codeine
-morphine with an O-methyl group at position 3
- may cause dysphoria and agitation
- cough suppressant
- may cause anaphylactoid reactions due to displacement of histamine from tissue mast cells
- codeine is biotransformed via CYP2D6 to its active metabolite leading to polymorphism of effects
heroin
morphine O acetylated at positions 3 and 6
meperidine
- opioid agonist
- rapidly absorbed, fast onset, wide distribution and rapid clearance
- may cause seizures, especially in patients with renal insufficiency (poor clearance of the polar metabolite)
- may cause anaphylactoid reactions due to displacement of histamine from tissue mast cells
naloxone
- an opioid antagonist
- rapidly reverses opioid overdose
- short effect
- used to treat opioid induced respiratory depression
"give nala oxygen"
Morphine
- opioid agonist
- relatively hydrophilic drug, so CNS penetration and exit are slow accounging for its slow onset and long duration
- may cause anaphylactoid reactions due to displacement of histamine from tissue mast cells
methadone
- a long acting opioid used for opioid agonist addiction
- more mild withdrawal symptoms
- develops cross tolerance so that heroin injection does not produce as satisfying an effect
fentanyl
- opioid agonist
- extremely lipophilic - rapidly crosses BBB so that plasma concentrations match effects
- lipophilicity enables many routes of administration
naltrexone
opioid antagonist
- used orally in high doses to treat detoxified heroine addicts (blocks the euphoria of injected heroin)
methylnatrexone
opioid antagonist
- selective because its a quat ammonium (can't cross BBB).
- Means that it can antagonize opioid induced constipation without dampening analgesic opioid agonist effects
buprenorphine
- a partial opioid agonist at the mu receptor
- has morphine like effects, but when given with morphine it dampens morphine effect via competition
- a long acting opioid used for opioid agonist addiction
- more mild withdrawal symptoms
- develops cross tolerance so that heroin injection does not produce as satisfying an effect
nalbuphine (nalorphine, pentazocine)
- partial agonist at the ku receptor
- produces analgesia at ku receptor
-but competitively antagonizes mu receptor
butorphanol
- a partial agonist at the mu receptor
- an agonist at the ku receptor
ACh
- endogenous NT agonist
- acts on N and M receptors
- degrades by acetylcholinesterase
- quaternary ammonium - does not cross BBB
Carbamylcholine
- agonist that acts on N and M receptors
- NOT degraded by acetylcholinesterase
- quaternary ammonium - does not cross BBB
Nicotine
- agonist of N receptors
- a tertiary ammonium so does cross BBB and have CNS effects . can also be administered transdermally due to lipophilicity
- acute toxicity via insectisides or tobacco based products
- rapid onset of symptoms
- abdominal pain, nausea, diarrhea, disturbed hearing and vision, weakness,
mental confusion
stimulates both SNS and PSNS system as well as NMJ
tubocurarine
- a nondepolarizing skeletal muscle relaxant
- a competitive antagonist of ACh at nicotinic receptors
- results in flaccid paralysis
- can be antagonized by an acetylcholinesterase inhibitor to increase ACh at the NMJ and lead to activation of muscle fibers
- may cause an allergic reaction via histamine release
- can produce hypotension by blocking ganglia
succinylcholine
- a depolarizing muscle relaxant
- actually a nicotinic agonist, meaning that it binds initially causing muscle fasiculations, but then causes receptor insensitivity to ACh and voltage sensitive sodium channel inactivation
- rapid onset
- short duration
- resistant to acetylcholinesterase
- hydrolyzed by cholinesterase
- patients with atypical cholinesterase have prolonged paralysis
- hyperkalemia due to sodium channel inactivation
- malignant hyperthermia due to runaway Ca+2
botulinum toxin
- prevents release of ACh at cholinergic nerve terminals
- voluntary muscle paralysis
- used for: cosmetics, focal dystonia, spasticity, CP, MS, spasms, tics, tremors, localized muscle cramps, smooth myscle hyperactive disorders, sweating disorders
- can lead to many adverse effects like dysphagia and anaphylaxis
neostigmine
- an acetylcholinesterase inhibitor
- the only acetylcholinesterase inhibitor that doesn't enter the CNS
- can be used to reverse the effects of nondepolarizing muscle relaxants like tubocurarine
- forms a reversible bond (unlike organophosphates)
- treatment for: myasthenia gravis, hyperthermia due to antimuscarinic intoxication, glaucoma treatment (enhances PSNS effect, helping with drainage of aqueous fluid)
- SLUDGE toxicity, can be treated with atropine
physostigmine
- an acetylchoinesterase inhibitor (meaning increased muscarinic activity)
- a carbamate ester
- used to treat atropine overdose by increasing ACh at the neuromuscular junction
- treats myathenia gravis, atropine poisoning, glaucoma etc.
- SLUDGE toxicity
atropine
- a muscarinic antagonist
- causes mydriasis, decreased accomodation, dry mouth, decreased gastric secretion, urinary retention, bronchial dilation, increased HR
- "blind as a bat, red as a beet, mad as a hatter, dry as a desert"
- major antidote for muscarinic antagonist poisoning (organophosphates)
- little CNS effect
scopolamine
- muscarinic antagonist
- causes mydriasis, decreased accomodation, dry mouth, decreased gastric secretion, urinary retention, bronchial dilation, increased HR
- "blind as a bat, red as a beet, mad as a hatter, dry as a desert"
- pre-anesthesia sedation
- prevention of motion sickness
- has a CNS effect
trimethaphan
- a ganglionic blocker
- selective inhibitors of autonomic ganglia nicotinic receptors
- effects the predominating tone of an organ
- ex: PSNS - causes increased HR
- ex: SNS - causes vasodilation (has a orthostatic hypotension side effect)
- used for acute dissecting aortic aneyrysm to reduce blood pressure and inhibit reflexes to elevate blood pressure
- used to reduce bleeding in surgery (decreased BP)
- spinal hyperreflexia (exag autonomic response)
pilocarpine
- a muscarinic agonist
- causes miosis, decreased heart rate, increased secretions and sweat, vasodilation, increased GI tone, erection, bladder contraction and sphincter relaxation
- SLUDGE toxicity
- can be used to treat xerostomia (dry mouth)
- glaucoma to increase cillary muscle tone helping to drain fluid
bethanocol
- muscarinic agonist
- causes miosis, decreased heart rate, increased secretions and sweat, vasodilation, increased GI tone, erection, bladder contraction and sphincter relaxation
- SLUDGE toxicity
- used for promotion of bladder emptying
- simulation of GI activity
organophosphates
- irreversible acetylcholinesterase inhibitor (increased ACh in the NMJ, leads to SLUDGE toxicity).
- examples: sarin gas, parathion, malathion (in many insecticides)
- can be reversed by cholinesterase regenerators in the early stage (pralidoxeme - "put the lid on organophosphates")
epinephrine
- endogenous alpha and beta agonist
- favors beta over alpha receptors at low doses
- causes a decrease in TPR due to beta2 effects over alpha 1 effects
- causes an increase in systolic pressure but a decrease in diastolic BP
- causes an increase in HR due to beta1 affinity
- can be used in the treatment of glaucoma (alpha1 vasoconstriction and alpha 2 decreased secretion)
- used in the treatment of acute allergic reaction and anaphylaxis - causes a restoration of BP (vasodilation via alpha1) and an increased heart rate (beta1).
Dopamine
- D1 agonist
- beta1>alpha1
phenylephrine
- alpha 1 and alpha 2 agonist
- can be used as a nasal decongestant (causes vasoconstriction of nasal arteries --> decreased edema and swelling)
- can restore blood pressure when overdosed on hypotensive agents
- used for spinal damage and anesthesia
- used opthalmologically for myadriasis
- treatment of wide angle glaucoma (alpha 1 vasoconstriction and alpha 2 for reduced secretion)
- toxicity: hypertension, cerebral hemorrahage, rebound nasal congestion)
clonidine
alpha 2 agonist
- centrally active
- an anti-hypertensive (causes adrenergic agonist reuptake thereby acting as a vasodilator)
- can assist with opioid withdrawal
- side effects: withdrawal symptoms from alpha 2 agonists - hypertension and tachycardia)
isoproterenol
- beta 1 and beta 2 agonist
- causes a decrease in TPR due to beta2 affinity
- causes an increase in systolic BP and a decrease in diastolic BP
- causes an increase in HR
dobutamine
- beta 1 selective agonist (predominates despite some alpha1 agonism and antagonism)
- used for cardiogenic shock (severely decreased BP --> increased HR and contractility)
- side effects: cardiac arrhythmia, tachycardia, myocardial ischemia
albuterol
- beta2 agonist (some beta1 activity)
- treatment of asthma by increasing bronchial smooth muscle relaxation
- side effect: risk of asthma exacerbation with long term use
tyramine
- a sympathomimetic
- found in wine, cheese and produced by gut flora
- usually degraded by MAO - becomes a problem with MAO inhibitor. can precipitate a hypertensive crisis via increase NE release from nerve terminals
- converted into octopamine which is stored in presynaptic vesicles in place of NE - octopamine has little agonist effect at the adrenergic receptor. ln the long term, this can lead to SNS impairment
-
cocaine
- sympathomimetic
- inhibits SER, NET and DOP reuptake pumps, increasing endogenous dopamine, NE and serotonin
- centrally active
- similar effects to d-amphetamine (anorexia, wakefullness, euphoria)
d-amphetamine
- sympathomimetic
- Releases norepinephrine and dopamine
- acts directly (α + β1)
- Orally active, marked CNS effects: wakefulness, anorexia,
euphoria, locomotor stimulation, stereotyped behavior. High abuse potential.
Psychotomimetic with prolonged abuse. Primary clinical use for ADHD
methylphenidate
- a sympathomimetic
- effects similar to amphetimine - releases NE and dopamine
- leads to wakefullness, anorexia euphoria and stereotyped behavior
phentolamine
- alpha 1 and alpha 2 antagonist
- treats hypertension (causes vasodilation)
- treatment of pheocromocytoma (tumor of adrenal gland --> increased catelcholamines--helps to dampen the widespread effect--> must be administered before a beta blocker
- treatment of Raynaud's
- treatment of heart failure (reduces TPR)
- treatment of benign prostatic hyperplasia (decreases smooth muscle tone in the bladder to ease difficult of urination)
- toxicity: postural hypotension (due to systemic vasodilation), reflex tachycardia, myocardial ischemia, salt and water retention and peripheral edema (happens because the decreased blood pressure leads to beta1 reflex stimulation which then activates renin release at the afferent arteriole), GI stimulation (abdominal pain, nausea, exacerbation of peptic ulcer), inhibition of ejaculation p
prazosin
- an alpha 1 antagonist
- assists with urination (benign prostatic hyperplasia)
- doesnt have as bad a side effect of orthostatic hypotension as other alpha antagonists
propranolol
- beta 1 and beta 2 antagonist
- centrally active
metoprolol
- beta 1 antagonist
- management of heart failure
- reduce mortality after MI
- treatment of hypertension (decreases CO, inhibition of renin production to prevent potent vasodilation and increased TPR)
- relief of angina
- treatment of cardiac arrhythmia
- treatment of hyperthyroidism
- migrain prophylaxis
- pheochromocytoma
toxicity: new onset diabetes, bradycardia, exacerbation of angina, fatigue, cold feeling, potentiation of epinephrine vasconstriction
carvedilol
- beta1, beta2 and alpha1 antagonist
- management of heart failure
- reduce mortality after MI
- treatment of hypertension (decreases CO, inhibition of renin production to prevent potent vasodilation and increased TPR)
- relief of angina
- treatment of cardiac arrhythmia
- treatment of hyperthyroidism
- migrain prophylaxis
- pheochromocytoma
toxicity: new onset diabetes, bradycardia, exacerbation of angina, fatigue, cold feeling, potentiation of epinephrine vasconstriction
Norepinephrine
- alpha and beta agonist
- alpha1>alpha2>beta1>>>beta2
- causes an increase in TPR via alpha1 agonism
- causes a decrease in blood pressure despite beta 1 agonism due to baroreceptor vagal reflex response
- causes an increase in both systolic and diastolic BP
- increase in BP
Diphenhydramine
- first generation H1 antagonist
- benadryl
- used to treat allergic response such a allergic rhinitis, conjuctivitis and urticaria
- anti-emetic, motion sickness, sedative hypnotics (because of CNS access)
- CNS effects because of lipophilicity
- side effects: sedation, antimuscarinic effects (acute toxicity resembling atropine poisoning), allergic dermatitis
loratadine
- second generation H1 antagonist
- claritin
- treats allergic response such as rhinitis, conjuctivitis, urticaria, nasal itching, watery eyes, rhinorrhea, sneezing
- does not treat nasal congestion
- treats mastocytosis (accumulation of mast cells)
- no CNS effects because of polarity
acetaminophen
- not really an NSAID- no real inflammatory response
- provides analgesia
- lacks NSAID side effects
headache, dysmennorea, joint pain, dental procedures
- decreased body temperature via action on hypothalamic nuclei - leads to increased peripheral blood flow and sweating --> increased heat loss
- no increased bleeding time (inadequate COX1 inhibition)
- used as analgesic of choice for babies (reyes syndrome via aspirin) and in asthmatics (increased allergic risk with NSAIDS)
- does not provide adequate analgesia in autoimmune disease such as RA and lupus
- toxicity: hepatic necrosis due to overworking CYP450 (biotransformer) - toxic minor metabolite
celecoxib
- selective cox2 inhibitor
- reduced GI side effects (as side effects are due to COX1 inhibition)
- can cause blood clotting
- risk of fluid retention and renal sodium excretion due to decreased renal PGL synthesis (more prevalent in patients with preexisting renal illness)
methotrexate
- Small, Low MW Antiinflammatory/Immunosupressant
- an antimetabolite - blocks purine or pyrimidine synthesis required for B and T cell replication
- drug of choice in RA
infliximab
- large, high MW biologic agent
- TNFalpha inhibitor
- blocks proinflammatory effects
hydrocortisone (cortisol)
- endogenous steroidal antinflammatory (glucocorticoid)
- short half life (8-12 hrs)
- anti -I effects via: inhibition of phospholipaseA2 (inhibits entire arachidonic acid cascade), decreased transcription of COX2, increase in MAPK phosphatase (inactivates proinflamm cascades), decreased cell adhesion factors, decreased fibrosis
- immunosupression via: increase in transcription of ikbeta which binds NF-kbeta - blocks transcriptional activity, inhibition of multiple interleukin cytokines, TNFalpha, IFNgamma, inhibition of Tcell and macrophage cytokine activity, inhibition of T and B cell replication, decreased IgG production
- used to treat adrenocortical insufficiency (Addison's)
- asthma, COPD
- RA, lupus
- psoriasis
- IBD
- emesis (surgery, chemo)
- leukemia
- organ transplants
- premature labor to stimulate surfactant production
- toxicity: not safe for chronic use - inhibits hypothalamic axis, Cushing's syndrome, hyperglycemia, osteoporosis, infection, impaired wound healing
prednisone
- glucocorticoid steroidal anti-inflammatory (see hydrocortisone)
- longer half life than cortisone (12-36h), shorter than dexamethasone
dexamethasone
- steroidal anti-inflammatory, glucocorticoid. see cortisone
- longest half life of the GC's - 36-72 hours
-
aspirin
- COX1 and COX2 inhibitor
- NSAID
- irreversibly binds COX
- analgesic, antipyretic, antiinflammatory
- headache, dysmennorea, joint pain, dental procedures
- decreased body temperature via action on hypothalamic nuclei - leads to increased peripheral blood flow and sweating --> increased heat loss
- bleeding risk due to COX1 inhibition, leads to decreased thromboxane and platelet aggregation, highest bleed risk of all NSAIDS
- because of decreased thromboxane and platelet aggregation, apsirin in small doses ("baby aspirin") is used to decrease risk of thromboembolic disorders (MI and ischemic attacks)
- GI risk due to COX1 inhibition of PGE2 (decreased alkaline mucous protection leads to increased risk of gastric ulcer and lack inhibition of PGE2 on parietal cell acid secretion)
- AVOID IN CHILDREN WITH FEVER - causes Reyes syndrome
- risk of fluid retention and renal sodium excretion due to decreased renal PGL synthesis (more prevalent in patients with preexisting renal illness)
- can cause bronchospasm, rhinorrhea, urticaria (mediated by leukotrines). more likely to occur in asthmatics - suggest acetaminophen as analgesic
- evidence suggests high concentrations inhibit KF-Kbeta (TF that promotes expressoin of certain inflammatory mediators)
ibuprofen
- COX1 and COX2 inhibitor
- NSAID
- analgesic, antipyretic, antiinflammatory
- headache, dysmennorea, joint pain, dental procedures
- decreased body temperature via action on hypothalamic nuclei - leads to increased peripheral blood flow and sweating --> increased heat loss
- helpful with analgesia in autoimmune diseases (unlike acetominophen)
- black box warning risk of MI due to prostacyclin decrease (a vasodilatory and antiplatelet factor)
- GI risk due to COX1 inhibition of PGE2 (decreased alkaline mucous protection leads to increased risk of gastric ulcer and lack inhibition of PGE2 on parietal cell acid secretion)
- bleeding risk (causes decreased thromboxane because of COX1 inhibition), prolongs bleeding time.
- risk of fluid retention and renal sodium excretion due to decreased renal PGL synthesis (more prevalent in patients with preexisting renal illness)