Pharmacology Flashcards

Question

Tenofovir

Answer 1

Group: Anti Virals nucleotide analog reverse transcriptase inhibitor (NtRTI) Pharmacodynamics Blocks reverse transcriptase enzyme which is essential for viral replication Pharmacokinetics Prodrug Renal excretion Clinical Use PEPSE: Tenofovir 245mg/emtricitabine 200mg given in combination with Raltegravir 1200mg OD for 28 days PREP: On Demand (anal sex only)- Double dose 2-24hrs before and continue daily until 48hr after last sexual risk Daily – seven days before and seven days after Side Effects/cautions/interactions Headache, nausea, diarrhoea, bloating Avoid antacids, multivitamins, iron, protein supplements CAution in patients with chronic hep B/C The most serious side effect is the potential for renal toxicity, particularly in those aged over 40 and/or with pre-existing kidney issues  Bone health: 1.5-2% reduction bone mineral density at hip and spine at 48 weeks

Answer 2

Group: Anti Virals nucleoside reverse transcriptase inhibitor (NRTI) Pharmacodynamics Blocks reverse transcriptase enzyme which is essential for viral replication Pharmacokinetics Prodrug Renal excretion Clinical Use PEPSE: Tenofovir 245mg/emtricitabine 200mg given in combination with Raltegravir 1200mg OD for 28 days PREP: On Demand (anal sex only)- Double dose 2-24hrs before and continue daily until 48hr after last sexual risk Daily – seven days before and seven days after Side Effects/cautions/interactions Headache, nausea, diarrhoea, bloating Avoid antacids, multivitamins, iron, protein supplements CAution in patients with chronic hep B/C The most serious side effect is the potential for renal toxicity, particularly in those aged over 40 and/or with pre-existing kidney issues  Bone health: 1.5-2% reduction bone mineral density at hip and spine at 48 weeks

Answer 3

Group: Synthetic steroid Pharmacodynamics Binds to both isoforms of oestrogen receptor (Alpha and beta) Binding to ER alpha exerts anti gonadotrophin effect Pharmacokinetics Metabolised liver Clinical Use COCP > Primary mode of action is prevention of ovulation via inhibition of LH/FSH > Secondary effects from progestogens (changes to cervical mucus, endometrium and tubal motility) Side Effects/cautions/interactions Glucuronide metabolites of oestrogen (particularly from EE) impair bilirubin metabolism and excretion. This happens to a lesser extent with endogenous oestrogens which are metabolised much faster

Answer 4

Group ‘natural’ - mimics endogenous oestrogen Pharmacodynamics the skin functions as a semipermeable membrane and there is a concentration gradient between the application site of transdermal estradiol and capillary blood, with the rate of diffusion of estradiol across the stratum corneum being the specific rate-limiting factor in absorption.[10][194] As a result, peaks and troughs in circulating estradiol levels are limited, and the skin and subcutaneous fat act as a reservoir of estradiol that maintains circulating estradiol levels between doses.[17] For these reasons, transdermal estradiol can provide near-constant circulating levels of estradiol, similarly to oral estradiol Pharmacokinetics oral route is subject to a high first-pass effect, which results in high levels of estradiol and consequent estrogenic effects in the liver and low potency due to first-pass hepatic and intestinal metabolism into metabolites like estrone and estrogen conjugates. - increases VTE risk and increase levels of SHBG(less free circulating oestrogen and testosterone ) Clinical Use Oestrogen in most HRTs and also in new COCP such as Zoely and Qlaira Estrogel Sandrena Lenzetto Patches Oral tablets Side Effects/cautions/interactions Trans Women 3-6 months after starting oestrogen therapy, trans women can expect to see the following physiological changes: Reduced muscle mass Breast tissue development Testicular atrophy Skin softening/dryness Body fat redistribution Bioidentical oestrogens (such as oestrodiol) are recommended Synthetic oestrogens (such as ethinylestradiol) have a higher risk of adverse effects The target serum oestrodiol level is the Trans Women upper half of physiological oestrogen levels during the follicular phase Serum oestrodiol levels normally plateau within a week of a dosage change Tests for serum oestrodiol will only detect bioidentical oestrogens; if synthetic formulations are being used results may be falsely low VTE risk is highest within the first two years of therapy Transdermal preparations have a lower thrombosis/hepatic risk Sperm quality may be adversely affected but does not confer sterility; contraception is still advised

Answer 5

Group Pharmacodynamics Pharmacokinetics Clinical Use Side Effects/cautions/interactions

Answer 6

Group Selective estrogen receptor modulators (SERMs) Pharmacodynamics Competitive partial agonists bind to estrogen receptors (Er Alpha ER Beta) and act as either agonists or antagonists. This allows them to target specific tissues and avoid major side effects. Pharmacokinetics the action of SERMs on the estrogen receptor affects bone homeostasis by downmodulating the activity of osteoclasts in a transforming growth factor-β3-dependent manner and reducing bone resorption Clinical Use Tamoxifen – breast cancer Raloxifene – osteoporosis – prevention vertebral fractures Side Effects/cautions/interactions Hot flushes, nausea, vaginal discharge Increased risk of blood clots Increased risk endometrial cancer (tamoxifen)

Answer 7

Group C21 progestins Pregnane derivatives Synthetic Pharmacodynamics Pharmacokinetics Clinical Use Medroxyprogesterone acetate Menorrhagia, HRT Cryproterone acetate Anti androgen, suppresses action of testotserone and DHT on tissues and LH, weak progestogenic activity Megestrol Acetate Side Effects/cautions/interactions

Answer 8

Group C19 Testosterone derived Synthetic Pharmacodynamics Bind to progesterone receptors Pharmacokinetics Clinical Use Norethisterone(1st) Levonorgestrol(2nd) Desogestrel(3rd) Norgestimate(3rd), Gestodene(3rd) Nomegestrol(4th) Dienogest(4th) Side Effects/cautions/interactions

Answer 9

Group Spironolactone derived (4th Generation) Synthetic Pharmacodynamics Aldosterone antagonist Pharmacokinetics Supress ovulation and increase cervical mucus Clinical Use Drospirenone COCP – recommended for PMS Side Effects/cautions/interactions Mild anti androgenic activity CAn increase K+ so avoid if renal impairment or if on other drugs

Answer 10

Group natural Pharmacodynamics Pharmacokinetics Clinical Use Side Effects/cautions/interactions

Answer 11

Group Pharmacodynamics Pharmacokinetics Clinical Use Hypoactive Sexual Desire Disorder - post menopausal women, Tostran 2% 1 pump on alternate days, Testogel 40.5mg/2.5g 1 sachet to be used over 8 days HSDD – common side effects – increased hair growth at site of application, acne Uncommon unless higher doses taken – deepening of voice, cliteromegally, male pattern alopecia HSDD – total testosterone level before commencement, after 8-12 weeks then annually to ensure stays within normal range for females Side Effects/cautions/interactions Gender Affirming treatment for Trans Men: Clitoral Hypertrophy (1-6mths) Voice deepening (3-12mths) FAcial/body hair growth (3-6mths) MAle pattern Baldness (>12mths) Trans Men Common side effects of testosterone therapy: Hot flushes Hypertension Hypertriglyceridaemia Polycythaemia Skin reactions Weight gain Testosterone therapy and haematocrit (TRANS MEN) Polycythaemia is a side-effect of testosterone therapy and increases the risk of VTE and arterial thrombotic events Haematocrit and haemoglobin should be within the normal cisgender male range If haematocrit and/or haemaglobin is raised, the testosterone level should be reduced The dosing interval for injectables may need to be extended or the transdermal dose reduced Haemaglobin and haematocrit should be measured every three months for the first year. If this is stable, it can be measured annually after this. Target trough serum testosterone levels for transmen using testosterone therapy: Intramuscular testosterone: lower third of the cisgender male physiological reference range Transdermal testosterone: middle third of the cisgender male physiological reference range

Answer 12

Group Pharmacodynamics GnRH is released at the median eminence of the hypothalamus Elevated prolactin suppresses GnRH release Pulsatile release of GnRH results in LH/FSH release Exogenous GnRH causes an acute rise in LH and FSH before falling quickly Pharmacokinetics GnRH is normally released by the hypothalamus in pulses to stimulate GnRH receptors at the anterior pituitary GnRH analogues initially cause a surge in LH and FSH release Continuous stimulation causes desensitisation of GnRH receptors resulting in a fall in LH and FSH release. This takes several weeks to take effect This results in falling sex steroid levels, arresting further development of secondary sexual characteristics This is a reversible process; on cessation of treatment, the hypothalamic-pituitary-gonadal axis reactivates Clinical Use Side Effects/cautions/interactions

Answer 13

Group Progesterone Receptor Modulator Weak anti androgen and anti glucocorticoid activity Pharmacodynamics Prevents ovulation up to LH peak inhibits follicular maturation and prevents follicular rupture (by at least 5 days) Cannot inhibit ovulation at the time of the LH peak or after it Ovulation still occurs later in the cycle unless further doses are taken Pharmacokinetics Clinical Use EC – 120 hours Hormonal contraception should not be quick started until 5 days after UPA-EC administration * Consistent use of condoms is recommended during the 5 days waiting and until the method started becomes effective Side Effects/cautions/interactions Efficacy effected : weight >85kg BMI>30 Repeat dose if vomiting within 3 hrs or severe diarrhoea persisting>24hrs PPI use Use of progestogen 7 days prior to use Avoid in severe asthmatic requiring oral steroids Can be used in breast feeding but should bottle feed for 5 days after, express and discard breast milk

Answer 14

Group Competitive progesterone receptor antagonist Anti glucocorticoid Anti androgen Pharmacodynamics Cervical dilatation and softening, decidual degeneration, release of endogenous prostaglandins, increases sensitivity of myometrium to prostaglandins Pharmacokinetics Half life 18-30 hrs Metabolised by liver p450 thus can be effected by enzyme inducers Clinical Use MTOP – 200mg oral dose Cervical preparation STOP <14 weeks 200mg oral 24-48hrs Side Effects/cautions/interactions Controlled Drug Nausea, D&V, constipation, fever, headache, Pain Contraindications: Severe asthma Chronic adrenal failure Ectopic Acute porphyria Hepatic and renal impairment

Answer 15

Group EC, progesterone Pharmacodynamics Prevents ovulation if taken before LH surge Pharmacokinetics Clinical Use EC < 96hrs post UPSI Consider 3mg if needing EC and on enzyme inducer but CU IUD declined Side Effects/cautions/interactions Weight >70kg BMI >26 double dose Repeat dose if vomiting within 3 hrs or severe diarrhoea persisting>24hrs Safe in breast feeding

Answer 16

Group Pharmacodynamics High affinity for hydroxyapatite crystals within bone mineral, especially sites of active bone remodelling Bind to the hydroxyapatite binding sites at the bone surface inhibiting their breakdown Also inhibit osteoclast mediated bone resorption May inhibit apoptosis of osteoblasts and osteocytes Pharmacokinetics Clinical Use Treatment of osteoporosis Alendronate Risendronate Ibandronate zolendronate Side Effects/cautions/interactions Osteonecrosis of the jaw and bisphosphonates: Incidence: 1-10/10,000 Symptoms: delayed dental wound healing, pain, soft tissue swelling, infection, paraesthesia. Often asymptomatic. Risk factors: recent dental treatment, pre-existing dental disease, high or intravenous bisphosphonate dose, use for >5 years, concurrent use of other bone resorbing drugs (e.g. oral glucocorticoids)

Answer 17

Group Pharmacodynamics Activates anti thrombin III causing inactivation of thrombin and Factor Xa Average molecular weight 4.5 kDa Pharmacokinetics Clinical Use Side Effects/cautions/interactions

Answer 18

Group Amide Pharmacodynamics Blocks voltage gated sodium channels-prevents neurone depolarization Pharmacokinetics Metabolized by liver Excreted by kidney Fast Onset Half life – 100 mins Clinical Use SDI insertions/removals vasectomy 1% = 10mg/ml 2% = 20mg/ml 3% = 30mg/ml Max Dose – 4.5mg/kg 7 mg/kg with adrenaline Side Effects/cautions/interactions Toxicity Sx: Circumoral anaesthesia Tinnitus Blurred Vision Seizures LOC Cardio-resp compromise ECG changes – widening PR int and QRS

Answer 19

Group Amide Pharmacodynamics Blocks voltage gated sodium channels-prevents neurone depolarization Pharmacokinetics Metabolized by liver Excreted by kidney Fast Onset Half life – 115 mins Clinical Use Para/cervical blocks Max Dose 4.5mg/kg Scandonest 3% Mep Vial = 2.2ml = 66mg Side Effects/cautions/interactions Toxicity Sx: Circumoral anaesthesia Tinnitus Blurred Vision Seizures LOC Cardio-resp compromise ECG changes – widening PR int and QRS

Answer 20

Group 25m each of prilocaine and lidocaine Both amides Pharmacodynamics Decreases excitability of neurons preventing sodium conduction/permeability which blocks the initiation and propagation of action potentials. Initial vasoconstriction then vasodilatation Pharmacokinetics Quality of cover depends on time in place and dose Clinical Use Apply 1-2 hrs before, shorter on face and genitals Side Effects/cautions/interactions Only use on intact skin Metheglobinaemia (rare serious adverse event) Safe in pregnancy Transient erythema of skin

Answer 21

Sodium valproate Topiramate Testosterone Potential teratogens include all the A drugs: Anticonvulsant Antibiotics Anticoagulants Antimetabolits Androgens Alcohol Antipsychotics

Answer 22

Heparin Insulin Tubocararine

Answer 23

Misoprostal Ergotamine Thrombolytics

Answer 24

<20days – Limb defects Day 20 – Anencephaly Day 34 – transposition of great vessels Day 36 Cleft Lip Day 42 VSD, syndactyly Day 82 hypospadias

Answer 25

Congenital Malformations Renal dysgenesis Oligohydramnios as a result of fetal oliguria Pulmonary hypoplasia IUGR Neonatal anuric renal failure

Answer 26

Choanal atresia GIT defects Omphalocoele Aplasia cutis

Answer 27

Hypoplasia of nasal bridge Congenital heart defects Ventriculomegaly Agenesis of the corpus callosum Stippled epiphyses VASC and nasal bridge

Answer 28

Diarrhoea Lactose intolerance

Answer 29

Ototoxicity

Answer 30

Yellowing of teeth Suggested link with cleft palate

Answer 31

Cardiac defects

Answer 32

Cardiac Defects

Answer 33

Withdrawal syndrome in neonates Some linked to CVS defects and Pulmonary Hypertension but evidence conflicting

Answer 34

IUD SDI Sterilisation Depot/OCP – with condoms Teratogenic Sodium valproate Phenytoin Topiramate Lithium

Answer 35

IUD Depo and condoms STerilisation induce hepatic cytochrome P450 enzymes and increase clearance of contraceptive hormones Antibiotics – rifampicin and rifabutin Antiseizure medications- carbamazepine, eslicarbazepine acetate, oxcarbazepine, perampanel, phenobarbital, phenytoin, primidone, rufinamide and topiramate (doses of 200mg daily or higher) Antiretrovirals – ritonavir, efavirenz and nevirapine St John’s Wort

Answer 36

Not Affected: IUDs Depot Use with Condoms: (and advise to monitor for signs of lamotrigine toxicity) SDI POP If unavoidable can use COCP but may need levels and dose of lamotrigine increased and skip HFI – liaise with there neurologist Sugammadex (used in GA) is likely to bind some serum contraceptive progestogen (and, with less affinity, estrogen). The effect is short-lived: sugammadex has a half-life of recommend follow missed pill rules for one pill if on OCP ------- Estrogen in combined hormonal contraception appears to induce glucuronidation of lamotrigine, significantly reducing serum lamotrigine levels. This could result in reduced seizure control (or reduced effectiveness of lamotrigine for other indications) when combined hormonal contraception is started and during pill taking. there could be a risk of lamotrigine toxicity during any hormone-free interval taken ---- It is possible that contraceptive effectiveness of combined hormonal contraception, all progestogenonly pills and the etonogestrel implant could be reduced during use of lamotrigine. ---- Lamotrigine toxicity – dizziness, ataxia, diplopia

Answer 37

The antiretrovirals most associated with cytochrome P450 enzyme-induction are certain non-nucleoside reverse transcriptase inhibitors (NNRTIs), particularly efavirenz, and ritonavir-boosted protease inhibitors (PIs) DMPA – avoid if on tenovir as can both cause increased bone loss IUDs EC – CU IUD and if not acceptable double dose LNG 3mg