Pharmacology and theraputics Flashcards
How does pregnancy impact the pharmacokinetics of drugs (what the body does to the drug) (8)
- Nausea and vomiting in early pregnancy decreases amount of drug available for absorption
- Increased gastric pH results in reduced absorption
- Delayed gastric emptying and slow bowel transit can impact bioavailability
- Increased vascularity of the respiratory mucosa increases absorption of inhaled medications
- Increased plasma volume means increased distribution of hydrophilic drugs and lower concentration
- Increased maternal body fat means increased volume of distribution of lipophilic drugs
- Reduced concerntration of albumin means reduced plasma binding of drugs and increased free drugs which can diffuse into tissue
- Increased renal blood flow and glomerular filtration rate means increased excretion of drugs via kidneys
Discuss teratogenicity
-Types of teratogens (5)
-Factors impacting teratogenicity (3)
-Key time for tetragenic impact on:
-CNS
-Heart
-Upper limbs
-Eyes
-Lower limbs
-Palate
-Ears
- Type of teratogen
-Infection
-Drugs
-Chemicals
-Deficiency
-Metabolic conditions - Factors impacting teratogenicity
-Timing of exposure
-Ability to cross placenta
-Duration of exposure - Key timing for abnormalities
-CNS 3-16 weeks
-Heart 3.5-6.5 weeks
-Upper limbs 4-6 weeks
-Eyes 4.5-8.5 weeks
-Lower limb - 4.5 - 7 .5 weeks
-Palate 6-8 weeks
-Ears 4-9 weeks
Describe the categories of pharmacuticals in pregnancy
-Cat A
-Cat B 1-3
-Cat C
-Cat D
-Cat X
- Cat A
-Medication has been taken by large number of pregnant women without increased frequency of malformations - Cat B
-Medication has been taken by limit number of pregnant women without increased frequency of malformations
Cat B1 - studies in animals have not shown increased fetal damage
Cat B2 animal studies are inadequate but suggest no increased risk of fetal harm
Cat B3 - Animal studies have shown increased occurance but significance is unknown for humans - Cat 3
-Have caused or suspected of causing harmful effects to human fetus without causing malformations
-These effects may be reversible - Cat D
-Drugs have caused or are expected to cause and increase in fetal malformations or irreversible damage - Cat X
-Very high risk of causing permanent damage to fetus that they should not be used in pregnancy
What are examples of:
-Cat D drugs (5)
-Cat X drugs (5)
Cat D drugs:
-ACEi
-Anticonvulsants
-Hydroxychloroquine
-Endocrine meds
-Tetracyclines
Cat X drugs
-Misoprostol
-Dienoprostol
-Finasterine
-Ribavirin
-Retinoic acids
Discuss breastfeeding and medications
-Prinicples
-Safe medication
-Medication properties that increase chance of passing to breastmilk
-Most common affects
- Principles - lowest dose for shortest time
- Medication of which <10% pass into breastmilk is considered safe
- Properties
-Basic
-High lipid solubility
-Low molecular weight
-Less bound to maternal proteins - Common affects
-GIT upset
-Sedation
-Irritability
Discuss transplacental drug transfer
-Factors influencing transfer (5)
-Mechanisms of transfer (3)
- Factors influencing drug transfer
-Most drugs will enter fetal circulation to some degree via passive diffusion
-Protein binding - less albumin in maternal circulation cf fetal so increased unbound drugs crossing placenta
-pH. Fetal pH slightly more acidici so weak bases more likely to cross placenta
-Moderately lipid soluable drugs can easily diffuse across placenta
-Drugs with low molecular weight can cross placenta (<1000g/mol)
-Increased in T3 due to increased maternal blood flow, decreased thickness and increased SA - Methods of transfer
-Facilitated diffusion (only minor transfer method)
-Active transport
-Pinocytosis - too slow to have any signficant effect on fetal drug concentration
Discuss the impact of magnesium sulphate on:
1. The vasculature
2. Cerebral oedema
3. As an anti-convulsant
- Impact on the vasculature
-Causes vasodilation by relaxation and dilation of smooth muscle
-Acts as calcium antagonist resultis in less calcium released to the smooth muscle
-Increased NO so increases vasodilation - Cerebral oedema
-Decreases oedema by acting on cerebral endothelia. Decreases calcium action (Antagonist) results in decreased smooth muscle contraction, decreased tight junction permenability
-Acts on astrocytes to decreased aquaporin 4 expression - As an anticonvulsant
-Increases seizure threshold by decreasing the effect of glutamate on NMDA receptors. Acts as an antogonist on NMDA receptors.
What are the mechanisms of action for radiation for cancer therapy (6 points)
Radiation acts in 2 ways
1. Direct damage to cell DNA (Rare)
2. Indirect damage. Radiation hits water which leads to the creation of free radicles which react with O2 creating super oxide. Super oxide damages DNA
3. The aim is cause damage to both strands of DNA - more difficult to repair
4. Cell death occurs if multiple DNA breaks occur
5. Best effect if cells in M-phase as rapidly dividing
6. More effective if cells are undifferentiated as have less repair mechanisms
What ways can radiotherapy be administered (3)
- External beam radiotherapy
-delivered from distant source and directed at patient tumour
-Create beam same shape as tumour to reduce damage to surrounding tissue - Internal radiotherapy (Brachytherapy)
-Radiation source is placed as close to the tumour or within the tumour - Radio-isotopes
-Liquid form of radiation administered through infusion or injection
What are the adverse effects of radiation
-Acute toxicity 0-6months post radiation (7)
-Late toxicitiy >6 months post radiation (8)
- Acute toxicitiy
-Enteritis
-Proctitis
-Cystitis
-Anaemia
-Neutropenia
-Thrombocytopenia
-Dermatitis - Late toxicitiy
-Enteritis
-Proctitis
-Fistula - GIT and GU
-Strictures in GIT
-Vaginal stenosis
-Menopause
-Osteopenia
-Avascular necrosis
Describe alkylating agents for chemotherapy
-MOA
-Examples
-Used for
- Acts to stops cells proliferating by causing cross-linkg of DNA strands, abnormal base pairing and DNA strnad breakage
- Cisplatin, carboplatin
- Best used for slow growthing cancers as not cell cycle specific
Describe antimetabolities for chemotherapy
-MOA
-Examples
- Acts during S phase of cell cycle to prevent DNA/RNA metabolism
- 5-fluorouracil, methotrexate, mercaptupurine
Describe plant alkaloids in chemotherapy
-MOA
-Examples
- Blocks the function of microtubules to prevent mitosis. Acts during M phase.
- Paclitaxel, docetaxel
Describe anti-tumour antibiotics for chemotherapy
-MOA
-Examples
- Several MOA which are not cell cycle dependant
-Inhibits DNA replication - Doxorubicin, bleomycin
What are the side effects of chemotherapy (9)
- Hair loss
- Mood changes
- Poor concentration
- Organ toxicitiy
- N+V +D
- Mucositis
- Reduced appetite
- Peripheral neuropathy
- Bone marrow toxicity - anemia, thrombocytopenia, neutropenia
