ICS - Pharmacology Flashcards
Specificity vs sensitivity
Specificity - Number of true negatives
Sensitivity - Number of true positives
Alcohol units equation
(alcohol % by volume * volume of liquid in ml)/1000
Sympathetic vs parasympathetic nervous system
Sympathetic (Nad) - fight or flight
Pupil dilates
Increased heart rate
Bronchodilation
Decreased GI motility and secretion
Detrusor relaxes
Ejaculation
Parasympathetic (Ach) - rest and digest
Pupil constricts
Decreased HR
Bronchoconstriction
Increased GI motility and secretion
Detrusor muscle in bladder contraction
Penis points (erection)
Define Pharmacokinetics
How the body affects the drug:
Absorption, Distribution, Metabolism, Excretion (ADME)
Explain drug absorption, distribution, metabolism, excretion (Pharmacokinetics)
Absorption - Route and entry into body
Distribution - Drug distributed in plasma according to properties and size, may be taken up by organs
Metabolism - Drugs metabolised in kidney (small/water soluble) or liver (hydrophobic)
Excretion in urine or faeces
First pass vs second pass metabolism
First - Metabolism before drug reaches systemic circulation (gut/liver wall metabolism, bioavailability reduced)
Second - Actual metabolism (Phase 1 - CYP450, Phase 2 - conjugation)
Define Pharmacodynamics
How the drug affects the body
Name 4 drug targets
Usually proteins
1. Receptors
2. Enzymes (COX-1 and ACE)
3. Transporters (e.g. PPI, Diuretics)
4. Ion channels (CCB, local anaesthesia)
Define summation, synergism, antagonism, and potentiation (physicochemical)
Summation - Drugs used together and effect is as you would expect (1+1=2)
Synergism - Drugs used together and effect greater than expected (1+1>2)
Anatagonism - effect less than expected (1+1=0)
Potentiation - Drug A given with Drug B, increases effect of Drug B without effecting Drug A (1+1=1+2)
Routes of administration
Oral
IM
IV
Sublingual
Inhaled
Topical
Rectal
Intrathecal (into CSF)
Define bioavailability
Amount of drug taken up as proportion of amount administered
Bioavailability of IV drugs
1, or 100%
Factors affecting drug absorption
Motility - Certain drugs e.g. codeine affect gut motility. Impaired transit=reduced absorption
Acidity - certain drugs (antacids,PPI) can affect pH so absorption of drugs
Solubility - Eating high fat food with a fat soluble drug can cause the drug to dissolve: no absorption
Factors affecting drug distribution
Protein binding causes reduced concentration of drug in plasma. This can be overcome by using another protein binding drug to make the first one more bioavailable.
Effect of amiodarone in patient taking warfarin
Amiodarone is a protein binding drug. Will mean less warfarin binds to protein so plasma concentration will be higher
Importance of metabolism in pharmacokinetics
Enzyme induction or enzyme inhibition can cause increased or decreased effect of drug.
E.g. morphine metabolised to morphine-6-glucuronide by CYP450. Drug A inhibits CYP450 leaving more morphine in blood, increasing effect.
Drug B induces CYP450, increasing metabolism of morphine, less effect.
Examples of excretion in pharmacokinetics
Furosemide causes increased but dilute urine. As a result, drug clearance, particularly of gentimicin, is decreased.
pH of urine can be altered to purposefully remove drugs from blood.
E.g. weak bases are cleared quicker if urine acidic, and weak acids are cleared faster if urine is alkali. Therefore urine pH can be changed to alter excretion.
Give the 4 types of receptors
- Ligand-gated ion channels
- G protein coupled receptors (most common - opioids act here)
- Kinase linked receptors
- Cytosoloic/nuclear receptors
Explain action of ligand-gated ion channel
Pore forming membrane proteins that allow ions to pass through shifting electrical charge distribution
Explain G protein coupled receptors
GPCRs consist of large polypeptide chains that go intracellular and extracellular.
On activation, G proteins catalyse exchange of GDP (guanosine diphosphate) to GTP (guanosine triphosphate), causing signal cascade
Explain kinase linked receptors
kinases catalyse phosphorylation.
Binding of ligand on extracellular side causes phosphorylation of tyrosines on intracelullar side, allowing it to recruit intracellular signal mediating components.
Explain Cytosolic/ nuclear receptors
Intracellular molecules that modify gene transcription upon steroid hormone ligand binding.
N domain on outside, C on inside, zinc fingers bind to DNA.
Give examples of how chemical/receptor imbalance can lead to pathology
Chemical increase: Allergy (increased histamine)
Chemical decrease: Parkinson’s (decreased dopamine)
Receptor increase: Mastocytosis (increased c-kit receptors)
Receptor decrease: Myasthenia gravis (loss of ACh receptors)
Define agonist/antagonist
Ligands that bind to a receptor and activates it
Define Potency and EC50
Potency - measure of how well a drug works, as measure of amount of drug given to produce an effect of a given intensity.
(highly potent drug produces more effect than a less potent one at the same concentration)
EC50 - concentration that gives half the maximal response
Define full/partial agonist
An agonist that can elicit a maximal response, no matter how great a concentration is required.
Partial agonists have a maximum efficacy lower than 100% response.
Define efficacy
the ability of an intervention to produce a desired or intended result (or for a ligand to activate a receptor)
Define intrinsic activity, and provide equation for it
ability of drug-receptor complex to produce maximum functional response
IA = E(max) of partial agonist ÷ E(max) of full agonist
E(max) = max efficacy
Example question.
Drug A starts providing response at lower concentration than Drug B. However, Drug B can provide a greater overall response. Which is more efficacious, and which is more potent?
Drug A more potent. Drug B more efficacious.
As drug A more effective at lower doses, but drug B can achieve greater % response
Define antagonist
A compound that reduces the effect of an agonist
Define competitive antagonism and explain how it affects dose-response curve
Competitive antagonists bind to receptor, preventing agonist from having an effect. This shifts curve to right - more agonist required to achieve same effect
Define non-competitive antagonism and explain how it affects dose-response curve
Non-competitive antagonist binds to allosteric (non-agonist) site, preventing its activation. Shifts curve right and down - agonist can bind but cannot activate the receptor, so Emax cannot be reached.
Define affinity
The ability of a ligand to bind to a receptor
Why can antagonists have high affinity but always 0 efficacy
Antagonists can bind well to receptors but never activate them
What will happen to drug action when irreversible antagonists are added to a receptor?
Less receptors will be available so response will be slower. Drug-response curve will shift right. Max effect will still be possible but will need higher concentrations.
(spare receptors exist for full agonists, however there are no spare receptors for partial agonists)
Why can activation of receptors cause different responses in different tissues
Signal amplification in different tissues cause comparatively increased/decreased responses.
Define inverse agonism
A drug that binds to the same receptor as an agonist but induces a response opposite to that of the agonist
(Efficacy of full agonist = 100%, efficacy of antagonist = 0%, efficacy of inverse agonist < 0%)
Drug tolerance vs desensitisation
tolerance is a slow reduction in agonist effect over time
desensitisation is rapid, due to receptor degrading, uncoupling, internalising etc.
Statins MoA
HMG-CoA reductase inhibitors.
Block rate limiting step in cholesterol pathway
3 effects of NSAIDs
Analgesic
Anti-pyretic
Anti-inflammatory
NSAID MoA
COX inhibitors
Aspirin MoA
Non selective COX inhibitor (COX1+COX2)
3 types of protein ports
- Uniporters: Energy from ATP pulls molecules in
- Symporters: Co transport, movement of one molecule pulls another with it
- Antiporters: One substance moves against gradient, using energy from second substance moving down gradient
What pathology are Epithelial Sodium channels implicated in?
Heart failure
Define afferent signals
Signals towards brain/spinal cord
Define efferent signals
Signals away from brain/spinal cord
Define adrenergic
Relating to noradrenaline
Define cholinergic and muscarinic/nicotinic
Relating to ACh and its receptors.
Musc/nico are types of Ach receptor
Sympathetic nerve system anatomy properties
- 2 nerve system
- Preganglionic nerve in lateral horn of spinal cord (T1-L2)
- Sympathetic ganglia in chain beside vertebrae
- Preganglionic fibre synapses with post ganglionic in chain
Treatment of C diff infection
Vancomycin or metronidazole 4x10 days
Explain adverse drug reactions
Rawlins classification
Augmented - Common (dose related)
Bizarre - Odd (allergy/non dose related)
Chronic - Taking for long time (dose and time e.g. HPA suppression of steroids)
Delayed - Months/years after (time e.g. teratogenesis, cancer - has drug in PMH caused?)
End of use - Withdrawal
Treatment of opioid overdose
Methadone
Naloxone
Side effects of steroids
CUSHINGOID MAP
Cataracts
Ulcers
Striae
Hypotension
Infection
Necrosis of bone
Growth restriction
Osteoporosis
Increased ICP
Diabetes type 2
Myopathy
Adipose hypertrophy
Pancreatitis
