Pharmacology Flashcards
Precursor of all steroids?
Cholesterol
Where are the steroid receptors located? How do they produce effects?
Cytoplasm of cells - act as gene transcription factor
Where is oestrogen produced, what stimulates production?
Produced in ovarian follicles stimulated by FSH and LH
Where is oestrogen produced, what stimulates production?
Produced in ovarian follicles stimulated by FSH and LH
Main enzyme involved in oestrogen synthesis?
17β-oestradiol
Actions of oestrogen
Development of secondary sexual characteristics
Positive effect on the ovulatory cycle (low blood conc)
Progesterone actions?
Negative feedback on FSH and LH
Prepares endometrium for implantation by thickening cervical mucus, suppresses lactation and inhibits uterine contractility (pregnancy hormone)
Mechanism of the combined oral contraceptive pill?
Suppresses LH and FSH
Prevents ovulatory surge of LH
Thickens cervical mucus
Progestin only contraceptive S/E?
Ectopics, menorrhoea (breakthrough bleeding)
Non-contraceptive uses of progestin?
HRT
Dysmenorrhoea/menorrhoea
Abortion (morning-after)
Growth of 60% of breast tumours driven by what?
Oestrogen
Common treatments for oestrogen driven breast cancer? Examples?
Aromatase inhibitors (Reduce oestrogen synthesis)
Irreversible: Exemestane
Reversible: anastrazole
Anti-oestrogens (ER antagonist): Tamoxifen
S/Es of Aromatase inhibitors?
osteoporosis
What cells mainly produce testosterone, where?
Leydig cells in testes (also in adrenals)
Testosterone functions?
Primary and secondary sexual characteristic development
Spermatogenesis
Increased bone and lean muscle mass
Aggression, libido
Anti-androgen uses? examples?
Used in benign prostatic hyperplasia and prostate cancer
Finasteride, Flutamide
Anabolic steroids actions?
Increase lean muscle mass, accelerate recovery from injury
What are anabolic steroids?
testosterone derivatives e.g. nandrolone
What are anabolic steroids?
testosterone derivatives e.g. nandrolone
What do combined hormonal methods include in them?
Combination of synthetic oestrogen and progesterone
Effects of combined hormonal methods?
Reduced contractions and frequency of cilia beat in the fallopian tube
Ovary: Progestin inhibits LH surge and inhibits FSH release
Cervix: progestin produces a thick mucus plug
Thick mucus in endometrium
What is Ethinylestradiol, and oestradiol valerate
Ethinylestradiol - synthetic oestrogen
oestradiol valerate - prodrug metabolised to oestrogen
What are synthetic progesterones called?
Progestins
What receptor to progestins bind to?
Progesterone receptors (induce thick mucus and create mucus plug) - good effect
Others include: GnRHR, Androgen Receptors, Oestrogen Receptors, Glucocorticoid Receptors, Mineralocorticoid receptors
Difference in mono/bi/triphasic preperation of the Combined oral contraceptive pill?
Monophasic - steady levels of bothe oestrogen and progestins
Biphasic and triphasic have constant oestrogen levels and increase the progestin component once (biphasic) and twice (triphasic)
Other combined hormonal methods that are not pill-based?
Combined transdermal patch
Combined vaginal ring
S/E associated with combined contraceptive methods?
Increased anti-clotting factors and decreased anti-thrombin can lead to venous thrombosis/MI/stroke
Nausea/mood changes
Hypertension (water/sodium retention)
Androgenic effects (Oily skin/acne/weight gain)
Rare increased risk of breast cancer
What do single contraceptice methods contain?
Progestin only
Examples of single hormonal methods?
Progestin only pill
Subdermal implant
Injectables
Intra-uterine coils
Contraceptive effects of single hormonal methods?
Fallopian tubes: reduced cilia bet frequency and contractions
Inhibits GnRH release and LH surge
Cervix: thick mucus plug
Endometrium: thick mucus induction
Benefits to single hormonal contraceptive methods?
No effect on thromboembolism and blood clotting
No increased risk of cancer
Return to fertility more rapid
Good tolerance
S/E’s of single hormonal methods?
Altered menstrual pattern
Nausea/mood changes
Hypertension
Atherosclerosis
Mechanism of action of the copper IUD?
Inhibits fertilisation as copper is toxic to sperm and Oocytes
Endometrial inflammation has anti-implantation effects
Inhibit sperm penetration
Reasons the copper IUD could be contra-indicated?
UKMEC3:
Examples of barrier methods to contraception?
Male condoms
Female condoms
Diaphragms
Cervical cap
Dams
Do diaphragms reduce risk of STI?
No
Methods of sterilisation?
Female - Tubal occlusion:
- Laparoscopic: 1 in 200 failure rate, reversible
- Hysteroscopic: 1 in 500 failure rate, irreversible
Male: Vasectomy failure rate 1 in 2000
Choice for emergency hormonal contraception?
Levonorgestrel
Ulipristal
Taken 3-5 days post-coital
Choices for non-hormonal contraception?
Copper IUD - 120 hours after
Method of Levonorgestrel to prevent pregnancy?
Inhibits ovulation
Method of Ulipristal function?
Selective progesterone receptor modulator
5 points of Fraser guidance to prescribing contraception to teenagers?
- Understand implications and advice
- Cannot be persuaded to involve parent/guardian
- Likely to have sex with/without treatment
- Physically/mentally likely to suffer
- In best interest to proceed
What age is sex considered rape regardless of consent?
Signs of grooming/sexual exploitation in a young person asking for contraception?
Reluctance to say partners name
Repeat STI testing
Repeat pregnancies
Expensive clothes/gifts
Where can you refer to if you believe teen is in danger?
Specialist sexual Health nurses/safeguarding nurse
Children’s social care
Police
Changes in pharmacokinetics in pregnancy?
Greater Vol. of distribution means a higher loading dose may be required
Increased clearance means higher maintenance doses are needed
Drugs of concern in pregnancy?
Lithium
Anti-convulsants
Iodine
Sex hormones
NSAIDS
Tetracycline
ACE inhibitors
Aminoglycoside antibiotics
Recommendations on prescribing new drugs in pregnancy?
Avoid in first trimester
Use lowest effective dose
Use for shortest possible time
Potentially harmful drugs in lactation?
Metronidazole
Barbituates
BDZ
Opioids
Lithium
Immunosuppressants
Main drug treatments for Type 2 diabetes?
Sulphonylureas
Post-prandial glucose regulators
Insulin sensitisers Metformin and Thiazolidinediones
Alpha glucosidase inhibitors
New therapies:
GLP-1 analogues/
DDP4 inhibitors
SGLT-2 inhibitors
How do sulphonylureas work in diabetes?
Bind to ATP-sensitive K+ channel on beta cells in the pancreas, which then closes. Causes a depolarisation wjich then opens Ca++ channels causing increased insulin exocytosis
S/E’s of sulphonylureas?
Hypoglycaemia
Weight gain
Example of a post-prandial glucose regulator?
Repaglinide
Mechanism of action of post-prandial glucose regulator?
Binds to a site on Beta cell distinct from sulphonylurea binding site and also acts on K+ channels
Stimulates early insulin secretion without prolonged stimulation during later periods of fasting
S/Es of Repaglinide (post-prandial glucose regulator)
Hypoglycaemia - less so than sulphonylureas
Quite well tolerated
Mechanism of action of metformin?
Increased glucose uptake in skeletal muscle and adipocytes
Decreased hepatic gluconeogenesis
Decreased glucose absorption in intestines (only at high concentrations
How is metformin used in diabetes? Prescribing patterns.
1st line in patients with an increased BMI or normal BMI
Reduce appetite and can lead to weight loss
Given with food 2-3 times daily
Metformin S/Es?
Lactic acidosis
GI upset
Thiazolidinedione mechanism of action?
Causes increased transcription of insulin-sensitive genes in adipose tissue/liver/skeletal muscle
Adipose:
- Increased glucose uptake
- Fatty acid uptake and utilisation
Liver:
- Decreased glucose output
Skeletal muscle:
- Increased glucose uptake
S/Es of Thiazolidinediones?
Weight gain
Cardiac failure
Anaemia and oedema
Hepatotoxicity
Alpha glucosidase inhibitors mechanism of action?
Inhibit alpha glucosidase involved in glucose absorption in the gut - so reduce post-prandial glucose peaks
Alpha glucosidase S/Es?
Flatulence and diarrhoea
GLP-1 analogues mechanisms of action?
Decreased hepatic glucose production
Increased pancreatic insulin secretion and decreased glucagon secretion
Increased glucose uptake in muscle cells
Decreased gastric emptying and decreased hunger
Why is GLP-1 of limited use? What other drug is more useful due to this?
It is rapidly broken down by DPP-4
DPP-4 inhibitors are therefore quite useful and have similar effects to GLP-1 receptor agonists
Examples of DPP-4 inhibitors?
Sitagliptin
Drug combinations in Hodgkins Lymphoma and the way to remember it?
ABDV:
Adriamycin
Bleomycin
Dacarbazine
Vinblastine
Breast cancer combinations and way to remember it?
CMF:
Cyclophosphamide
Methotrexate
Fluorouracil
Followed by tamoxifen
Examples of direct DNA targeting drugs in anti-cancer therapies?
Alkylating agents Platinum compounds Cytotoxic antibiotics Topoisomerase I inhibitors Topoisomerase II inhibitors
Example of a cytotoxic alkylating agent? Mechanism?
Cyclophosphamide - pro-drug, damages DNA causes guanine ring opening
Cyclophosphamide S/Es?
Destruction of high turnover normal tissue - bone marrow, gut epithelium, hair
Sterility
Teratogen
Cardiac and bladder toxicity
Example of cytotoxic platinum compound? Mechanism?
Cisplatin - Cross-links DNA
Example of Cytotoxic antibiotics? Mechanism?
Doxorubicin (adriamycin) - blocks DNA polymerase by forming a complex with DNA
Example of topoisomerase I inhibitor? Mechanism?
Topotecan - DNA needs breaks during replication, so forms gap, will block the reformation of this gap and therefore lead to a halt in DNA synthesis
Example of topoisomerase II inhibitor? Mechanism?
Etoposide - Binds to topoisomerase II and prevents DNA replication and causes strands breaks
Cytotoxic antimetabolite examples?
Methotrexate
Leucovorin
Hydroxyurea
Methotrexate mechanism?
Inhibits dihydrofolic acid reductase and therefore inhibits the formation of folic acid
What cytotoxic drugs affect microtubule function as their mechanism? Example
Vinca alkaloids:
Vincristine
Mechanism of action of Vincristine?
Bind to tubulin, block division at metaphase and stimulate depolymerisation of tubulin
What cytotoxic drug affects protein assembly? Mechanism of action?
Asparaginase - Asparagine is essential in cancer cells as they cannot produce it, asparaginase breaks down asparagine
Example of a monoclonal antibody used in cancer treatment?
Trastuzumab - herceptin:
HER-2 recruits EGF (human epidermal growth factor)
20% of patients over-express HER-2 and Herceptin binds to receptors inactivating them
What cytotoxic drugs cause high, moderate and low nausea and vomiting?
Mild: Fluorouracil, etoposide, low dose methotrexate, vinca alkaloids
Moderate: Doxorubicin, high dose methotrexate, low/intermediate dose cyclophosphamide
High: cisplatin, high dose cyclophosphamide
Acute nausea and vomiting treatment in cancer
Domperidone/metaclopramide
Lorazepam/dexamethosone (potentiate 5-HT antagonists e.g. ondansetron)
What antibiotic might you use for pneumonia, what might you use for hospital acquired pneumonia?
Pneumonia - amoxicillin
Hospital acquired - Vancomycin
What factors might the success of chemotherapy depend on?
Size of the tumour
Number of cells dividing at any one time
Endocrine environment of the cell
Rate of recovery of normal tissue from the effect of treatment
What is addisons disease?
Autoimmune destruction of adrenal cortex, reducing the amounts of all corticoid hormones
What tests can you do to diagnose phaeochromocytoma?
Metadrenaline and clonidine suppression tests
Two theories behind PCOS?
ACTH theory:
High aromatase results in incraesed breakdown of cortisol, results in feedback resulting in increased ACTH release
DHEA conversion to testosterone is increased by ACTH
High aromatase in adipose converts androgen to oestradiol (E2)
Feedback of oestradiol decreases GnRH and therefore LH, leading to amenorrhoea and cysts in ovaries
Insulin theory:
Increased peripheral adiposity
Insulin resistance causes hyperinsulinaemia
Insulin stimulates androgen release
Which is converted to E2 by aromatase, the negative feedback again decreases the amount of GnRH and LH
Macroscopic hallmarks of cancer?
Autonomous growth
Evasion of apoptosis
Angiogenesis
Insensitive to growth inhibitors
Two branches for treatment of PCOS, and the drugs within them?
Management of hirsutism:
- Oral contraceptive pill
- Anti androgens e.g. spironolactone
Management of infertility:
- Clomiphene (blocks oestrogen)
- Gonadotrophin therapy
