Session 4 Flashcards
What is pharmacovigilance?
What was the concern of the cocp and result?
Identification and prevention of adverse drug reactions.
Thought to cause venous thromboembolism which led to lower OC thus abortions.
Differentiate type a/b ADR
Type A-augmented,reversible by dose adjustment,common, predictable. Warfarin (bleeding), Diabetes Meds (hypoglycaemia).
Type B-bizarre,not dose related,irreversible,unpredictable,uncommon.
Penicillin (anaphylaxis).
4 modes of action for an ADR?
Therapeutic effect at wrong site-Diethylboestrol prevents premature labour but vGinal cancer if exposed in uterosacral.
Exaggerated response-CF patients with fibrosing colonopathy due to too many given pancreatic enzymes.
Additional pharmacological effect
Triggering of immune response (anaphylaxis)
What is in place to prevent ADR’s?
Issues with pre marketing clinical trials?
Yellow card scheme by professionals and patients, new drugs all suspected ADR’s reported, and established products only serious reactions reported.
Smaller number, limited by gender/age,concomitant therapeutics excluded so hard to get enough
Evaluate the yellow card scheme
Improvement by us?
Good-accessible by all patients/professionals, detects common and rare conditions
Bad-inevitable under-reporting, positive bias
Involvement in undereporting areas such as secondary care and oncology
Pharmacogenetics?
E.g?
Often confusion if drugs ain’t workin?
Examples of this all going wrong?
How an individual gene by affect response to a drug
Stations limited use in 3/10
Adherence or pharmacogenetics
Abacavir in HiV reacting with split antigen causing hypersensitivity in 8%. Carbamazepine again split antigen reactions causing cutaneous reaction.
Why ACEi/ARB not used in hypertensive treatment for African carribean population and elderly but CCB instead?
What can also effect PK and PD? Two examples?
Use of pharmacogenetics knowledge?
That pop has low renin levels
Genetic polymorphism, aldehyde dehydrogenase deficiency in east Asia,mutated AlDH2 genes, flushing/headaches.
CYP 2D6, metabolism of 25% drugs, antidepressants, BB’s, some Caucasians carry two null alleles decreasing first pass metabolism causing bradycardia.
Personalising drug therapy
What are sex steroids synthesised from?
Amines?
How do steroid hormones exert their effects?
Role of the sex hormones?
Cholesterol
Tyrosine
Through gene transcription
O and P stimulate breast growth and development of endometrium. P maintains pregnancy and inhibits O. O increases P.
Effects of oestrogen?
Side effects?
Effects of progesterone?
Side effects?
Where are they metabolised?
Anabolic, NA h20 retention, decreases bone absorption, raises HDl lowers LDL.
Breast tenderness,nausea, thromboembolism
Secretory endometrium,anabolic,fluid retention, increase bone mineral density.
Weight gain,acne,nausea,fluid retention
Liver by CYP 450
Where is oestrogen readily absorbed?
How excreted?
Progesterone stored?
Excreted?
GI,skin,mucous membranes
Urine as glucorides and sulfate
Bound to albumin and some stores in adipose
In urine conjugated in glucuronic acid
What increases the risk of thromboembolism in combined pill?
Why can reduce oral contraceptive efficacy?
Effect of soya protein products?
Smoking, over 35 long term use, hypertension
Drugs inducing CYP 450, carbamazepine (anti-epileptics), antibiotics (rifampacin), St. John’s Wort.
Enhance oestrogen absorption and reduce storage reducing the half life from 15-7 hours.
Benefits of HRT?
What does it not help?
Risks of HRT?
Stops flushes,sweats,dysparuraenua,osteoporosis
Heart disease
Unopposed oestrogen (ERT) leading to endometrial and ovarian cancers, (HRT) increases breast cancer risk.
Increase risk of venous thromboembolism as increased thrombin activation and increased activated protein c resistance.
Small increase of stroke, and slightly beneficial to heart disease due to better lipid profile.
What is mifepristone/RU486?
SERMS?
Use of clomiphene?
Progesterone receptor antagonists thus sensitising the myometrium to prostaglandin induced contractions so used for termination of pregnancy.
Selective oestrogen receptor modulator, agonists and antagonists.
Competes with oestrogen at the binding site stimulating ovulation through increased anterior pit hormones. So for annovulation.
What is tamoxifen?
Use?
A pro drug metabolised in the liver. Metabolites compete with oestrogen binding sites.
Breast cancer as ER antagonist causing cells to arrest the cycle, although agonist in endometrium.
What is ulipristal acetate?
SPRM, emergency contraception, delay or inhibits ovulation. Also treats uterine fibroids.
