General principles 2 Flashcards
(19 cards)
What are the main secondary messengers?
Examples of what triggers them and effects?
Adenyly cyclase
- alters levels of cAMP
- increased by Gs (GPCR) e.g. beta and glucagon receptors and reduced by Gi e.g. alpha 2 receptors and opioid
Phosphlipase C
- increases IP3 and DAG
- activated by alpha 1 and muscarinic (Gq)
- IP3 increases Ca release in ER and DAG activates protein kinase C causing a phosphorylation cascade
CGMP is activated by NO
Describe GPCR’s and how they work?
Structure:
- 7 transmembrane proteins with an external receptor and associated with an internal GP
- GP = alpha and beta/gamma subunits
- activate secondary messengers and one receptor can be associated with several different GP’s
Mechanism:
- ligand binds to receptor
- GTP binds to alpha subunits
- BY and alpha/GTp dissociate
- A/GTP triggers secondary messengers
- Alpha has intrinsic GTPase and GTP to GDP
Once occurs the trimmer rejoins and reassociates with receptor, dumping GDP
What different mechanisms can drugs trigger effects?
Receptors e.g. LGIC, TK or GPCR
Ion channels e.g. lignocaine on Na or verapamil on L-type Ca
Enzymes e.g. neostigmine on ACHe or COXi
Hormones e.g. carbs azoles reduces thyroid or meteor in increases insulin
Neurotransmitters e.g. ephedrine
Transport systems e.g. digoxin on NA/K ATPase
What patient factors can affect drug metabolism?
Age: reduced renal, muscle mass, CO etc.
Race: ACE better for HF in black people than white people
Sex: men have more alcohol dehydrogenase
Disease states e.g. liver
Genetics polymorphisms: different genotype giving different phenotypic expression e.g. sux apnoea, codeine, alcohol in Asians
What are the different relevant esterases and drugs they metabolise?
Plasma; esmolol
Tissue and plasma: remi
Red cells: aspirin and diamorphine
What are the properties of an exponential decay curve?
- plasma concentration approaches but never touches the x-axis
- amount of drug eliminated per minute varies but proportion is constant
- rate of decline varies according to the plasma concentration at that time
- gradient is the elimination constant k
Give examples of exponential decay and exponential growth curves?
Decay: N washout, drug wash out or lung volumes during passive expiration
Growth: bacterial, wash-in and IPPV lung volumes
What can be derived from a log concentration time curve?
K, tau, C0, T1/2, VD and Cl.
What are first order kinetics?
Constant proportion eliminated and rate varies due to non-saturable enzymes
What are zero order kinetics?
Constant amount eliminated, therefore there is a constant rate of elimination. Enzymes become saturated
Why are zero order kinetics important clinically?
Drugs with a narrow therapeutic index I.e. therapeutic doses are close to enzyme saturation levels can be toxic if doses are increased even by small amounts.
What is TIVA?
TIVA i.e. Propofol
The infusion can be run at a specific rate, or targeted at plasma concentration or at effector site concentration (brain)
What are TIVA indications?
Gasses unavailable e.g. field or ICU
When inhalational difficult e.g. bronchoscopy
Contraindicated e.g. MH
PONV
To reduce occupational exposure or pollution
What are the limitations of pharmacokinetic models?
No in vivo so based on assumptions:
All people have same tissue proportion
All people have same metabolism rate
All people become anaesthetised at samelvel
And tissues have homogenous blood flows in each department
What is CSHT?
Applicable to IV infusions.
Is the time taken for the plasma concentration to reduce to half once an infusion designed to maintain a constant plasma concentration is stopped
This varies with different drugs
Context refers to duration of time the infusion has been running
What causes CSHT?
During infusion, plasma will have the highest concentration, therefore will travel down gradients to tissues, but will eventually reach equilibrium if run long enough
Highly perfused tissues equilibrate faster than low
Tissues with poor perfusion and high lipid content act as a store
Once stopped, plasma concentration falls and highly perfused empty faster than poorly
Longer the infusion, the more the accumulation
What were NAP 3-7 about?
3: complications of neuroaxial
4: airway management
5: awareness
6: allergic
7: cardiac arrest
What are metabotropic receptors
Bring about an intracellular effect by a ligand binding to an external receptor
List the three different types of GPCR, triggers and effects
Gi: opioid and alpha 2. Decrease camp
Gs: beta and glutamate. Increase camp
Gq: alpha 1 and muscarinic. Increase phospholipase C = Ip3 and DAG
