Clonidine

• hypertension, sedative, opioid withdrawal
• centrally acting sympatholytic
• α-2 agonist = ↓ cAMP = inhibitory
• can also ↓ aqueous humor in the eye to ↓ intraocular pressure
• causes ↓ ACh release ➞ ↓ M3 activation in GI ➞ ↓ GI motility (constipation or treat diarrhea 
• α2 agonist in respiratory ➞ ↓ respiration
• ↓ NE in CNS = ↓ SNS and ↑ PSNS = ↓ CO + PVR

Propanolol

• hypertension, heart failure + excessive tachycardia, angina, arrhythmia 
• non-selective β-blocker
• ↓ HR and CO
• b/c ↓ HR ➞ vasoconstriction of organ and skin
• used frequently
• also causes: ↓ secretion in eye, contraction of smooth muscle, and vasoconstriction in skeletal muscle
• toxicities are with β2 blockade (asthma)

Metropolol

•  hypertension, heart failure + excessive tachycardia, angina, arrhythmia
• selective β1-blocker
• block β1 in heart = ↓ CO
• b/c ↓ HR body compensates ➞ vasoconstriction
• block β1 in juxta-glomerular of kidney = ↓ renin release = ↓ PVR
• also causes: ↓ secretion in eye

Prazosin

• hypertension
• selective α1-blocker
• block α1 in arterioles and venules = relax blood vessels
• body compensates with ↑ HR and ↑ renin = may need diuretics or β-blockers too
• also causes: relaxation of dilator muscle, ↑ secretion in eye, relaxation of sphincters, relaxation of pilomotor muscles
• toxicity = rare and mild (dizziness and headache)

Sodium Nitroprosside

• hypertension
• nitric oxide donor
• used in emergencies (short-acting)
• toxicities = hypotension and cyanide accumulation

 Varapamil

• hypertension, angina, arrhythmia
• calcium channel blocker 
• inhibits calcium influx into atrial smooth muscle cells ➞ relaxation ➞ vasodilation
• toxicity = bradycardia

Enalapril

•  hypertension, mild heart failure, left ventricular dysfunction (no edema)
• ACE inhibitor

Losartan

• hypertension, mild heart failure, left ventricular dysfunction (no edema)
• AT1 receptor blocker
• effectiveness similar to ACE inhibitor

Hydrochlorotriazide

• hypertension, mild heart failure, heart failure + edma
• thiazide diuretic
• inhibit NaCl transport in distal convoluted tubule = ↑ NaCl in urine = ↑ H2O in urine = ↓ blood volume = ↓ BP
• toxicities: hypokalemia, gout, dehydration

 Furosemide

• hypertension
• loop diuretic
• inhibits cotransport of Na+, K+, and Cl- = inhibit NaCl reabsorption inhibited 
• severe hypertensino and pulmonary edema
• toxicities: same as hydrochlorotriazide, and does-dependent ototoxicity (hearing loss)

Digoxin

• congestive heart failure + atrial fibrillation or enlarged/dysfunctional left ventricle 
• cardiac glycoside 
• inhibits Na+/K+ ATPase
• direct effect: ↑ Na+ inside cell ➞ ↓ Ca2+ efflux out of cell ➞ ↑ intracellular Ca2+ ➞ ↑ interaction between actin + myosin ➞ ↑ cardiac contractility (strengthen output)
• indirect effect: ↑ PSNS and ↓ SNS activity from improved circulation ➞ ↓ baroreceptor activation (↓ rate and how hard heart has to work)
• therefore ↑ force and ↓ rate of contraction 
• toxicities: arrhythmia (people with low K+) ➞ tachycardia and fibrillation, Quinidine reduces clearance, GI toxicities (anorexia, nausea, vomiting, and diarrhea) 

Nitroglycerin

• angina
• nitrate goup converted to NO ➞ ↑cGMP ➞ relaxation of smooth muscle ➞ vasodilation (and other tissues ie. bronchioles)
• effects = ↓ venous return, ↓ PVR, dilation of coronary arteries ➞ ↓ O2 requirements and ↑ O2 delivery
• toxicities: hypotension, tachycardia (baroreceptore reflex), headaches, and when used with sildenafil

Quinidine

• arrhythmia (all types)
• Na+ channel blocker
• prolongs Na+ channel in inactive phase ➞ subsequent stimulation of Na+ is delayed
• long-term treatment

Lidocaine

• arrhythmia 
• ventricular tachycardia/fibrillation
• emergency situations
• same mechanism as Quinidine

Amiodarone

• arrhythmias
• K+ channel blocker
• prolongs action potential duration ➞ delays time for next AP
• also effects β-receptors + Na+/Ca+ channels
• most common for atrial fibrillations, ventricular tachycardia)

Donepezil

• mild-moderate Alzheimer’s 
• Acetylcholine esterase inhibitor 
• inhibit breakdown of ACh
• side effects = similar to peripheral acting AChE inhibitors (primarily autonomic)

L-Dopa (levodopa)

• precursor to dopamine, norepinephrine, epinephrine
• can ↑ dopamine levels in brain 
• converted to dopamine by L-amino acid dexarboxylase (DDC)
• side effects = hypotension, arrhythmias, nausea, disturbed respiration, hair loss, confusion, extreme emotions (ie. anxiety), insomina, narcolepsy

Ropinirole

• Parkinsons
• dopamine agonist (D2, D3, D4 receptors)

Selegiline, deprenyl

• Parkinsons
• MAO inhibitor

Benztropine

• Parkinsons
• antimuscarinic  

Haloperidol

• psychosis
• butyrophenone derivative 
• receptor antagonist: D2 > α1 > D4 > 5-HT2a > D1 > H1 
• side effects: parkinson-like symptoms (D2 blockade), hypotension (α1 blockade)

Olanzapine

• psychosis
• atypical receptor antagonist: 5-HT2a > H1 > D4 > D2 > α1 > D1
• side effects: sedation (5-HT2a blockade)

Lithium

• bipolar (most effective against mania)
• may ↑ serotonin and ↓ NE + dopamine neurotransmission
• lithium ➞ ↓ in precursors for IP2 and DAG synthesis ➞ ↓ IP3 + DAG when receptors linked to second messengers are activated (ie. muscarinic, α1, 5-HT2a receptors)

Imipramine

• depression
• tricyclic antidepressant 
• ↓ NE and serotonin re-uptake
• adverse effects b/c = blocks cardiac sodium channels and is antagonist at muscarinic, histaminic, and α1 receptors

Bupropion

• depression
• weak inhibitor of re-uptake and stimulates release of NE and dopamine
• doesnt block histaminic, adrenergic, or muscarinic receptors
• increases dopamine levels (not good in psychosis)

Fluoxetine (Prozac)

• depression, anxiety, OCD, bulemia
• most widely prescribed
• serotonin re-uptake inhibitor 
• side effect: insomnia, sexual dysfunction, ↑ suicide rates in children, inhibits CYP2D6 (overdose when taken with other antidepressants)

Phenelzine

• depression
• MAO inhibitor
• not selective for MAO-A or MAO-B therefore ↑ NE, serotinin, and dopamine
• only used when tricyclic don’t work 
• no significant side-effects when taken on their own
• when taken with a tyarmine-containing food or with CNS stimulants ➞ hypertensive crisis
• do not take with any seroternergic agents (SSRIs, SNRIs, tricyclics) ➞ serotonin syndrome 
• sympatheticomimetics contradicted in people taking MAOIs

Diazepam (Valium)

• anxiety, ethanol withdrawal
• a benzodiazepine
• all metabolites are active
• enhances GABA neurotransmission by binding to GABAa receptor at different site and ↑ binding frequency of GABA-mediated opening of Cl- channel
• enhance Cl- conductance ➞ ↑ inhibition of many neurons in many brain regions

Phenobarbital

• anxiety
• a barbiturate
• enhances GABA neurotransmission by binding GABAa at different site and ↑ duration of opening of GABA-mediated Cl- channels
• at high doses can directly activate GABAa and inhibit glutamate receptors and high-frequency sodium channels (lower therapeutic margin)
• also ↑expression of some cytochrome P450 enzymes

Ethanol

• a sedative-hypnotic
• ↓ membrane excitability, ↑GABAa, ↓NMDA activation ➞ dose-dependent CNS depression
• also: ↓ myocardial contractility, ↓ anxiety, slurred speech, impaired judgment 
• toxicicity: CNS and respiratory depression
• chronic use: fatty liver ➞ hepatitis ➞ cirrhosis ➞ liver failure, pancreatitis, gastritis, malnutrition

Methanol

• metabolizes ➞ formaldehyde ➞ formic acid
• formic acid accumulation causes blindness
• treat with ethanol (compete for alcohol dehydrogenase)

Heroine

• drug of abuse
• opioid
• presynaptic: binds to μ receptor linked to G-protein ➞ ↓ Ca+ ➞ ↓ release of neurotransmitters (GABA and glutamate)
• postynaptic: binds to μ receptor ➞ ↑ K+ efflux ➞ inhibits postsynaptic renurons (more negative and harder to activate)
• overdoes: respiratory depression ➞ coma ➞ death
• methadon and chlonidine to treat withdrawal

Cocaine

• drugs of abuse
• stimulant
• highly addictive
• ↓ re-uptake of NE, dopamine, and serotonin ➞ ↑ alertness and euphoria
• side-effects: psychosis, delusions, excess SNS activity
• overdoes: intracranial hemorrhage, stroke, seizure, arrhythmia, heart attack, hyperthermia, coma, death

 Amphetamines

• drug of abuse
• stimulant
• ↑ release of NE, dopamine, and serotonin ➞ ↑ alertness and euphoria
• side-effects: psychosis, delusions, excess SNS activity
• overdose: hyperthermia, serotonin syndrome, seizures, neuronal damage

LSD (lysergic acid diethylamide), mescaline, psilocybin

• drug of abuse
• 5-HT2a partial agonist 
• causes visual illusions and perceptual distortion
• side effects: panic, psychosis, strong uterine contractions

Phencyclindine (PCP)

• drug of abuse
• NMDA receptor antagonist
• causes visual illusions and perceptual distortion
• side effects: panic, psychosis
• can be fatal in overdose 

Marijuana, Hashish

• drug of abuse, cancer, glaucoma, AIDS
• THC binds cannaboid receptor (CB1 and CB2) linked to G-protein ➞ inhibits GABA or glutamate release
• initial effect: euphoria, laughter, altered sense of time
• secondary effect: relaxation, introspection, ↓ reaction time, ↓ learning/memory
• side effects: can causes paranoia, anxiety, hallucinations
• chronic: bronchitis, lung cancer 

Dexmedetomidine

• sedative and analgesic
• α-2 agonists
• stimulate α2 receptor ➞ open K+ channels ➞ inhibit neurotransmitter release in brain
• causes: sedation, analgesia, hypotension, muscle relaxing, ↓ O2 exchange

 Diazepam (Valium)

• sedative-hypnotic, muscle relaxant
• benzodiazepine
• enhances GABA neurotransmission by binding to GABAa receptor at different site and ↑ binding frequency of GAMA-mediated opening of Cl- channel
• enhance Cl- conductance ➞ ↑ inhibition of many neurons in many brain region
• little effect on cadiovascular system and little respiratory depressant at therapeutic doses
• side effect: drowsiness and confusion, CNS depression with alcohol use
• adverse effects reversed by flumazenil (GABAa antagonist)

Fentanyl

• analgesic, sedative, cough suppression
• opioid
• stimulate pre-synaptic μ-opioid receptor in CNS ➞ inhibits GABA and glutamate release ➞ intense analgesia
• side effects: constipation, nausea, urine retension, dose-dependent resp depression (death in overdose)

Pentazocine

• good analgesia but weaker effect at μ receptor (partial agonist)
• opioid

Naloxone

• reverse opioid overdose, opioid effects after surgery, or for shocky patients 
• opioid receptor antagonist

Etorphine (M-99)

• 1000-8000 X more potent than morphine 
• opioid
• used in wild-life
• reversal agent = M5050

Thiopental Sodium

• induction agent and short term anesthesia
• barbituate 
• enhances GABA neurotransmission by binding GABAa at different site and ↑ duration of opening of GABA-mediated Cl- channels
• at high doses can directly activate GABAa and inhibit glutamate receptors and high-frequency sodium channels (lower therapeutic margin)
• does-dependent CNS but partial does causes excitement, less smooth recovery (esp if multiple doses)
• effects: does-dependent resp depression, 30 second apnea,  hypotension, and extravascular damage

Propofol

• induction agent and short procedures
• facilitates effect of GABA at GABAa in brain ➞ inhibits action potentials
• smooth induction without excitement stage, rapid smooth recovery
• adverse effects: dose-dendent resp depression, 60 second apnea, hypotension, diarrhea

Ketamine

• dissociative anasthetic and moderate analgesic
• inhibits NMDA and GABA 
• inhibits perception of signals associated with senses without totally abolishing consciousness
• dissociative = open eyes, swallow, can hear, intense muscle rigidity, hallucinations, disconnected from surroundings and pain 
• adverse effects: hypo- or hyperthermia, mood alterations, floating, vivid dreams, hallucinations, ↑ BP, minimal resp depression, can precipitate seizures, excitement if used alone

Halothane

• inhaled anesthetic
• halogenate hydrocarbon
• facilitates GABA at low concentrations and directly activates GABA receptors at high concentrations ➞ opens Cl- channels ➞ inhibits APs
• adverse effects: liver damage (25% metabolism), ↓ CO + EP release + ↑ sensitivity to EP ➞ arrhythmias, hypothermia, malignant hyperthermia (inherited disorder)

Isoflurane

• inhaled anesthetic
• halogenate hydrocarbon
• facilitates GABA at low concentrations and directly activates GABA receptors at high concentrations ➞ opens Cl- channels ➞ inhibits APs
• only 0.2% metabolized and low solubility in tissues ➞ less hepatic damage, less depression of CO, less potenet than halothane
• adverse effects: dose-dependent ↓ in BP and bad odour

Sevoflurane

• inhaled anesthetic
• halogenate hydrocarbon
• facilitates GABA at low concentrations and directly activates GABA receptors at high concentrations ➞ opens Cl- channels ➞ inhibits APs
• less odour and even less soluble in tissues than isoflurane but slightly more metabolized 

Nitrous Oxide (N₂O)

• inhalant analgesic but not anesthetic
• weak CNS depressant 
• used to decrease amount of other inhalants needed and increase speed of gas anesthetic uptake 
• no respiratory depression and little cardiovascular effects 
• can cause toxicity (rapid uptake of other inhalants), gas pockets in GI, and hypoxia

Atracarium

• non-depolarizing neuromuscular blocker
• competitive antagonist of AChRs (Nm)➞ intense relaxation or paralysis of voluntary muscle (dose-dependent)
• prevents eye movement during ocular surgery
• rapid reversal with AChEs (neostigmine, edrophenium)
• adverse effects: can trigger histamine release, metabolized to laudacarium and can trigger seizures
• now use lisatracarium (less adverse effects)

Local Anesthetics

• bind receptor on cytoplasmic surface of voltage-sensitive Na+ channels and block pore ➞ Na+ cant enter cell ➞ inhibits APs in axons
• small fibers (ie pain) are blocked at lower concentrations ➞ motor fibers blocked last 
• adverse effects: dose-dependent drowsiness ➞ excitations (seizures), ↓ excitability of myocardium ➞ AV block, arrhythmias, high concentrations = cardiac arrest, when with vasoconstrictor (ie. EP) ➞slow delayed healing and removal of drug ➞ prolongs action and doubles duration (toxicity)

 Lidocaine

• local anesthetic, arrhythmia (ventricular tachycardia/fibrillation)
• various administrations
• overdose = drowsiness or seizures ➞ muscle twitching and possibly cardiac arrest ➞ death
• emergency situations
• same mechanism as quinidine

Bupivacaine

• local anesthetic
• slower onset but greater duration 
• greater CVS toxicity

 Levobupivacaine

• local anesthetic 
• S-enantomer of Bupivacaine
• doesnt distribute to CNS and heart ➞ less CVS toxicities

 Proparacaine

• local anesthetic 
• least irritating for eye