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Y2B3 - Reproductive πŸ“˜ > Pharmacology πŸ’Š > Flashcards

Pharmacology πŸ’Š Flashcards

1
Q

what are the types of estrogen?

A

Natural estrogens: estradiol, estrone and estriol

Semisynthetic estrogens: Ethinyl estradiol and mestranol.

Synthetic estrogens: diethyl stilbosterol.

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2
Q

Mechanism of action of estrogen

A
  • It acts via binding to Intracellular receptors which are ligand activated transcription factors that controls gene transcription.
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3
Q

whata re the pharmacological effects of estrogen?

A
  • Development of genital tract and breast.
  • Development of ♀ secondary sex characters.
  • Metabolic effects:
    1. Increase bone mass and prevent bone resorption.
    2. Increase blood glucose and TGs.
    3. Salt and water retention.
    4. Increase blood coagulation and platelet adhesiveness
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4
Q

absorbtion of estrogen

A

Oral, Parenteral, Transdermal or topical.

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5
Q

Distribution of estrogen

A

Bind to albumin and sex hormone binding globulin (SHBG).

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6
Q

Metabolism of estrogen

A

Metabolized by sulfate and glucuronide conjugation in the liver and undergo enterohepatic recycling.

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7
Q

Elimination of estrogen

A

Excreted via bile and urine.

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8
Q

what are the therapeutic uses of estrogen?

A
  1. Contraceptive pills.
  2. Dysfunctional uterine bleeding.
  3. Replacement therapy in ovarian hypofunction.
  4. Postmenopausal symptoms e.g. atrophic vaginitis and osteoporosis.
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9
Q

what are the adverse effects of estrogen?

A
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10
Q

Contraindications of estrogen

A
  • Hypertension or ischemic heart disease (IHD).
  • History of thrombosis.
  • History of cancer breast.
  • Migraine headache.
  • Depression
  • Diabetes mellitus.
  • Liver disease and gall stones.
  • Obese, smokers, or women over 35 years.
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11
Q

what is the mechanism of action of Clomiphene citrate (Clomid)?

A
  • Blocks estrogen receptors in hypothalamus and pituitary →↑ FSH and LH β†’ stimulate ovulation.
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12
Q

Uses of Clomiphene citrate (Clomid)

A

Infertility

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13
Q

Adverse effects of Clomiphene citrate (Clomid)

A
  • Ovarian cysts
  • Hot flushes.
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14
Q

what are Selective estrogen receptor modulators (SERMs)?

A
  • Tamoxifen
  • Raloxifene
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15
Q

Compare between Tamoxifen and Raloxifene in terms of (mechanism of action, uses & adverse effects)

A
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16
Q

what are Aromatase inhibitors?

A
  • Nonsteroidal competitive inhibitors
  • Steroidal, irreversible inhibitor
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17
Q

Nonsteroidal competitive inhibitors

A

Anastrazole and letrozole (Femara).

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18
Q

Steroidal, irreversible inhibitor

A
  • Exemestane
  • Used for treatment of postmenopausal women with estrogen- receptor positive breast cancer who have received two to three years of tamoxifen and are switched to them to complete five years of hormonal therapy.
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19
Q

Hormonal contraception

A
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20
Q

Mechanism of action of Hormonal contraception

A

They inhibit ovulation by exerting –ve feedback on LH and FSH secretion.

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21
Q

what are the Causes of failure of contraceptive pills?

A
  • Enzyme inducers e.g. rifampin, phenytoin
  • Broad spectrum antibiotics: e.g tetracycline
  • Laxatives: ↓ intestinal absorption of contraceptive pills.
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22
Q

Types of Progesterone

A

Natural: Progesterone injection

Synthetic: Medroxy progesterone acetate.

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23
Q

Mechanism of action and pharmacokinetics of Progesterone

A

Like estrogen

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24
Q

Therapeutic uses of Progesterone

A
  • Contraceptive pills.
  • Threatened abortion.
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25
what are the adverse effects of Progesterone?
- **Menstrual irregularities:** spotting bleeding, breakthrough bleeding, amenorrhea, and dysmenorrhoea. - Acne. - Hirsutism.
26
what is the mechanism of action of Antiprogesterone (Mifepristone)?
It is a competitive blocker of progesterone receptors.
27
what are the uses of Antiprogesterone (Mifepristone)?
It is used with PGF2Ξ± to induce medical abortion in the first trimester.
28
what are examples of Androgens and anabolic steroids?
- **Natural androgens:** androsterone and testosterone - **Synthetic androgens:** testosterone propionate. - **Anabolic steroids:** Stanazol.
29
Mechanism of action & pharmacokinetics of Androgens and anabolic steroids
Like estrogen
30
what are the uses of Androgens and anabolic steroids?
- Chronic debilitating diseases e.g renal failure. - Chronic refractory anemia - Illicit use by athletes: to increase muscle bulk
31
what are the adverse effects of Androgens and anabolic steroids?
1. Reduction in spermatogenesis after stopping. 2. Precocious puberty and premature closure of epiphysis in children. 3. Cholestatic jaundice. 4. Verilizing effects in females.
32
what are examples of Antiandrogens?
- Ξ±-reductase inhibitors: Finasteride - Testosterone receptor blockers
33
what is the mechanism of action of Ξ±-reductase inhibitors (Finasteride)?
Inhibits 5 Ξ±-reductase enzyme responsible for conversion of testosterone into the active form di-hydro-testosterone (DHT).
34
Uses of Ξ±-reductase inhibitors (Finasteride)
- Treatment of benign prostatic hyperplasia (BPH). - Treatment of male baldness. - Treatment of female hirsutism.
35
what are examples of Testosterone receptor blockers?
- Cyproterone acetate - Flutamide
36
what are the uses of Testosterone receptor blockers?
**Cyproterone acetate:** Used in hirsutism in females. **Flutamide:** Used in cancer prostate.
37
what are Oxytocic drugs? and what are they used for?
- Oxytocin - Prostaglandins - Mifepristone - Ergot alkaloids Used in induction of delivery.
38
what is the mechanism of action of oxytocin?
- Stimulation of Oxytocin receptors (which are expressed by the uterus and myoepithelial cells of mammary gland): 1. ++ contraction of uterine muscle (facilitate delivery). 2. Stimulates smooth muscles of mammary glands (milk-ejection). 3. Weak pressor and anti-diuretic activity.
39
Uses of Oxytocin
**1. Induction of labor.** 2. Control postpartum hemorrhage. 3. Stimulate milk ejection
40
Adverse effects of Oxytocin
**Mother:** - Uterine rupture. - HTN. - Arrhythmia. - Water intoxication. - Afibrinogenemia. - Death. **Fetus:** - Arrhythmia - Fetal death
41
CI of Oxytocin usage
- Fetal distress - Prematurity - If vaginal delivery is contraindicated.
42
when is vaginal delivery contraindicated?
- Abnormal fetal presentation - Cephalopelvic disproportion - Invasive cervical cancer - Active genital herpes - Prolapse of the cord
43
what are examples of Prostaglandins?
- Dinoprostone (PGE2) - Carboprost (PGF2Ξ±) - Misoprostol (PGE1 analogue)
44
mechanism of action of prostaglandins
- Potent stimulation of uterine contractions. **- PG plays an important role in cervical ripening (Softening of the cervix ).**
45
uses of prostaglandins
1. Induction of abortion. 2. Cervical ripening before induction of labor.
46
what are the adverse effects of prostaglandins?
- Colic and diarrhea - Carboprost aggravate bronchial asthma.
47
what is the mechanism of action of Mifepristone?
Antagonize Progesterone at its receptor in the uterus.
48
uses of Mifepristone
Medical termination of intrauterine pregnancy
49
what are the adverse effects of Mifepristone?
- GI cramps - Vaginal bleeding - Urticarial rash
50
examples of Ergot alkaloids
**(Methylergometrine)**
51
what is the mechanism of action of Ergot alkaloids?
Increases motor activity of the uterus results in forceful, prolonged contraction
52
Uses of Ergot alkaloids
Only for postpartum bleeding
53
what are the adverse effects of Ergot alkaloids?
- Hypertension & tachycardia - Acute myocardial infarction - Nausea, vomiting and colic
54
what are tocolytic drugs?
- Atosiban - Beta-sympathomimetics - Calcium channel blockers - Magnesium sulphate - Ethyl alcohol - Prostaglandin inhibiting agent
55
Mechanism of action of **Atosiban**
- Modified form of oxytocin that competitively blocks oxytocin receptor leading to halting uterine contractions.
56
what are tyhe uses of **Atosiban**?
Prevention of premature labor
57
Adverse effects of **Atosiban**
* Headache * Hypotension * Hot Flushing * Hypersensitivity * Tachycordia.
58
what are examples of **Beta-sympathomimetics**?
* Ritodrine. * Isoxuprine. * Terbutaline. * Salbutamol.
59
Increases cAMP via activation of B2- adrenoceptors leading to relaxation of uterine smooth muscle.
60
what are the uses of **Beta-sympathomimetics**?
Prevention of premature labor
61
Adverse effects of **Beta-sympathomimetics**
**Fetal:** * Tachycardia. * Hypotension. * Arrhythmia. **Maternal:** * Tachycardia * Hypokalaemia * Tremors * Hypotension. * Arrhythmia * Flushing
62
Contraindications of **Beta-sympathomimetics**
a. Hypotension. b. Heart disease. c. Hyperthyroidism. d. Uterine bleeding : (dilatation of uterine arteries increase bleeding).
63
what are examples of **Calcium channel blockers**?
Nifedipine
64
what is the mechanism of action of **Calcium channel blockers**?
Block voltage gated Ca channel ---> decrease Ca concentration within the myometrial cells and reduce its contractility.
65
whata are the uses of **Calcium channel blockers**?
Prevention of premature labor
66
Adverse effects of **Calcium channel blockers**
1. Hypotension and reflex tachycardia. 2. Gingival (gum) hyperplasia. 3. Salt & water retention (ankle edema).
67
Contraindications of **Calcium channel blockers**
a. Hypotension. b. Angina c. Tachycardia
68
what is the mechanism of action of **Magnesium sulphate**?
Calcium efflux outside myometrial cells leading to uterine relaxation.
69
what are the uses of **Magnesium sulphate**?
- Prevention of premature labor - Prevention & It of seizures in preeclampsia - TTT of arrhythmia (torsade de pointes)
70
Adverse effects of **Magnesium sulphate**
- Shock and hypotension - Nausea and vomiting - Pulmonary edema - Cardiovascular collapse - Hypotonia (ms weakness)
71
Contraindications of **Magnesium sulphate**
Myasthenia gravis is an absolute contraindication for magnesium sulfate.
72
what reverses the side effects of magnesium sulphate?
ca gluconate
73
what is the mechanism of action of **Ethyl alcohol**?
1. Inhibits oxytocin release from posterior pituitary. 2. Suppresses myometrial activity directly. 3. Inhibits prostaglandin F2 synthesis.
74
Adverse effects of **Ethyl alcohol**
a. Nausea, vomiting. b. Drunken mother and foetus. c. Maternal and foetal acidosis. d. Congenital anomaly
75
what is the mechanism of action of **Prostaglandins inhibiting agents**?
Inhibit uterine contraction by inhibiting PGs synthesis. e.g. indomethacin
76
what are the uses of **Prostaglandins inhibiting agents**?
- Relief of cramps associated with menstruation (dysmenorrhea)
77
Contraindications of **Prostaglandins inhibiting agents**
Don't administer NSAIDs during late 2nd or 3rd trimester of pregnancy ---> premature closure of ductus arteriosus.
78
79
Absorbtion of drugs in pregnancy
- Slow drug absorption does not occur except at term, Thus parenteral drug administration is preferred to obtain quick response. - Increased emesis is seen due to morning sickness.
80
Distribution of drugs during pregnancy
- Pregnancy is accompanied by a **30% increase in plasma volume**, with **consequent decrease in plasma albumin**. - This may **alter the Vd and plasma concentration of drugs** given.
81
Metabolism of drugs during pregnancy
Hepatic drug metabolising enzymes are induced during pregnancy.
81
Execretion of drugs during pregnancy
- During pregnancy, renal plasma flow increases by 100% and GFR by 70%. * Drugs are eliminated more rapidly than in the non-pregnant state.
82
what are the Factors affecting transfer of drugs to fetus?
**1. Physicochemical properties of the drug:** - Molecular weight (size) - Lipid solubility **2. Rate & amount of drug reaching the fetus:** - Protein binding - Variables affect uterine blood flow & rate of drug transfer **3. Genetic Fetal Predisposition** **4. Stage of placental and fetal development at time of exposure to drug:** - The human gestation period is approximately 40 weeks from first day of last menstrual period (38 weeks' post-conception).
83
Molecular size & its relation to placental transfer of drugs
- Most drugs (MW <600) cross easily. - Drugs with very large MW (e.g Insulin & Heparin) have negligible transfer.
84
Lipid solubility & ionization relation to placental transfer of drugs
- **Lipophilic, unionized** drugs **cross** the placenta **more easily than polar** drugs. - Molecules that are **ionized** at physiological pH **cross slowly (e.g. salicylates, tubocurarine)** - **Weakly basic drugs become 'trapped' in fetal circulation** due to slightly lower pH compared with maternal plasma.
85
Protein binding relation to placental transfer of drugs
- Drugs which are **highly protein bound** tend to achieve **higher maternal and lower fetal concentrations**. - The **penetration of highly protein-bound drugs is inhibited** - Only **free unbound drugs, cross placenta.**
86
uterine blood flow & rate of drug transfer relation to placental transfer of drugs
**Uterine & umbilical bl. Flow :** 1. Maternal blood pressure 2. Cord compression 3. Drug therapy e.g. alpha-stimulant **Maternal diseases :** 1. Pregnancy-induced hypertension 2. DM -> change permeability of placenta
87
what are the 3 stages of development of embryo & fetus?
1. Pre-embryonic Stage 2. Embryonic stage 3. Fetal stage
88
what is another name for Pre-embryonic stage
fertilization and implantation period
89
Duration of Pre-embryonic stage
0-14 days
90
Effect of teratogenic drugs during Pre-embryonic stage
- Drugs in this stage leads to death of fetus at a very early and sub-clinical stage.
91
what is another name of Embryonic stage?
Organogenesis period
92
Duration of Embryonic stage
14-56 days (weeks 3-8 post-conception)
93
Effects of teratogenic drugs during Embryonic stage
- The **most sensitive period to Teratogenic effects** therefore represents greatest risk of major birth defects. - Avoid or minimise all drug use in the first trimester.
94
what is another name of fetal stage?
growth and development period
95
Duration of fetal stage
57th day onward (weeks 9-38 post-conception)
96
Effect of administration of teratogenic drug during fetal stage
- Fetus remains susceptible to some drug effects.. - NSAIDs ----β€Ί premature closure of fetal ductus arteriosus (inhibit prostaglandin synthesis).
97
Results of trimethoprim adminstration in: - 3-4 weeks post-conception - after 32 weeks' gestation
- Folic acid antagonists (trimethoprim): are associated with an increased risk of **neural tube defects if exposure occurs 3-4 week post-conception** but not after this period - Trimethoprim: should be avoided after **32 weeks' gestation** in view of the theoretical risk of **severe jaundice in the neonate (Kernicterus).**
98
what is a **Teratogen**?
- Any **agent** that results in **structural or functional abnormalities** in **fetus, or in child after birth**, as a consequence of maternal exposure during pregnancy. - **Agent** that **has the potential** **under certain exposure conditions** to **produce abnormal development** in the **fetus**.
99
what is the mechanism by which a teratogen causes its effect?
Direct effects of the drug on fetus and or as a consequence of indirect physiological changes in mother or fetus.
100
Manifestations of congenital anomalies
- Congenital anomalies are non-reversible birth defects. - Include 4 major manifestations of abnormal fetal development : 1. Growth alterations. 3. Structural malformations. 2. Functional deficits. 4. Fetal death.
101
what are the types of congenital anomalies?
102
Give examples for congenital anomalies at birth
- Obvious at birth - Delayed many years to manifest clinically
103
Give examples for congenital anomalies which delayed many years to manifest clinically
* limb abnormalities. * Spina bifida. * Hydrocephalus.
104
what is the first teratogen discovered?
Thalidomide
105
what drugs were proven to be teratogenic?
- ACE inhibitors - Corticosteroides - Warfarin - Androgens - Vitamin A (Isotritenoine) - Antithyroid drugs - Diethylstilbestrol - Phenytoin - Lithium - Valproic acid - Carbamazpine - Cyclophosphamide - NSAIDs - Trimethoprim
106
Teratogenic effects of ACE inhibitors
Pulmonary hypoplasia. **(CAPTOPRIL) for example**
107
Teratogenic effects of Corticosteroids
Oral cleft lip and palates if used during organogenesis
108
Teratogenic effects of Warfarin
- Fetal warfarin syndrome with nasal hypoplasia, stippled epiphyses, and skeletal and CNS defects
109
Teratogenic effects of androgens
Masculinization of female fetus
110
Teratogenic effects of Vitamin A (Isotritenoine)
- Microtia (under developed ear pinna). - Anotia (complete under developed ear pinnae). - Thymic aplasia. - Cardiovascular defects
111
Teratogenic effects of antithyroid drugs
- Fetal and neonatal goiter with iodine use. - Small risk of aplasia cutis with methimazole. (Atrophy of skin)
112
Teratogenic effects of diethylsilbestrol
- Vaginal carcinoma and other genitourinary defects
112
Teratogenic effects of Phenytoin
- Fetal hydantoin syndrome. (Cleft lip, Microcephaly, MR) - Growth retardation. - CNS deficits
113
Teratogenic effects of Lithium
- Ebstein anomaly (Tricuspid valve regurge)
114
Teratogenic effects of Valproic acid
- Neural tube defects, developmental delay and deficits
115
Teratogenic effects of Carbamazpine
- Neural tube defects, minor craniofacial defects. - Fingernail hypoplasia
116
Teratogenic effects of Cyclophosphamide
- Craniofacial, eye, and limb defects. - IUGR & Neurobehavioral deficits
117
Teratogenic effects of NSAIDs
- Constriction of the ductus arteriosus - Oral clefts, cardiac defects. - Spontaneous abortion
118
Teratogenic effects of Trimethoprim
- Neural tube defects and cardiac defects
119
Adverse effects of ACE inhibitors during later stages in pregnancy
- Fetal and neonatal hypoxia - Hypotension. - Fetal kidney anuria, neonatal renal failure, oligohydramnios "Hypo renal" - Infra-uterine growth retardation. "Hypo growth" | 4 Hypo
120
Adverse effects of phenothiazines during later stages in pregnancy
- Neonatal withdrawal. - Transient extrapyramidal symptoms.
121
Adverse effects of Benodiazepines during later stages in pregnancy
- Floppy infant syndrome. - Withdrawal reactions.
122
Adverse effects of opiods during later stages in pregnancy
- Respiratory depression. - Withdrawal reactions.
123
Adverse effects of B-blockers during later stages in pregnancy
- Neonatal bradycardia. - Hypotension & hyperglycaemia.
124
Adverse effects of corticosteroids during later stages in pregnancy
- Fetal adrenal suppression
125
Adverse effects of NSAIDs during later stages in pregnancy
- Premature closure of ductus arteriosus - Fetal renal impairment (decreased urine output),
126
Adverse effects of Tetracycline during later stages in pregnancy
- Permanent discoloration of deciduous teeth
127
Tips for prescribing during pregnancy
- Minimize prescribing - Use the smallest effective dose - Remember that the fetus is most sensitive in the first trimester - Consider pregnancy in all women of childbearing potential - Discuss the potential risks of taking or withholding therapy with the patient - Warn the patient about the risks of smoking, alcohol, over-the-counter drugs and drugs of abuse.
128
what are drug categories according to FDA?
A, B, C, D & X
129
Definition of Category **A** drugs
- Well controlled **studies in human fail to demonstrate a risk to the fetus in all trimesters** & possibility of fetal harm appears remote (no demonstrable risk)
130
Definition of Category **B** drugs
- **Animal** studies have **not demonstrate a fetal risk** But **no controlled studies in human** OR - **Animal** studies have demonstrate **adverse effect** that **not confirmed** by Well controlled studies **in human**
131
what are examples of category **B** drugs?
- penicillin - Cephalosporin - Paracetamol
132
Definition of Category **C** drugs
- **Animal** studies **positive (Teratogen)** and **no Well contralled studies in human** OR - Studies in **human and animal are not available** **(Drugs given only if potential benefits justifies potential risk)**
133
what are examples of category **C** drugs?
- Anti-histaminic drugs
134
Definition of Category **D** drugs
- There is **positive evidence of human fetal risk**, but benefit from use may be acceptable despite risk ( life threatening situation)
135
what are examples of category **D** drugs?
Lithium
136
Definition of category **X** drugs
- Studies in **animals or human have demonstrated fetal abnormalities** OR - There is evidence of fetal risk based on human experience or both and risk of drug outweigh any possible benefit. **(Teratogenic &The drug is contraindicated)**
137
Mention condition, Drugs prevented in pregnancy & Safer options in pregnancy - Anti-emetics
138
Mention condition, Drugs prevented in pregnancy & Safer options in pregnancy - Antacids
139
Mention condition, Drugs prevented in pregnancy & Safer options in pregnancy - Laxatives
140
Mention condition, Drugs prevented in pregnancy & Safer options in pregnancy - Analgesics
141
Mention condition, Drugs prevented in pregnancy & Safer options in pregnancy - Anti-bacterials
142
Mention condition, Drugs prevented in pregnancy & Safer options in pregnancy - Anti hypertensives
143
Mention condition, Drugs prevented in pregnancy & Safer options in pregnancy - Anti-diabeteic
144
Mention condition, Drugs prevented in pregnancy & Safer options in pregnancy - Anti thyroid
145
Mention condition, Drugs prevented in pregnancy & Safer options in pregnancy - Anti-coagulants
146
what are drugs that may cause problems at later stages of pregnancy?
- ACE inhibitors - Phenothiazines - Benzodiazepines - Opioids - Beta blockers - Corticosteroids - NSAIDs - Tetracycline

Y2B3 - Reproductive πŸ“˜ (9 decks)

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