pharmacology 6 Flashcards
how does TXA work
TXA works by inhibiting fibrinolysis.
1. inhibits plasminogen activation and activity (enzyme responsible for breaking down fibrin, the structural framework of clots)
can cause hypotension if given too quickly. CI: active DVT, PE, recent stroke/MI, severe renal impairment (renally excreted), SAH (risk of rebleeding)
CRASH 2 trial (2010) major trauma:
-TXA reduces mortality due to bleeding when given within 3hours of injury
-greatest benefit if given within 1hour
-1g over 10 mins loading dose
-maintenace 1g IV over 8 hrs
risk of harm if given over 3hours post injury
*avoid in isolated HI- no sig benefit in TBI
WOMAN Trial (2017)
-TXA reduces death from PPH when given within 3 hours of delivery, no increase in thrombosis risk.
-1g IV over 10 mins
-use prophylactically in high risk C-section and vaginal births
In heavy menstrual bleeding- 1g TDS oral upto 5/7 during menses
How do you calculate loading dose
LD= plasma conc target x Vd
divide this by bioavailability, if IV this will be 1, otherwise it will be fraction of bioavail eg 0.7
how to calculate clearance
- Cl= rate of elimination/plasma conc
- Cl= (dose x bioavail)/ AUC
bioavail is 1 if given IV - CLrenal= (urine conc x flow rate)/ plasma conc
(UxV)/P
CLrenal =GFR (eg creatinine, inulin): filtered only
Vd calculation
give an example of drugs with
a.) low VD
b) medium VD
c.) high VD
VD= dose/ plasma conc at time 0
a.) low VD: drug stays mostly in plasma e.g heparin
b) medium VD: drug distributes to extra cellular fluid e.g aminoglycosides
c.) high VD: distributes extensively into tissues e.g digoxin, propofol
patient factors that increase Vd: obesity, sepsis pregnancy
that decrease: ageing, dehydration
what does the same heigh mean on log dose response curve
What does it mean the further to the right the drug is on a log dose response curve?
that the drugs have the same efficacy
The further to the right, the less potent. e.g pethidine is less potent than morphine therefore will be further to the right of the log dose response curve (sigmoid in shape)
what is the steady state calc for infusions?
how long does it take to reach steady state?
Css= rate/ clearance
steady state is reached after 5 half lives
e.g if t1/2 is 4 hours, Css is reached in 20 hours (t1/2 x 5)
why isn’t GTN used orally?
GTN orally would undergo large first pass metabolism thus have poor bioavailability (of almost zero!).
sublingually and IV bypasses this first pass metabolism, releasing GTN directly into systemic circulattic
name examples of SSRIs
Examples of selective serotonin re-uptake inhibitors (SSRIs) include:
Citalopram
Fluoxetine
Paroxetine
Sertraline
Fluvoxamine, and
Escitalopram.
Venlafaxine is a serotonin and noradrenaline re-uptake inhibit
what causes delayed gastric emptying?
anticholinergics
alcohol
opioids
dopaminne
pain, fear anxiety
how to treat lithium toxicity
- ensure hydration & correct electrolyte imbalance.
- haemodialysis
*forced diuresis is CI as can worsen toxicity
(activated charcoal is not effective due to lithiums small molecular size and high solubility.
which drugs can cause pulm fibrosis
Pulmonary fibrosis is a side effect of the following drugs:
Gold, penicillamine and methotrexate which are used in rheumatology (not nalidixic acid)
Cytotoxic drugs, for example, for example, bleomycin and cyclophosphamide
Sulphasalazine, amiodarone and nitrofurantoin also cause pulmonary fibrosis.
does midazolam acto on GABA A or GABA B
like other benzos, midazolam acts on GABA A
and has anxiolytic, sedative and anticonvulsant properties
examples of inotropes:
Positive inotrope:
-digoxin (cardiac glycoside, which acts via inhibition of Na+/K+ -ATPase within the sarcolemma cell membrane. This causes an increased intracellular Na+ and decreased intracellular K+. This increase in Na+ displaces bound Ca2+ and positive inotropy. The decreased K+ leads to slowing of AV conduction.
-glucagon has a positive inotropic effect via an increase in cAMP synthesis. It can be used to this effect in beta-blocker overdose.
Enoximone - is a phosphodiesterase III inhibitor (which metabolises cAMP) thereby increasing cAMP, causing inotropy and peripheral vasodilatation (an inodilator).
Negative inotrope:
Bupivacaine (an amide local anaesthetic) has a negative inotropic effect at toxic concentrations (recall the definition above!), it binds avidly to myocardial proteins decreasing the peripheral vascular resistance and myocardial contractility.
