pharmacology Flashcards
How do aquaretics reduce preload?
Vasopressin (ADH) receptor antagonists
What are the isomerases of prostaglandins?
prostacyclin and thromboxane A2
action of calcium channel blockers
inhibit voltage-gated L type calcium channels in myocardium and vasculature
adverse effects of Ca channel blockers
facial flushing, peripheral oedema, dizziness, bradycardia, headache, nausea
what causes an increased warfarin activity
vitamin K deficiency
hepatic disease
- impaired synthesis of clotting factors
hypermetabolic states
drug interactions
what are the compensatory mechanisms the body does when taking statins
increase in hepatic LDL receptors –> increased clearance of LDL from the blood and therefore decreased plasma total cholesterol and LDL (and increased HDL)
side effects of ezetimibe
diarrhea headache tiredness allergic reactions severe joint or stomach pain
when is ezetimibe used?
can be used alone in statin-intolerant patients, or in combination with all other lipid-lowering agents including statins (to reduce statin dose)
cholinergic muscurinic antagonist effects
reduced salivation, lacrimation, urination and defecation reduced sweating tachycardia (dependent on how dominant the resting PNS was) bronchodilation
action of Monoamine oxidase in normal neuron secreting NA as its neurotransmittter
limits the physiological leak of NA out of the neuron
How is NO relaxation physiologically controlled?
Cyclic nucleotide phsphodiesterase converts cGMP back into GMP
actions of NSAIDs
- anti-inflammatory - analgesia - antipyretic
angiotensin receptor antagonists are the what family
sartans
adverse effects of calcium channel blockers
oedema flushing headache bradycardia (verapamil, diltizaem) reflex tachycardia (dihydropyridines)
action of Na+ channel blockers
reduced phase 0 slope and peak of ventricular action potential
mechanism of vasoconstriction in haemostasis
collagen exposed on damaged vessel wall platelets stick to collagen and activate” –> release ADP and 5-HT –> vasoconstrictor”
adverse effects of heparin
haemorrhage thrombocytopaenia osteoporosis
what does streptokinase do
- activates plasminogen –> plasmin
common adverse effects of statins
mild GI symptoms headache insomnia dizziness
Action of metoprolol
Beta1 blockade Decreases HR and cardiac work Inhibits renin release and its subsequent effects Protects against downregulation of B1 receptors
definition of thrombus
fibirin clot that forms in vivo
How is arachidonic acid released from membranes?
phospholipase A2 activated by increase in intracellular calcium, which cleaves glycerol from arachidonic acid
Types of cholinergic nicotinic receptors
Nm type - in skeletal muscle Nn types - in both branches of the ANS (ganglion)
When is bradykinin generated?
after plasma exudation during inflammation leading to coagulation cascade and the cleavage of inactive peptide to bradykinin
drugs that act as indirectly acting sympathomimetics
amphetamine ephedrine (psuedoephedrine) tyramine
What are the endothelium derived vasoactive factors?
Prostacyclin, NO and EDHF cause relaxation Endothelin causes contraction
how does mercury affect kidney function
1) direct toxicity and vasoconstriction - reducing flow to the glomerulus 2) binds to protein thiol groups - initiating imune response in nephron 3) reduced brush border and mitochondrial changes in the proximal tubule
what causes a decrease in statin levels
phenytoin barbituites glitazones
atropine
anti-muscarinic reduces secretions and produces bronchodilation in the lungs for certain types of bradychardia pupil dilation (for examination of the eye) ACHe-inhibitor poisoning
what are the stimuli that induce histamine release
antigen via IgE complement fragments (C3a and C5a) neuropeptides cytokines and chemokines bacterial components physical trauma
where does gentomycin act in the kidney
on the apical membrane of the proximal tubule
drugs of ACE inhibitor family are the what family
prils
common adverse effects of fibrates
nausea, dry mouth, headache, rash
Neostigmine/pyridostigmine
anti-AChE Used to reverse the effect of non-depolarising neuromuscular blockers used in the treatment of myasthenia gravis
clinical uses of osmotic diuretics
raised intracranial P intraoccular P prevention of acute renal tailure
hyoscine
anti-muscurinic used for motion sickness
difference between SA and ventricular Action potentials
SA node depolarisation is Calcium dependent Ventricular cells depolarisation is Na dependent
Side effects of beta-blockers
Hypotension and fatigue (B1 and B2) Bronchoconstriction (B2) Cold extremities (A1 reflex) Mask signs of hypoglycaemia
histamine is stored in and released from which cells
mast cells and basophils
Actions of bradykinin
vascular - releases PGs and NO to dilate arterioles and venules neural - stimulates sensory nerve endings (pain) other - contracts uterus, airways and gut. Epithelial secretion in airways and gut
adverse effects of ivabradine
brightness in the visual field due to retinal effects (have the same funny current) conduction abnormalities
calcium channel blocker action for angina
blocks Ca entry into the heart and into the vessels –> decreased HR, SV, CO, arterial dilation —> reduced demand and reduced afterload and demand
clinical use of spironolactone
in combination with loop or thiazide diuretics heart failure hyperaldosteronism
how do aldosterone receptor antagonists reduce preload?
Inhibit aldosterone action on the cortical and distual tubules of the nephron (K+ sparing - monitor for hyperkalaemia)
Examples of adrenoceptor agonists
Dobutamine Na Adrenaline
action of angiotensin receptor antagonists
block Angiotensin 1 receptor
what is the mechanism behind NSAIDs causing gastric ulcertation/irritation?
PGE2 promotes blood flow/angiogensis/mucus secretion and reduces gastric acid secretion. Therefore inhibition of PGE2 will cause increased likeliness of ulceration of the stomach
adverse effects of loop diuretics
hypokalemia metabolic alkalosis hypovolaemia hypotension
Receptors for bradykinin are what?
both GPCR (B1 and B2)
agonist and antagonist for b1 and b2 adrenocepgtors
agonist: isoprenaline antagonist: propranolol
adverse effects of spironolactone
hyperkalemia GI upset
Name the Ca channel blocker drugs used for angina
verapamil nifedipine
Clinical uses of agonists for cholinergic nicotinic receptors
Smoking cessation contraction of skeletal muscle
what tests are used for monitoring of warfarin
PT INR
action of sympathomimetic on B1 adrenoceptor in the heart
increased heart rate and force of contraction
what is the precursor for biologically active lipids
arachodonic acid
action of beta-adrenoceptors antagonism
decrease the rate and conduction of the SA and AV nodes (decreased sympathetic drive) and membrane stabilising effects in Purkinje fibres
5 types of antihypertensive drugs
Angiotensin system inhibitors beta-adrenoceptor antagonists calcium channel blockers diuretics other
what type of drug is aspirin?
NSAID
nitrates predominant effect is on what
venous vessels –> reduces preload
What is co-transmission?
when nerves release more than 1 neurotransmitter
structure of eicosatetraenoic acid
20 carbon fatty acid with 4 double bonds (first double bond is at Carbon 6) Omega 6 molecule
How does PNS slow SA node
ACh on M2 receptors - activates GPCR (inhibitory) –> decreased cAMP leading to opening of K+ channels –> slowing Na and Ca fluxes, slowed prepotential (takes longer to reach threshold (SA) and slows rate of conduction (AV))
mechanism of platelet activation and adhesion
ADP from activated platelets causes others to activate and secrete more ADP and 5-HT Thromboxane synthesised Platelets aggregate and adhere via fibrinogen bridging between GPIIb/IIIa receptors
where do the 4 types of diuretics act?
loop diuretics - ascending limb of loop of henle
thiazide diuretics - distal tubule
K+ sparing diuretics - collect duct
osomotic diuretics - mainly proximal tubule
What metabolises arachidonic acid? And what are the outcomes?
- COX-1 (constitutive) –> physiological prostaglandins - COX-2 (inducible by inflammatory stimuli) –> pathophysiological PG overproduction - lipoxygenase (expressed in mast cells and basophils) –> products associated with inflammation
action of resins?
they bind bile acid - preventing gut absorption –> up to 10 fold increase in bile excreted. This increases the demand for cholesterol for bile acid synthesis causing upregulation of hepatic LDL receptors and removal of LDL from the plasma
Ca2+ channel blockade
reduce rate and conduction in SA and AV nodes (reduces slope of pre-potential)
why are statins contraindicated in pregnancy?
cholesterol is needed for the normal synthesis of fetal myelination
What are the receptors for NA, and what are there structures?
alpha-adrenoceptors (GPCR) beta-adrenoceptors (GPCR)
action of angiotensin converting enzyme inhibitors
block the conversion of Ang 1 to Ang 2 Prevent bradykinin breakdown
definition of venous thrombus
fibrin + platelets + RBCs usually associated with blood stasis breaks off leading to embolus lodging in lungs or brain
precaution for fibrates
causes mild elevation of serum aminotransferase –> liver toxicity
rationale for drugs used in angina…
they try to either increase oxygen supply (dilate coronary arteries, reduce HR) or decreased oxygen demand (reduce HR, SV, preload, afterload)
onset and duration of triamterene and amiloride
tiamterene: onset - 2hours, duration 12-16hrs amilordie: onset: slow, duration 24 hours
which tests are used for the monitoring of a patient on heparin
APTT - time for clot formation in citrated plasma after addition of Ca, contact activator and phospholipid
action of heparin
enhances the activity of antithrombin III (inactivates Xa and thrombin) Inhibits factors 2, 9, 10, 11, 12
action of beta-blockers in the treatment of angina
blocks the effects of the SNS on cardiac B1 adrenoceptors –> decrease contractility, HR and SV –> increased diastole and therefore increased coronary perfusion
action of monoamine oxidase inhibitors
enhanced leak of NA out of the pre-synaptic neuron and into the synaptic cleft –> enhance NA action
max effect time and duration of action of thiazide diuretics
max effect at 4-6 hours duration 8-12 hours
what is a longer acting nitrate
isosorbide dinitrate
furosemide is what kind of drug
Diuretic
what are the main drug interactions of warfarin
- aspirin
- NSAIDs - competition for plasma protein binding
- alcohol - competition for cytochrome p450 pathway
- cimetidine - competition for cytochrome p450 pathway
What are the receptors for ACh, and what are there structures?
Nicotinic - ligand gated ion channel Muscurinic - GPCR
negative aspect of streptokinase
used IV antigenic - so single use only
How does SNS increase SA node
NA on B1-adrenoceptors –> activates GPCR (stimulatory) –> increases cAMP leading to opening of Ca channels –> increases slope of pre-potential and therefore increased firing rate and more rapid conduction
How do phosphodiesterase inhibitors work?
Increase the cAMP in the cell by inhibiting conversion to AMP This increases PKA and Ca influx
action of sympathomimetic on B2 adrenoceptor in the lungs
relaxation of bronchial smooth muscle
agonist to b2 adrenoceptor in the lungs
salbutamol
4 types of drugs used to treat angina
1) nitrates - affect preload 2) Ca channel blockers - affect afterload and myocardium 3) beta-adrenergic antagonists - affect myocardium to reduce HR and SV 4) ivabradine - affect myocardium - reduce HR only
action of beta-adrenoceptor antagonists
act on beta-1 receptors and reduce CO (by reducing HR and contractility) and reduce renin release (by reducing blood volume and TPR)
how is bradykinin degraded?
cleave by kininase I and kininase II (AGE)
major ACh removal is by
degredation –> AChE
action of leukotrienes
bronchoconstrictor vasoactive –> leaky vessels and tissue oedema
problem with taking nitrates over time
desensitization can occur
examples of anti muscurinic drugs
atropine hyoscine ipratropium
how do indirectly acting sympathomimetics work with noradrenaline
They get taken up by the uptake 1 receptor and go to the NA vesicles and kick out NA. This NA then goes out into the cleft via the reverse action of uptake 1 –> increased NA affects
synthesis of Noradrenaline
tyrosine converted to L-DOPA (tyrosine hydroxylase) L-DOPA converted to dopamine (DOPA decarboxylase) Dopamine converted to NA within vesicle (dopamine B-hydroxylase)
action of thromboxane A2 and where is it produced?
produced by platelets to increase platelet activation and vasoconstriction pro-thrombotic - promotes CAD
clinical uses of antagonists for cholinergic nicotinic receptors
pre-surgical skeletal muscle relaxants (non-depolarising) Ganglion blockers
Treatment of myasthenia gravis at early stages
Give the patient more ligand to compensate for the lack of receptors
how does the action of angiotensin receptor antagonists decrease BP?
reduces vasoconstriction reduces aldosterone (decreased water retention) reduced cardiac hypertropy reduced sympathetic activity
clinical use for loop diuretics
salt and water overload hypertension
What are the types of prostaglandins?
PGE, PGF, PGD
action of ivabradine
treatment for angina specific and selective inhibition of the funny current in the sinus node –> decreases HR –> reducing oxygen demand and increasing oxygen supply
definition of clot
fibrin clot that forms in static blood in vitro
adverse effects of nifedipine
flushing, headache, oedema, hypotension, reflex tachycardia
action of alpha 1 adrenoceptor
vasoconstriction in the blood vessels
drugs that block the metaboilsm of NA
Monoamine oxidase inhibitors
How is NO generated?
ACh/Bradykinin and mechanical shear stress on the endothelium causes an increase in Ca in the wall and the activation of nitric oxide synthase and the production of NO from arginine
common adverse effects of resins?
abdominal discomfort bloating constipation flatulence
what are two bile acid sequestrants/resins
cholestyramine colestipol
action of PGE2
- relaxes vascular smooth muscle –> decreases BP - hyperalgesic - pyrogenic - angiogenic
How can drugs influence the production of NO?
Block the synthesis! analogue of arginine
Why do cardiac glycosides have a narrow margin of safety?
They affect all excitable tissues: gut, CNS, cardiac
agonist and antagonist to a1 adrenoceptors
agonist: phenylephrine (nasal decongestant) antagonist: prazosin (hypertension)
distal consequence of loop diuretics
increases the osmotic P in the distal tubule –> reducing water reabsorption in distal tubule
Variabilities within anti-AChE drugs?
They have: Variable selectivity (between NMJ and postganglionic parasympathetic junctions) Variable CNS access Variable duration of action
adverse effects of beta-adrenoceptor antagonists
cold extremities fatigue dreams/insomnia bronchoconstriction
mechanism of diuretics
increase Na and water excretion from kidney lowering blood volume and blood pressure
angiotensin system inhibitors are contraindicated in who?
pregnant women bilateral renal stenosis angioneurotic oedema
rare but serious adverse effects of statins
myopathy rhabdomyolysis renal failure liver failure
how does the action of ACE inhibitors decrease BP
no Ang 2 –> vasodilation, reduced aldosterone production (preventing water rentention) and reduce cardiac hypertropy
mechanism of action of gentomycin toxicity on the kiney
bins to phsopholipids and effects calcium levels –> effects mitochondria –> cell damage –> apoptosis
adverse effects of nitrates
1) effects on other SM –> gut and airways 2) postural hypotension 3) venous pooling 4) headache and flushing due to cerebral, head and neck arterial dilation 5) reflex tachycardia
What is the unstable intermediate of arachidonic acid to prostaglandins?
cyclic-endoperoxide
Bradykinin is a local peptide mediator involved in what?
pain and inflammation
What type of drug is digoxin?
Cardiac glycoside
PNS control of heart rate involves
ACh acting on muscarinic receptors on SA and AV nodes –> slows HR most dominant at rest
how does botulinum toxin act
cleaves the snare protein that allows the vesicles of ACh to bind to the presynaptic neuron to exocytose their contents. Therefore stops exocytosis of ACh into the synaptic cleft
bad points about walfarin
- haemorrhage - reversed by Vit K - diet dependent - delayed onset of action - very labile
major adverse effect of NSAIDs
gastric irritation/ulceration
mechanism of action of spironolactone
acts as an aldosterone R antagonist - decreases activation of Na channels in the Collecting duct - decreases the stimulation of Na pump synthesis this reduces osmotic P and therefore reduces water reabsorption
3 isoforms of nitric oxide synthase
nNOS (nerves, epithelial cells) iNOS (inducible - macrophages, smooth muscle) eNOS (endothelial cells)
agonist and antagonist to b1 adrenoceptors in the heart
agonist: dobutamine antagonist: atenolol
what is an example of an aldosterone receptor antagonist
spirolactone
What causes myasthenia gravis?
Autoimmune response to the post-synaptic cleft causing decreased surface area and degredation of the architecture of post-synaptic cleft and loss of nicotinic receptors on the muscles. With degredation of ACh by AChE in the background –> unable to create contraction –> weakness in the muscles
mechanism of action of triamterene and amiloride
blocks the luminal Na channels in the collecting duct - inhibiting Na reabsorption and K secretion
alpha 1 and 2 adrenoceptor antagonist drug
phentolamine
What is “The Triple Response”?
The actions of histamine: Reddening - due to vasodilatation at initiating site Wheal - due to increased vascular permeability (localised oedema response) Flare - spreading response through the sensory fibres
common adverse effects of niacin
vasodilation, flushing, hypotension nausea, vomiting
definition of coagulation
formation of a fibrin clot in a blood vessel
H2 receptor antagonist were originally used for what?
treatment of peptic ulcers
beta-adrenoceptor antagonists are the what family
olols
How do venodilators reduce preload
Increase venous dilation - blood reservoir –> less going back to he heart
3 broad causes of heart failure
Decreased contracility Pressure overload (increased afterload) Volume overload (increased preload)
difference in action between regular heparin and low molecular weight heparin
- low MW heparin has less effect on thrombin - longer elimination half life - can be used for self administration
what two changes in body metabolism can statins cause? (other than decreased cholesterol synthesis)
mild elevation of serum aminotransferase –> liver toxicity minor increases in creatine kinase –> can lead to muscle pain and tenderness
definition of haemostasis
arrest of blood loss from damaged vessels
Where is 5-lipoxygenase found
restricted in distribution to inflammatory cells
What are the two main dietary poly unsaturated fatty acids?
linoleic acid arachidonic acid
SNS control of heart rate involves
NA (and adrenaline) acting on beta-adrenoceptors on SA node, conducting tissue and myocardial cells –> increases HR and contracility
fibrinolytic drugs
streptokinase alteplase
how is fibrin synthesised
formed from fibrinogen (which is activated itself by thrombin)
when is niacin used?
not widely used except in combination with other lipid lowering drugs
5 types of drugs to reduce preload
venodilators Diuretics Aldosterone receptor antagonists Aquaretics Beta-adrenoceptor antagonist
types of angina
stable - CP on exertion or with stress (not affected at rest) variant - coronary vasospasm at rest unstable - angina at rest and with effort
what does clopidigrel do
ADP receptor antagonists prevents binding of ADP to its receptor on platelets –> preventing platelet activation
How do beta-adrenoceptors help in heart failure?
bring back operating point on cardiac function curve to more linear part of the curve Despite blockade - stroke volume increases
action of ezetimibe
specifically inhibits cholesterol absorption in the intestine by binding to a sterol transporter (does not affect absorption of bile acids or fat soluble vitamins)
mechanism of action of statins
competitive inhibitor of HMG-CoA reductase this decreases the synthesis of mevalonic acid and therefore cholesterol synthesis
how does grapefruit juice interact with statins
they use a common metabolic pathway
3 mechanisms that can cause kidney toxicity
reactive oxygen species causing cell damage
interference with calcium metabolism protein
interference with enzyme binding
when are adrenoceptor agonists used for heart failure?
Used for short term support for acute heart failure and cardiogenic shock
uses for botulinum toxin
Bo-Tox - cosmetic Over active sweat glands overactive blink response
physiological roles of NO
flow-dependentvasodilatation inhibits platelet adhesion and aggregation neurotransmitter
what are some modifiable risk factors to try and change to try treat dyslipidaemia
stop smoking, avoid alcohol, weight reduction, increase exercise, modify diet (reduce saturated fat, plant sterol esters, mediterranean diet, fish oils)
Role of Vitamin K in haemostasis
essential for formation of clotting factors 2, 7, 9, and 10 reduced vitamin K is a cofactor in carboxylation of glutamate (which is required of the blood factors after synthesis)
Examples of anti-AChE drugs?
Edrophonium Neostigmine/Pyridostigmine Donepezil
adverse effects of angiotensin receptor antagonists
hyperkalemia headache dizziness
when look at a serum profile of a patients lipids…. What is the most important variable to look at?
total cholesterol/HDL
action of PGD2
bronchoconstrictor (act locally only)
ipratropium
anti-muscurinic used for COPD
2 major neurotransmitters of the PNS
ACh Noradrenaline
What do diuretics (in general) do?
increase Na and water excretion by reducing the Na and Cl reabsorption in the nephron
what does niacin cause
decreased secretion of VLDL particles from the liver –> reduces LDL and TG and increases HDL potentially lowers atherogenic lipoprotein a
symptoms of arrhythmia
SOB fainting fatigue chest pain
How do diuretics reduce preload
Act on the loop of Henle to decrease Na and Water reabsorption –> increase urine output –> decrease blood volume
onset and half life of spironolactone
slow onset short half life of 10 mins, but metabolite longer half life of 16 hours
examples of fibrates
gemfibrozil fenofibrate
action of prostacyclin and where is it produced?
reduces platelet activation and vasodilation. Produced by endothelial cells. non-thrombotic - protects against CAD
when are fibrates used?
generally used as adjunct to dietary changes for high TGs, mixed hyperlipidaemia and second line therapy for hypercholesterolaemia
Major sites for pharmacological manipulaion
transmission of action potential synthesis of neurotransmitter storage of NT Release of NT Action of post-syn receptor Degredation in the cleft reuptake in pre syn membrane action on pre-syn receptor metabolism of NT in pre-syn terminal
adverse effects of amiodarone
blocks Na and CA and beta-adrenoceptors as well reversible photosensitisation, skin discolouration and hypothyroidism pulmonary fibrosis with long term use
action of K+ channel blockade
delay phase 3 of ventricular action potential and prolong APD
Tensilon test
Test for myasthenia gravis Gives short duration anti-AChE –> prevent breakdown of ACh in the cleft and therefore more time for the ACh to work in the cleft –> contraction
adverse effects of thiazide diuretics
hypokalaemia increased plasma uric acid - gout
How does dobutamine work
Selective B1 adrenoceptor - increases contractility and HR
How does digoxin relieve symptoms of heart failure?
inhibits the Na/K ATPase Increases I/C Na and therefore reduces Ca extrusion through Na/Ca cotransporter This increases the Ca in SR and therefore increases Ca release with each AP Increased Ca - increased contractility of heart
Benefits of having pre and post ganglionic neurons compared to one long neuron
allows amplification of downstream signalling and integration of signalling
3 classes of H1 receptor antagonists
sedative, non-sedative, newer non-sedative
action of PGF2a
bronchochonstrictor (act locally only)
What type of receptors are histamine receptors
GPCR
definition of arterial thrombus
platelets plus WBCs in a fibrin mesh usually associated with vessel wall damage. Breaks off leading to BV obstruction
what are the effects of antineoplastics on the kidney?
causes proteinuira, increased blood urea and electotrolyte imbalance –> focal necrosis
adverse effects of verapamil
flushing, headache, oedema bradycardia, AV block
How do anti-AChE work?
it blocks the degradation of ACh in the synaptic cleft and therefore leads to enhancement and longeivity in the synaptic cleft
beta-adrenoceptor antagonists contraindicated in who?
asthma diabetes AV block
what does abciximab do
it is a GPIIb/IIIa receptor antagonist - monocolonal antibody –> stops platelet aggregation by blocking the binding of fibrinogen to the receptor
Movement and action of NO
NO diffuses out of the endothelial cells very rapidly and into the smooth muscle cells. In the smooth muscle, NO activates Guanylate cyclase and causing the convertion of GTP into cGMP causing relaxation
how do calcium channel blockers decrease BP?
reduce cardiac/vascular contractility
what is hereditary angioedema?
C1esterase inhibitor deficiency –> no braking system on the production of bradykinin causing vasodilation and angioedema
adverse effects of beta-adrenoceptor antagonists?
bradycardia, reduced exercise capacity, hypotension, AV conduction block, broncoconstriction, hypoglycaemia
risk factors for hypertension
smoking, diet, weight stress
size of pre and post ganglionic fibres in PNS and SNS
PNS tend to have longer pre-ganglionic fibres compared to post SNS tend to have longer post ganglionic fibres compared to pre
action of 5-lipoxygenase?
Converts arachidonic acid into leukotrienes
mechanism of action of osmotic diuretics
decrease the passive reabsorption of water, with only a small decrease in Na reabsorption
What is arachidonic acid metabolised to?
eicosanoid - biologically active metabolites of arachidonic acid
principle mechanisms underlying dysrhythmia
altered impulse formation altered impulse conduction triggered activity
How does aspirin work?
- it is an irreversible COX inhibitor –> reduced thromboxane synthesis –> decreased platelet aggregation and decreased vasoconstriction
absorption and duration of action of loop diuretics
well absorbed - onset less than 1 hour plasma protein bound - duration 3-6 hours
definition of thromboembolus
a blockage in a BV caused by a dislodged thrombus
Neurotransmitters used in PNS, SNS,somatic and ganglionic transmission
Somatic uses ACh PNS uses ACh SNS uses NA (except for ACh in sweat glands and adrenals) Ganglionic transmission uses ACh
indications for resins?
hypercholesterolaemia mixed hyperlipidaemia
3 types of drugs that can act on kindeys
1) diuretics 2) drugs that alter pH of urine 3) drugs that alter secretion of organic molecules
types of dyslipidaemia
hypercholesterolaemia hypertriglyceridaemia mixed hyperlipidaemia
adverse effects of adrenoceptor agonists during heart failure
Increases the oxygen demand of the heart muscle Increases risk of arrythmias
action of walfarin
inhibits reduction of vitamin K, thereby inhibiting gamma carboxylation of glutamate in factors 2, 7, 9 and 10
what causes a decrease in warfarin activity
- pregnancy - drug interactions
action of fibrates
agonists at nuclear receptors –> regulate gene expression –> increase synthesis of lipoprotein lipase (LPL) –> breaks down TGs into free FA moderate increase in HDL variable effects on LDL
4 major classes of antidysrhythmics
Na+ channel block B-adrenoceptor antagonism K+ channel blockade Ca2+ channel blockade
What is an example of a drug that prevents ACh action?
Botulinum toxin
what causes an increase in statin levels
grapefruit juice antibiotics, antifungals, fibrates
drugs that affect reuptake of NA in the synaptic cleft
cocaine tricyclic anti-depressants
4 types of diuretics?
loop diuretics thiazide duiretics osmotic diuretics postassium sparing diuretics
mechanism of action of thiazide diuretics
inhibit the Na/Cl cotransporter in the distal convuluted tubule –> decreasing the osmotic P and therefore reducing water reabsorption
indications for taking statins
hypercholesterolaemia mixed hyperlipidaemia
What is the action of aspirin?
increases the ratio of prostacylcin to thromboxane promoting non-thrombotic actions
Clinical use of agonists for cholinergic muscurinic receptors
pilocarpine–> used for reducing intraoccular pressure in glaucoma
cardiac blood supply depends on
oxygen demand (cardiac workload - preload, afterload, HR and SV) oxygen supply (coronary artery blood flow)
how is arachidonic acid stored?
stored in the esterified form (joined with glycerol) in membrane phospholipids of the plasma membrane and nuclear membrane
where is cholesterol derived from
diet (in animal fats, eggs) –> absorbed by intestine do novo synthesis (liver) - adequate for needs
loop diuretics - mechanism of action
the Na/K/Cl carrier in the ascending limb of the loop of henle –> decreases the hypertonicity in the interstitium, decreasing osmotic P and therefore reduces water reabsorption
What is the front line therapy for heart failure
ACE inhibitors Reduce effects of angiotensin II –> decrease blood volume Slows the progression of cardiac hypertrophy
rare adverse effects of resins?
increased TGs faecal impaction decreased absorption of fat soluble vitamins steatthorea
Donepezil
anti-AChE enters the CNS well - able to pass the BBB Used in the treatment of Alzheimer’s disease
action of nitrates in angina
drug undergoes transformation once absorbed –> releases NO –> stimulates guanylate cyclase in vascular smooth muscle –> converts GTP to cGMP –> activates myosin light chain –> vascular relaxation
major NA removal is by
uptake Uptake 1 in pre-synaptic cleft (high uptake) Uptake 2 is extranueronal (low affinity)
what is considered chronically high BP
> 140/90
synthesis of ACh
Choline + ACoA —> ACh (with CoA)
Why does ACh act as a vasodilator in vivo but a vasoconstrictor in vitro?
ACh induces endothelium of blood vessels to release EDRF/NO causing vasodilation in vivo
what are the effects of gentomycin kidney toxicity
proteinuria
decreased GFR
altered concentrating ability
Icatibant
selective bradykinin 2 antagonist used in the treatment of hereditary angioedema
drugs for anticoagulation
walfarin
heaprain
direct and indirect Xa inhibitors
direct thrombin inhibitors
Why is the long term use of B-adrenoceptor agonists bad in general?
Chronic stimulation of beta-adrenoceptors results in downregulation of B1-adrenoceptor expression and impaired B1-adrenoceptor coupling Leads to decreased sensitivity to B1 adrenoceptor agonist or sympathetic drive
when is 5-lipoxygenase activated?
activated by an increase in intracellular calcium by inflammatory stimuli
4 drugs for reducing afterload in heart failure
Arterial vasodilators ACE inhibitors Angiotensin 1 antagonist Beta-adrenoceptor antagonist
definition of thrombosis
pathological formation of a haemostatic plug in a blood vessel in the absence of blood loss
where do antineoplastics act in the kidney
acts in the distal tubule and collecting duct
anti-platelet drugs
thromboxane A2 inhibitor - aspirin
ADP R antagonists - clopidigrel
glycoprotein IIb/IIIa R antagonist - abciximab
Action of carvidelol
B1 and A1 blockade Vasodilation –> reduces afterload Decreases HR and cardiac work Inhibits renin release and its subsequent effects Protects against downregulation of B1 receptors
Which drugs act like B1 adrenoceptor agonist but does not effect he receptor?
Phosphodiesterase inhibitors
What does histamine act on?
H1, H2, H3 and H4 receptors
Cholinergic muscurinic agonist effects
Salivation, lacrimation, urination, defecation Sweating Slowing of heart bronchoconstriction vasodilation
adverse effects of all ACE inhibitors
first-dose hypertension drug cough loss of taste hyperkalaemia acute renal failure itching, rash, angio-oedema foetal malformations
