Pharm 1 Flashcards
Treatment for Hodgkin’s lymphoma?
(I) ABVD:
Adriamycin = doxorubicin
Bleomycin
Vinblastine
Da/carbazine
(II) Escalated BEACOPP:
Bleomysin
Eto/po/side
Adriamycin=doxorubicin
Cyclophosphamine
Oncovin=vincristine
Procabazine
Prednisone
(III) Stanford V (doxorubicin, vinblastine, chlormethine, vincristine, bleomycin, etoposide, prednisolone)
(I)/(II)/(III)+RT
Relapse:
HSCT +:
- ICE
- DHAP
- ESHAP
Chemo for non-Hodgkin’s lymphoma?
DLBCL:
R-CHOP:
Rituximab
Cyclophosphamine
Hydroxydaunomycin = Doxorubicin
Oncovin
Prednisone
Relapse:
- R-ICE
- R-DHAP
- R-GDP
+/- autologous HSCT
Other types:
- no standard first line tx
What are the types of cytotoxic drugs?
- Alkylating agents:
MOA: causes crosslinking of DNA (alkylayion of N7 of guanine)
- leads to breaking of DNA, inhibits DNA replication
- (cell-cycle specific)
E.g.
- nitrogen mustards (cyclophosphamide (requires p450 activation))
- nitrosurea (carmustine, lomustine)
2. Platinum complexes
MOA: - similar to alkylating agents
e. g.
- cisplatin, carboplatin, oxaliplatin
3. Antimetabolites
MOA: - inhibit nucleic acid synthesis by competing with natural substrates
e. g.
- folate analogues - methotrexate (purine synthesis)
- pyrimidine analogues- 5-FU, capecitabine, cytarabine
- purine analogues- mercaptopurine (6-MP)
4. Mitotic inhibitors
e. g.:
- vinca alkaloids (vincristine)
MOA: binds to microtubules and prevent formation of mitotic spindles
- taxanes (paclitaxel)
- topoisomerase inhibitors (topotecan, etoposide)
5. Cytotoxic antibiotics
MOA:
- intercalates DNA strands->interferes with topoisomerase II actions
- genetes free radicals, causing DNA breakage
e. g.: - anthracyclines (doxorubicin, dounorubicin)
- bleomycin
6. Signal transduction inhibitors
e. g. tyrokinase inhibitor (imatinib,dasatinib)
EGFR inhibitor (gefitinib)
- Monoclonal antibodies
e. g.
- trastuzumab (HER-2)
- rituximab (CD20)
- cetuximab (EGFR) (CRC)
- bevacizumab (vascular endothelial growth factor VEGF) (CRC) - Others
- procarbazine (inhibits nucleic acid synthesis)
- hydroxyurea (inhibits ribonuclease reductase)
Alkylating agents? Platinum complexes?
- Alkylating agents:
MOA: causes crosslinking of DNA (alkylayion of N7 of guanine)
- leads to breaking of DNA, inhibits DNA replication
- (cell-cycle specific)
E.g.
- nitrogen mustards (cyclophosphamide (requires p450 activation))
- nitrosurea (carmustine, lomustine)
2. Platinum complexes
MOA: - similar to alkylating agents
e. g.
- cisplatin, carboplatin, oxaliplatin
Antimetabolites?
- Antimetabolites
MOA: - inhibit nucleic acid synthesis by competing with natural substrates
e. g.
- folate analogues - methotrexate (purine synthesis)
- pyrimidine analogues- 5-FU, capecitabine, cytarabine
- purine analogues- mercaptopurine (6-MP)
Mitotic inhibitors?
- Mitotic inhibitors
e. g.:
- vinca alkaloids (vincristine)
MOA: binds to microtubules and prevent formation of mitotic spindles
- taxanes (paclitaxel)
- topoisomerase inhibitors (topotecan, etoposide)
Cytotoxic antibiotics?
- Cytotoxic antibiotics
MOA:
- intercalates DNA strands->interferes with topoisomerase II actions
- genetes free radicals, causing DNA breakage
e. g.: - anthracyclines (doxorubicin, dounorubicin)
- bleomycin
Signal transduction inhibitors, monoclonal antibodies and others?
- Signal transduction inhibitors
e. g. tyrokinase inhibitor (imatinib,dasatinib)
EGFR inhibitor (gefitinib)
- Monoclonal antibodies
e. g.
- trastuzumab (HER-2)
- rituximab (CD20)
- cetuximab (EGFR) (CRC)
- bevacizumab (vascular endothelial growth factor VEGF) (CRC) - Others
- procarbazine (inhibits nucleic acid synthesis)
- hydroxyurea (inhibits ribonuclease reductase)
What are the common immunosuppressants?
Steroids, calcineurin inhibitors, anti-metabolite, anti-TNFa antibodies, TNFa inhibitor, others.
Steroids
Calcineurin inhibitors (inhibits synthesis of IL-2, Th-2 cells actions):
- cyclosporin
- tacrolimus
Anti-metabolite:
- azathioprine (pro-drug of 6-mercaptopurine, acts preferentially on lymphocytes)
- methotrexate (RA. anti-folate)
- myco/phenolate (mofetil) (MMF) (inhibits purine synthesis)
- leflu/no/mide (RA, pyrimidine synthase inhibitor)
Anti-TNFa (in RA):
- infliximab
- adali/mumab
TNFa inhibitor: (RA)
- etanercept
Others:
- abata/cept (binds CD80,86, prevents bindingof CD28 on T cells)
- hydroxychloroquine (SLE. Blocks toll-like receptors on dendritic cells, prevents antigen presentation) (also in malaria: unknown mechanism)
What are the common anti-coagulation drugs?
Antiplatelets:
- 1st L: COX inhibitor (aspirin, inhibits TXA2 synthesis)
S/E: gastric bleeding
- 2nd L: ADP-R antagonits (clopidogrel reduce aggregaion)
Glycoprotein IIb/IIIa receptor inhibitors
- abciximab (antibody against GPIIb/IIIa, prevents binding of PLT to fibrinogen)
Heparin and related:
- heparin (increase ATIII activity) (IV) (doesn’t cross placenta)
- enoxaparin (clexane) (SC)
Warfarin (antagonist of vit K, reduce factor synthesis)
NOAC/DOAC (direct oral anti-coagulant)
- rivaroxaban (inhibits FXa)
- apixaban (inhibits FXa)
- dabigatran (inhibits thrombin)
Osteoporosis medical Mx?
Medical:
- Ca and vit D supplements PLUS
1st line - bisphosphonate
2nd line - raloxifene OR denosumab (every 6m)
3rd line- teriparatide OR HRT
ADD testosterone (if low in men)
Bisphosphonate: (anti-resorptive) (eg alendronate, risendronate)
- MOA: binds to bony surface, inhibits osteoclastic activity and maturation
- S/E: Osteonecrosis of the jaw, atypical subtrochanteric and diaphyseal femoral fractures, hypocalcemia
- contra: low Ca/vit D, CKD
Raloxifene:
- MOA: selective estrogen receptor modulator, ↓osteoclast differentiation, ↑osteoblast activity
- S/E: Hot flushes, sweating, peripheral oedema, VTE, leg cramps
- Contra: VTE, stroke, immobilisation
Denosumab: (anti-resorptive)
- MOA: antibody binding to RANKL, prevents maturation of osteocyte to osteoclast
- S/E: Rarely myalgia, infections e.g. cellulitis, cystitis, hypersensitivity, hypercholesterolaemia
- osteonecrosis of the jaw and atypical femur factures, hypocalcaemia
- contra: low Ca/vit D , pregnancy
Teriparatide: (anabolic)
- MOA: recombinant PTH, intermittent dose stimulates osteoblast activity and bone growth
- S/E: osteosarcoma if prolonged use (>2y), Nausea, muscle cramps, arthralgia, dizziness, headache, injection site reactions,
HRT:
- MOA: stimulates osteoblasts and inhibits osteoclasts
- S/E: Increased risk of breast/endometrial cancer, stroke, VTE, CAD
Open angle glaucoma mx?
Mx:
Medical: (goal: lower IOP to slow down progression) (lifelong)
1st line:
- Prostaglandin analogues (e.g. Latanoprost) (topical)
MOA: increasing the sclera’s permeability to aqueous humour, promotes uveoscleral outflow (uvea=choroid + lens + iris)
S/E:
Ocular:
- *Conjunctival hyperaemia
- *Iris hyperpigmentation
- *eyelash thickening and lengthening
2nd line: combination with:
(I) Alpha-2-agonist (eg Apraclonidine) topical
MOA: Decreases production of aqueous humour by
- Activate alpha-2 receptors in presynaptic sympathetic neurons in CNS → ↑ negative feedback → ↓ catecholamine release (Dopamin, NA) → ↓ Sympathetic tone
S/E:
- *High allergy rate
- *Conjunctival blanching (pale)
- *Pupil dilation
- Lid retraction
Contraindications
- *Pregnancy, Children (central hypotension), MAOI users
(II) Non-selective B-blockers (eg timolol) topical
- MOA: Reduces aqueous humour production by non-selective inhibition of B-adrenergic receptors
S/E:
Ocular:
- * allergy
- *reduced tear production
Systemic:
- *Decreased HR, BP, bronchospasm
- lethargy, sleep disturbance, depression, reduced libido, reduced exercise tolerance
Contraindications
- *asthma, severe COPD
- *heart failure, bradycardia, heart block
(III) Carbonic anhydrase inhibitors (Dorzolomide) topical
- MOA: reduces aqueous humour production by decreasing HCO3 production by the ciliary epithelium
Indications: acute angle closure, chronic angle closure where other treatments have failed
Adverse effects
Ocular:
- *conjunctivitis
- *keratitis
- *stinging
Systemic:
- *diuresis, hypoNa, hypoK
- *metabolic acidosis
- *Bitter metallic taste
Contraindications
- *Hepatic or renal failure
3rd line (add to tx regimen)
Cholinergics (eg pilocarpine)
MOA: binds to M3 receptors and causes ciliary muscles to contract increasing drainage through the trabecular meshwork
S/E Systemic:
- salivation, bronchospasm, hypotension, bradycardia and diarrhoea
Surgical:
- laser therapy (eg laser trabeculoplasty)
Monitoring:
- IOP
- optic disc
- peripheral vision fields
Mx of DM?
Non-pharm:
- diet and exercise
Choosing pharm agent:
- LFT, EUC
- weight
- GI diseases
- patient’s preference (needles)
- S/E when used
- clinician’s preference
Glycaemic targets:
- HbA1c < 7% (3-monthly)
- Fasting BSL 4-8 mmol/L (monitor daily in the morning and 2h post prandial before bed)
- Post-prandial <10 mmol/L
- add agents if target not reached
Pharm:
1st line:
Metformin (diaformin, diabex)
- MOA: - ↓ Hepatic gluconeogenesis + ↑ insulin sensitivity peripherally
- ↓ carbohydrate absorption + reduced LDL/VLDL
- initiate with lifestyle changes, cease if satisfactory levels are reached with both
- excellent efficacy (1.5-2% HbA1c), highly tolerable
- promotes weigh loss, reduction in CV risk
- CI: CKD, liver failure
2nd line:
Sodium-glucose co-transporter 2 (SGLT2) inhibitor: canagliflozin, dapagliflozin, or empagliflozin
- MOA: ↓ glucose reabsorption in PCT in kidneys → ↑ glucose excretion via kidneys
- excellent reduction in CV risk
- SE: glucosuria (UTI, thrush), hypoglycaemia, volume depletion
- CI: CKD
Alpha-glucosidase inhibitor: acarbose or miglitol
- MOA: Inhibits alpha-glucosidase at brush border of small intestine → ↓ digestion of carbohydrates into monosaccharides
- controls post-prandial glucose
- top second line choice in China
Thiazolidinedione: pioglitazone
MOA: Agonist for nuclear receptor PPAR-y → regulates gene expression for glucose and lipid metabolism → ↑ lipogenesis → cells dependent on glucose for energy → ↓ hepatic gluconeogenesis + ↑ insulin sensitivity peripherally- true insulin-sensitising agent
- excellent efficacy, beta cell protective
SE:
- increase in CV mortality and events
- weight gain, peripheral edema
- also ?decrease in bone density, risk of bladder cancer
CI: heart failure, severe liver disease, pregnancy
Injections:
Glucagon-like peptide-1 (GLP-1) agonist: liraglutide, exenatide, lixisenatide, semaglutide, or dulaglutide
- MOA: Stimulates glucagon-like peptide-1 production in duodenum + proximal jejunum → ↑ insulin secretion + ↓ glucagon secretion
- SE: pancreatitis (rare), hypoglycaemia, N/V
Dipeptidyl peptidase-4 (DPP-4) inhibitor: sitagliptin, saxagliptin, linagliptin, or alogliptin
- MOA: Inhibits dipeptidyl peptidase 4 → prolongs action of GLP1 + GIP → ↑ insulin secretion + ↓ glucagon secretion
- flexible with PBS
- SE: pancreatitis (rare), hypoglycaemia, N/V
3rd line:
Sulfonylurea: glimepiride, gliclazide, or glipizide; meglitinides (e.g., repaglinide, nateglinide) are an alternative
- MOA: Bind to sulfonylurea receptor 1 (ATP-sensitive K+ channels on beta cells) → depolarisation → ↑ insulin secretion
- Not useful in late T2DM, it requires functioning Beta cells
SE: weight gain, hypoglycaemia, bone marrow toxicity (rare)
Insulin
- short acting for before meals
- long acting for baseline
Antiemetics?
D2 antagonist (metoclopramide,droperidol, domperidone)
MOA:
Inhibits on chemoreceptor trigger zone (medulla)
Inhibits visceral afferents from GIT (PNS)
Prokinetic effect (GI)
Indications: Post-surgical N/V, Gastroenteritis, **Migraine headache, Hyperemesis gravidarum
SE: Sedation, extrapyramidal effects, QT prolongation, severe hypotension; Arrhythmias (Domperidone)
CI: Intestinal obstruction, PD
5HT3 antagonist (ondansetron)
MOA:
Inhibits on chemoreceptor trigger zone
Inhibits visceral afferents from GIT (PNS)
Indications: Post-surgical N/V (1st line), Gastroenteritis, Chemo/radiotherapy N/V, Hyperemesis gravidarum
SE: QT prolongation, QRS widening; rarely, hypersensitivity reactions
CI: Prolonged QT interval
Extra: newest, most expensive
Antihistamines (H1 antagonists) cyclizine, meclizine, dimenhydrinate
MOA: Inhibits on vestibular nuclei,
Indications: **Motion sickness, **Vertigo, Hyperemesis gravidarum
SE: Sedation,
Anticholinergic effect: Dry mouth, Tachycardia, urinary retention, mydriasis, blurred vision, exacerbation of narrow-angle glaucoma
CI: Tachycardia, CCF, Glaucoma, Urinary retention, BPH
Anticholinergics (anti-muscarinic) scopolamine
MOA: Inhibits on vestibular nuclei, Inhibits area postrema (vomiting center) centrally
Indications: Motion sickness, Vertigo
SE: Anticholinergic effect: Dry mouth, Tachycardia, urinary retention, mydriasis, blurred vision, exacerbation of narrow-angle glaucoma
CI: Tachycardia, CCF, Glaucoma, Urinary retention, BPH
