Drugs Flashcards
Chloramphenicol
In neonates interferes with mitochondrial ribosomes and causes gray baby syndrome. Sx- poor feeding, decreased breathing, CV collapse, cyanosis, and death
Succinylcholine
short acting muscle relaxer used in surgery. Butyrylcholinesterase (BChE) hydrolysis of this creates a decreased rate of metabolism of succinylcholine resulting in prolonged paralysis after drug exposure.
N-acetyltransferase 2 (NAT2)
Catalyzes the acetylation (route of metabolism for specific drugs) of isoniazid, hydralazine, and procainamide. This does either slow or fast acetylators (slow=build up and fast = not working)
CYP2D6
Metabolizes metoprolol (lowers <3 rate), haloperidol (Antipsychotic), codeine, and fluoxetine (Depression)
Metoprolol
A beta blcoker used to decrease the heart rate. A poor metabolizer has potential toxicity with standard doses of this medication.
Codeine
Ineffective w/out metabolism by CYP2D6 to from the more potent opioid morphine. Normal codeine does not result in overdose.
Thiopurine S-Methyltransferase (TPMT)
Catalyzes the S-mehtylation of thiopurine drugs such as 6-mercaptopurine and azathiprine immunosuppressant agents (Used in CHEMO)
Zileuton
used for asthma by decreasing the airway inflammation by inhibitiing 5-lipoxygenase.
Warfarin
Metabolized predominately by CYP2C9. Warfarin’s target is viamin K epoxide reductase (an enzyme that is required for vitamin K dependant generation of clotting factors)
Abacavir
HIV medication that has an idiosyncratic reaction with HLA-B*5701 by inducing hypersensitivity.
Aminoglycoside Antibiotics
Gentamicin, tobromycin, amikacin, neomycin, and streptomycin. Must be administered via a parenteral route due to poor GI absorption. Very water soluble w/ poor distribution into adipose tissue. Clearance is almost entirely renal
Vancomycin
Antibiotic.
Poorly absorbed orally although useful in tx of C.diff with PO route. Systemic infections require parenteral dosing.
Increases levels/effects of aminglycosides- used for infections together.
Half life of 5-11 hrs.
Phenytoin
Absorption from oral route is slow.
Highly protein bound
Consider diseases that result in decreased serum albumin concentration such at burns, nephrotic syndrome, and renal failure.
An example of a P450 inducer
Moves from 1st order quickly to zero order occurring even at therapeutic levels
Valproic acid
Used as antiepileptic and as a mood stablizer.
Bioavailability 90% relative to IV dose
Saturable protein binding 80-90% free fraction.
Metabolism extensively hepatic via glucuronidation (conjugation)
Only p450 inhibitor (in antiepileptic class.
Relationship b/w dose and total valproate [ ] is not linear.
Draw levels 2-4 days of initiation to etermine total valproic acid.
Carbamazepine
Anti-epileptic
Slow absorption
Highly protein bound to plasma albumin and alpha1-acid glycoprotein.
Concamitant tx w/ valproate sodium results in higher free fraction
Eliminated primarily by metabolic route, one active metabolite, carbamazepine 10, 11 epoxide.
Metabolized primarily by CYP3A4
Induces own metabolism and goes from a long 1/2 life to a shorter one.
Steady state= 2-5 days
Warfarin
Oral anticoagulant-rapid complete absoption. Onset of action 24-72 hrs. Peak effect 5-7 days Highly protein bound (99%) Metabolism primarily by CYP2C9
Digoxin
Cardiac medication
Absorbed by passive non-saturable diffusion in SI.
Distribution phase lasts 6-8 hrs.
Large volume to distribution. After distribuiton you have a 70:1 in the heart vs. in the blood.
Very narrow therapeutic index
Epinephrine
Andrenergic Agonist
Interacts with both alpha and beta
Low dose- mainly beta effects (vasodilation); high dose- alpha effects (vasoconstriction
CV: + inotropic, + chronotropic- increased CO
Alpha effects- vasoconstricts arterioles
B2- vasodilates vessels to liver and skeletal muscle
Net result- increased SBP w/ slight decrease in DBP
Respiratory- bronchodilation of smooth muscle (B2)
Hyperglycemia-decreased insulin release (alpha2) increased glycogenesis, increased release of glucagon (B2)
Lypolysis B1
Epinephrine therapeutic uses
Emergent tx of asthma, glaucoma, anaphylaxis, w/local anesthetics to prolong DOA through vasoconstriction
Epinephrine ADRs
CNS- anxiety, fear, tension, HA, tremor, hemorrahage, increased BP, cerebral hemorrhage
CV-arrhythmias
Pulmonary edema
Norepinephrine
Adrenergic Agonist
At therapeutic doses alpha 1 and beta 1 receptors are afected
CV- vasoconstriction in periphery (including kidney) reulting in elevated BP, baroreceptor reflex: increase BP -> increased vagal activity stimulation baroreceptors causing bradycardia.
Tx use shock through vascular resistance, increase BP
Dopamine
Adrenergic Agonist
Low doses act predominately on D1 receptors in renal, mesenteric, and coronary vascular beds (vasodilation).
Higher doses a positive inotrope (action at beta1)
High doses- vasoconstriction via alpha 1 receptors
DOC for shock, at appropriate doses is useful in management of low CO associated with compromised renal function such as in severe CHF.
Methoxamine
Adrenergic Agonist
Alpha 1 selective agonist
Not used often but used to tx shock
Phenylephrine
Adrenergic Agonist
Alpha 1 selective agonist
Used like psuedofedrin, Topical constrict vascular smooth muscle in relief or nasal congestion
Not catechol derivative so substrate for COMT
Induces reflex bradycardia when given parenterally, raises BP due to vasoconstriction.
Oxymetazoline
Adrenergic Agonist
Alpha 1 selective agonist
Topical, constrict vascular smooth muscle in relief of opthamic hyperemia.
Chlonidine
Adrenergic Agonist
Alpha 2 selective agonist
Lowers BP by suppressing sympathetic outflow
ADR dry mouth and sedation
a-methyldopa
Adrenergic Agonist
alpha 2 selective agonist
Metabolized to a-methylnorepinephrine which is an a agonist in CNS to decrease sympathetic outflow
Gaunfacine
Adrenergic Agonist
a-2 agonist in CNS to decrease sympathetic outflow
ADR dry mouth and sedation
Isoproterernol
Adrenergic Agonist
Nonspecific B agonist (acts at B1 and B2)
CV: + inotropic and chronotropic effects (B1); vasodilation of arterioles of skeletal muscle (B2)
Pulmonary- bronchodilation (B2)
Uses- stimulates heart in emergencies
Dobutamine
Adrenergic Agonist
B1 selective
Increases cardiac rate and output, usted to increased CO in CHF, racemic mixture cancers out alpha
Albuterol, pirbuterol, terbutaline
Adrenergic Agonist- B2 selective
Short acting bronchodilators (less cardiac stimulation)
Salmeterol and formoterol
Adrenergic Agonist
B2 selective agents
B2 long acting bronchodilator
Amphetamine
Indirect adrenergic agonist
CNS stimulant, increases BP by alpha effect of vasculature, beta effect on heart
Ephedrine
Mixed action
Alpha, beta, and CNS stimulant
Use- nasal sprays due to local vasoconstrictor activity; urinary incontinence
Long DOA
Phenoxybenzamine
Adrenergic antagonist Alpha blocker
Irreversible, nonselective and noncompetitive block, tx of pheochromocytoma to preclude HTN crisis that can result from manipulating tissue.
Phentolamine
Adrenergic antagonist Alpha blocker
Competitive, nonselective block (alpha 1 and 2 response is more E being created and alpha 1 decreased vasoconstriction)
Prazosin, doxazosin, terazosin
Adrenergic antagonist Alpha blocker
Selective alpha1 blocker- used for vasodilation
Tx- hypertension, BPH, CHF by relaxing the arterial and venous smooth muscle and decreased PVR.
Tamsulosin
Adrenergic antagonist Alpha blocker
Tx of BPH (benign prostate hyperplasia)
Inhibitor of Alpha 1 receptor on smooth muscle of prostate (decreases tone of bladder neck and prostate and improves urine flow.)
Propranolol (prototype)
Adrenergic antagonist beta blocker
Nonselective
Uses- lowers BP, used to tx angina, cardiac arrhythmias, MI, glaucoma, prophylaxis for migraines
Effects- lowers cardiac output (rate and force), prevents vasodilation, bronchoconstriction, increased Na retention, decreased glycogenolysis, and glucagon secretion
Timolol and nadolol
Adrenergic antagonist beta blocker
Nonspecific beta blocker
Uses- glaucoma and HTN
Acebutolol, atenolol, metoprolol, esmolol
Adrenergic antagonist beta blocker
Preferentially blocks beta 1 receptors- cardioselective
Eliminates unwanted bronchoconstriction, little effect of CHO- metabolims, or PVR
Useful in hypertensive DM pt on insulin or oral hypoglycemics
Pindolol and acebutal
Adenergic antagonists w/ partial activity
Weakly stimulate B1 and B2. Used for HTN
labetolol and carvediol
Antagonists of alpha1 and beta 1&2 receptors. Peripheral vasodilation, dont alter lipid of glucose levels. Carvediol decreased lipid peroxidation and vascular wall thickening to benefit CHF
Uses of labetolol- HTN, CHF, PIH, HTN emergenies -> rapidly lowers BP
Benzodiazepines
Midazolam, diazepam, alprozolam, chlorazepate, lorazepam, chlordiazepoxide, clonazepam, flurazepam, temazepam, triazolam, zolpidem
Do not activate receptor in absence of GABA. Still require 2 GABA to bind then benzo makes it work better
Highly selective, high affinity drugs that bind a single site on GABA receptor a1, a2, a3, or a5, and a y subunit.
Potency is correlated to hydrophobicity
Highly protein bound
Benzodiazepines
Admin via oral, transmucocal, IM and IV.
Metabolized by CYP3A4
Used as sleep enhancers, anxiolytics, sedatives, antiepileptics, muscle relaers, and for the tx of ETOH withdrawl.
ADRs related to therapeutic effects- amnesia
Antagonist Flumazenil reverses effects
High potential for development of tolerance, dependence, and addiction
Barbiturates
Butabarbital, butalbital, methohexital, pentobarbital, primidone, secobarbital, and thiopental.
Affect CNS sites in spinal cord, brainstem, and the brain.
Cause sedation, amnesia, and LOC by affecting GABA receptors,
Spinal cord- relaxes muscles and suppressed reflexes
Anesthetic barbiturates
Ionotrophic GABA receptor
Thiopental, pentobarbital, and methohexital
Act as agonists at GABA-a and enhance the receptors response to GABA (dont not require the presence of GABA at receptors)
Phenobarbital
Anticonvulsant Barbiturates
Less direct agonist. Works for inhibiiton effects but does not cause the same amount of sedation as anesthetics.
Barbiturates
Oral or IV admin.
Lipid solubility allows to enter CNS, termination effect depends on redistribution from CNS to highly profused areas.
Extensive hepatic metabolism P450 and induce P450 enzymes
Etomidate and Propofol
Ionotrophic GABA receptor
Used to enduce conscious sedation prior to surgery.
Enhance activation of GABA-A and at high doses acts as an antagonist. INduce anesthesia in high enough doses
Baclofen
Metabatrophic GABA receptror
GABA-B agonist
Used to tx spacicity associated with motor neuron disease.
Mild- oral absorbed slowly, primarily cleared in urine, no tolerance.
Severe- intrathecal- peaks at 4 hours, and tolerance develops after 1-2 years
Withdrawl can precipitate acute hypersensitivity, rhabdomylosis, pruritus, delerium, and fever.
Ethanol
Multiple targets including GABA-A and glutamate receptors
Chloral hydrate
originally used as anesthetic now used to commit crimes and to prevent memory
Gamma hydroxybutyric acid (GHB)
GABA isomer clinical use for narcolepsy, used for crime and date rape
Riluzole, memantine, amantadine
NMDA antagoists (block the glutamate receptor, blocks the damage from excitatory)
Riluzole
Blocks NA channels therby decreasing glutamate plus acts as an NMDA antagonist (neurodegenerative disease)
Memantine and amantadine
Non-competitive blocker of NMDA.
Memantine- alzheimers,
Amantadine decreases dyskinesia in parkinsons
Lamotrigine
Stabilizes inactivated state of Na channel reducing excitability and glutamate release
Used in seizures.
Felbamate
One mechanism inhibit NMDA receptors- seizures.
Tiagabine
competitive inhibitor of GAT-1
Used for epilepsy
Vigabatrin
inhibits GABA-T
used as an anticonvulsant
a-methyltyosine
inhibits tyrosine hydroxylase (first step in synthesis of catecholamines)
Reserpine
Blocks VMAT, transport of bioamines (NE, DA, 5-HT) from cytoplasm into storage vesicles.
Tyramine
Dietary amine usually meabolized by MAO in GI and liver. In patients with MAO inhibitors on board tyramine is absorbed, large amounts cause displacement of vesicular NE and non vesicular release leading to hypertensive crisis.
Guanethidine
Displaces NE in storage vesicles, leading to gradual depletion of NE.
Will be destroyed by MOA and CTOA
Amephetamine
Displaces endogenous NE.
Weak inhibitor of MAO.
Blocks reuptake by NET and DAT
Little agonist action at alpha and beta receptors, marked behavioral effects
Cocaine
potent inhibitor of NET, essentially eliminates catecholamine transport
Used as a local anesthetic
Imipramine, Fluoxetine
SSRI selective seratonin R inhibitor.
Inhibits NET
Tricyclic Antidepressants
Blocks Na+/K+ ATPase, blocks NET
Precents reuptake of epinephrine/norepinephrine leading to an increased DOA.
Phenelzine
Inhibits MAO-A, increasing NE and 5-HT (Serotonin) content.
Inhibits metabolism of NE and seratonin
Selegiline
Inhibits MAO, increasing DA
Low doses used for tx of Parkinsons
Procaine, tetracaine, cocaine
Ester linked anesthetics
Metabolized locally by tissue and plasma esterases
Minutes with short DOA
Eliminated via the kidney
Lidocaine, prilocaine, bupivicaine, articaine
Amide linked anesthetics
Primarily P450 in the liver
Metabolites eliminated via kidneys
Longer DOA differing from drug to drug
Procaine
Ester based local anesthetic
Short acting, low hydrophobicity- low potency
Used for infiltration anesthesia and dental procedures
Rapidly metabolize in plasma by cholinesterases
One metabolite PABA.
Tetracaine
Ester based local anesthetic
long acting, highly potent due to high hydrophobicity
Metabolized by cholinesterase in plasma but slower effect than with procaine as it is slowly released from tissues in the blood.
Spinal and topical anesthesia
Cocaine
Natural occurring Ester based local anesthetic
Medium potency and DOA
Inhibits catecholamine uptake peripherally and centerally= vasoconstriction and euphoria (cardiac toxicity)
Ophthalmic and tropical anesthesia
Lidocaine and Prilocaine
Amide based
Moderate hydrophobicity, large fraction of drug is in neutral form at physiologic pH= rapid onset, med DOA, and moderate potency
Metabolism by live by P450
Used for peripheral nerve blocks, epidural, spinal, and topical anesthesia.
Toxicities- CNS depression and cardiotoxicity
Prilocaine
vasoconstricive
Lidocaine
antiarrhythmic
Bupivicaine
Amide based
long DOA and highly hydrophobic (high potency)
Metabolized by live P450
R and S enatiomer
Cardiac toxicity due to blocking Na channels in cardiac myocytes during systole but is slow to dissociate during diastole.
Articaine
Amide based
Exhibits an ester group making it act differently
Partially metabolized in the plasma by cholinesterase and in the liver by P450
Bethanechol- cholinergic agonist
Acts on receptors M1, M2, M3
Poor substrate for AchE
Sites- smooth musculature of the bladder and GI
Actions- increased intestinal motility and tone, and stimulates detrusor muscles of the bladder while the trigone and sphincter are relaxed causing expulsion of urine.
Therapeutic action- stimulates atonic bladder in postpartum or postoperative urinary renention.
Bethanechol side effects
sweating, salivation, flushing, HPOTN, N/D, abd pain and bronchospasm.
Carbachol (carbamylcholine)
Poor substrate of AchE with DOA of as long as 1hr
Action- M1, M2, M3 and wak nicotinic agonist-CV and GI systems- may first stimulate then depress, can also cause release of epinephrine for adrenal medulla by its nicotinic acitons.
Therapeutics- used seldomly, sometimes as miotic for gluacoma
Carbachol (Carbamylcholine) adverse reactions
Little to no side effects when used in the eye
Methacholine
Muscarinic Receptor Drug
Receptors- M1, M2, M3
Used as diagnostic challenge for bronchial hyperreactivity and asthmatic conditions
Pilocarpine
Muscarinic Receptor Drug
Dominant muscarinic response at M1, M2, M3
Tertiary amine and less potent
Action- rapid miosis and contraction of the ciliary muscle
Therapeutic use- emergency lowering of the intraocular pressure of both narrow and wide-angle glaucoma.
Pilocarpine ADR
CNS effects, profuse sweating and salivation
Physostigmine
Indirect- acting cholinomimetic drug
Glaucoma (miosis in the eye); increased intestinal and bladder motility, reverse CNS and cardiac effects of TCA (tricyclic antidepressant); reverse CNS effects of atropine.
Action- amplifies effect of Ach
Neostigmine, pyridostigmine, edrophonium
Indirect- acting cholinomimetic drug
Myasthenia gravis, helps w/ reversal of neuromuscular block
Action- amplified effects of Ach, increased muscle strength.
Isoflurophate and echothiopate
Indirect- acting cholinomimetic drug
Glaucoma (not the 1st line therapy
Action- amplifies the effect of Ach
Pralidoxime
Cholinesterase reactivator that breaks bonds between drugs and enzymes if the enzyme has not aged.
Celecoxib (celebrex)
may cause an increased risk of serious cardiovascular thrombotic events, MI, and stroke which can be fatal
Isotertinoin (Accutane)
Contraindicated in pregnancy
Major human fetal abnormalities, spontaneous abortions, and premature death.
Nicotinic receptor drugs- antagonists
Curare, pancuronium, cisatracurium, atacurium, mvacurium, and succinylcholine