitors
- No asthma induced
- No gastric mucosal damage
- No excessive bleeding due to anti platelet action
Adverse effects of NSAID system wise
- GIT: nausea, anorexia, vomiting, epigastric distress, gastric ulceration, bleeding/perforation
- CNS: Tinnitus, Vertigo, Headache, mental confusion, hyperexcitability, seizures
- Hepatic: elevate transaminases, hepatic failure (rare), Reye’s syndrome
- CVS: increase BP, contraindicated in CHF
- Renal: Na+ and Water retention, edema, chronic renal failure
- Haematological: bleeding, thrombocytopenia, hemolytic anemia
- Others: asthma, angioedema, skin rash, pruritis
Actions of aspirin
- Antipyretic, analgesic and anti inflammatory
- GIT irritation
- Blood: anti platelet
- Systemic effects at high doses of 3-5g/day:
Increases cellular metabolism
Increases glucose utilization
Respiratory stimulation due to increased Co2
Compensated Respiratory alkalosis
Metabolic acidosis due to lactate, acetate, salicylic acid
No effect on heart directly but indirectly increases CO
Adverse effects in aspirin
- Side effects at 0.5-2g/day (analgesic dose): Nausea, Vomiting, increased blood loss, gastric mucosal damage, peptic ulceration
- Hypersensitivity
- Anti inflammatory doses at 3-5g/day: Salicylism, liver damage in children, Reye’s syndrome
- Acute salicylates poisoning at 15-30g/day
Salicylism
Dizziness
Tinnitus
Vertigo
Reversible impairment of hearing and vision
Excitement
Hyperventilation
Electrolyte imbalance
Acute salicylate poisoning
15-30g
Vomiting, dehydration, electrolyte imbalance, acidotic breathing, hypo/hyperglycemia, petechial hemorrhage, restlessness, delirium, hallucination, coma, death due to respiratory failure and cardiovascular collapse
Treatment: symptomatic
External cooling + IV fluids
Glucose if needed
Blood transfusion and Vit K to prevent bleeding
Interactions of aspirin
- Displaces warfarin, phenytoin, sulfonylureas hence overdose symptoms
- At analgesic doses antagonizes probencid and inhibit tubular secretion of uric acid
- Aspirin blunts diuretics
Uses of aspirin
- Analgesic at 0.5-2g/day
- Antipyretic
- Anti inflammatory at 3-5g/day
- Acute rheumatic fever
- Rheumatoid arthritis
- Osteoarthritis
- Post MI
- Prevention of preeclampsia
Ketorolac
Potent analgesic and modest anti inflammatory
Used in post operative, dental and musculoskeletal pain
Indomethacin
Potent anti inflammatory
Most common drug used in closure of ductus arteriosus
Preferential COX2 inhibitors
Nimesulide
Relatively weak inhibitor of PG synthesis and moderately selective COX2 inhibitor
Anti inflammatory action by other mechanism
Useful in painful conditions like sports Injuries, sinusitis, bursitis, dental surgery, dysmenorrhea.
High chance of liver failure hence not used. Preferred in patients who are asthmatics and intolerance to aspirin
Diclophenac Sodium
Inhibit PG synthesis and somewhat COX2 selective
No COX1 action hence no cardioprotective action of low dose aspirin
Selective COX2 inhibitors
Less gastric damage
Less occurrence of gastric ulcer and bleeding
Inhibit PGI2 and don’t inhibit TXA2 hence increases chance of thrombus. Therefore no cardioprotective action and only advices in patents prone to peptic ulcer, perforation or bleeds.
Actions of Paracetamol
Central analgesic action by reducing pain threshold
Good antipyretic
Weak peripheral anti inflammatory action due to inability to inhibit COX when peroxides produced by cells of inflammation are present
Manifestations of Acute paracetamol poisoning
Occurs in children having low hepatic glucoronide conjugating ability
>150mg/kg or >10g in adults
Early Manifestations include nausea, vomiting, abdominal pain, liver tenderness. After 12 hours: centrilobular liver necrosis, renal tubular necrosis, hypoglycaemia. After 2 days: Jaundice and liver failure followed by death
Mechanism of acute paracetamol poisoning
N Acetyl P Benzoquinoneimine (NABQI) is a highly reactive minor metabolite of paracetamol. It is detoxified by conjugation with glutathione. When glutathione stores are saturated, it binds with proteins in liver and kidney and causes necrosis
Treatment of acute paracetamol poisoning
Induced Vomiting or gastric lavage done
Activated charcoal given to stop further absorption
Antidote: N acetyl cysteine (replenishes glutathione stores)
Examples of topical NSAIDs
Dicophenac
Ibuprofen
Naproxen
Nimesulide
Classify drugs for gout
Acute gout: NSAId, colchicine, glucocorticoids
Chronic gout:-
Uricosurics: Probenecid
Synthesis inhibitor: Allopurinol
Classy drugs for RA
DMARDS:
1. Non biological:
Immunosuppressants: Methotrexate, Cyclosporine, Azathioprine
Other immuno modulators: Sulfasalazine, Leflunomide, hydroxychloroquine
2. Biological agents:
TNF alpha antagonists: Etanercept, infliximab, adalimumab
IL1 antagonist: Anakinra
T cell modulating agent: Abatacept
Adjuvant drugs: prednisolone
B cell depletor: Rituximab
First choice DMARD
Mtx
