Pharm Revision Flashcards
How does the SS and PS regulate HR
SS increase cAMP which increases opening of iF and iCa to inc depolarisation
PS dec cAMP which inc opening of iK to prolong repolarisation
How do beta 1 receptors regulate contractility
inc cAMP which inc pKA to promote contraction by decreased calcium going into the SR so more is available for contraction
What is the class of drug that verapamil comes under
Phenylalkylamines
What is the other class of rate slowing calcium antagonists (not verapamil)
Benzothiazepines such as Diltiazem
What is the problem with dihydropyridines for dec contractility
No effect on the heard but profound vasodilation can cause reflex tachycardia
How does vasodilation and venodilation affect preload and afterload
vasodilation dec afterload
venodilation dec preload
5 key beta blocker side effects
Bronchoconstriction
Cold extremities + worsening of peripheral artery disease
Dec heaptic gluconeogenesis and glycogenolysis DIABETICS
Bradycardia (heart block)
Worsening of cardiac failure (reduction in CO)
Side effects of both type of calcium blockers
Verapamil = bradycardia and AV block. Constipation Dihydro = ankle oedema, headache flushing, palpitations due to reflex tachy
Adenosine MOA and USE
stimulates alpha 1 in SAN and AVN to reduce cAMP and dec chronotropy and dromotopy
stimulates alpha 2 in vasc smooth muscle to inc cAMPt to relax
SVT’s short lived
Verapamil MOA and USE for anti arrhythmic
Depress SA atuoomaticity and AV
reduce ventricular responsivess to atrial arrhythmias
SVT and AF
Amiodarone moa use adverse
SVT and VT
multiple ion block
accumulates and can cause skin rash, hypo/hyper thyroidism, pulmonary fibrosis
effect of digoxin bc of blocking the pump
USE
Adverse effects
inc intracellular ca
positive ionotropic effect
vagal stimulation causes inc refractory period and reduced rate of conduction through AV node
AF and Flutter
Dysrhythmias and hypokalaemia can lower toxicity
M1 Receptors
neural tissue
M3 receptors
exocrine and smooth muscle
ACh enzyme to make
choline acetyl transferase
Dopamine to noradrenaline
Dopamine beta hydroxylase
COMT stands for
catechol-O-methyl trasnferase
SS vs PS response key words
coordinated and divergent
discrete and localised
why do effects of cannabis last so long
storage in adipocytes
Dronabinol
delta 9 thc = chemo NV
nabilone
delta 9 thc = chemo NV
sativex
delta 9 thc and cannabidiol = symptom improved for spasticity due to MS
rimonabant
CB1 antagonists = anti-obesity but depression and suicide
effect of enterohepatic recycling on measuring intoxication
11 OH THC is more potent and recycles so delta 9 thc is a bad indicator
what is anterior cingulate cortex function
performance monitoring and behavioural adjustment
part of brain for munchies
lateral hypothalamus
endogenous cannibinoid
anandamide
appetite neurones for pharm
Melanin concentrating hormone neurones
orexin
cannabis and hunger neurones
inhibits GABA on MCH so inc in MCH and orexin production so inc hunger
cannabis and psychomotor performance
depresses cerebral cortex
cannabis and CV system
TRPV1 receptor to cause calcium influx-> tachycardia
cannabis vasodilation
conjunctivae
cannabis memory loss
inhibits production of brain derived neurotrophic factor in hippocampus
cannabis levels in the brain
rise v quickly but fall v quickly bc brain is highly perfused
how much smoked cannabis reaches bloodstream
30%
define alkaloid
any class of nitrogenous compound of plant origin that has profound physiological actions on humans
THC =
tetrahydrocannabinol
what type of receptors is CB
g protein i = negative with AC
four types of cocaine
crack = precipitated with alkaline solution
cocain paste = plant mushed up
freebase= dissolve crack in a non-polar solvent
cocaine hcl = therapeutic
what is the cocaine plant name
erythroxylum coca
cocaine CVS risks (3 actions)
vasoconstriction
platelets
atherosclerosis
cocaine and seizures
vasoconstriction in brain arteries leading to inc in temp
why is nicotine in a cigarette so effective
melts the tar to make droplets
alkaloids dissolve in droplets
easily absorbed
why is nicotine not absorbed in the mouth
cigarette smoke is acidic and pKa of mouth is alkaline so ioniside
nicotine euphoria
nachr causes sodium influx so inc firing rate
nicotine and CVS
inc SS
vasoconstriction coronary arterioles
atherosclerosis
inc thromboxane A2
nicotine and parkinson’s and alzheimers
inc cyp450 which remove neurotoxins which contribute to onset of parkinson’s
diminishes some of the proteins
caffeine and euphoria
adenosine antagonist so removed inhib effect on dopamine and D1 receptor function
nicotine metabolism
CYP2A6 in liver
produces cotinine
excreted in urine
cocaine pKA
weak base so less absorbed in stomach
cocaine half life
20-90 mins
cocaine metabolism
liver = inactive ecgonine methyl ester and benzoylecgonine plasma = plasma cholinesterases
how to work out how much alcohol in g/100ml
ABV% x 0.78
how much alcohol is metabolises
90%
acetaldehyde metabolism
aldehyde dehydrogenase -> acetic acid
chronic alcohol and ataxia
cerebellar cortex degeneration
Alcohol receptor targets in CNS
Allopregnelone -> enhances GABA
dec NMDA
reduces Ca2+ influx so less exocytosis
why alcohol and cutaneous vasodilation
less calcium influx and more prostaglandins
acetaldehyde
alcohol and reward pathways
less dopamine bc inc gaba and reduces nmda
brain targets of alcohol
hypothaalmus RAS hippocampus cerebellum basal ganglia= time
alcohol and HR
dec sensitivity of baroreceptors so less baroreceptor firing so inc HR
benefits of alcohol
dec mortality from coronary artery disease inc HDL inc tPA dec platelet aggregation POLYPHENOLS
alcohol hepatitis
cytochrom p450 -> oxygen freeradicals inflammation
alcohol cirrhosis
fibroblasts recruited
connective tissue laid down
alcohol endocrine (3)
inc cortisol
dec DDAVP
dec testosterone
why do u get nausea
gastric irritation
vagus
vomiting centre
wernicke korsakoff
thiamine B1 deficiency
oxidative stress
wernicke encephalopathy = mitochondrial injury
K psychosis = apoptosis in the brain
alcohol and liver
uses up NAD+ no beta oxidation of lipids pyruvate -> lactate acetyl coA -> ketones lipids build up
BAC limit
80mg/100ml
heart contractility
calcium enters thru dihydropyridine receptors
ryanodine receptors on SR causing more calcium release
SERCA2a
removal of calcium
rate of relaxation and contractility of next beat
how is calcium removed from the cell
plasma membrane calcium ATPase
sodium calcium exchanger
SERCA2a
why is hypokalaemia dangerous with digoxin
digoxin competes with potassium so if less potassium then more effect
organic nitrates MOA
NO -> GC vasodilaiton
verapamil target
l type calcium channel so less depolarisation
gastric vs duodenal ulcer symptoms
gastric while eating, duodenal after eating 3 hours
molecule that is protective in the stomach
prostaglandins
PS and gastric acid
inc histamine which inc acid
what type of transporter in parietal cells
H/K ATPase
PPI’s in stomach active why
weak base accumulates in canaliculi
histamine receptor antagonist side effects
dizziness headache
H pylori antibiotics
tetracycline/quinolone
amoxicilin
clarithromycin/metronidazole
why is ondasteron used for chemo NV
chemo is toxic to enterochromaffin cells
cause excessive serotonin release
antagonises receptors on NTS, VC, CTZ
what is ondasteron given with
glucocorticoids to reduce free radical production
aprepitant = neurokinin 1 receptor antagonists NTS = VC
motion sickness MOA
neural mismatch
vestibular sustem Machr receptors
hypothalamic histamine release into ctz
muscarinic to VC
anti-emetic side effects
histamine = drowsy serotonin = headaches muscarininc = dry mouth constipation dopamine = EPS
aldosterone sodium channel antagonist
amiloride
when is mannitol used
major oedema
which diueretics lead to loss of potassium recyclcing so inc loss of calcium and magnesisum
acetazolimide
frusemide
thiazide
side effects of loop diuretics and thiazides
hypovolemia
metabolic alkalosis bc inc cl-loss
hyperuricaemia
hypokalaemia
side effect of carbonix anhydrase inhib
metabolic acidosis due to inc bicarb loss
side effect of potassium sparing
hyperkalaemia
why are thiazides used in htn
chronic thiazides vasodilate leading to reduced tpr
PGE2 unwanted actions
acute inflam
immune
tumorigenesis
inhibition of apoptosis
what are the receptors thought to lower pain threshold with prostanoids
ep1 ep4
pge2 derisable actions
bronchodilation
renal salt and water homeostasis
gastroprotection
vasoregulation
how do NSAIDs cause renal toxicity
constriction of afferent renal arteriole
reduction in renal artery flow
reduced glomerular filtration rate
aspirin side effects
gastric
bronchospasm
bleeding times
nephrotoxicity
why is paracetamol overdose
NAPQI has to metabolised by glutathione-S-trasnferase
if glutathione is depleted then NAPQI oxidises thiol group of hepatic enzymes causing cell death
antidote for paracetamol poisioning
add compound with SH
IV Acetylcysteine
Oral Methionine
paracetamol laws
16 x 500mg
2 packs in transaction
illegal to sell more than 100
aminosalicylates MOA
inhibit IL1 - TNF alpha and PAF
dec antibody secretion
reduced cell migration
localised inhibition of immune responses
problem with anti-tnf alpha
anti-drug antibodies and inc drug clearance
TB
septicaemia
heart failure
3 immunosuppressives for IBD
azothioprine
methotrexate
cyclosporin
2 x aminosalicylates
olsalazine
mesalazine
azothioprine side effects
pancreatitis
bone marrow suppression
hepatotoxicity
lymphoma and skin cancer
Manipulation of microbiome for IBD
Nutrition based for UC
Faecal microbiota replacement therapies
Rifaximin - binds to RNA polymerase sustains remission in CD
anti tnf alpha eg
infliximab
new targets IBD
integrins
interleukins
interleukin rececptors
janus kinase cell signalling
Type a not atenolol
anticholinergics and dry mouth
nsaids and peptic ulcers
tybe c not methotrexate
aantimalrials and ocular toxicity
type d
immunosuppressants and thalidomide
type 2 pharm
methyldopa and haemolytic anaemia
type 3 pharm
procainamide induced lupus
overlapping toxicities
ethanola nd BDZ
antagonistic effects
amitriptyline and acetylcholinesterase inhibitors
cyp450 inducers
- grapefruit
- fluoxetine
- cimetidine
- erthryomycin
ketoconazole
ciprofloxacin
ritonavir
inhibitions vs induction of cyp450
induction days
inhibition quick
drug elimination reactions
probenecid and pencillin
lithium and thiazides
asthma deliberate interaction
salbutamol and ipratropium
nAChR in skeletal muscle structurs
5 subunits alpha x 2 beta gamma delta
ach opens both alpha to allow sodium influx to generate end plate potential
example of a spasmolytic that stops propagation of AP
dantrolene
dec release of calcium from DR to dec force of contraction and dec spasticity
administration of suxamethonium and metabolism
IV bc highly charged
pseudo-cholinesterases
unwanted effects of suxamethonium
post op muscle pains
bradycardia bc stimulates M2
hyperkalaemia so avoid in soft tissue injury
inc intra-ocular pressure
how to reverse tubocurarine
anticholinesterases to inc endogenous acetylcholine
tubocurarine side effects
hypotension due to ganglion blockade and histamine release
reflex tachy due to blockade of vagal ganglia
bronchospasm
excessive secretions
apnoea
side effects of ACEi ARBs
Cough hypotension urticaria/angioedema hyperkalaemia fetal injury renal failure if renal artery stenosis
describe smooth muscle contractision
membrane depolarisation opens VGCC
Ca binds to calmodulin
complex binds to and activated myosin light chain kinase
phosphorylation leads to SMC
what is in red thrombi and white thrombi
red = high fibrin white = high platelet
three stages of cell based theory
initiation
amplification
propagation
dabigatran vs rivaroxaban
2a vs 10a
example of low molecular weight heparin
Dalteparin
heparin route of administration
IV/SC
anticoag indications
AF stroke
ADP receptor name
P2Y12
abciximab route
IV/SC
antiplatelets indication
acute coronary syndormes MI
AF stroke
thrombolytics indication
stroke
STEMI
other antiplatelet that i forget
aspirin cox 1 thromboxane
nucleic acid synthesis
paraaminobenzoate
dihydropteroate
dihydrofolate
tetrahydrofolate
what inhibits bactoprenol
bacitracin
methods of antibiotic resistance
Destruction enzymes additional target alteration in target enzyme inc levels of target reduction in aquaporins and inc efflux
polyene example
amphotericin
azole moa
cyp450 sterol synthesis
ribavirin moa
nucleoside analogue prevents viral rna synthesis
boceprivir moa
protease inhibitor
enfuvirtide target
HIV GP41
zidovudine
nucleoSide RT inhibitor
what encodes all viral proteins
Gag precursor
HSV sturcutre
dsDNA with tegument and lipid bilayer
influenza structure
multipartite ssRNA
