NSAIDs cellular pharmacodynamics
Irreversible, non-selectively inhibits COX enzymes preventing production of prostanoids.
Systemic pharmacodynamics of NSAIDs
Due to decrease in PGE2 and prostacyclin causing reduced vasodilation and oedema.
Due to decrease prostaglandin production and thus less sensitisation of nociceptive nerve endings to inflammatory mediators such as bradykinin.
Antipyretic as NSAIDs prevent IL-1 activating COXs in the CNS which produce prostaglandins which raise the hypothalamic set point.
Aspirin analgesic dose
300-900mg every 4 hours.
Contraindications of NSAIDs
Beware 'tripply whammy' combination of ACEI/ARB + diuretic + NSAID causing acute renal failure.
Children <12 years due to risk of Reye'ssyndrome when taen during a viral illness.
Adverse drug reactions of NSAIDs
GI bleeding: due to inhibition of COX1 which normally provides prostaglandins to maintain themucosal lining of the stomach.
Ibuprofen is 'gentlest' on the stomach.
Selective COX-2 Inhibitor indications
Long term pain relief (arthritis, dysmenorrhea)
NSAID and COX-2 inhibitor comparison
While COX-2 theoretically cause fewer GI side effects than non-selective NSAIDs, CLASS trial showed no real difference.
Rofecoxib did show fewer GI side effects, but 5x more MI.
Cellular pharmacodynamics of COX-2 Inhibitors
Selectively inhibits COX-2 enzymes avoiding adverse effects. COX-2 is thought to be responsible for the most inflammation, pain and fever; wile adverse effects are throught to be mosty due to inhibition of COX-1 (housekeepning enzymes).
Contraindications to COX-2
Any CVD hisory.
Adverse drug reactions of COX-2 Inhibitors
Cardiovascular events: due to inhibitionof COX2 - this is predominantly responsible for producing PGI2 which normally inhibits platelet aggregation.
Acute and chronic rhinitis
Decongestants cellular pharmacodynamics
Sympathomimetic amines. Agonise alpha adrenoreceptors on smooth muscle in the respiratory tract, producing vasoconstriction of dilated nasal vessels.
Decongestants systemic pharmacodynamics
Reduces tissue hyperaemia, oedema and nasal congestion.
Contraindications to decongestants
HTN, coronary artery disease (arrhythmias)
Adverse drug reactions of decongestants
Hypertension, tachycardia, palpitations, CNS stimulation, insomnia, tremor etc
Dru cough - opioid dervicatives
Productive cough - expectorants, demulcents, muclytics.
Investigate underlying disorder as coughing is usually desirable! Stop smoking.
Cellular pharmacdynamics dry cough antitussives
Activate neuronal G-protein coupled oiioid receptors, inhibit adenylate cyclase, reducing cAMP levels and activating K+ channels hyperpolarising neuron. This reduces release of substance P, which is a neurokinin binding NK-1 which activates the cough centre in the medulla.
Expectorant antitussive cellular pharmacodynamics
Thought to promote bronchial secretions, ciliary action and productive coughing by irritant action on mucosal membranes.
May also soothe by lubricating dry tissues.
Mainly placebo affect,
Demulcents cellular pharmacodynamics
For productive cough.
Thought to suppress coughs by forming a protective layer over sensory receptors in the pharynx.
Mucolytics cellular pharmacodynamics
Acetylcysteine reduces mucus viscosity by splitting disulfide bonds in mucoproteins, bromhexine thought to improve mucous flow by enhancing hydrolysing activity of lysosomal enzymes.
Systemic pharmacodynamics antitussives
Opioid derivates reduce frequency of dry, irritating cough.
Expectorants increase mucous production and movement
Demulcents suppress coughing
Mucolytics reduce mucus viscosity and aid its digestion
Opioids in respiratory failure, asthma and COPD and children <2 years.
Adverse drug reactions antitussives
Opioids may cause opioid dependence, lethargy, stupor etc.
Expectorants and mucolytics may cause nausea, vomiting and abdominal pain.
Histamine antagonsists indications
Allergic rhinitis, chronic urticaria
Histamine antagonists cellular pharmacodynamics
Cellular: selectively antagonise the action of histamine at H1 receptors in both CNS and periphery. Histamine released from mast cells and basophils causes local inflammation, smooth muscle contraction and blood vessel dilation. Older 'drowsy' drugs penetrate blood brain barrier well and so cause CNS sedation, cognitive impairment and motor retardation. Newer, less sedating drugs do not penetrate the blood brain barrier well
Systemic pharmacodynamics of histamine antagonists
Suppress symptoms of allergies such as runny nose and watery eyes.
Histamine antagonists contraindications
Children <2 years
Adverse drug reactions to histamine antagonists
Drowsiness, fatigue (ever newer drugs to some extent)
Inhaled beta angonists indications
Acute asthma, COPD.
'Relievers' and 'Symptom controllers'
Inhaled beta agonist comparison
SABAs are first line treatment in acute asthma. If needed >2 times a week, preventative treatment should be used.
Step 2 is an ICS
Step 3 is ICS + LABA
Step 4 is other symptom controllers
In acute exacerbations, an oral corticosteroid may be used.