Molecules and Cells Flashcards
describe the basic principles of cell biology, including components of eukaryotic cells and their functions.
cells are vital and their disturbance underpins disease processes
all cell types possess membranes, dna, cytoplasm and ribosomes
cell membrane is important for communication due to receptors and allowing passage of molecules in and out of the cell
composed of lipid bilayer of fluid mosaic model, with phospholipids. these have polar, hydrophilic heads and non polar, hydrophobic tails. also contains cholesterol to provide membrane integrity and prevent lysis and proteins, to create channels for other molecules to pass through.
nucleus is found only in eukaryotic cells, and contains a nucleolus where the ribosomes are constructed. dna is largely restricted to the nucleus. nuclear envelope is double membrane structure that allows rna to pass but not dna.
ribosomes are larger in eukaryotes and prokaryotes, with a small and larger subunit. they facilitate protein translation.
they have a P site, E site and A site. P is the peptidyl tRNA binding site. A is the aminoacyl tRNA binding site. E is the exit site. PEA is found on the large subunit. the small subunit has the mRNA binding site.
the endoplasmic reticulum is a mesh of interconnected membranes involved in protein synthesis and transport. rough connects to nuclear envelope, functions in protein modification and production. smooth produces lipids. it detoxifies organic chemicals.
smooth er in liver breaks down glycogen. doubles surface area when drinking to break down the alcohol, returns to normal after this.
smooth er in adrenal cortex produces steroid hormones
smooth er in muscle stores calcium.
dysfunction of er leads to alzheimers, parkinsons and epilepsy and is associated with ageing.
muscular dystrophy is when functionality is lost due to mutations in proteins making up the golgi.
mitochondria have two membranes - outer membrane is smooth and seive like, inner is folded into cristae, surfaces where atp is generated.
describe the significance of acids and bases in dentistry
oral bacteria produce lactic acid, formic acid, acetic acid, propionic acid, and butyric acid. they cause tooth decay.
this is due to dissolution of calcium phosphate cuased by acid.
buffers in saliva include bicarbonate, phosphate and protein.
pH of saliva is normally 6.7, blood is 7.4
the three pH ranges that phosphate will act as a buffer are 2.16, 7.21 and 12.32
describe the principles of pharmacology
pharmacology is the study of the action of drugs on the function of living systems
drugs are chemical substances or natural products that affect the function of cells, organs, organ systems or the whole body
pharmacokinetics is what the body does to the drug, the term for the fate of the drug molecule following administration
pharmacodynamics is what the drug does to the body, a generic term to describe the mechanism of drug action or what happens to cells, organs, sysems, as a result of drug exposure
describe the common sources of drugs
Drugs from plants
- Willow trees - aspirin - painkiller
- Cocoa plant - cocaine - local anaesthetic
- Cinchona tree - quinine - anti malarial
- Poppy - morphine - painkiller
- Foxgloves - digoxin - heart failure
- Guggul tree - statins - cholesterol lowering
Drugs from animals
- Leech - hirudin - anticoagulant
- Cone snail - ziconotide - powerful painkiller
- Bothrops jararaca snake - peptide that lowers blood pressure - forerunner of ace inhibitors
Drugs from repurposing
Sildenafil - used to lower blood pressure, became viagra
describe pharmacokinetics
what the body does to the drug
administration
- oral or intravenous
- oral must be absorbed via GIT or liver, before distribution.
- distribution can occur in the intravascular space, extravascular space, and protein binding
- metaboilsm occurs next. this can occur in the liver, there is phase I and phase II.
- phase I - reaction (oxidation, reduction, hydrolysis) then effect (functionalisation, addition or unmasking of a reactive group)
- phase II - reaction (glucuronidation, sulphation, acetylation, amino acid conjugation, glutathione conjugation) then effect (conjugation, addition of large or charged groups. inhibitory effect.
- after metabolism it is excreted through bile, intestines, or kidneys.
drug pentration to tissues
- diffuses through lipid membrane if lipophilic
- if too large, diffuse through aqueous channels
- if hydrophilic, diffuse via carrier proteins
describe the process of oral dosing of drugs
Cmax - max concentration. rate of absorption equals rate of elimination, net concentration change is zero
Tmax - time to achieve Cmax, independent of dose, determiend by the rate constants for absorption and elimination.
AUC - area under the concentration time curve that is the measure of the total exposure to the drug
describe the common targets of drugs
most drugs bind to cellular constituents that are proteins:
- receptors
- enzymes
- ion channels
- transporters
receptor types
- Type 1 - ligand gated ion channels (ionotropic) - very fast signal transduction, eg nicotinic acetylcholine
- Type 2 - g protein coupled receptors - fast signal transduction - eg muscarinic acetylcholine
- Type 3 - kinase linked receptors - slow signal transduction - cytokine receptors
- Type 4 - nuclear receptors - very slow signal transduction - oestrogen receptors
describe some of the ways in which the effects of drugs are measured
- at the level of the cell - receptors, ion channels, enzymes, transporters, DNA
- at the level of the organ system - kidney, heart, CVS, CNS
- at the level of the organism - therapeutic effect on disease state or process
- at the level of society - cost, misuse, drug resistance
many drugs mimic or block the action or endogenous molecules like neurotransmitters or hormones
affinity is the measure of the strength of association between ligand and receptor
efficacy
- measure of the ability of an agonist to evoke a cellular response
describe how local anaesthetics work and how their activity can be modulated
- All local anaesthetics comprise of aromatic moiety linked by ester or amide bonds to basic side chains
- The esters are rapidly hydrolysed in plasma and tissues
- Amides are more stable and have a longer half life
- They are weak bases
- Mechanism of action: local anaesthetic binds to target site on intracellular side of sodium channel, prevents influx of sodium, prevents depolarisation, prevents action potential propagation, prevents perception of pain.
- Local anaesthetics can prevent sodium influx in two ways: both blocks channels and stabilises it in the inactivated conformation. This causes reversible block of nerve conduction.
- To be effective, local anaesthetics need diffuse from the site of administration, across the nerve cell membrane to the intracellular side, and then bind to the target site.
Ester linked anaesthetics
- Rapidly metabolised by tissue and plasma cholinesterase. Last less than 3 minutes.
Amide linked anaesthetics
- Primarily metabolised slowly in the liver by P450 enzymes.
Last 1-3 hours
describe the different uses of local anaesthetics
- Topical - mucous membranes only, not effective on skin, lidocaine, tetracaine, benzocaine
- Subcutaneous - infiltration into tissue, combined with vasoconstrictor - most local anaesthetics
- Intravenous regional - used with pressure cuff to limit spread - lidocaine and prilocaine
- Nerve block - injected close to nerve plexuses, for minor surgery and dentistry - most local anaesthetics
- Spinal - surgery to the abdomen and pelvis when general is not suitable - mainly lidocaine
Epidural - spinal anaesthesia in childbirth - lidocaine and bupivacaine
describe the properties of the different local anaesthetics
- the side effects are caused by escape into systemic circulation
- they are often administered alongside a vasoconstrictor like adrenaline
describe the adrenergic receptors
they bind noradrenaline and adrenaline
noradrenaline is a neurotransmitter
adrenaline is a hormone
adrenergic receptors have sympathetic effects
Alpha 1
- Stimulate
- Smooth muscle, glands, and organs (other than heart or kidney) relevant to the sympathetic nervous system.
- Needs to be stimulated to lead to vasoconstriction in the skin - tell the blood vessels to constrict.
Alpha 2
- Inhibit
- Found at presynaptic terminals of sympathetic neurons.
- Negative feedback to stop the SNS to have too great of an effect.
- Important CNS structures like the hypothalamus to inhibit the sympathetic response.
- Also found on blood vessels to relax blood vessels.
Beta 1
- Stimulate
- Found at the heart, juxtaglomerular cells
- Increased heart rate, increased contraction
- JG cells found at the nephrons of the kidney. Maintains long term blood pressure. JG produce renin to stimulate RAAS to increase blood pressure and blood volume.
- Big involvement in cardiovascular system.
Beta 2
- Inhibit
- Same as alpha 1, found in all relevant smooth muscle glands and organs relevant to the sympathetic nervous system.
Need to tell bronchioles to relax and open up.
describe cholinergic receptors
nicotonic and muscarinic
stimulated by acetylcholine
parasympathetic effects - cranialsacral.
parasympathetic cranial nerves: oculomotor, facial, glossopharyngeal and vagus
sacral nerves: 2, 3, 4
Nicotinic
- Stimulate nerves are NN
- Stimulate muscle are NM
NN: action potential from CNS going along pre ganglionic neuron where Ach is released which binds to receptors which allows sodium to come in to form another action potential that goes to the organ. Receptors that allows Ach to bind is the NN receptor. So NN receptors are found on the post ganglionic neuron.
NM: to muscle - skeletal muscle. Receptors on the muscle and when nerve comes in, Ach is excreted across synapse. This results in sodium coming in and there is depolarisation of muscle membrane which releases calcium. This leads to sliding filament mechanism.
Muscarinic
- M1-M5
- M4 and M5 focuses on receptors in the brain.
- M1 is a stimulator, M3 is a stimulator, M2 is an inhibitor.
- M1 is brain and stomach. When Ach binds to M1 receptors, in the stomach, there is release of hydrochloric acid and pepsinogen.
- M2 is found in the heart, and if Ach binds, the heart is inhibited (the conduction system of the heart and the muscle), reduction in atrial contraction of the force.
- M3 is categorised into glands or smooth muscle axons. Glands: lacrimal and salivary glands, broncho secretions as well, pancreatic digestive enzymes, insulin release as well, mucous secretion as well. Smooth muscle: pupil constriction, ciliary body (lens), bronchioles, stomach, GIT, peristalsis, bladder for urination by contraction of the detrusor muscle, uterus can contract for childbirth and pregnancy.
