1.2 Pharmacodynamics Flashcards

Question

``` Context-sensitive half lives after eight hours: Remi propofol alfentanil thio fentanyl ```

Answer 1

Context-sensitive half life is the time taken for the plasma concentration of a drug to fall by 50%, after the cessation of infusion designed to maintain a steady state plasma concentration. ``` Remifentanil - 5 minutes Propofol - 40 minutes Alfentanil - 50 minutes Thiopental - 150 minutes Fentanyl - 250 minutes. ```

Answer 2

When an agonist interacts with a receptor on the cell surface, second messengers relay signals to target molecules in the cytoplasm or nucleus. They also amplify the strength of the signal. Calcium is the most ubiquitous and abundant second messenger that regulates multiple cellular functions in the body. These include: Muscle contraction (skeletal, smooth and cardiac) Exocytosis (neurotransmitter release at synapses and insulin secretion) Apoptosis Cell adhesion to the extracellular matrix Activation of lymphocytes Biochemical changes mediated by protein kinase C. cAMP is either inhibited or stimulated by G proteins.

Answer 3

angiotensin and thyroid stimulating hormone.

Answer 4

``` Beta (β1, β2, and β3) Dopamine (D1 and D5) Histamine (H2) Glucagon Vasopressin (V2). cGMP is the second messenger for the action of nitric oxide (NO) and atrial natriuretic peptide (ANP). ```

Answer 5

The therapeutic index in humans is the toxic dose50 for 50% of the population (TD50) divided by the minimum effective dose50 for 50% of the population (ED50). The therapeutic index in animals is the lethal dose50 for 50% of the population (LD50) divided by the minimum effective dose50 for 50% of the population (ED50).

Answer 6

Additive interaction (summation) (1 + 1 = 2) The actions of combinations of intravenous agents such as ketamine and thiopentone or ketamine and midazolam are described as additive. They have different mechanisms of action. Ketamine is an NMDA receptor antagonist whereas thiopentone and midazolam are GABAA receptor agonists. Another example is nitrous oxide and halothane.

Answer 7

Synergism (supra-additive interaction) (1 + 1 >2) Refers to the administration of two drugs with similar pharmacological properties and closely related sites of action that produces an effect in combination that is greater than would be expected from the summation of the contribution of each component. These can be interpreted and understood by construction of an isobologram. The hypnotic effect of benzodiazepines and intravenous induction agents such as propofol is the best example. Midazolam is often administered prior to propofol as part of a co-induction technique.

Answer 8

Potentiation Volatile agents potentiate the effects of neuromuscular blocking agents in a dose dependent manner. Effects of the neuromuscular blocking agents can be increased by electrolyte disturbance (hypermagnesaemia), Penicillin and probenecid (the latter has no similar pharmacological activity). Infra-additive interaction (antagonism) (1 + 1 <2)

Answer 9

Michaelis-Menten kinetics describes the reaction of substrate (S) and enzyme (E) to form product (P), via an enzyme substrate complex (ES). The kinetics are saturatable and therefore are initially first order (rate is proportional to substrate concentration), becoming zero order (rate independent of substrate concentration, that is, constant rate) as the enzyme's active sites become occupied.

Answer 10

The constant Km is the concentration of substrate at half maximal reaction velocity, that is, ½Vmax (not Vmax). The equation may be applied to drug absorption, elimination and distribution. An enzyme is a protein based catalyst, and as defined it is not consumed by the reaction it catalyses.

Answer 11

Sux mivac ester LA Diamorphine - pro drug - converted active by esterase Nestogmine hydrl cholinester

Answer 12

Gq - plc/ip3/dag = increase calcium

Answer 13

Gi inhib AC inhib camp

Answer 14

Gs Increase AC Incr CAMP

Answer 15

stim GC + cgmp = red ca

Answer 16

stim TKr reduce camp

Answer 17

inhib pde increase camp cgmp

Answer 18

if hepatic extraction ratio small

Answer 19

filtration and secretion if drug uni - pass freely into tubules clearnce reduce why alter ph urine - % alter uni - absorbed - clerance drug altered Aspirin and alkaline urine

Answer 20

Warfarin low d/t high protein binding not case for all highly protein bound eg propofol 98% prot bound but highly distrib d/t dynamic nature protein binding negligible across bbb - contain MAoxidase placetna affected fetus ph pethidine - more ionised in lower fetal pH = ion trapping

Answer 21

``` Time Plasma drug conc to halve after cessation contin infusion Designed maintain constant concentration ``` may be very diff to drug elim half time High if conductance ratio is high prop 20min after 2h remi is fairly constant

Answer 22

Lidocaine .7-1.5l kg warfarin - .14lkg roc .2-.3 paracetamol .9 <20% prot bind pen .5-.6l kg