F- MODA important things

-curonium, curium

non-depolarising neuromuscular blockers

Benzodiazepines vs barbituates

Benzodiazepines -> enhance GABA channel opening frequency

Barbituates -> increase single channel opening time & can act as an agonist

supramaximal effect

-stigmines

medium acting anti-cholinesterase

- carbamic acid not acetic acid so longer to hydrolyse

imipramine

TCA

- inhibits NET & SERT on presynaptic neurons-> increases NA & 5-HT levels in synapse

Off-target effects- antagonism:

- H1 = sedation

- muscarinic ACh receptor -> dry mouth, consipation, tachycardia

- Alpha 1 -> postural hypotension

- VGNaC -> increase in arrythmia risk

Fluoxitine & citalopram

SSRI

Vortioxetine

SSRI plus drug

- 5-HT3 antagonist

- 5HT1a agonist & 5HT1b partial agonist

Mirtazapine

noradrenaline & specific serotonin antidepressant

- alpha 2 adrenoreceptor antagonist (more 5-HT release)

- 5-HT2A/C 5-HT3 antagonist (side effects)

- H1 antagonist (sleepiness)

pertussis toxin action

ADP-ribosylation of Gi -> unable to activate so AC produces excess cAMP

Cholera toxin

ADP ribosylation of Gs -> blocks GTPase activity

- constitutively active

volume of distribution equation & definition

Theoretical volume that would contain the total body content of the drug at a concentration equal to that in the plasma

Volumes of different body compartments

plasma: 3L

interstitial: 11L

intracellular: 28L

plasma protein binding on Vd vs tissue binding to drug on Vd

plasma protein binding: increases the total concentration of the drug in the plasma without increasing the Cfree→ more drug present in plasma & higher C = lower volume of distribution

tissue binding/ partitioning in fat: decreases local free drug concentration

• more drug leaves plasma → lower C → higher Vd

Clearance

clearance is constant & via different routes are additive

How to work out loading dose amount?

for multiple IV injections: loading dose= Vd x Cmax,ss instead

-Coxib

COX-2 inhibitor (upregulated in inflammation) = less GI side effects

• due to presence of hydrophobic side pocket for bulky side chains

clotting risk: balance between TXA2 & PGI2 (prostacyclin) via specific inhibition