CPTP 3.14 15 16 Drugs Inflammation Allergy Repair 1 2 3 Flashcards
(32 cards)
Describe the effects of histamine in the inflammatory process
Lungs - bronchoconstriction
Vascular smooth muscle dilation - erythema
Vascular endothelium contraction and separation - edema, wheal response
Peripheral nerves - sensitation - itch and pain
Heart - increased heart rate (minor)
What does histamine receptor stimulation lead to?
Increased expression of endothelial adhesion molecules
Release inflammatory cytokines and eicosanoids
Activation of NFkB
Mechanism of action of antihistamines
Negative modulation of receptor activity, tipping it towards inactivation compared to the basal level where there is slight activity.
Pharmacokinetics of antihistamines
Most are oral administration
Well absorbed
2-3 hours peak plasma
Liver metabolism, some have cyp450 interaction
Major side effects of antihistamines
1st gen - antimuscarinic SE, drowsiness, dry mouth
2nd gen - less sedation, does not cross BBB
3rd gen - less cardiotoxicity and muscarininc activity
What are the eicosanoids
Prostanoids such as prostacyclin and thromboxane
Leukotrienes
Two pathways used to target inflammation
5-lipooxygenase And COX (better)
How does ibuprofen work?
Competitive inhibitor of COX enzymes against arachidonic acid
How does aspirin work?
Irreversible acetylisation of COX enzyme
Effects of aspirin
Inhibits COX
Anti-platelet activity
Risk of GI bleeding/irritation
Explain why NSAIDs cause GI bleeding
COX1 is a “house keeper” enzyme in the GIT, inhibition causes perforation and ulceration risk.
Describe how celecoxib works
Specific COX 2 inhibitor, fewer GI side effects
Increased cardiovascular risks
Describe how a serotonin agonist can be used to treat migraines
E.g. Sumatriptan
Sumatriptan inhibits a specific subtype receptor for 5-ht that is present in the cranial vessels.
It is a vasoconstrictor, by constricting large blood vessels, reduces the vascular inflammatory effects of a migraine.
5-ht also decreases activity of the trigeminal nerve
What are the interactions of sumatriptan
Medications of anxiety, OCD, SSRIs, MAOIs, St. Johns wort.
What are some prophylactic treatments for migraines
Antihistamines
Beta agonists
Serotonin antagonists (pizotifin)
TCAs
How does pizotifin work?
Similar to TCAs, use for prophylaxis for migraines.
Side effects of pizotifin
Antimiuscarinic effects
Weight gain
Increased appetite
What are the 3 types of hormones made by the adrenal gland?
Glucocorticoids, mineralcorticoids and sex hormones
What do the three zones in the adrenal cortex each do?
Zona reticularis -> precursor sex hormones
Zona fasciculata -> glucocorticoids e.g. Cortisol & corticosterone
Zona glomerulosa -> mineralcorticoids e.g. Aldosterone
What do mineralcorticoids do?
Regulate electrolyte levels through RAAS cascade
How do glucocorticoids do?
Manage stress, pain, metabolism and inflammatory response.
What is the hypothalamus-pituitary-adrenal axis?
Hypothalamus secrets CRH which stimulates pituitary gland to make ACTH which tells the adrenal glands to make cortisol.
There is a negative feedback effect of cortisol on the hypothalamus to reduce production of cortisol
3 biological effects of glucocorticoids
Modulate metabolism - lipid, glucose and protein
Stress resistance - control nutrient availability, stress coping
Immuno-modulators - control release of inflammatory and antiinflammatory cytokines
How do glucocorticoids affect the immune reaction?
It is an anti-inflammatory molecule. It inhibits production of inflammatory cytokines made by cells. It does so by binding to the glucocorticoid receptor which downregulates proinflammatory protein expression and upregulates antiinflammatory proteins.
