pharmacology Flashcards
enteral administration
entering the body by alimentary canal
oral, sublingual, buccal, rectal
paretnal administration
introduces drugs directly across the bodys barriers and into the systemic circulation or other vascular tissue
intravenous (most direct route), intramuscular, subcutaneous, intrathecal/intraventricular (directly into cerebrospinal fluid or intracranial ventricles), intraperitoneal, intraosseous (into bone marrow),
inhalation adminitration
breahting of the drug through the nose and into the bronchi and lungs
intranasal administration
aka transmucosal
administration directly into the nose
topical
direct application of a drug to the desired point of action (ex. to skin or eye)
transdermal
applied directly to the skin to achieve systemic effects
define absorption
movement of a molecule from its site of administration to the blood
what molecule characteristics affect a drugs ability to be absorbed
lipid solubility: more soluble = more likely to cross membrane
ionization state: charged are less like
molecular size: smaller more likely
how is lipid solubility tested in drugs
add drug to mixture of equal volumes of water and lipd and shake, let settle and separate
amount in lipid divided by the amount in water is the partition coefficient
higher the coefficient he more lipophilic the compound and more likely to cross membranes
weak acid dissociation equation
weak acid drug + water base conjugate acid + weak base drug anion/conjugate base
aka: HA + H2O H+ + A-
weak base dissociating equation
weak base drug + water acid conjugate base + weak base drug conjugate acid
aka: B + H2O BH+ + OH-
Kd
dissociation constant, at equilibrium at this point
pKa
negative log of dissociation constant
is equal to the pH when half of the molecules are non ionzed and half are ionized
how to find pKa from pKb
pKa + pKb = 14
henderson hasselbach equation
pH = pKa + Log (concentration of non-protonated species/concentration of protonated species)
in what environments do acidic compounds absorb well
acidic environments
in what environments do basic compounds absorb well
basic environments
ex. small intestine
describe ion trapping
when a molecule becomes ionized after crossing a membrane thus becoming trapped in its new environment
ex. weak acids are not ionized in stomach so can be absorbed into blood but then are ionized in the blood bc more basic than stomach
what facilitates restrictions of molecule permeability based on size
water filled pores - aquaporins
allow small molecules to cross the membrane along with water
Fick equation
Rate of diffusion = DRAdeltaC/deltaX
delta C: concentration gradient across membrane
R: lipid/H2O partition coefficient of the molecule
D: the diffusion coefficient
A: the area of the membrane through which the molecules must diffuse
X: the thickness of the membrane
advantages and disadvantages of oral administration
advantages: convenient, safe, economical, can be removed by emesis or activated charcoal
disadvantages: requires conscious and non-vomitting patient, slow onset, poor control of plasma level (bc GI tract absoprtion), drug must be potent and very lipid soluble, must survive first pass effect
more basic drugs are less able to be absorbed in stomach because
first pass efffect
once an orally administered drug is absorbed by the digestive system, it first enters the hepatic portal system. it is then carried through the portal vein into the liver
the liver metabolizes many drugs and may alter the concentration reaching the circulatory system. this “first pass” through the liver thus can greatly reduce the bioavailability
bioavailibility
fraction of administered drug that reaches the systemic circulation in a chemically unchanged form
calculated by: (AUC oral/AUC injected) x 100
AUC= area under curve in reference to plotting the plasma concentration of drug over time
factors that affect bioavailibility
first pass hepatic metabolism solubility of the drug chemical stability (or instability) nature of the drug formulation (ie. coatings, crystal structure, salt form, etc. )
bioequivalence
how drugs compare in terms of bioavailabilityand therefore time to achieve peak blood concentrations
factors affecting absorption of drugs from the gi tract
lipid solubility
drug concentration at absorbing surface
vascularity
surface area
GI tract disease
rate of movement of contents through GI (greater time means greater absorption)
food in GI tract (solid food delays gastric emptying which will delay absorption of drugs that are absorbed mainly from small intestine but not those absorbed from stomach)
enzymes, acid, bacteria, etc. in GI tract
factors affecting drug absorption regardless of route administration
physicochemical properties of the drug
vascularity of the area
concentration gradients
surface area
define pharmacokinetics
measurement and interpretation of changes in drugs concentrations over tiem in body regions in response to dosing
“what the body does to/with the drug”
pharmacodynamics
events consequent on interaction of the drug with its receptor or other primary site of action
describe the two-neuron pathway in the nervous system
preganglionic neuron (in CNS), axon, postganglionic neuron (in ganglion), axon, effector cell
two divisions of autonomic nervous system
sympathetic/thoracolumbar
parasympatheitc/craniosacral
autonomic effects of sympathetic vs parasympatheic stimulation on the heart (what receptors)
sympathetic: B1 receptor, increase HR, force, and conductionvelocity
parasympathetic: mus2 receptor, decrease HR, force, and conductance velocity
autonomic effects of sympathetic vs parasympathetic stimulation on the coronary blood vessels (what receptors)
sympathetic: alpha1 receptor: constriction, beta1 and 2: dilation
parasympathetic: mus: dialation
describe parasympathetic outflow w common neurotransmitters
CNS, preganglionic cholinergic axon, acetylcholine release in ganglion on postganglionic neuron, postganglionic cholinergic axon, acetylcholine release at neuroeffector junction on effector cell
*can produce NO instead of ACh
describe sympathetic outflow w common neurotransmitters
CNS, preganglionic cholinergic axon, acetylcholine release in ganglion on postganglionic neuron, postganglionic adrenergic axon, norepinephrine release at neuroeffector junction on effector cell
*postganglionic is cholinergic and produces ACh in sweat glands
epinephrine and alpha, beta adrenoceptor activation
epinephrine is generally classified as a mixed a-b agonist, it is primarily a b receptor agonist at low doses and an a receptor agonist at high doses
when first administered and at low doeses will only affect b receptors
isoproterenol and alpha, beta adrenoceptor activation
isoproterenol is virtually a pure b agonist
NE and alpha, beta adrenoceptor activation
NE is primarily an a agonist but does activate excitatory b receptors in the heart
parasympathetic innervation of the heart
vagus nerve stimulate release of ACh which increases K+permeability making it hyperpolarize–> decreased excitability
define chronotropy
rate
define dromotropy
conduction velocity
define inotropy
force of contraction
define lusitropy
time to relaxation
coronary artery regulation by alpha vs beta sympathetic stimulation
beta sympathetic stimulation by iso, epi, NE causes dilation (beta receptors dominate these vessels)
alpha stimulation by iso, epi, NE results in constriction
catecholamines on the heart
ex.
direct acting sympathomimetic amines
NE, Epi, Iso
clinical uses of epi
epi used to promote local vasoconstriction to delay absorption of anesthetics, local hemostatic to control bleeding, increase cardiac activity after cardiac arrest, treats allergic reactions: counteracts hypotension and cardiac irregularities and counter constriction of bronchiolar pathways
clinical uses of NE
pressor agent: blocks systemic hypotension in spinal anesthesia
prolongs action of inflitration anesthesia
clinical uses of iso
increases cardiac activity after cardiac arrest but can produce excessive tachy
nonselective B1-B2 agonists function and ex
postitive intropic (contraction force) and chronotropic (rate) effects with some local vasodilation ex. isoproterenol
B1 selective agonists
ex
increases contractile force (inotropic) without great effects on HR (chronotropic) relatively cardioselective effects
ex. dobutamine
B2 selective agonists
selective for bronchodilation with less cardiac excitability
ex. arformoterol tartrate
effects of B1 receptor blockers
decrease HR, contractile force, cardiac output, and conduction veolcity
effect of B2 receptor blockers
inhibits sympathetic bronchodilator activity and results in bronchiolar contriction
nonselective B blockers
ex.
ex. propranolol
at rest = minimal decrease in HR, CF, and CO
suring increased sympathetic tone= blocking the affect of catecholamines so decrease in HR, CF, and CO which may cause a reflexive increase in BP via vasoconstriction if the effects are dramatic enough
b1 selective beta blockers
ex.
cardioselective
produce less bronchoconstriction than nonselective so these are given to patients with pulmonary difficulties
ex. metoprolol, atenolol, esmolol, nadolol
alpha receptor blockers
ex.
ex. prazosin, terazosin, doxazosin
decrease peripheral vascular resistance (lower bp)
useful for treating hypertension without effecting cardiac output, RBF, or GFR
muscarininc agonists
ex.
stimulate effects of ACh (parasympathetic response)
ex. direct (receptor agonists): pilocarpine, carbachol
indirect (inhibit AChE): neostigmine, physostigmine, organophosphates
muscanarinic antagonists
inhibit responses causes by stimulation parasympathetiv neurons
direct block of mus receptors (atropine, ipratropium)
atropine is used to block pNS effects on the heart leading to an increase in heart rate and therefore increases cardiac output
define parasympathomimetics
drugs that act either by directly stimulating the muscarinic receptor or by inhibiting the enxzyme acetylcholinesterase which hydrolyses the acetylcholine in the synapse
define parasympatholytics
drug that reduces the activity of the parasympathetic nervous system
define sympathomimetics
drug that stimulates the sympathetic nervous action
define sympatholytics
drug that opposes physiological results of sympathetic nervous
arrhythmia vs dysrrhythmia
arrhythmia: loss of rhythm without rhythm being re established
dysrrhythmia: defective rhythm, any abnormality in the rate, regularity or site of origin of the cardiac impulse, or a disruption in impulse conduction changing the normal sequence of atrial and ventricular activation
List the the classes and mechanisms of the antiarrhythmic drugs (according to Vaughan-Williams classification)
Class I: sodium channel blockers Class II: beta blockers Class III: potassium channel blockers Class IV: calcium channel blockers Class V/non-classified: miscellaneous
Class I antiarrhymic drug mechanism
explain how they are state dependent
block sodium channels: slows rapid inward Na+ which slows the depolarization and decreases the maximal rate of depolarization with little or no effect on resting membrane potential
many of these drugs are “state dependent”, they bind more rapidly to open or inactivated channels than closed ones, they are often more likely to work on tissues frequently depolarizing (ie. during tachycardia)
explain the 3 groups of Class I antiarrhymic drugs
IA: intermediate block of AP duration, slow phase 0 depolarization, prolong action potential, and slow conduction
IB: shortest channel block, shorten phase 3 repolarization and decrease the duration of the action potential
IC: long channel block, slow phase 0 depolarization
theraputic uses for class I antiarrythmic drugs
abolish reentry by producing a bidirectional block inplace of a unidirectional block (mainly class IA)
slow tachyarrhythmias by increasing required stimulus to reach threshold
inhibit spontaneous diastolic depolarizations in cells that have abnormal automaticity (mainly class IA and flecainide)
examples in class IA, IB, and IC antiarrhythmic drugs
IA: procainamide
IB: lidocaine
IC: flecainide
class II antiarrhythmic drugs
beta blockers
block beta adrenergic receptors thereby inhibiting adenylyl cyclase and decrease PKA and intracellular calcium- has most effect when sympathetic tone
supress positive inotropic (contraction force) and chronotropic (rate) effects of catecholamines thus reduce rate and contractility of the heart
ex of class II antiarrhymic drugs
propranolol, metrolol, nadolol, atenolol
theraputic uses of class II antiarrhythmic drugs
effective in controling tachyarrhythmias associated with sympathoadrenal discharge by blocking hyperactivity of SNS
minimal effects at rest, more effects as sympathetic tone increase
*b1-selective antgonists/cardioselective b blockers are safer to administer to cardiac patients with pulmonary difficulties because they will not have the side effect of bronchoconstriction that non-selective have
class III antiarrhythmic drugs
K+ channel blockers
block potassium channels and prolong repolarization thereby increase effecctive refractory period, action potential depolarization, and prolong AV conduction, many depress phase 4 depolarization and automaticity
ex class III antiarrhythmic drugs
amiodarone (most commonly used antiarrythmic), sotalol
theraputic use of class III
treat supraventricular and/or ventricular tachyarrhythmias
class IV
calcium channel blockers
decrease slope of phase 4 action potential (especially in AV node), prolongs effective refractory period, slows conduction in tissues dependent on calcium currents (especially depresses AV node conduction)
predominent action is in AV node bc it has a lot of Ca ++ channels there and therefore reduces AV conduction
depresses normal and abnormal automaticity
theraputic use class IV
control supraventricular arrhythmias that involve AV reentry and ectopic stimulation
ex class IV
verapamil, dilitiazem
digitoxin (class and mechanism)
class V (miscellaneous) increases intracellular calcium by affecting Na+/K+ pumps and Ca+ exchangers and increase contractile force enhances PNS/cholinergic tone at nodal areas: decreases automaticity (can result in bradycardia) predominant action at AV node (decreasing AV conduction)
atropine (class and mechanism)
class V mus blocker used during bradycardia or sinus arrest secondary to vagal discharge and accumulation of ACh
epinephrine (class and mechanism)
class V can be used to restart the heart after cardiac arrest increases heart rate in cases of sinus bradycardia associated with impaired sympathetic tone
isoproterenol (class and mechanism)
increase heart rate in cases of sinus bradycardia associated with impaired sympathetic tone
adenosine (class and mechansim)
class V adenosine receptors are prevalent on atrial myocytes and SA and AV nodes, when adenosine binds to these receptors it inhibits adenylyl cyclase resulting in decreased Ca++ and increased K+ resulting in decreased conduction velocity, prolonged refractory period and decreased AV node automaticity
define volume of distribution (Vd)
volume of body fluid in which a drug appears to be dissolved, assuming uniform distribution
TBW is what % of body weight
60% (about 40 L)
extracellular water is what % of body weight
20% (about 12-14 L)
whole blood volume and plasma volume are each what % of total body weight
whole blood volume = 8%
plasma= 4%
Vd equation
Vd=Q/Cp
Vd= amount of drug in cells
Q= total drug in body
Cp= plasma drug concentration
equation to find how much to increase dose for desired Vd
Q=Vd(C2-C1)
mechanisms of blood brain barrier
lack fenestrations (no leaky holes) tight junctions (hold cells together tightly letting little through) astrocytes (wrap around cells providing extra membrane layer) P-glycoprotein transporters (transport molecules out of brain back into the blood)
which drugs cross the blood-brain barrier well
highly lipophilic compounds
mechanisms of blood-placental barrier
3 layers: epithelial layer, chorionic layer, endothelium of fetal capilaries
which drugs cross the blood-placental barrier well
highly lipophilic although blood flow rate here is not high so even highly lipophilic drugs take a long time to cross
mechanisms of drug-testicular barrier
tight junctions between sertoli cells
which drugs bind best to albumin and which drugs bind best to alpha1-acid glycoprotein
albumin binds well with acidic and neutral drugs
alpha1-acid glycoprotein binds well to basic drugs
OAT and OCT functions
OAT: organic anion transporters/acid transporters pump acidic compounds against their gradient into the lumen of tubules using ATP
OCT: organic cation transporter/base transporter transports basic compounds down their gradient
does plasma protein binding affect drug excretion
no, tubular transit time is long enough that dissociation from plasma proteins can take place and as drug is excreted the equilibrium drives more proteins to become unbound
**however, transporters can become saturated which would effect excretion
define theraputic index
ratio of toxic dose divided by therapeutic does
want this to be large
ex. warfarin has low therapeutic index
thiopental
good for inducing anesthesia because high lipid:water partition coefficient so travels to the brain very quickly
define biotransformation
metabolism of lipophillic drugs into more easily excreted hydrophillic compounds (making more polar and more water soluble)
first pass effect
drugs entering through GI are carried to the liver first by portal circulation
what organ has the highest density of drug metabolizing enzymes
liver
detoxication reaction (liver)
when the liver acts upon compounds making them less active/toxic
activation reaction (liver)
when liver acts upon compounds making them more active/toxic
define prodrug
medication that is administered in an inactive or less than fully active form and then is converted to its active form through a normal metabolic process
how can using a prodrug alter how a drug is absorbed/distributed
prodrug may be able to cross a a barrier that the drug may not be able to
michaelis-menten kinetic equation for first and zero order kinetics
first order: V = (Vmax * concetration)/Km
zero order: V= (Vmax * concentration)/concentration
v= rate of metabolism vmax= maximum rate at which reaction can occur Km= substrate concentration that is required for the reaction to occur at .5 vmax
what order kinetics are observed in drug metabolism at high and low doses
low doses: first order
high dose: zero order kinetics (bc enzymes saturated)
first order kinetics
rate of metabolism is directly proportional to the concentration of free drug
a constant fraction of drug is metabolized per unit of time
ex. 50% every hour
zero order kinetics
a constant amount of drug is metabolized per unit time
enzyme is saturated by free drug concentration thus the rate of metabolism remains constant over time
phase I reactions
generally make compounds less active or less toxic and or more water soluble but can make them more toxic, may add or unmask existing polar functional group
reduction (add H+)
hydrolysis (lyse using H2O)
oxidation
phase II reactions
generally conjugation reactions which make compounds more water soluble
microsomal oxidation reactions
enzymes of the smooth ER
- cytochrome P450s (CYP)
- FAD-containing monooxygenase
Cytochrome P450s (CYP) oxidation reactions
heme-containing enzymes which are generally in smooth ER
uses molecular oxygen to oxidize drug
CYP must be oxidized in order for O2 binding drug
NADH acts electron donor which is supplied by electron transport chain
FAD-containing monooxygenase oxidation reactions
it is a flavoprotein
uses NADPH cofactor and FAD
competes with CYP450s for oxidation of amines
aliphatic hydroxylation
add hydroxy group to aliphatic group (C’s and H’s)
aromatic hydroxylation
adding hydroxide to aromatic group
O-dealkylation
removing alkyl group (CH3) from oxygen leaving an OH
N-oxidation
adding oxygen to nitrogen
oxidative deamination
removing amine group and add double bond O via H20
S-dealkylation
removing alyl group (CH3) from S
sulfoxidation
adding oxygen to S
desulfuration
remove S
N-dealkylation
removes alkyl group (leaving polar NH)
inducers of CYP450 enzymes
more quickly metabolize drugs
ex. phenobarbital, rifampin and carbamazepine, cruciferous vegetables, smoking
inhibitors of CYP450 enzymes
less quickly metabolize drugs, may cause build up of drugs which would cause a higher response of drugs
ex. omeprazole, erythromycin, grapefruit juice, cumin
rhabdomyolysis
can be caused by high plasma concentrations of HMG-CoA reductase inhibitors (lowers cholesterol production, statins)
increased muscle breakdown –> increased myoglobin –> kidney damage
what CYP breaks down HMG-CoA reductase inhibitors
CYP3A4 (promotes cholesterol synthesis)
effect of high CYP3A4
if CYP3A4 is high HMG-CoA inhibitors are broken down
HMG-CoA is therefore not broken down
therefore high levels
nonmicrosomal oxidations
generally in cytosol or mitochondria
include oxidation (breakdown) of catecholamines, alcohol, and histamine
MAO
breaks down catecholamines and serotonin
inhibitors of MAO
inhibit breakdown of catecholamine and serotonin
can lead to build up of these neurotransmitters and increase their stimulation to the post synaptic neurons
MAO-A preferentially deaminate what
serotonin melatonin tyramine epinephrine norepinephrin
MAO-B preferentially deaminate what
phenylethylamine
trace amines
what may people on non-selective MAOIs or high doses of MAO-BIs need to restrict in their diet? why?
wine and aged cheese
they have high levels of tyramine which is normally broken down by MAO-A
high levels of tyramine can result in hypertensive crisis
3 ways that alcohol is metabolized
microsomal ethanol oxidizing system (MEOS)
alcohol dehydrogenase (ADH) in cytosol Of stomach (most common pathway) producses acetaldehyde which enters mitochondria to be reduced to acetic acid via aldehyde dehydrogenase (ALDH)
catalase in the peroxisome
disulfiram
inhibits aldehyde dehydrogenase
when drinking alcohol, aldehyde builds up and causes person to become ill very quickly
causes person to associate alcohol with sickness
naltrexone
blocks m opiod receptor in brain thus decreasing ethanol-induced activation of the dopamine reward pathway
person will not have pleasurable effects of alcohol
acamprosate
blocks ability of glutamate to cause excitatory activity in CNS so decreases cravings for alcohol
glucuronic acid conjugation
glucuronic acid is a glucose derivative that is transfered to an acceptor molecule from UDP-glucuronic acid with the action of the enzyme UDP-glucuronosyl transferase
functional groups that can undergo glucuronic acid conjugation
carboxyl (-COOH)
alcohol (-OH)
sulfhydryl (-SH)
amino groups (-NH2)
ethyl glucuronide test (EGT)
small amount of ethanol is conjugated to glucuronic acid and can be detected in urine for up to 5 days or more after alcohol consumption
used in legal proceedings
glucuronic acid conjugation in jaundice
UDP-glucuronosyl transferase is low so bilirubin is not conjugated with glucuronic acid for excretion
bilirubin builds up causes jaundice
glutathione conjugation
catalyzed by glutathione S-transferase
glutathione group is conjugated to nitro group, hydroxylamines, or epoxides
these are then cleaved into cysteine derivatives which are acetylated forming mercapturic acid which is excreted in urine
sulfate conjugation
sulfertransferase in liver takes sulfate group from PAPS and puts in on phenols, alcohols, and aromatic amines
acetaminophen undergoes this conjugation
acetylation
N-acetyltransferase puts acetyl group from acetyl-CoA and is conjugated preferentially to amino acids
glycine conjugation
in the mitochondria of liver cells acylCoA glycinetransferase puts amino acid glycine onto aromatic carboxylic acids
ex. salicyaltes (i.e. aspirin)
methylation
methyltransferase puts methyl groups from S-adenosylmethionine onto S, N, and O groups
list all phase I reactions
reduction
hydrolysis
oxidation: microsomal (CYP450 and FAD-containing monooxygenase) and non-microsomal (MAO, ADH, diamine oxidase)
list all phase II reactions
conjugation reactions glucuronide conjugation glutathione conjugation acetylation sulfate conjugation glycine conjugation methylation
aspirin metabolism
salicylic acid group is active part of compound
the acetyl group aids in absorption and with crossing the blood-brain barrier
what is the dosing technique in people with liver insufficiencies
dosage is adapted empirically base upon serum drug concentrations because they will not handle drugs the same
drug elimination routes
- renal clearance (most common)
- biliary clearance
- intestine
- lung
- sweat
- tears
- milk
enterohepatic cycling
increase time of drug in body by reabsorption in the intestine and return to systemic circulation
why is there typically not back flow of of metabolized molecules back out of the lumen of the kidney
when metabolized they are made polar
how does pH and altering urine pH aid in drug elimination
weak acids can be eliminated by alkalinization of the urine via bicarbonate treatment
elimination of weak bases may be enhanced by acidification of the urine via ammonium chloride treatment
if creatinine clearance is 50% of the normal value what can renal elimination of a drug expected to be
renal elimination of a drug is expected to be affected the same way as creatinine clearance is, so in this case it would also be decreased to 50% of normal and the drug dosage should be adjusted accordingly
3 factors that affect plasma drug concentrations
- rate at which drug is administered
- volume in which drug distributes
- drug clearance
equation for total clearance
total clearance = Ke (Vd)
Ke= a constant used to represent the fraction of drug eliminated per unit of time
4 most commonly used antihypertensice drugs
ACE inhibitors
AT1 antagonists
calcium channel antagonist
thiazide diuretic
ACE inhibitor examples
captopril (short duration of action)
enalapril and lisinopril (longer durations of action)
ACE inhibitors are more often used to treat what populations
younger or people of european origin who are more likely to have normal or high plasma renin
ARB mechanism of action
block receptors of angiotensin II which inhibits vasoconstriction to occur
ARB examples
losartan, candesartan, valsartan, and irbesartan
ARBs are more often used to treat what populations
younger and people of european origin who are more likely to have normal or high plasma renin
calcium channel antagonist examples
dihydropyridines (nifedipine, amlodipine) act preferentially on smooth muscle anda re used as casodilators but may cause tachy
verapamil: causes vasodilation but it also acts directly on heart producing negative chronotropic and inotropic effects
dilitiazem: works a little bit on vasodilation and a little bit on the heart
calcium channel antagonists are more often used to treat which populations
older people or people of African origin who are more likely to have lower plasma renin
HYZAAR
combination of losartan, potassium, and hyrochlorothiazide
vaseretic
enalapril, maleate, and hydrochorothiazide
renin inhibitor example
aliskiren
alpha 1 antagonist mechanism of action
inhibit sympathetic vasoconstriction and cause vasodilation
alpha 1 antagonists ex
doxazosin and terazosin
phenoxybenzamine
non selective alpha receptor antagonist which binds irreversibly and produces a drop in blood pressure, only used for patients undergoing surgery to remove phaeochromocytoma (catecholamine secreting tumor) to prevent effects of sudden catecholamine when the tumor is disturbed
metroprolol
beta receptor antagonist
useful in patients with other indication or beta blockade such as angina
low doses are combined with diuretic for example metoprolol and HCTZ are combined in Lopressor HCT
aldosterone antagonist mechanism of action
normally aldosterone increases reabsorption of Na and H2O and the release of potassium in the kidneys which increases BP, useful when potassium sparing is desired
aldosterone antagonist examples
spironolactone
potassium channel activator mechanism of action
open KATP channels to hyperpolarize smooth muscles and switch off voltage dependent calcium channels, calcium levels drop resulting in vasodilation
potassium channel activator ex
minocidil: very potent and long lasting, used as last resort
endothelin receptor antagonist mechanism of action
block receptors of endothelin (normally causes vasoconstriction, synthesis stimulated by trauma or inflammatio) receptors: ETA, ETB
used mainly for pulmonary artery hypertension
endothelin receptor antagonist ex
bosentan
alpha methyldopa
safely used in pregnancy, decreases blood pressure as a sympatholytic without affecting renal function and is suitable for renal insufficient patients
hydralazine
decreases BP by unknown mechanism acting mainly on arteries and arterioles
often accompanied by reflex tachy and increases CO, mainly used for short term treatment of severe hypertension during pregnancy
Nitric Oxide treating hypertension, mechanism of action
activates guanylyl cyclase –> cGMP –> PKG, cyclic nucleotide phosphodiesterase, and ion channels –> inhibits calcium induced smooth muscle contraction
nitric oxide donor example
nitroprusside
neprilysin
neutral endopepridase that cleaves natriuretic peptides: ANP, BNP, CNP to produce vasodilation
sacubitril
inhibits neprilysin (normally cleaves natriuretic peptides- ANP, BNP, CNP) leading to increased levels of natriuretic peptides and the subsequent vasodilation neptrilysin also degrades angiotensin II therefore sacubitril increases angiotensin II
